Autistic Spectrum Disorders in Children, Pediatric Habilitation Series Volume 12 (Marcel Dekker, 2004)

Autistic Spectrum
Disorders in Children
edited by
Vidya Bhushan Gupta
New York Medical College
and Columbia University
New York, New York, U.S.A.
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PEDIATRIC HABILITATION
Series Editor
ALFRED L. SCHEWER
Joan and Sanford 1. Weill Medical College
Cornell Universdy
New Yo&, New York
1. Prevention of Mental Retardation and Other Developmental Disabilities,

edited by Michael K. McCormack
2. Developmental Disabilities: Management Through Nutrition and Medica-
tion, Eric Denhoff and Steven Feldman
3. Early Diagnosis and Therapy in Cerebral Palsy, Alfred L. Scherzer and
Ingrid Tscharnuter
4. Parenting Children with Disabilities: A Professional Source for Physicians
and Guide for Parents, Peggy Muller Miezio
5. Visual Disorders in ths Handicapped Child, John L. Goble
6. Early Diagnosis and Therapy in Cerebral Palsy: A Primer on Infant Develop-
mental Problems, Second Edition, Revised and Expanded, Alfred L. Scher-
zer and Ingrid Tscharnuter
7. Attention Deficit Disorders and Hyperactivity in Children: Early Diagnosis
and Intervention, edited by Pasquale J. Accardo, Thomas A. Blondis, and
Barbara Y. Whitman
8. Medical Care in Down Syndrome: A Preventive Medicine Approach, Paul
T. Rogers and Mary Coleman
9. Manual of Developmental and Behavioral Problems in Children, Vidya
Bhushan Gupta
10. Attention Deficits and Hyperactivity in Children and Adults: Diagnosis
Treatment Management, Second Edition, Revised and Expanded, edited
by Pasquale J. Accardo, Thomas A. Blondis, Barbara Y. Whitman, and
Mark A. Stein
11. Early Diagnosis and lnterventional Therapy in Cerebral Palsy: An Inter-
disciplinary Approach, Third Edition, edited by Alfred L. Scherzer
12. Autistic Spectrum Disorders in Children, edited by Vidya Bhushan Gupta
ADDITIONAL VOLUMES IN PREPARA TION

About the Editor
VIDYA BHUSHAN GUPTA, M.D., M.P.H. is Associate Professor of Clinical Pediatrics

at New York Medical College, New York, and Associate Research Scientist at the
Gertrude H. Sergievsky Center, Columbia University, New York, New York. Dr. Gupta is
the author, coauthor, editor, or coeditor of three books, four book chapters, and numerous
scholarly articles published in journals such as Pediatrics, the Journal of Clinical
Epidemiology, and Clinical Pediatrics. He is a Fellow of the American Academy of
Pediatrics and has board certifications from the American Board of Pediatrics,
Neurodevelopmental Disabilities, and Developmental–Behavioral Pediatrics. An invited
expert to the 2003 American Academy of Pediatrics committee for early intervention and
autism and the 2004 Pediatric Subspecialty Care/Medical Home panel organized by the
U.S. Department of Health and Human Services, Dr. Gupta received the M.B.B.S. (1971)
and M.D. (1976) degrees from the University of Delhi, New Delhi, India, and the M.P.H.
degree (1989) from Columbia University, New York, New York.

Foreword
For over 25 years, the Pediatric Habilitation series has brought to readers the
latest information and significant emerging clinical approaches in the field of
developmental disabilities in children. Focus has always been on those specific
conditions demanding the greatest concern at the time. And developments have
been regularly updated with new editions when there has been rapid change, as in
the areas of cerebral palsy and attention deficit disorders.
Over this period of time there has been considerable shift in the disabilities
encountered by health professionals, from the high-morbidity, low-frequency
conditions, such as cerebral palsy and neural tube defects, to the low-morbidity,
high-frequency attention deficit disorders, learning disabilities, and, more re-
cently, the autistic spectrum disorders. These changes reflect advances in obstetric
and neonatal care and consequences of genetic, environmental, and social factors.
In addition, developmental disabilities in children are now seen as spectrum
disorders that usually occur with closely related comorbid conditions, rather than
as single and uniquely diagnosed entities that stand alone.
Since the inception of this series, nowhere has change been more striking
and, indeed, more stressful than in the area of autistic spectrum disorders.
Emerging data suggest a marked increase in incidence and prevalence, with a
corresponding demand for accurate diagnosis and more effective long-term
management. This comes at a time when accepted etiology of the autistic spec-
trum disorders has shifted dramatically from a psychiatric to a neurodevelop-
mental focus. Moreover, this field has been virtually flooded with literature

dealing with etiology, diagnosis, therapy services, treatment, and pharmacological
approaches. In addition, there has been a plethora of often confusing and
conflicting claims concerning complementary and alternative medical treatments
(CAM), to which both the health provider and lay public are constantly exposed.
Finally, much more frequent literature reference is made to the family of the child
with autistic spectrum disorder than in all other developmental disabilities. Yet
neither the impact of this diagnosis on family functioning nor the unique role of
the family in providing optimum care has been well delineated.
To provide for a comprehensive, multidisciplinary text that incorporates
the emerging issues in this field, Autistic Spectrum Disorders in Children has
been developed by a group of outstanding authorities and edited by Dr. Vidya
Bhushan Gupta, who has made major contributions to the work. Like all the other
books in the Pediatric Habilitation series, it is designed for a wide spectrum of
providers, emphasizes the habilitation approach to care and management, and can
lead to a better understanding of where further research is needed. It will clearly
have an important role in helping to clarify and unify current understanding of the
autistic spectrum disorders, and it is hoped this will result in a significant impact
on clinical practice as well.
Alfred L. Scherzer

Preface
Only a few decades ago, autism was a medical curiosity, conjuring up visions of a
child who walks on his toes like a ballerina, staring vacantly into space but is
capable of performing complex mathematical operations at the speed of light. Its
prevalence was reported to range from 0.7 to 4.5=10,000 children. Today, autism
is being diagnosed in 5–6 of 1000 children and an epidemic is suspected. A
debate is raging as to whether the prevalence of autism has truly increased or data
merely reflect heightened awareness of the condition. It is now agreed that autism
occurs along a spectrum, with only a few children manifesting the full range of
symptoms. Inclusion of milder and atypical variants of autism, such as Asperger’s
and Rett’s syndromes, under the rubric of pervasive developmental disorders, has
also contributed to the increasing prevalence of autism. Nosology of the syn-
drome is still in flux, with terms such as autism, autistic spectrum disorder,
pervasive developmental disorder, and mutlisystem disorder in vogue.
Our thinking about the origins of autism has undergone radical change.
Long gone are Kannerian ideas of refrigerated mothers. Instead, autism is now
regarded as a neurobiological disorder. However, as with any common disorder
that does not have an incontrovertible candidate as its cause, autism has become a
fertile ground for theories. There are theories about what part of an autistic brain
is abnormal, the nature of the abnormality, and how the abnormality translates
into abnormal behavior. No single area of the brain has been found to be
consistently abnormal in children with autism, but abnormalities have been
noticed in the cerebellum and the limbic system. The nature of the defect is

uncertain—findings include fewer neurons, excessive but smaller neurons, and
decreased dendritic branching. It is unclear as to how abnormal structure
translates into abnormal behavior, through serotonin or some other neurotrans-
mitter. What causes these neurobiological abnormalities? Is it an abnormal gene
or an infectious, toxic, or immunological agent? Perhaps both interact; a toxic or
infectious agent unmasks vulnerable genes, which then cause abnormal devel-
opment of certain areas of the brain. This neurobiological abnormality, in turn,
translates into abnormal behavior through abnormal neurotransmitter or electric
discharge through critical neural networks. Perhaps many pathways lead inde-
pendently or interactively to the constellation of symptoms that we call autism.
While many of these theories are grounded in valid research, such as the
cerebellar and serotonin theories, many are perpetuated by folklore and special
interest groups, such as the MMR vaccination theory and the ‘‘yeast connection.’’
Management of autism, too, has undergone sweeping change in the last few
decades. We have come a long way from institutions such as Vineland and
Willowbrook, where children ‘‘who did not grow’’ used to be incarcerated for a
lifetime. The emphasis today is on early detection and intervention. A substantial
body of literature now suggests that if intensive interventions are started early in
children with autism, many of them will be able to lead functional lives in the
mainstream. Therefore, platitudes such as ‘‘he will outgrow this, he is just a little
shy, give him some time,’’ have given way to early intervention to improve the
social and communication skills of these children. Better pharmacological agents
are available to address maladaptive behaviors such as inattention, compulsive
actions, and aggression.
There are many unanswered questions in the arena of autism and pervasive
developmental disorders. How can the frontline clinicians detect the condition
early? Is eliciting parental concerns or making informal observations during
clinical encounters sufficient? Are generic developmental screens effective in
diagnosing autism or should autism-specific screening tools such as CHAT be
used? How should autism be confirmed once it is suspected? Few conditions in
medicine can be pigeonholed into one discipline today. Autism sits on the mind–
body cusp, a neurobiological disorder with behavioral symptomatology. Which
professionals are competent to make the diagnosis—pediatricians, psychologists,
neurologists, or psychiatrists—and which evaluations should be performed to
develop a comprehensive management plan?
As a corollary to the myriad of theories about the causation of autism, a
myriad of cures for autism are being promoted by both conventional and
alternative schools of medicine. The purveyors of some of the unsubstantiated
therapies are exploiting the desperation of parents for selfish ends.
A quantum change has occurred in physician–patient relations and the
health care industry. Parents today are in the driver’s seat directing the manage-
ment of their child, instead of sitting in the backseat taking orders. While they

demand that providers use the newer genetic and neuroimaging tools to diagnose
and manage their children, the managed care organizations curtail their use to
contain costs. Both the consumers and payers demand of the providers that
they practice medicine according to the evidence-based guidelines developed by
academic societies and use outcome research to guide their therapeutic decisions.
The clinicians are caught in the crossfire of parental demand and payer oversight.
The idea for this book emerged in this radically changed environment.
Autism in this book has been approached from a broad, multidisciplinary
perspective, because many disciplines interact in the diagnosis and management
of autism. Attempting to bridge the gap between science and strategy, some
contributors have presented in depth the relevant scientific research available on
the subject, while others have focused on practical guidelines to professionals to
diagnose and manage children with autistic spectrum disorders in the context of
current scientific research and the health care climate. We hope that this book will
serve both the inquisitive, who want to explore the complex maze of autism, and
the practical, who in the trenches provide services to children with autistic
spectrum disorder.
I want to thank Dr. Alfred Scherzer, who inspired me to undertake this
monumental task, and Dr. Raksha Gupta, my wife, who put up with my
compulsive preoccupation with this book to the exclusion of almost everything
else at home. I would also like to thank Moraima Suarez at Marcel Dekker for
working so diligently with me.
Vidya Bhushan Gupta

Contents
Foreword Alfred L. Scherzer

Preface
Contributors
1. History, Definition, and Classification of Autistic Spectrum

Disorders
Vidya Bhushan Gupta
2. The Epidemiology of Autism and Autism Spectrum Disorders

Tanya Karapurkar, Nora L. Lee, Laura Kresch Curran,
Craig J. Newschaffer, and Marshalyn Yeargin-Allsopp
3. Etiology of Autism
Vidya Bhushan Gupta
4. Neurological Basis of Autism

Vidya Bhushan Gupta
5. Early Clinical Characteristics of Children with Autism

Chris Plauché Johnson
6. Screening and Diagnosis for Autistic Spectrum Disorders

Pasquale J. Accardo

7. Informing, Educating, and Supporting the Family
Alfred L. Scherzer
8. Behavioral and Educational Interventions for Young
Children with Autism
John M. Suozzi
9. Communication Disorders in Children with Autism:
Characteristics, Assessment, Treatment
Elaine Dolgin Schneider
10. Sensory Integration and Occupational Therapy Intervention
for Autistic Spectrum Disorders
Patricia M. Stevens, Sallie Tidman, and Kari A. Glasgow
11. Drug Therapy (Pharmacotherapy) of Autistic Spectrum
Disorders
Vidya Bhushan Gupta
12. Complementary and Alternative Treatments for Autism
Vidya Bhushan Gupta
13. Planning Education Programs for Students with Autism
Spectrum Disorder
Catherine Trapani
14. Science as a Candle in the Dark: Evidence-Based Approach
to Evaluating Interventions
Charlene Butler
14. Appendix: Prognosis in Autistic Spectrum Disorders
Chris Plauché Johnson and Vidya Bhushan Gupta

Contributors
Pasquale J. Accardo, M.D. James H. Franklin Professor of Developmental

Research in Pediatrics, Department of Pediatrics, Virginia Commonwealth
University, Richmond, Virginia, U.S.A.
Charlene Butler, Ed.D. Special Education Consultant, Seattle School District,

Seattle, Washington, U.S.A.
Laura Kresch Curran, B.A. Center for Autism and Developmental Disabil-
ities Epidemiology, Johns Hopkins Bloomberg School of Public Health, Balti-
more, Maryland, U.S.A.
Kari A. Glasgow, O.T.R./L. Occupational Therapist, Department of Rehabi-

litation, Children’s Hospital, Richmond, Virginia, U.S.A
Vidya Bhushan Gupta, M.D., M.P.H. Associate Professor of Clinical Pedia-

trics, Department of Pediatrics, New York Medical College, and Associate
Research Scientist, Gertrude H. Sergievsky Center, Columbia University, New
York, New York, U.S.A.
Chris Plauché Johnson, M.Ed., M.D. Professor, Department of Pediatrics,

University of Texas Health Science Center at San Antonio, San Antonio, Texas,
U.S.A.

Tanya Karapurkar, M.P.H. Centers for Public Health Research and Evalua-
tion, Batelle Memorial Institute, and Centers for Disease Control and Preven-
tion, Atlanta, Georgia, U.S.A.
Nora L. Lee, B.S. Research Program Coordinator, Center for Autism and
Developmental Disabilities Epidemiology, Johns Hopkins Bloomberg School of
Public Health, Baltimore, Maryland, U.S.A.
Craig J. Newschaffer, Ph.D. Associate Professor, Department of Epidemiol-

ogy, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland,
U.S.A.
Alfred L. Scherzer, Ed.D., M.D., F.A.A.P. Clinical Professor Emeritus of

Pediatrics, Department of Pediatrics, Joan and Sanford I. Weill Medical College,
Cornell University, New York, New York, U.S.A.
Elaine Dolgin Schneider, M.A., C.C.C. Speech Language Pathologist, Pedia-

tric Neurological Associates, White Plains, New York, U.S.A.
Patricia M. Stevens, B.S./O.T.L. Occupational Therapist, Department of

Rehabilitation, Children’s Hospital, Richmond, Virginia, U.S.A.
John M. Suozzi, Ph.D. Clinical Psychologist, Department of Psychology,

Children’s Hospital, Richmond, Virginia, U.S.A.
Sallie Tidman, B.S., O.T./L. Community Rehabilitation Manager, Depart-

ment of Rehabilitation, Children’s Hospital, Richmond, Virginia, U.S.A.
Catherine Trapani, Ph.D. Director of Education, Marcus Institute, and

Clinical Professor of Pediatrics, Emory University, Atlanta, Georgia, U.S.A.
Marshalyn Yeargin-Allsopp, M.D. Medical Epidemiologist, National Center

on Birth Defects and Developmental Disabilities, Centers for Disease Control
and Prevention, Atlanta, Georgia, U.S.A.

1
History, Definition, and Classification
of Autistic Spectrum Disorders
Vidya Bhushan Gupta

New York Medical College and Columbia University, New York,
New York, U.S.A.
I. ORIGINS
The term autism, meaning “living in self” (in Greek aut means self, and ism refers to
a state), was coined by a Swiss psychiatrist, Eugen Bleuler, in 1911, to describe self-
absorption due to poor social relatedness in schizophrenia (1). Leo Kanner (Fig. 1), in
1943, borrowed this term to describe 11 children who “were oblivious to other people,
did not talk or who parroted speech, used idiosyncratic phrases, who lined up toys in long
rows, and who remembered meaningless facts.” In his classic paper, “Autistic
Disturbances of Affective Contact,” Kanner described the features of classic autism with
uncanny detail (2). Describing the social isolation of his first case, Kanner said, “Donald
got happiest when left alone, almost never cried to go with his mother, did not seem to
notice his father’s homecomings, and was indifferent to visiting relatives. The father
made a special point of mentioning that Donald even failed to pay the slightest attention
to Santa Claus in full regalia.” His second child played abnormally, “He never was very
good with cooperative play. He doesn’t care to play with the ordinary things that other
children play with, anything with wheels on.” The third child said “no recognizable
words, although he did make noises (3).” In 1956, Eisenberg and Kanner suggested two
essential criteria for the disorder: inability to relate in the ordinary way to people and
situations and failure to learn to speak or inability to convey meaning to others through
language, both occurring from the beginning of life (4).
In 1944, Hans Asperger, a Viennese pediatrician, independently described a
condition similar to that described by Leo Kanner and called it autistic psychopathy

2 Gupta
Figure 1 Leo Kanner, M.D., is credited with the first description of autism.
(5), because of “severe and characteristic difficulties of social integration.” Like

Kanner, he also noted peculiarities of the content and delivery of speech in these
children. In addition, he commented on the oddity of gaze in these children: “His
eye gaze was generally directed into the void and he darted short peripheral looks
and glanced at people and objects only fleetingly.” According to Uta Frith,
Asperger’s paper was ignored by the global academic community because it was
written in German during the height of World War II (6).
II. AUTISM AS A TYPE OF CHILDHOOD PSYCHOSIS
Use of the term “autism” by both Kanner and Asperger led to confusion about
the relation of the newly described condition to schizophrenia. Although Kanner
commented on the similarity of the clinical picture of autism with “some of
the basic schizophrenic phenomena,” he underscored the difference that autism

History, Definition, Classification 3
was present since birth while schizophrenia occurred after years of normal
development. Asperger, too, emphasized that while both autistic children
and schizophrenics have “complete shutting off [of] relations between self
and the outside world,” the latter have a “gradual disintegration of personality”
while the former have social withdrawal “from the start.” To underscore this
point, Asperger called the condition he described a psychopathy rather than
psychosis.
Bender described a group of children similar to those described by Kanner
in 1942, labeling them “childhood schizophrenics of the pseudodefective type
(7).” Anthony (1958) described two types of autism, primary and secondary, both
as subtypes of childhood psychosis (8). Primary autism described by him was
similar to autism described by Kanner. In 1961, a group of British clinicians
(the British Working Party, or BWP) gave nine points—the Nine Points—for
the diagnosis of “schizophrenic children.” The criteria included symptoms of
autism described by Eisenberg and Kanner, but promoted the notion that autism
was a type of childhood psychosis (9). These nine points were incorporated in the
classification of childhood psychiatric disorders by the Group for the
Advancement of Psychiatry (GAP) in 1966. Autism as described by Kanner
(Kanner’s syndrome) was included in the category of psychosis of infancy and
early childhood (10).
Although clearly differentiated from childhood psychoses of late onset,
autism continued to be labeled a childhood psychosis, albeit of early onset, until
the early 1970s (11,12). Keeping in line with the then-prevalent views,
DSM (Diagnostic and Statistical Manual of the American Psychiatric
Association) I and II did not have a separate category of autism (13,14). In
1956, Eisenberg and Kanner challenged the view that childhood schizophrenia
and autism were the same condition (4). In 1968, Ornitz and Ritvo, described
autism as a specific syndrome with a cluster of symptoms, including
abnormalities of perceptual integration (15). They clearly distinguished between
the two conditions by their age of onset, autism occurring before the age of 30
months and schizophrenia later. Makita (16) and Rutter (17) made a case for
separating autism from childhood schizophrenia. In his theoretical paper
“Childhood Schizophrenia Reconsidered,” Michael Rutter discussed the
confusion between the terms “childhood schizophrenia” and “autism.” He
laid to rest the notion that autism was a type of childhood psychosis and
argued that the term “childhood schizophrenia” be dropped forever, and that
children with schizophrenia be simply called schizophrenic (17). Kolvin et al.
(18) in England and Green et al. (19) in the United States restated the
differences between autism and schizophrenia: early onset of autism, presence
of positive symptoms such as hallucinations in schizophrenia, waxing and
waning of symptoms in schizophrenia, and generally higher intelligence of
children with schizophrenia. In 1978, Rutter gave criteria for autism that were

4 Gupta
incorporated in DSM-III under the category of infantile autism (20). These

included (1) social delay or deviance that was not just a function of mental
retardation, (2) communication problems, again not as a function of mental
retardation, (3) unusual behaviors such as stereotypic movements and
mannerisms, and (4) onset before the age of 30 months. In 1978, the
professional advisory board of the National Society for Children and Adults
with Autism defined autism as a behavioral disorder that had the following
characteristics: signs and symptoms prior to the age of 30 months,
characteristic disturbances of developmental rate/sequence, characteristic
disturbances of responsiveness to sensory stimuli, characteristic disturbances
of speech, language, and cognitive capacities, and characteristic disturbances
of relating to people, events, and objects (21).
DSM-III followed through in resolving the confusion between autism
and schizophrenia by including autism in the newly created category of
pervasive developmental disorder (22). The term “pervasive” recognized that
multiple domains of a child’s functioning are affected by autism—social,
communicative, and cognitive. DSM-III had four categories under pervasive
developmental disorders: infantile autism, childhood-onset autism, atypical
autism, and residual autism. Infantile autism and childhood-onset autism were
differentiated by the age-of-onset criterion of 30 months. Because the age-
of-onset criterion is dependent on age of recognition and not on the true age
of onset, few cases of childhood-onset pervasive developmental disorder were
described (23), DSM-IIIR replaced the category of infantile autism with
autistic disorder, removed the category of childhood-onset pervasive
developmental disorder, and extended the age of onset to 36 months (24).
It included all cases that did not meet the full criteria of autistic disorder in
the category of pervasive developmental disorder, not otherwise specified and
eliminated the categories of atypical and residual autism. However, the
criteria of DSM-IIIR were overinclusive and led to an overdiagnosis of
autistic disorders (25) DSM-IV addressed the overinclusiveness of DSM-IIIR
by reducing the criteria for autism from 16 to 12 and brought the
classification more in line with the International Statistical Classification of
Diseases and Related Health Problems (ICD-10) by creating independent
categories of Asperger’s syndrome, Rett’s syndrome, and childhood
disintegrative disorder (26). ICD-10, on the other hand, became closer to
DSM-IV by finally moving pervasive developmental disorders from the
category of childhood psychoses to an independent category (Table 1) (27).
DSM-IV/ICD-10 criteria are more specific and have better interrater
reliability than DSM-IIIR criteria, and diagnose autism (diagnosis made by
expert clinicians) with a sensitivity of 0.79, specificity of 0.87, positive
predictive validity of 0.87, negative predictive validity of 0.83, and interrater
reliability of 0.70 (28).

Table 1 DSM-IV and ICD-10 Classification of Autism and Pervasive

Developmental Disorders
Pervasive developmental disorders, Pervasive developmental disorders,

DSM-IV (26) ICD-10 (27)
Autistic disorder Childhood autism

PDD (NOS) including atypical autism Atypical autism
Atypicality in age of onset
Atypicality in symptomatology
Atypicality in both
PDD, unspecified and residual
Asperger’s syndrome Asperger’s syndrome
Childhood disintegrative disorder Childhood disintegrative disorder
Rett’s syndrome Rett’s syndrome
Overactive disorder associated with MR
and stereotyped movements
PDD (NOS), pervasive developmental disorder not otherwise specified; MR, mental retardation.
III. AUTISM: FROM A PSYCHOGENIC

TO A NEUROBIOLOGICAL DISORDER
Families of the 11 children described by Kanner were “highly intelligent families,

with few warm fathers and mothers who were preoccupied with abstractions of a
scientific, literary, and artistic nature, and limited in genuine interest in people
(3).” Like William John Little, who, more than a century ago, had implied that
asphyxia caused cerebral palsy, based on a case series (29), Leo Kanner
suggested that this family constellation “had contributed to the condition of the
children.” Although he noted that “these children came into the world with innate
inability to form the usual, biologically provided affective contact with people,”
he wondered if “obsessiveness and lack of warm-heartedness in the family”
somehow caused the condition. In 1949, Kanner described parents of children
with autism as “refrigerators,” who fail to provide emotional warmth to their
children (8,30,31). However, the original sample of Kanner was self-selected,
because only prosperous and intelligent parents might have had access to such a
renowned psychiatrist (32). Alternatively, the parents were indeed abnormal,
either by chance, or because they, too, suffered from a mild type of autism. The
latter explanation is more plausible in view of the recent reports of a higher
prevalence of autistic traits in first-degree relatives of children with autism.
Bruno Bettelheim, a psychoanalytically oriented author, whose views were
shaped by his personal experiences of emotional trauma in a Nazi concentration
camp, further promoted the psychogenic theory of autism, in his book The Empty
Fortress: Infantile Autism and the Birth of the Self (33). The effects of maternal

6 Gupta
deprivation on the infant also suggested that mental disorders could be caused by
lack of maternal availability and responsivity (34 –36). For the next three decades
autism was attributed to “refrigerator mothers” who did not show affection to
their children. Widely publicized stories of feral children reinforced the view that
autism was due to faulty nurture and not faulty nature (37). But the social skills of
abandoned and neglected children often improve with nurturing care contrary to a
little improvement in social relatedness of most autistic children despite
intervention (38). Kasper Hauser, who was neglected and maltreated for many
years, recovered and acquired some communication skills even after the age of 17
years (39). A follow-up of children who suffered severe psychosocial deprivation
during the Ceausescu regime in Romania showed that with intervention many
such children learned to communicate and make social approach, although
deviant in quality (40). Moreover, abused or neglected children show unhealthy
attachment to their caregivers, while autistic children are attached to primary
caregivers (41).
The psychogenic theory of autism held sway until Bernard Rimland in his
book Infantile Autism proposed that autism was neurogenic and not psychogenic
(42). He argued that many autistic children were born to loving and caring parents
and many perfectionist professional parents had normal offspring. Moreover,
most autistic children did not acquire the disorder but were born with it. Kanner
himself changed his views about his theory of “refrigerator mothers” when in
1969, at the National Association of Autistic Children, he declared, “Herewith I
officially acquit of you people as parents” (43).
IV. AUTISM: A NEW DISORDER OR RECENTLY

DISCOVERED OLD DISORDER?
Although autism was described as a distinct syndrome in 1943, it most certainly

occurred before 1943. As early as 1867, Maudsley drew attention to severe
mental disorders in young children with severe distortion of the developmental
process (44). De Sanctis, in 1906, described a schizophrenia-like condition
in prepubertal children under the term “dementia precocissima” (45).
Disintegrative psychosis, a condition similar to autism, and according to some
indistinguishable from autism, was first described in 1908 (46). In 1919, Lightner
Witmer, considered the father of clinical psychology in the United States,
described a 2 years and 7 months old boy, Don, who behaved like an autistic child
(47). In the 1920s, a Russian child psychiatrist described children having
characteristics similar to those described by Asperger (48).
Historians are now looking for signs of autism in two groups of individuals:
low-functioning feral children who suffered severe psychosocial deprivation
early in their lives, and highly accomplished individuals with poor social skills.

Although popular myth gives the impression that psychosocial deprivation

explains most of the behaviors of the feral children, scientific examination
suggests that many of these children had preexisting conditions such as mental
retardation or autism (49). It is now believed that Victor, the Wild Boy
of Aveyron, who was discovered in a jungle of Southern France in 1797 and
was cared for and described by a French physician, Jean-Marc-Gaspard Itard,
was abandoned by his parents during the French revolution because he was
autistic. Like Fritz V of Asperger, he did not love anyone and could not show
genuine affection (50 –52). Feral children who are not autistic, such as Kasper
Hauser, who was found in Germany in 1828, at the age of 16 years, recover
partially and acquire communication skills even after many years of neglect and
maltreatment (39,53).
Many famous individuals are now suspected to have Asperger’s syndrome
because they were socially aloof or inept. Among these are Henry Cavendish and
Thomas Jefferson. Henry Cavendish was a famous British scientist of the
eighteenth century, who “worked in complete solitude and rarely spoke to
anyone” (54). Doubts are being raised if Thomas Jefferson’s early aloofness,
awkwardness, and ineptitude in social situations, and his fixations are compatible
with the diagnosis of Asperger’s syndrome (55). Rabson and Frith have written
about Hugh Blair, an eighteenth-century Scottish landlord whose marriage was
annulled on the ground of mental incapacity, but whose behavior as described in
the court documents is suggestive of autism (56). Frith, in 1992, suggested that
the fictional character of Sherlock Holmes was perhaps autistic (6), but others
reached a different conclusion (57). Because making retrospective diagnoses, or
“pathographies,” based on scanty and unreliable old records is unreliable, the real
diagnosis of these celebrities will never be known, but these reports underscore
the fact that pervasive developmental disorders including autism and Asperger’s
syndrome occurred even prior to Kanner’s description.
V. NOSOLOGY
Originally, Eugen Bleuler used the word autism to describe a state of extreme
social withdrawal in schizophrenia (1). Kanner and Asperger borrowed the term
as an adjective to describe a constellation of symptoms that included not only
social withdrawal but communication difficulties and rigid and stereotypic
behavior (2). The former called this syndrome “autistic disturbance of affective
contact” and the latter, “autistic psychopathy.” Although both Kanner and
Asperger had described high-functioning children, the syndrome described by
Kanner, consisting of severe impairments of social and communicative behavior,
became known as autism and the syndrome described by Asperger, with a wider

8 Gupta
range of severity and better cognitive and communicative function, became

known as Asperger’s syndrome.
The American Psychiatric Association, recognizing that autism was a
heterogeneous disorder affecting many, if not most, domains of a child’s
functioning, introduced the term “pervasive developmental disorder” in DSM-III as
a generic term to include all shades and degrees of autism (22). In 1994, the DSM-IV
incorporated five diagnoses under pervasive developmental disorders: autism, Rett
disorder, childhood disintegrative disorder (CDD), Asperger disorder (ASP), and
pervasive developmental disorder–not otherwise specified (PDD-NOS) (26). Not
everyone agrees with the term “pervasive developmental disorder.” According to
Bernard Rimland, this term is meaningless because autism may not be pervasive in
all children and other disorders such as mental retardation may cause more pervasive
damage to a child’s function. Other objections have been raised about the DSM-IV/
ICD-10 classification of pervasive developmental disorders. DSM-IV does not
differentiate autistic disorder clearly from other pervasive developmental disorders,
especially Asperger’s syndrome (58,59). DSM-IV criteria for Asperger’s syndrome
ignore the abnormal use of language by individuals with Asperger’s syndrome
(60,61). DSM-IV/ICD-10 system does not recognize the heterogeneity of
presentation, functioning, response to treatment, and natural history within each
group. While the symptoms of autism differ qualitatively and quantitatively at
different ages, DSM-IV offers a common yardstick for all ages and developmental
stages, increasing the possibility of diagnostic errors (62).
Because there are many shades of autism depending on which behavior is
predominant and how severe it is, the term “autistic spectrum disorder” has been
proposed as an umbrella term to include the whole range of autistic symptoms
from mild to severe (63 – 65). Contributors to this volume prefer this term because
it reflects the unifying social deficit more poignantly than the term ‘pervasive
developmental disorders,’ and it mirrors the clinically common scenario of cases
that do not meet the DSM-IV/ICD-10 criteria strictly but have significant
impairments in social skills, pragmatic communication, or sensorimotor
behavior. Another term, “broad autism phenotype,” has gained currency
among medical geneticists to include the relatives of children with autism who
have subtle deficits in social and communicative domains, but do not meet the
criteria of pervasive developmental disorders (66,67).
The National Center for Clinical Infant Programs/Zero to Three proposed
the term “multisystem developmental disorder” (MSDD) for children who have
dysfunction in many domains, such as communication, sensory processing, and
motor planning, but have some capacity for engaging in an emotional and social
relationship with the primary caregiver. The authors of the term emphasize that
deficits in relating are not the defining characteristic of this condition in contrast
to the pervasive developmental disorders of DSM-IV/ICD-10, but may be
secondary to abnormalities of sensory processing and motor planning and,

therefore, can improve with intervention. This term has not gained popularity,
because the DSM-IV category of PDD-NOS includes atypical and subthreshold
cases of autism (68).
Another term, multiple complex developmental disorder, has been
proposed both as a separate category or as a subtype of pervasive developmental
disorders. The defining characteristic of this disorder is deficit in affect regulation
with secondary deficits in relatedness and thought. The symptoms of this
condition include disturbed attachments, idiosyncratic anxiety reactions,
episodes of behavioral disorganization, and wide emotional variability (69 –
71). Although both multiplex complex disorder and multisystem disorder have
not become popular, they highlight abnormalities of affect regulation and sensory
processing as part of the litany of problems in pervasive developmental disorder.
The differential connotations of the terms used to describe pervasive
developmental disorders are given in Table 2.
VI. TAXONOMY
Some of the foregoing difficulties may be resolved if autism is considered a

heterogeneous disorder with many subtypes, but attempts to identify separate entities
within autism have not fared well. Both categorical and dimensional approaches have
been tried. The concept of autistic spectrum disorder is a popular dimensional
approach but is vague with no clear-cut end points. It does not state clearly when
normal variation ends and disorder begins. It does not address the issue of
discordance among the three key domains of autistic symptoms—a child may have
minimal abnormality in the communicative domain while having significant
limitations in social reciprocity, making distinction from Asperger’s syndrome
impossible. Similarly, a child with a limited range of repetitive behaviors but few
problems in the communicative and social domains may resemble a child with
obsessive compulsive disorder. A vast range of permutations and combinations will
be possible along the spectrum of the three key domains (Fig. 2). Both false positives
and false negatives are likely to be high in this dimensional scheme. Lack of clear-cut
diagnostic criteria in such a scheme can create doubt leading to conflicts in obtaining
necessary services and cash benefits for some children. Neither does such an
approach have any heuristic value. Thus instead of defining subtypes, this
dimensional approach lumps different shades of the disorder under one rubric (Fig. 2).
Categorical subtyping of autism has been attempted on the basis of social
behavior and intelligence quotient (IQ)/developmental level. Among the social
typologies, Wing’s (1997) “triad of subtypes” based on social interaction,
communication, imagination, and behavior is the most accepted (72,73). The
most severely autistic or aloof type avoid social contact except to fulfill a need,
show poor attachment behaviors, have severe impairments in verbal and

Table 2 Various Terms in Vogue for Pervasive Developmental Disorders
Communication Low
Social Sensory Affective nonverbal
deficit Qualitative Quantitative Stereotypies disintegration dysregulation IQ
Autism
High functioning þþ þ + þ + + 2
Low functioning þþ þ þ þ + + þ
Asperger’s syndrome þþ þ 2 þ + 2 2
Multisystem disorder + + + + þþ + +
Multiplex complex + + + + + þþ +
disorder
PDD-NOS þ þ + þ + + +
Language disorder 2 þ + 2 2 2 2
Affective dysregulation, lack of or inappropriate facial expression; þ, mild; þþ, severe; 2, absent.

Figure 2 Autistic spectrum.
nonverbal communication, do not engage in pretend play or joint attention, have

stereotypic behaviors and motor abnormalities such as toe-walking, and have low
IQ. The passive type do not seek contact but are more accepting of social advances
by others, imitate others in play or otherwise, have repetitive speech, and
intermediate IQ. The active-but-odd type seek interactions but in odd and eccentric
ways, talk but do not take turns in conversation, have poor eye contact, are
motorically clumsy, and have higher IQ. Although there is some empirical support
for aloof and active-but-odd subtypes (74,75), support for the third group (passive)
is not so strong (76). Moreover, most of the variance in the groups is explained by
IQ, aloof children having low IQ and active-but-odd having higher IQ (77).
Several studies have supported a two-type, low and high functioning,
classification of autism, based on nonverbal IQ and adaptive behavior (78,79).
Two groups emerged in the Autism and Language Disorders Nosology Project, a
higher-functioning group that resembled Wing’s active-but-odd group and a
lower-functioning group that resembled Wing’s aloof group. The former received
the diagnosis of PDD-NOS and the latter, autistic disorder. The natural course of
the first group was improvement, while the latter group remained stable (75).
Cluster analyses have generally confirmed the two-type solution with a few
overlapping intermediate subtypes (80 – 82).
Intellectual level has emerged as a strong predictor of outcome in most
studies, high-functioning children with nonverbal IQ above 65 having better

12 Gupta
Table 3 Two-Type Model of Pervasive Developmental Disorders
High-functioning Low-functioning
Onset Later Early

Nonverbal IQ Above 65 Below 65
(performance IQ)
Head circumference Normal to large Normal to small
Dysmorphic features Attractive appearance None to present
with few dsysmorphic
features
Seizures Infrequent Frequent
Neurological examination Normal Normal to abnormal
Development Deviant Delayed and deviant
Social behavior “Active but odd” “Aloof”
Identifiable cause Unlikely Likely
Prognosis Better Poor
outcome at school age than low-functioning children with nonverbal IQ of less

than 65 (83,84). The two-type model has some heuristic value as well. DeLong
has proposed that the low-functioning type is caused by bilateral brain damage in
early life and the high-functioning type is idiopathic without evidence of brain
damage and may be related to familial affective psychopathology (85). The
differences between these two types are given in the Table 3.
Although the purpose of classification is to identify homogeneous subtypes
that suggest a particular etiology, natural history, treatment approach, and outcome,
such clear subtypes have not emerged in pervasive developmental disorders (86).
This may never happen because autism, perhaps, represents several discrete
disorders with a common overlapping phenotype. Until this happens a descriptive
approach listing each child’s behavior in the three DSM-IV/ICD domains of social
behavior, communication skills, and stereotypic behaviors may be preferable to a
diagnostic label. Additionally, severity of the condition may be judged by assessing
the delay/deviance in relation to the child’s nonverbal IQ, frequency of symptoms,
and level of adaptive dysfunction (62).
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2
The Epidemiology of Autism
and Autism Spectrum Disorders
Tanya Karapurkar
Battelle Memorial Institute and Centers for Disease Control and
Prevention, Atlanta, Georgia, U.S.A.
Nora L. Lee, Laura Kresch Curran, and Craig J. Newschaffer
Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland,
U.S.A.
Marshalyn Yeargin-Allsopp
National Center on Birth Defects and Developmental Disabilities, Centers
for Disease Control and Prevention, Atlanta, Georgia, U.S.A.
I. INTRODUCTION
In the 1940s, Dr. Leo Kanner described 11 children with “autistic disturbances of
affective contact,” and even today, that characterization continues to form the
basis of the diagnostic criteria for autistic disorder (1). Epidemiological studies
describing the prevalence and risk factors for autistic disorder and autism
spectrum disorders (ASDs) did not appear in the scientific literature until the late
1960s and early 1970s (2 –4). Since these earlier investigations, several
population-based prevalence studies have been conducted. However, these vary
in terms of their methods, case definitions, and population size; hence,
comparisons of estimates from these studies are difficult. Other factors
contributing to the lack of epidemiological understanding of autism stem from
the paucity of well-designed studies that are able to examine trends over time, as
well as a range of risk factors, both biological and sociodemographic, for autism.

18 Karapurkar et al.
For instance, there have been few studies that reflect racially heterogeneous
populations, such as from the United States.
To examine the current prevalence of autism and trends in prevalence over
time, we conducted a MEDLINE literature search for prevalence studies that
have been published between 1966 and the present (January 2003). The criteria
used for inclusion in the review included: peer-reviewed articles in the English
language, book chapters, and summaries of articles published in other languages
(1) that describe studies with temporally and geographically defined population-
based cohorts; inclusion of case definitions that used clinical examinations or
review by expert clinicians’ assessment and diagnosis; and (2) that used the
accepted clinical diagnostic criteria for autism/ASDs as a basis for case
definition. This chapter will describe these studies according to (1) diagnostic
criteria; (2) time period; (3) size of population; and (4) methods of ascertainment.
We will also present what is currently known about autism risk factors and
discuss challenges to conducting epidemiological studies of autism. In this
chapter, we will use the term ASD to refer to the Diagnostic and Statistical
Manual of Mental Disorders, 4th Edition (5) diagnosis of autistic disorder,
Asperger disorder, and pervasive developmental disorder –not otherwise
specified (PDD-NOS). Where possible, we will indicate those studies that
attempted to differentiate between autistic disorder and the broader spectrum
of ASDs.
II. EPIDEMIOLOGICAL CONCEPTS IN THE

MEASUREMENT OF DISEASE OCCURRENCE
Two basic statistics are used to measure disease occurrence in a population:

incidence and prevalence. In general, prevalence is a proportion with numerators
that reflect the number of individuals with the disease and denominators that
include the number of individuals in the study population at a particular point in
time. Persons counted in the numerator must also be counted in the denominator.
Point prevalence, involving an estimate taken at a particular point in time, is the
most intuitive. Prevalence is typically described as a snapshot of the extent of
disease in a population. It can be described either as a percentage or, more
commonly, as the number of cases found per some unit of individuals in the
population, the unit being dependent on how common the disease. Most of
the published estimates of autistic disorder and ASD frequency are point
prevalence estimates and are often described using a unit of 10,000 individuals.
On the other hand, incidence reflects the number of newly occurring cases
emerging in a population over a defined period of time. Incidence differs from
prevalence in that it counts only new cases in its numerator, limits its
denominator to those who have not yet but still may develop the disease

Epidemiology of Autism 19
(excluding those in the numerator), and always incorporates an explicit time

element. For example, the incidence rate is the number of new (or “incident”)
cases per 10,000 individuals per years of follow-up. Because of its emphasis on
new cases, incidence reflects closely the underlying risk of disease occurrence,
while prevalence, which counts both new and existing cases, reflects most closely
the burden of disease in a population that is a function of both the risk and
duration of a condition. Given its close relationship with risk, examination of
time trends in disease incidence, not prevalence, is typically emphasized in
classical epidemiology as a means of assessing whether the etiology of a disease
(e.g., the risk factors contributing to disease causation and/or the population
susceptibility) is changing over time. However, for autism and other
developmental disabilities, there have been few attempts to directly estimate
incidence. Instead, trends in prevalence have been more commonly used to make
etiological inferences. The reasons for this are twofold. First, it is generally more
difficult to develop studies that measure the true incidence of autism because of
inherent difficulties defining newly occurring cases. The at-risk population
consists of children typically diagnosed between 2 and 5 years of age although it
is still not uncommon for older children and even adults to receive an initial first
ASD diagnosis (6). Further, the clinical diagnosis of ASD may have more to do
with the ability and willingness to make an ASD diagnosis than with the true
onset of pathology. In fact, much neuropathological evidence supports a prenatal
origin (7). The second reason why autism prevalence trends are often used to
infer trends in incidence is that when the average duration of a disease is
unchanging, trends in prevalence will approximate trends in incidence. For a
lifelong condition with no cure that is not strongly associated with premature
mortality, like autism, the average duration of disease is not expected to change
drastically with time.
Unfortunately, both prevalence and incidence trends will be influenced by
changes in the manner in which cases of disease are defined and detected. If
available data are based on a diagnostic or ascertainment approach(s) that misses
true cases, both the prevalence and incidence will be underestimated. For
example, if education records are used to capture cases, young children who have
not come to the attention of education authorities will be underascertained. In
general, young children are more likely to be underascertained because they have
not come to the attention of school officials. Furthermore, many clinicians or
evaluators, including those at educational facilities, do not make it their practice
to “label” children so young in age, particularly those children whose condition is
less severe. Therefore, studies primarily using younger children or those that
include younger children in their prevalence estimate might underestimate the
true prevalence of the disorder. In addition, if the approach used to define and
detect disease changes with time, this change will impact the trend for the
estimation of prevalence or incidence—a trend not in any way attributable to a

change in the real risk of disease occurrence. Considering this, the evolution of
autism diagnostic criteria and the impact it has had on the prevalence of autism
and ASDs will be described in this chapter.
III. INCIDENCE STUDIES
For the reasons described above, only four studies have attempted to report the
incidence of autism (8 – 11). The investigators in all of these studies used the year
of diagnosis as the year of onset of autism. However, the age of diagnosis in most
studies is much later than the age of recognition of the behaviors that are
characteristic of autism. In fact, although the current diagnostic criteria for autism
require that the onset of behaviors that define the condition occur prior to 3 years
of age, the mean age of recognition of the condition was closer to 4 years of age
(12) in one study and was as late as 6 years of age in an earlier study (13). In
addition to not having a precise time of onset, the diagnosis was not confirmed in
any of these studies and the investigators did not take into account that the
diagnostic criteria for autism that were used changed during the periods of study.
Nevertheless, all of these studies, covering birth cohorts from the 1980s and
1990s, report increases over time. However, only carefully designed prospective
studies after there was more certainty over how to detect the true biological onset
of ASDs would allow us to determine precisely the onset of autism in the
population, and thus, the true incidence of the disorder in a given population.
IV. TIME TRENDS IN DEFINED POPULATIONS
From our literature review, we were able to identify only three studies that
described trends in autism prevalence or incidence within a defined population.
In one study, the prevalence was estimated for two French birth cohorts (1972
and 1976) from the same region; no change in prevalence (5.1 and 4.9/10,000
children) occurred over that short period of time (14). In Göteborg, Sweden, the
prevalence of autism was estimated for two time periods, 1962 – 1976 and 1975–
1984 (15). Over the 1975 –1984 time period, the prevalence increased from 4.0 to
11.6/10,000 children. The Swedish investigators offered a possible explanation
for the increase. Rates of autism in children with mild mental retardation
remained relatively stable, while the rates increased in children with severe
mental retardation (IQ , 50) and in children with normal intelligence (IQ . 70).
The investigators postulated that changes in the overall prevalence were
influenced by the ability to better identify children with autism with very low as
well as normal to high functioning. A third study that examined trends in autism
occurrence measured incidence between 1991 and 1996 in preschool children in

two areas on the west Midlands, UK, and found that although the rates for
classical autism increased by 18% per year, there was a much larger increase for
the other ASDs, i.e., 55% per year (8). The investigators attributed this increase in
incidence to increased awareness among clinicians rather than to true changes in
disease occurrence.
V. PREVALENCE STUDIES
We identified 35 studies that met inclusion criteria in our evaluation of autism

point prevalence studies (Table 1). However, only 31 of the studies will be used
in our evaluation of the trends in prevalence based on the criteria indicated
earlier. The four studies that were excluded are: Hoshino et al., 1982; Fombonne
and du Mazaubrun, 1992; Fombonne et al., 2001; and Yeargin-Allsopp et al.,
2003. The Hoshino et al. and the Fombonne and du Mazaubrun studies were
excluded because only an average prevalence rate was provided, without giving
the sample sizes or the prevalence estimates used to derive that average rate. The
Fombonne et al. and Yeargin-Allsopp et al. studies were excluded because
separate rates for autism and other pervasive developmental disorders (PDDs)
were not reported for those studies.
The trends in the prevalence estimates will be discussed in terms of
weighted prevalence rates and mean prevalence rates. While the mean rate
simply describes the prevalence in terms of the sum of the observed cases divided
by the total sample size, the weighted prevalence estimate is derived by pooling
the estimates of the individual prevalence studies and then weighting the
estimates by the inverse of the variance. In contrast to the mean prevalence rate,
the weighted prevalence estimate takes into account the variance heterogeneity
that exists among the pooled studies. With the weighting approach, more weight
is placed on those studies with larger sample sizes. This approach provides a
more accurate portrayal of trends in the prevalence of autism as compared to
using the mean rate, which may exaggerate the trends seen in certain populations
owing to their size. Because other factors, such as the intensity of follow-up, play
a role in the prevalence estimates, both the mean and weighted prevalence rates
are described below.
VI. THE EFFECT OF DIAGNOSTIC CRITERIA

ON MEAN PREVALENCE RATES
To discuss the effect of changing diagnostic criteria on the classification of autism

and ASDs over time, the evolution of the diagnostic criteria are provided here.

Table 1 Summary of Autism Prevalence Studies
Prevalence
rate (PR) for
Time Age Number of autism/other
Year period range children in Criteria ASD per IQ , 70
Author published Country studied studied population used Methodology used 10,000 (%)
Lotter 1966 England 1964 8–10 78,000 Kanner Case enumeration and 4.5/— 84
direct exam
Brask 1970 Denmark 1962 2–14 46,500 Kanner Case enumeration 4.3/— NR
Treffert 1970 U.S.A. 1962– 1967 3–12 899,750 Kanner Case enumeration 0.7/2.4
Wing and 1979 England 1970 0–14 35,000 Kanner Case enumeration and 4.6/15.7 70
Gould direct exam
Hoshino et al.a 1982 Japan 1977 0–17 234,039 Kanner Case enumeration and 5.0/— NR
direct exam
Ishii and 1983 Japan 1981 6–12 35,000 Rutter Case enumeration and 16.0/— NR
Takahashi direct exam
Bohman et al. 1983 Sweden 1979 0–20 69,000 Rutter Case enumeration and 3.0/2.6 NR
direct exam
McCarthy et al. 1984 Ireland 1978 8–10 65,000 Kanner Case enumeration and 4.3/— NR
direct exam
Gillberg 1984 Sweden 1980 4–18 128,584 DSM-III Case enumeration and 2.0/1.9 80,77
direct exam
Steinhausen 1986 Germany 1982 0–14 279,616 Rutter Case enumeration and 1.9/— 44
et al. direct exam
Steffenberg and 1986 Sweden 1984 ,10 78,413 DSM-III Case enumeration and 4.5/2.2 88
Gillberg direct exam
Matsuishi et al. 1987 Japan 1983 4–12 32,834 DSM-III Case enumeration and 15.5/— NR
direct exam
Burd et al. 1987 U.S.A. 1985 2–18 180,986 DSM-III Case enumeration and 1.2/2.1 NR
direct exam

Table 1 Continued
Prevalence
rate (PR) for
Time Age Number of autism/other
Year period range children in Criteria ASD per IQ , 70
Author published Country studied studied population used Methodology used 10,000 (%)
Magnusson and 2000 Iceland 1997 5–14 43,153 ICD-10 Population screen and 8.6/4.6 95/65
Saemundsen direct exam
Chakrabarti 2001 England 1998 2.5–6.5 15,500 DSM-IV Population screen and 16.8/45.8 24,70
and direct exam
Fombonne
Fombonne 2001 UK 1999 5–15 12,529 DSM-IV Population screen and 26.1 44
et al.b direct exam
Bertrand et al. 2001 USA 1998 3–10 8,996 DSM-IV Case enumeration and 40.0/67.0 49,58
direct exam
Croen et al. 2001 USA 1987–1999 0–21 4.6 million DSM-III-R Case enumeration 11.0/— NR
or DSM-IV
Yeargin- 2003 USA 1996 3–10 290,000 DSM-IV Case enumeration 34 64,68c
Allsopp
et al.b
NR, not reported; MR, mental retardation.

a
The prevalence rate that is provided represents an average prevalence rate.
b
The prevalence study provided overall rate only.
c
64% had MR-based IQ data and 68% had cognitive impairment based on IQ and developmental tests.

Although Kanner recorded brilliant descriptions of the clinical features of

autism, it was not until 1956 that he and Eisenberg published the Kanner
diagnostic criteria for early infantile autism, which included (16):
1. a profound lack of affective contact with other people;
2. an anxiously obsessive desire for the preservation of sameness in the
child’s routines and environment;
3. a fascination for objects that are handled with skill in fine motor
movements;
4. mutism or a kind of language that does not seem intended for
interpersonal communication; and
5. good cognitive potential shown in feats of memory or skills on
performance tests, especially the Séguin form board.
Kanner emphasized that the onset had to be from birth and before 30 months of
age. In the same paper that listed these criteria, Kanner and Eisenberg modified
the criteria by emphasizing that two features were essential for the diagnosis: a
profound lack of affective contact and repetitive, ritualistic behaviors, which
must be of an elaborate kind.
In 1978 Rutter published his criteria for childhood autism, which
included (17):
1. early onset, by 30 months of age;
2. impaired and distinctive social development, i.e., social development
that has a number of special characteristics out of keeping with the
child’s intellectual level;
3. delayed and deviant language development that also has certain
defined features and is out of keeping with the child’s intellectual level;
4. unusual behaviors, similar to the Kanner concept of “insistence on
sameness,” as shown by idiosyncratic responses to the environment,
stereotyped play patterns, motor mannerisms, abnormal preoccupa-
tions, or resistance to change.
The Rutter criteria emphasized that the social and communication

difficulties were not just a manifestation of any associated mental retardation.
With the publication of the American Psychiatric Association’s third
edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-III)
in 1980 (18), autism and schizophrenia were differentiated. For the first time,
autism was categorized as a developmental disorder, rather than a psychiatric
one. Autism was listed under the more general term of PDD and a subgroup under
PDD was infantile autism, which had as its features:
1. lack of responsiveness to others;
2. absence or abnormality of language;
3. resistance to change or attachment to objects;

4. absence of schizophrenic features; and

5. onset before 30 months of age.
DSM-III also included childhood-onset PDD (onset after 30 months of age and
before 12 years of age) and described a subthreshold condition, atypical PDD.
In 1987 the DSM-III criteria were revised and led to the broadening of the
concept of PDD. The concept of autism as a spectrum of disorders was first
described by Wing and Gould in 1979 (19) and was likely influenced by the work of
Hans Asperger, whose writings describing related behaviors did not become well
known in the English literature until the 1980s (20). These writings introduced the
concept of Asperger disorder, which represents behaviors that vary widely in their
presentation as well as severity. These descriptions may have contributed to the
changes seen with the revision of the DSM-III (21), which is referred to as the
DSM-III-R. In this revision, the PDD category was retained but the subgroups were
divided into autistic disorder and PDD-NOS and the age requirement was dropped.
The DSM-III-R diagnostic criteria for autistic disorder were (21):
1. impairment in reciprocal social interaction (at least two from a list of
five items);
2. impairment in verbal and nonverbal communication (at least one item
from a list of six items);
3. markedly restricted repertoire of activities and interests (at least one
from a list of five items);
4. a total of at least eight from among a list of 16 items.
The term PDD-NOS was used to refer to a qualitative impairment in the development
of reciprocal social interaction and of verbal and nonverbal communication skills,
but when criteria for autistic disorder, schizophrenia, or schizotypal or schizoid
personality disorder were not met. It was also noted that some individuals with PDD-
NOS will exhibit a markedly restricted repertoire of activities and interests (21).
With the fourth revision of the DSM, additional subgroups of PDD were
described: autistic disorder, childhood disintegrative disorder, Rett disorder,
Asperger disorder, and PDD-NOS (22). The diagnostic criteria for autistic
disorder were revised and included:
A total of at least six items from (1), (2), and (3), with at least two from (1),
and one each from (2) and (3):
1. qualitative impairments in social interaction;
2. qualitative impairments in communication;
3. restricted repetitive and stereotyped patterns of behavior, interests and
activities.
In addition, there must be delays or abnormal functioning in at least one of these
areas: (1) social interaction; (2) language; or (3) symbolic or imaginative play, and

the behaviors cannot be due to Rett’s disorder or childhood disintegrative disorder.

DSM-IV also described research criteria for the subgroups.
The International Classification of Diseases, Tenth Revision (ICD-10),
which was introduced in 1992 (23), has diagnostic and research criteria for autism
overall and for the subgroups that are very similar to the PDD subgroups in DSM-
IV. The umbrella term in ICD-10 is pervasive developmental disorders and the
subgroups are childhood autism, which has diagnostic criteria similar to autistic
disorder; atypical autism, which has criteria similar to PDD-NOS; and Rett’s
syndrome and other childhood disintegrative disorder, both of which have criteria
similar to the criteria for these disorders in DSM-IV.
An examination of the 31 prevalence studies from 1966 to 2003 showed
that the five studies that used the Kanner diagnostic criteria yielded a weighted
prevalence rate of 0.9/10,000 and a mean prevalence of 3.9/10,000 (2– 4,19,24).
The three studies that used the Rutter criteria showed a slight increase in
prevalence, with a weighted prevalence of 2.2/10,000 and a mean prevalence of
7.0/10,000 (25 – 27). The prevalence of autism increased further after the
introduction of the DSM-III and, particularly, the DSM-III-R criteria as seen by
the weighted (2.7 and 7.1/10,000) and mean prevalence rates (8.3 and 7.1/
10,000), respectively (28 – 38). While the weighted prevalence rate decreased
slightly to 5.5/10,000 with the introduction of the ICD-10 criteria, the weighted
prevalence rate increased substantially with the introduction of the DSM-IV
criteria, 13/10,000. The trend using the mean rates shows a very large increase
in the mean prevalence reported from the 10 studies that used the ICD-10 and
DSM-IV criteria, 21 and 23/10,000, respectively, as compared to previous
investigations that used other diagnostic criteria (39 – 48). Two studies that used
other criteria had a weighted prevalence of 10.9/10,000 and a mean prevalence of
10.3/10,000 (Fig. 1) (8,49). In summary, while there is a large difference in the
Figure 1 Trend in prevalence of autism by diagnostic criteria.

mean prevalence rates of studies that used DSM-IV or ICD-10 diagnostic criteria
as compared with Kanner, Rutter, DSM-III, or DSM-III-R diagnostic criteria, the
weighted prevalence shows a less exaggerated difference in the prevalence by
diagnostic criteria, but more accurately shows the rise in prevalence based on the
criteria that have been used over time. Further, these data support the notion that
the broadening of the case definition at the time that the DSM-III or DSM-III-R
was introduced may have contributed to the rise in prevalence seen in more recent
investigations.
VII. THE RELATIONSHIP OF TIME PERIOD STUDIED

TO PREVALENCE RATE
We examined trends in the weighted and mean prevalence rates of the 31 studies
by time period studied. For the studies that reported period or birth prevalence
rates over a specific range of time, we took the midpoint of that range of time to
represent the year studied. For the studies that did not provide such information,
we identified the study year as 2 years prior to the year of publication (31,44).
If we examine the weighted and mean prevalence rates of the 31 studies by
year studied, there is an increasing trend over the four decades of published
reports, with an exception in the weighted prevalence rate for those investigations
that took place from 1980 to 1989 (Fig. 2). The weighted prevalence was 0.9/
10,000 for the three studies published between 1960 and 1969 (2 –4); 3.8/10,000
for the three investigations that were studied between 1970 and 1979 (19,24,26);
2.6/10,000 for the 12 studies that were conducted between 1980 and 1989
(25,27 –37); and 10.1/10,000 for the 13 studies that were conducted between
Figure 2 Trend in prevalence of autism by time period studied.

1990 and 1999 (8,38 – 49). The mean rates that were established for each decade
that the studies were conducted show a similar pattern as the trend seen with the
weighted prevalence estimates; however, larger differences are seen in the mean
rates from one decade to the next. The mean prevalence rate ranges from 3.1 in
the 1960s to 19.8 in the 1990s (Fig. 2). These data, showing the rise in prevalence
by time period of study, may be reflective of the changing diagnostic criteria used
over these four decades, but may also be reflective of other factors such as
increased awareness and diagnosis of the disorder.
VIII. THE EFFECT OF POPULATION SIZE

ON PREVALENCE RATE
As has been noted by Fombonne (50), when we examine the mean prevalence
rates of the 31 studies by size of population (denominator), there is a trend toward
higher prevalence rates in smaller populations. The weighted prevalence for
studies with a population size of 100,000 or more children was 3.3/10,000, while
the mean rate was 5.5/10,000 (4,27,28,31,34,36,40,45,49); for the one study with
a population in the range of 80,000 – 99,999 (33), both the weighted and mean
prevalence rate was 13.8/10,000. The lowest weighted and mean prevalence rates
are seen in populations of 40,000 – 59,999 (weighted prevalence, 5.7/10,000 and
mean prevalence, 6.4/10,000) (3,46) and 60,000– 79,999 (weighted prevalence,
4.6/10,000 and mean prevalence, 4.9/10,000) (2,24,26,29,37,38,42). The
weighted and mean prevalence starts to increase as the population becomes
smaller, with a weighted prevalence of 9.2/10,000 and a mean prevalence of
11.2/10,000 for studies with a population of 20,000 –39,999 (8,19,25,30,32).
The prevalence is highest in the seven studies that had a population size of
0 –19,999 children, with a weighted prevalence of 20.8 and a mean prevalence
Figure 3 Trend in prevalence rate by case ascertainment methodology used.

of 30.4/10,000 (Fig. 3) (35,39,41,43,44,47,48). Based on these rates, we found

that both the weighted and mean prevalence rates of studies using a population
size of less than 20,000 individuals as the denominator were higher than those
with a population of 100,000 or more. This finding supports the argument that
more intensive surveillance for autism and its spectrum of disorders is possible in
smaller populations and, therefore, may lead to greater identification of children;
hence, the higher prevalence of the disorder in these study areas.
IX. THE EFFECT OF METHOD OF CASE

ASCERTAINMENT ON PREVALENCE RATES
Of the 31 studies that were included in the review, over half (58%) of the
investigators identified the cases using case enumeration, based on record review
or surveys of a given population, followed by clinical examination of the
children. For studies that used this methodology, a weighted prevalence of 2.9/
10,000 and a mean prevalence of 10.9/10,000 was found (2,19,24 – 32,36–
38,40,42,43,48). However, although the number of studies using case
enumeration only (N ¼ 7) (3,4,8,33,34,45,49) was almost the same as the
number of studies using population screening followed by clinical examination
(N ¼ 6) (35,39,41,44,46,47), the weighted and mean prevalence rate of
the studies using population screening and direct examination was higher than
those using case enumeration only (Fig. 4). The weighted and mean prevalence
estimates among the studies that used population screening and direct
Figure 4 Trend in prevalence rate for autism by number in population.

examination were 12.4 and 20.2/10,000, respectively, while the weighted

and mean rates for the studies that used case enumeration were only 3.6 and
8.1/10,000, respectively. It is worth noting that studies that used the method of
population screening and direct examination were also those that had smaller
study populations. Therefore, this method may have been more plausible in such
populations and, again, reinforces the notion that perhaps, it is possible to do a
more intensive and comprehensive survey in these populations, leading to a
greater number of individuals identified with autism or ASD.
X. RISK FACTORS FOR AUTISM
The vast majority of autism cases are idiopathic, and no specific causal factor
has been identified for ASDs. It is clear from twin (51 – 54) and family studies
(55 – 58) that there is a substantive heritable component to ASDs. Although
there is some consistent indication that suceptability genes may reside on
chromosomes 7q (59 – 63) and 15q (64 –67), no putative autism gene has been
identified. At the same time, few nonheritable factors have been implicated in
autism etiology. However, as much of the existing research on nonheritable
factors are small studies with case groups defined under older, more restrictive
diagnostic criteria, the evidence base ruling out particular factors of theoretical
appeal is also quite weak. Nonheritable risk factors have increasingly become of
concern in recent years owing to the apparent rise in autism prevalence. Should
the prevalence increase prove to be attributable in part to a real increase in risk,
this short-term fluctuation suggests the influence of a nonheritable as opposed to a
heritable risk factor or factors. The remainder of this section discusses each class
of potential nonheritable risk factors.
XI. OCCUPATIONAL EXPOSURES
Parental occupational exposures prior to conception have been reported to be

associated with autism in two small, retrospective studies completed in the
1970s and 1980s. The parents self-reported exposures to chemicals and both
studies found statistically significant associations with ASDs in the offspring
(68,69). In the 1990s, a larger study was initiated in Leominster,
Massachusetts, when ASDs appeared to be clustered among parents who
resided near plastic manufacturing plants in the past, before conception of the
affected child (70). The Massachusetts Department of Public Health followed
up on this initial report by attempting to locate additional cases and reviewing
a chromosomal study of the initial cases. They issued a report with the
conclusion that further investigations were not warranted since their estimated

prevalence of children with ASDs among former and current residents of

Leominster was 7.6/10,000 (71). This estimated prevalence was lower than
the generally accepted population prevalence of that time, which was 10– 15/
10,000.
XII. ENVIRONMENTAL EXPOSURES
Another cluster of ASD cases was investigated in the 1990s in the New Jersey
community of Brick Township, but the concern was prenatal and postnatal
exposure to environmental chemicals. Unlike Leominster, however, the
prevalence of autistic disorder in Brick Township was higher than expected,
4/1000. After examining potential exposures such as swimming in the river,
the local landfill, and drinking water, the Agency for Toxic Substances and
Disease Registry reported “no apparent public health hazard” from these
sources (72,73). Levels of chemicals in the river were not sufficient to cause
adverse health effects. Trihalomethanes, tetrachloroethylene, and trichloroethy-
lene were measured in the drinking water, but the sites and times of high
measurements did not correspond with the residences of the cases during the
study period.
XIII. XENOBIOTICS
A. Thalidomide
The discovery of a high prevalence of autism among a thalidomide-exposed
cohort and subsequent follow-up of the autism subjects has established that
prenatal xenobiotic exposure, defined as chemicals foreign to the body, can cause
autism (74). In the mid-1990s a small, retrospective study of thalidomide
embryopathy (75) first reported a higher-than-expected number of autism cases
among a cohort prenatally exposed to the drug. The autism cases were all exposed
between days 20 and 24 of gestation, the period when the neural tube is formed
(76). Although today thalidomide exposure is not an important autism etiological
factor since the drug is only approved for use in extremely limited circumstances,
other in utero exposures during this critical window of embryonic development
may play a role in autism etiology.
B. Other Pharmaceuticals
Other prenatal and intrapartum pharmaceutical agents have not shown such a
strong correlation with autism as thalidomide, but the epidemiological
evidence is limited. A few case reports point to prenatal use of valproic acid

and other anticonvulsants as a possible cause of autism (77 – 79), but published
epidemiological studies on this suggested link were not found. Interestingly,
up to 30% of ASDs cases have comorbid epilepsy (80 – 82), and anti-
convulsants appear to ameliorate ASD symptoms among nonepileptic children
(83 – 85).
Two relatively large case-control studies, each with at least 50 cases,
examined any prenatal medication use. One study, based on self-reporting,
showed a slight increase in use among the ASDs group (86), but the other
study, based on obstetrical records review, did not find any association (87).
Epidemiological evidence on use of labor-inducing drugs and risk for autism is
just as mixed. A 10-year birth cohort from four hospitals in Japan had twice
the prevalence of autistic disorder from one hospital that routinely used labor-
inducing drugs as well as more frequent use of general anesthesia, sedatives,
and analgesics compared to the three other hospitals. In contrast, a case-control
study of 180 children with ASDs that used two control groups—language
impaired and cognitively impaired—found similar prevalences of labor
induction (about 20%) among all groups. Two other relatively large case-
control studies had conflicting results—one finding a significant difference in
labor induction rates between the autism group and the general population
(29% vs. 16%, respectively) (88) and the other finding no association with
labor induction in 17% of both the autistic probands and their nonautistic
siblings (87).
C. Vaccines
Beginning in the late 1990s, exposures via childhood vaccination, particularly
the measles-mumps-rubella (MMR) vaccine and the ethylmercury-containing
vaccine preservative thimerosal, have received considerable attention in both
the scientific and lay media as potential autism risk factors. The
epidemiological evidence that has since accumulated with respect to MMR
has been consistent in showing no association with ASD risk (9–11,89– 92).
Fewer epidemiological studies have been able to assess thimerosal exposure.
One unpublished analysis, based on CDC’s Vaccine Safety Datalink, found no
significant association (93). Reports on mercury-poisoned populations and
populations with long-term low-dose methylmercury exposure have been
reviewed and no unusual observations were found with regard to more frequent
occurrence of autism (7). Further, the characteristic pathological features of
brains of individuals with methylmercury poisoning do not appear to match
those of the brains of persons with autism (7) and the toxicokinetics of ethyl-
and methylmercury may differ with indications being that ethylmercury could
be more efficiently eliminated (94).

XIV. INFECTIONS
A. Maternal
One of the earliest published reports of prenatal maternal infection possibly being
associated with ASDs was a 1971 study of 243 preschool children with congenital
rubella, 18 of whom had ASDs (95). In a follow-up report, however, six of the 18
ASD cases were reclassified so that only 12 of the 243 children had ASDs. A few
other case reports of ASDs following prenatal maternal infection with herpes
simplex, rubeola, syphilis, and varicella-zoster have been published (96).
Using a broader definition of infection exposure status, which includes
documented fever in medical records to self-report of an ill person in the home,
Deykin and MacMahon (97) analyzed maternal infection during pregnancy and
found significantly increased risk of having a child with ASD following exposure
to measles, mumps, rubella, and influenza. Other studies with broadly defined
infection measures have not reported statistically significant associations,
although risks were elevated in infection-exposed groups (86 – 88).
B. Child
Several published case studies describe sudden onset of autistic symptoms,
or regressive autism, in older children after contracting herpes encephalitis
(98 –100). Secondary hydrocephalus (e.g., from bacterial meningitis) as a
precursor to late-onset autism has also been reported in a few cases (98,100,101).
Others have implicated the viral or bacterial infection, rather than the secondary
hydrocephalus, as the pathogenic factor in autism (97,102,103). Deykin and
MacMahon (97), using the broad definition of exposure as being in a household
with another person who is infected during the first 18 months of the subject’s
life, found more autism cases exposed to mumps, chickenpox, herpes, and fever
of unknown origin than their control siblings. The relative risks for autism when
there was actual clinical illness during the first 18 months of life, after adjustment
for sibship size, were even higher. These illnesses included measles, mumps,
rubella, chickenpox, CNS infections, influenza, ear infections, and fever of
unknown origin.
XV. PERINATAL COMPLICATIONS
No individual perinatal complication has emerged as a clear autism risk factor.

Given the small sample sizes of many autism studies, another approach to
studying perinatal risk factors is to consider combinations of perinatal events and
factors as representing a pathophysiological cascade having a common source.
This approach has been borrowed from other areas of perinatal research,

producing a composite “optimality” score for pregnancy and delivery. Perinatal

complications, or suboptimal conditions, may include maternal diabetes,
neonatal respiratory distress (104), placental insufficiency (105), and frequency
of intercourse during pregnancy (106). Optimality scores are generally
heterogeneous, a combination of antepartum, intrapartum, and even postpartum
factors into a single measure. While this approach may be valid as an indicator of
perinatal mortality risk, it may not be appropriate for inferring autism risk. Some
published studies using this approach, however, have found lower optimality
scores among autism cases than controls (32,104,107,108), while others have not
found any association between obstetric optimality and autism risk (109 –111).
XVI. SUMMARY
Epidemiology is a tool that is useful for describing the occurrence of and risk
factors for a disease or condition in human populations. In this chapter, we have
described the epidemiology, specifically measures of occurrence, trends over
time, and risk factors for autism and ASDs.
The most commonly used measure of disease frequency for most
developmental disabilities, including autism, is prevalence, which has been used
to approximate incidence because measurement of the true incidence of autism is
problematic. Since the 1960s, with the conduct of the first prevalence studies of
autism, a solid body of literature examining the prevalence of autism from
population-based studies has been accumulating. We conducted a literature
review and identified 35 population-based prevalence studies of autism/ASD,
which we organized by diagnostic criteria, time period, size of population, and
method of ascertainment in an attempt to better understand trends in autism
prevalence over time; however, only 31 of the studies met our criteria for
inclusion in the examination of possible trends.
When we examined trends in prevalence by diagnostic criteria used over
time, we found that while there is a large difference in the mean prevalence rates
of studies that used DSM-IV or ICD-10 diagnostic criteria as compared with
other criteria, this trend toward increased prevalence rates based on use of these
diagnostic criteria persisted, although the pattern was attenuated when weighted
prevalence rates were used. When the 31 studies were examined by the year of
study, overall, we found that the prevalence rates increased over time; however,
the exact influences on such apparent trends cannot be easily elucidated. As noted
previously, there seems to be a trend toward higher prevalence rates associated
with smaller study populations. We were able to confirm this observation; i.e., we
found that both the weighted and mean prevalence rates of studies with
denominators of 20,000 or less yielded higher prevalence rates than study
populations of 100,000 or more. The type of case ascertainment method is also

believed to influence prevalence rates. Examining the 31 studies, we found that

studies that used population screening followed by direct examination yielded
higher rates than those using case enumeration only.
At this point there is no strong body of evidence supporting any specific
nonheritable autism risk factor. However, it may be premature to interpret the lack
of evidence in support of environmental and other nonheritable risk factors as
being equivalent to strong evidence against their existence. Studies of autism risk
factors completed to date have, for the most part, been conducted on small, select
populations of cases and have often involved quite flawed exposure assessment
approaches. Further, the fact that research attempting to fit models of inheritance
to family data have not yet been able to characterize the familiality of autism
suggests strongly that the etiological mechanism behind the disorder is quite
complex. It is known from these studies, as well as others of chromosomal
abnormalities and genetic conditions associated with autism, that there is
undoubtedly a major genetic component to autism. One explanation consistent
with this and the fact that no inheritance model appears to fit the family data is that
genetic and nongenetic factors may interact—with certain nongenetic factors
increasing risk only when key predisposing genes are present. If this is the case,
not only will future epidemiological studies investigating nonheritable autism risk
factors need to be of larger size and stronger design, they will also need to be able
to look for these factors within strata defined by level of genetic susceptibility.
This may require knowing the actual susceptibility genes but it may be possible to
categorize by phenotypic markers for these genotypes before they are actually
known. Either way, the challenges facing autism risk factor epidemiology are
substantial but not insurmountable as genetic research proceeds apace and new
efforts are now underway to conduct large, population-based studies of autism.
Our understanding of the prevalence of autism, trends in prevalence over
time, and identification of specific genetic and environmental risk factors will be
enhanced by our efforts to assemble large numbers of cases using the same case
definitions and study methods over time and our ability to accurately classify
these cases into relatively homogeneous grouping for further study of a range of
pre-, peri-, and postnatal factors. Only by using the most rigorous scientific study
methods will we be able to make significant progress in our understanding of this
complex disorder.
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3
Etiology of Autism
Vidya Bhushan Gupta
New York, U.S.A.
I. INTRODUCTION
Etiologically, autism can be divided into idiopathic (without an identifiable risk

factor) and secondary (with an identifiable risk factor). About 80 – 85% of cases
of autism are idiopathic and 15– 20% are secondary (1). In a meta-analysis of 23
surveys of autism published between 1966 and 1998, “a medical condition of
potential causal significance” was found in only 6% of cases (2). Although many
causes of autism have been proposed for the idiopathic group, few meet the
essential criteria of causation. According to Hill, to be causal, an association
should be strong, consistent, sufficient, and necessary, and should precede the
condition. There should be a dose relationship between the cause and the
condition, a plausible and coherent biological explanation, and an experimental
model (3). No single factor meets all these criteria, suggesting that autism is not
due to a single cause. Most likely it is a heterogeneous disorder caused by many
factors that work either independently, or in tandem, or in concert to cause
neurological dysfunction, that, in turn, manifests as the syndrome of autism
(Fig. 1). The foremost among these factors is genetic susceptibility.
II. GENETIC FACTORS
Kanner, in his seminal paper, noted that the parents of children in his case series
were “highly intelligent, preoccupied with abstractions of a scientific, literary,

44 Gupta
Figure 1 Etiological cascade in autism.
and artistic nature, limited in genuine interest in people, obsessive and lacking
warm-heartedness” (4,5). Although he wrongly attributed autism to this lack of
warmth in the parents, his observation was not without merit. Like Kanner, Piven
et al. have also reported that the parents of autistic subjects have higher rates of
aloof, rigid, hypersensitive, and anxious personality traits and of speech and
language deficits (6). Family studies suggest that there is an increased prevalence
of both autism and autistic-like behaviors in the first-degree relatives of persons
with autism (7 –9). The prevalence of autism in siblings is 3– 9% (10,11), while
the prevalence of a broad autism phenotype, comprising of subtle communication
and social impairments, is 12.4– 20.4% (7). Many families with multiple cases of
autism (multiplex families) have been described. Relatives of multiple-incidence
families have even higher rates of social and communication deficits and
stereotypic behaviors (8). The recurrence rate for autism after the birth of one
child is 8.6% and the relative risk of a sibling having autism is 50– 175 (12,13).
These data suggest that genetic factors cause subtle and obvious social,
communication, and sensorimotor deficits among family members of the
probands and influence the development of autism.
A genetic basis of autism is also suggested by twin studies, because
monozygotic twins have a higher concordance rate for autism than dizygotic
twins (14 – 16). However, the concordance for typical autistic disorder in
monozygotic twins is only 50%, and the symptoms of autism are often different in
monozygotic twin pairs (17,18). Concordance for a broad autism phenotype
consisting of social and language deficits, on the other hand, is much higher
(92%) (17). This suggests that either a broad autism phenotype or a susceptibility

Etiology of Autism 45
to autism is inherited but the full manifestation of autism requires additional

environmental factors.
Linkage studies suggest that the inheritance of autism is likely to be
polygenic with involvement of three to seven or perhaps as many as 20 genes
located on a number of chromosomes (19). The International Molecular Genetic
Study of Autism Consortium (IMGSA, 1998) narrowed the search for
susceptibility loci for autism to chromosome 7q and 16p, and to a lesser degree
to chromosomes 4, 10, 19, and 22 (20), but Shao et al. identified candidate regions
on chromosomes 2, 7, 15, 19, and X (21). Abnormalities of the long arm fifteenth
chromosome, region 15q11 –13, such as intrachromosomal and supernumerary
[(isodicentric chromosome 15, or idic (15))] inverted duplications and deletions,
have been reported frequently (22,23). The intrachromosomal inverted
duplication is more likely to be associated with developmental delay and
pervasive developmental disorder if it is maternally derived (24). The higher
prevalence of autism in Prader Willi and Angelman syndromes and linkage
disequilibrium at the Angelman syndrome gene UBE3A in autism families
suggest that Prader-Willi/Angelman syndrome critical region (PWACR) may be
an important locus for autism susceptibility genes (25).
Linkage with 7q has been found to be associated with severe
developmental delay and delayed expressive language (21). Various genes on
chromosome 7 seem to be promising candidates for autistic spectrum disorder.
Autism-related gene (ARG-1), a new gene identified in a concordant twin pair
with autism at 7q11.2 breakpoint in a translocation involving chromosomes 7
and 20, is highly expressed in adult and fetal brain (26). A gene has been
identified at 7q22 that regulates the production of Reelin, a secretory
glycoprotein responsible for cell lamination in cerebellun, and Bcl-2, a
regulatory protein responsible for control of programmed cell death in the brain.
This gene may be responsible for the observed Purkinje cell abnormalities. The
risk of autism is increased 3.5 times if this gene is present (27). Deletion of a
subtelomeric region of chromosome 2 is being reported with increasing
frequency in autism (28,29).
No major genes on the X chromosome have been linked to autism (30).
Although 2 – 5% of persons with fragile X have symptoms of autism, no specific
abnormalities have been discovered in the FMR gene or in the fragile X region in
individuals with autism (31,32).
About 3 –5% of children with autism have a chromosomal anomaly
(33,34). Although chromosomal abnormality of every chromosome has been
described to be associated with autism in one or two individuals, Down syndrome
and fragile X are the predominant chromosomal disorders among individuals
with autistic disorder (35). Autistic disorder may occur in as many as 7% of
individuals with Down syndrome. The likelihood of autistic disorder in children
with Down syndrome is increased if there is history of autism or other pervasive

46 Gupta
developmental disorders in first- or second-degree relatives, infantile spasms,

early hypothyroidism, and brain injury following heart surgery (36).
Between 2.5 and 6% of individuals with autism have fragile X syndrome
(37,38) and 15 –25% of persons with fragile X syndrome have symptoms of
autism (39). The wide variation in the prevalence of autism in children with
fragile X syndrome and of fragile X syndrome in autistic individuals is due to
differences in methodology and diagnostic criteria in different studies. Some
recent studies suggest that the usual behavioral phenotype of the fragile X
anomaly is distinct from autism as usually defined and the two conditions are
unrelated (40,41) Although 50 –90% of children with fragile X syndrome have
social anxiety that causes gaze aversion and difficulties in pragmatic use of
language, ability to identify the emotional states of others and to understand the
perspective of others in the theory of mind tasks is not impaired in fragile X
syndrome (42,43). Among other sex chromosome aberrations, children with
XYY syndrome seem to have a high prevalence of autism, especially those with
perinatal brain damage (44).
Among the single-gene disorders, tuberous sclerosis and untreated
phenylketonuria (PKU) seem to be the most important associations of autism.
Autistic spectrum disorder has been reported in approximately 40% of persons
with tuberous sclerosis (45,46), an autosomal dominant disorder that occurs due
to mutation of the tuberous sclerosis complex 1 (TSC1) or TSC2 genes. Among
autistic populations, the frequency of TSC is 1 – 4% and perhaps as high as
8 – 14% among those with mental retardation (MR) and seizures, particularly
infantile spasms (2,46). Although the number of tubers seen on magnetic
resonance imaging (MRI), especially in the temporal lobes, is correlated with
severity of MR and autism (47), autism in tuberous sclerosis is not secondary to
seizures or MR. According to Smalley, autism occurs due to effect of TSC
gene mutation on brain development at a stage critical in the development of
autism (46).
Untreated PKU was perhaps an important cause of autism before newborn
screening became routine in the United States (48). Pearl S. Buck, in The Child
Who Never Grew, describes the autistic features of a child with untreated PKU:
“At three years she did not talk yet. The child’s span of attention was very short
indeed. Much of her fleet light running had no purpose—it was merely motion.
Her eyes, so pure in their blue were blank when one gazed into their depths. They
did not hold or respond. They were changeless” (49).
The behavioral phenotype of Smith-Lemli-Opitz syndrome, an inborn error
of cholesterol biosynthesis, includes autism spectrum behaviors in as many as
46% cases. These children also demonstrate sleep cycle disturbance, sensory
hyperreactivity, irritability, language impairment, self-injurious behavior,
cognitive abilities from borderline intellectual functioning to profound mental
retardation, and a characteristic movement disorder. This disorder should be

considered in an autistic child who throws his upper body backward

(“opisthokinesis”) or stretches the upper body and flicks his hands (50).
The prevalence of autism is increased in neurofibromatosis (NF), a
common single-gene disorder. In the French epidemiological study, 0.6% of
children with autism had NF (51). Although the prevalence of neurofibromatosis
type 1 (NF1) is increased about 150-fold in autistic patients, NF1 region is not a
major susceptibility locus for autism (52).
The list of genetic syndromes occasionally associated with autism is too
large to be mentioned, but some important associations are given in Table 1.
In summary, no single genetic abnormality has been proven to be a
necessary or sufficient cause of autism. It seems that as many as 15 –20 loci on
different chromosomes may independently or additively play a minor role in
increasing susceptibility to a broad autism phenotype consisting of abnormalities
in social and communicative behavior, the typical syndrome occurring when a
threshold or epistasis is reached by the combination of both genetic and
exogenous causes (35,68).
From a practical point of view, a definitive cause, genetic or otherwise, is
identified in about 15 – 20% of individuals with autism or PDD (69,70). Others
have reported identifying an etiology in even fewer cases of autism (2,71). An
etiology is more likely to be identified in low-functioning children with mental
retardation, epilepsy, or dysmorphic features. Therefore, search for the etiology
of autism should be individualized according to the clinical presentation of each
case. Genetic counseling, too, should be individualized. If an obvious cause is
identified, the recurrence rate depends on the recurrence risk of the identified
condition. In idiopathic cases, if no other case is identified in the family,
Table 1 Syndromes Associated with Autism
Down syndrome (7%) (53,54)

Fragile X syndrome (3 – 6%) (31– 39)
Prader Willi syndrome (5%) (55,56)
Angelman syndrome (57 –59)
Hypomelanosis of Ito (10%) (60)
Williams syndrome (61,62)
XYY syndrome (35)
Duchenne muscular dystrophy (63)
Cornelia de Lange syndrome (67)
Tuberous sclerosis (45,46)
Neurofibromatosis (52)
Möbius syndrome (64,65)
Joubert syndrome (66)

48 Gupta
the prevalence of autism in siblings is 3 –9% (10,11) while the broad autism
phenotype, comprising more subtle communication/social impairments or
stereotypic behaviors, can occur in as many as 12.4 – 20.4% of siblings (7). The
risk of autism is particularly high if one of the parents has autism or Asperger’s
syndrome (72).
III. IMMUNOLOGICAL FACTORS
The immune system and brain communicate with each other through
neurotransmitters, hormones, and cytokines. The cytokines and immune cells
can activate neuronal pathways and release tropic hormones such as ACTH.
The latter, in turn, can influence immunological function by stimulating the
release of end-organ hormones, such as corticosteroids. The immune, nervous,
and endocrine systems are, therefore, tightly interwoven to regulate
homeostasis and changes in one can affect the other, and it is biologically
plausible that immune dysfunction can cause neurological dysfunction. Two
broad categories of immunological abnormalities have been described in
autism—qualitative or quantitative abnormalities of immune cells, and
autoantibodies against neural elements. However, it is difficult to make
meaningful generalizations from the available studies because of small and
heterogeneous samples, selection bias, and lack of uniform diagnostic criteria
across studies. The findings are often inconsistent and contradictory. While
decreased lymphocyte proliferation in response to mitogens, such as
phytohemagglutinin (PHA), concanavalin A, and pokeweed mitogen, was
reported in a few studies (73,74), other studies found normal (75), and both
high and low rates of T-cell proliferation in response to mitogens (76).
Decreased number of T cells, proportional to the severity of symptoms, was
reported by one group (74,77), but another group reported normal numbers of
T and B cells (75). Changes in the distribution of T-cell subtypes have also
been described in autism. The T lymphocytes are characterized by cluster of
differentiation (CD) surface molecules. CD4þ T cells, also called helper cells,
stimulate the differentiation of B lymphocytes into plasma and memory cells
and induce suppressor/cytotoxic cells, thus helping both the cellular and
humoral components of immune response. CD8þ cells, also called T
suppressor cells, kill the infected cells and suppress autoimmune response.
The lack of T helper cells can impair cell-mediated and humoral immune
response, while the lack of suppressor cells can set the stage for autoimmune
mechanisms to occur. Warren et al. reported reduced numbers of CD4þ cells,
in particular of the CD4 þ CD45RA þ lymphocytes that induce suppressor/
cytotoxic cells (77). A reversal of T helper/suppressor ratio due to a selective
decrease in CD4 helper cells has also been reported (78,79). Plioplys et al., on

the contrary, have reported normal CD4:CD8 ratios for the whole group, with
increased ratio in some and decreased ratio in others (75). Gupta et al.
reported lower proportions of (Th1) T cells and increased proportions of (Th2)
T cells in autistic children as compared to healthy controls (80). T helper-1
cells promote the expansion of active T cells by producing cytokines IL-2 and
IFN-g. Decreased numbers of Th1 cells can affect cell-mediated immunity
and NK cell activity, making an individual more susceptible to infection,
particularly by viruses.
Other studies have focused on the activity of natural killer (NK) cells in
autistic patients. These cells have the ability to function without prior exposure
to a particular antigen and are involved in the removal of viral-infected cells
as well as tumor cells. It is believed that these cells may have a regulatory role
in the immune system, preventing autoimmunity, because their activity has
been demonstrated to be reduced in several autoimmune disorders, such as
systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis.
Warren et al. reported significantly reduced killing activity by NK cells in 40%
of autistic subjects (81). Reduced NK cell activity can presumably place an
individual, or fetus, at an increased risk for the development of neurological
damage by viruses.
The second hypothesis linking the etiology of autism to the immune system
involves the breakdown of self-recognition mechanisms, or autoimmunity.
Autoimmunity is characterized by cellular and humoral immunological reactions
against components of the self. Production of autoantibodies to neuron-specific
antigens in autistic children has been described in several studies. Singh et al.
reported antibodies to neuron-axon filament proteins (NAFP) and myelin basic
proteins in children with autism (82,83), while Plioplys et al. reported antibodies
against cerebellar neurofilaments (84). Vojdani et al. measured autoantibodies
against nine different neuron-specific antigens, including myelin basic protein,
neurofilament proteins, and tubulin, and three cross-reactive peptides from
Chlamydia pneumonia, Streptococcus group A, and milk. In this study, autistic
children showed the highest levels of IgG, IgM, and IgA antibodies against all
neurological antigens as well as the three cross-reactive peptides compared to
controls (85).
Several studies have reported antibodies against neurotransmitter receptors
such as serotonin (5-HT) receptors (86,87), a2-adrenergic receptors (88), and
brain endothelia cell proteins (89) in children with autism. However, the
autoantibodies reported in the above studies are not specific to patients with
autism and are seen in demyelinating neuropathies such as multiple sclerosis and
Guillain-Barré syndrome as well. Antibodies reactive to CNS proteins are not
seen in the sera of most patients with autism. Unlike myasthenia gravis, in which
a clear antibody-receptor interaction has been identified, no consistent antibody
receptor interaction has been found in autism. There are few pathological findings

50 Gupta
suggestive of immune reaction or autoimmunity such as inflammation or

demyelination in patients with autism. Clustering of autoimmune disease in
families who have children with autism also suggests the role of autoimmune
factors in some individuals with autism (90). Forty-six percent of families with
autism had two or more family members with an autoimmune disorder, compared
to only 26% of controls. Although the risk of autism showed a positive
correlation with the number of affected family members with an autoimmune
disorder, patients with autism themselves did not exhibit an increase in
autoimmune disorders. Unlike autoimmune disorders, which have a progressive
or remitting-relapsing time course, the neurobehavioral symptoms of autism tend
to remain stationary or get better rather than intensify with time. Moreover, the
neuronal injury in autism is postulated to occur so early during gestation, at or
before 5 – 6 weeks of pregnancy, that immunological dysfunction is unlikely to be
the primary cause of autism.
It is unclear if immune dysfunction is the cause or effect of autism. Is it
primary or secondary to a genetic abnormality or an infection? Reduced
expression of C4B gene, a major histocompatibility complex gene that
regulates the immune system and is involved in eliminating viruses and
bacteria from the body, has been described in autism (91). A viral infection in
utero can damage the developing immune system of the fetus. Congenital
rubella infection is associated with immune dysfunction, autoimmune diseases,
and autism. Other prenatal infections, such as rubella, cytomegalovirus, herpes
simplex, syphilis, and toxoplasmosis, have been implicated in the causation of
autism. Infections can alter antigenic determinants on cell surface, activate
immune cells, and influence the nervous system through cytokine release.
Over 60 different microbial peptides have been reported to cross-react with
human brain tissue and myelin basic protein and are potentially capable of
triggering autoimmune encephalomyelitis. But the association between
congenital infections and autism is not strong as originally reported, with
less than 1% of patients with autism having histories of congenital rubella or
other congenital infections. An attempt to find viral genomes or proteins
in blood and CSF of patients with autism has also produced inconsistent
results.
The support for immune hypothesis of autism from trials of
immunomodulant therapies, such as intravenous gamma globulin, has been
weak and inconsistent. While a few open-label trials have suggested clinical
improvement with intravenous gammaglobulins in a small group of autistic
children (91,92), others reported transient or no improvement (93,94). Although
immune dysfunction may be involved in the causal pathway of autism in a few
individuals, the evidence for a major role of immune dysfunction in the etiology
of autism is meager at present and further research is needed to elucidate the
nexus between immune system and autism (Fig. 2).

Figure 2 The immune system and autism.
IV. GASTROINTESTINAL FACTORS
During the last two decades there has been a growing interest in the “central
nervous system and gut nexus.” The enteric nervous system develops from the
cells of neural crest (95) and shares neurotransmitters, such as serotonin,
vasoactive intestinal peptide (VIP), and secretin, with the main nervous system.
There is some evidence that VIP regulates immune response by microglia and
secretin affects GABA transmission in the Purkinje cells of the cerebellum
(96,97). Thus it is theoretically conceivable that the gut and brain can influence
each other.
The main premise of the “gut” theory of autism is that the gastrointestinal
(GI) tract is unable to adequately metabolize opioids derived from dietary
sources, in particular foods that contain gluten and casein, and permits them to be
absorbed via an abnormally permeable intestinal membrane (98 –102). These
peptides cross the blood-brain barrier and bind to the opioid receptors producing
symptoms of autism, such as inattention, inability to learn, and poor social
interaction (103,104). Children with autism have been reported to have increased
urinary excretion of low-molecular-weight peptides (99,105,106) and increased
opioid levels in cerebrospinal fluid (98,99).
The proponents of this theory cite increased rate of the gastrointestinal
symptoms, such as bulky, malodorous, loose stools or intermittent diarrhea, in
children with autistic spectrum disorder (103). A variety of gastrointestinal
abnormalities, such as lymphoid nodular hyperplasia of the terminal ileum,
enterocolitis with infiltration of T, plasma, and Paneth cells, mild duodenitis,
disaccharide malabsorption, and esophageal reflux, have been described in
children with autistic spectrum disorders (ASD) referred to the GI clinics
(103,107,108). The now largely discounted (109) association between MMR
vaccination and autism was allegedly mediated by vaccine-induced enterocolits
resulting in absorption of toxic peptides (101).

52 Gupta
A variety of other GI problems have been reported in small case series.

Colonization of the gut by neurotoxin-producing bacteria such as Clostridium
species was reported in a small group of children with regressive autism (110).
A poorly absorbed oral antibiotic, vancomycin, led to significant improvement in
a few children who developed regressive autism and persistent diarrhea following
treatment with antibiotics, but the improvement was not sustained when the
antibiotic was discontinued, suggesting that the association may have been
fortuitous (111). Horvath et al. reported an increase in the volume of
pancreatobiliary fluid after an intravenous injection of secretin in autistic children
as an evidence of altered secretin receptor sensitivity in autism. Because secretin
reactive receptors have been identified in the cerebellum, they argued that
the anecdotal reports of the benefits of secretin in autism are biologically
plausible (102). Megson has proposed that symptoms of autistic spectrum
disorder are caused by increased intestinal permeability and malabsorption of
vitamin A and other nutrients due to an inherited defect in G-alpha subunit
proteins, but there is no clinical or laboratory evidence for this hypothesis (112).
Most studies reporting an association between gastrointestinal symptoms
and autism have been clinic-based. Population-based studies of autism, on the
contrary, do not suggest an association between autism and inflammatory bowel
disease (IBD) or gastrointestinal symptoms. In a French population-based study,
no children with autism were diagnosed with IBD. The onset of IBD in children is
after the age of 5 years while the onset of ASD symptoms usually occurs at the
age of 1– 2 years (113,114). Except for food refusal and food fads gastrointestinal
symptoms are unusual in children with ASD. Many intervention studies based on
the gut theory, although initially promising, could not be replicated. Lucarelli
et al. noticed a marked improvement in the behavioral symptoms of patients after
a period of 8 weeks on a gluten- and/or casein-free diet (115), but a recent study
found no significant difference in the behavior pattern between the diet and
control groups of autistic children (116). In 1999, Horvath et al. (102) reported
increased expressive language and eye contact in three autistic children with
chronic diarrhea who received a single dose of hormone secretin during
endoscopy, but follow-up studies showed no effect of intravenous secretin on the
language or behavior of children with autism (117,118). Pharmacological trials
with the opiate antagonist naltrexone have produced mixed results and direct
measurement of blood or spinal fluid levels of endorphins do not suggest a link
between opiate excess and the core symptoms of ASD (119).
In summary, although a few clinic-based studies have shown increased
prevalence of GI symptoms in children with autism, population-based studies
have failed to show an association of GI disorders, including IBD, with autism.
The available evidence does not justify GI evaluation of every child with autism.
However, a child with autism who presents with GI symptomatology may be
worked up according to the “gut theory” of autism. The work-up for such patients

may include: stool studies for malabsorption and Clostridium, urine for opioid
and peptide levels, serum levels of IgG and IgM antibodies for casein,
lactalbumin, and b-lactoglobulin, and upper and lower endoscopic studies to
evaluate for lymphoid nodular hyperplasia and other signs of gut epithelial
dysfunction. Moreover, well-designed population-based studies are needed to
evaluate the prevalence of abnormalities of the GI tract and to test the hypothesis
that gut dysfunction can cause autism through the gut-brain nexus.
V. TERATOGENIC FACTORS
Because many studies point toward a prenatal onset of autism, it is conceivable

that a teratogen damages the fetal brain directly or makes it vulnerable to injury
by another factor. Time of neural tube closure seems critical for the development
of autism, because cases of thalidomide embryopathy with symptoms of autism
were exposed to thalidomide at the time of neural tube closure (120,121). Rodier
et al. have produced an animal model of autism using valproic acid, an inhibitor
of neural tube closure (122). Moore et al. reported autistic symptoms in 60% of
children exposed to anticonvulsants including valproic acid in utero (123).
Other substances that have been suspected to be associated with autism are
alcohol, cocaine, polychlorinated polyphenyls (PCBs), retinoids, and methyl-
mercury. Although a few cases of fetal alcohol syndrome have been reported to
have symptoms of autism, autism is uncommon in fetal alcohol syndrome (124).
One case series reported high prevalence of autism in children exposed to cocaine
in utero (125), but this has not been replicated. A study that examined children
exposed to both cocaine and alcohol in utero found that exposure to alcohol
accounted for most of the effect (126). The neurotoxic theory of autism was
examined by the Center for Disease Control (CDC) in Brick Township of New
Jersey. This town is close to several Superfund sites and has three contaminants
in drinking water, tetrachloroethylene, trichloroethylene, and trihalomethanes
(THMs). Although the town was believed to have higher prevalence of autism, an
epidemiological study by CDC did not find the prevalence of autism in Brick
Township to be higher than in other small communities (127). Studies that have
examined exposure to polychlorinated biphenyls (PCBs), dioxin, and
methylmercury have not shown any association with autism (128). Thus the
search for a chemical teratogen that is necessary or sufficient to cause autism has
been elusive so far.
VI. MMR VACCINATION AND AUTISM
The saga of measles, mumps, and rubella (MMR) vaccination and autism started
when Wakefield et al. reported a series of 12 cases that allegedly developed

54 Gupta
regressive autism after receiving MMR vaccination. The symptoms were

apparently mediated by MMR vaccine-induced enterocolitis that, in turn, allowed
neurotoxic metabolites to be absorbed from the gut (129,130). However,
population-based studies of autism have not found any association between
autism and MMR vaccination (131,132). In a retrospective cohort study
involving 537,303 children, Madsen et al. found no association between the date
of vaccination and the onset of autism. The relative risk of autism and autistic
spectrum disorder in the vaccinated group was not higher than in the
unvaccinated group (132). The prevalence of autism has increased in the 1990s,
while the MMR vaccine has been used in the United States since 1963 and the
rates of MMR vaccination have remained stable during the 1980s and 1990s.
There is no correlation between MMR time trends and autism prevalence (133).
Similarly, it is not proven that MMR vaccination causes enterocolits (134).
In a retrospective study that linked MMR vaccination with the hospital discharge
data, none of the autistic children were hospitalized for inflammatory bowel
disease (135). Even with the most sophisticated assays, measles viral material
has not been demonstrated consistently in the intestines of children with
inflammatory bowel disease (136,137). A detailed discussion of the GI theory of
autism was presented earlier in this chapter.
Because intrauterine exposure to high doses of methylmercury, often from
seafood contamination, is associated with neurobehavioral complications such as
developmental delay, cognitive deficits, and seizures, it has been suggested that
autism can occur due to intrauterine or postnatal exposure to mercury either from
contaminated fish or from thimerosal, an ethylmercury-containing preservative
used in infant vaccines (138). But, the symptoms of mercury poisoning include
seizures, ataxia, photophobia, and dysarthria, symptoms not seen in autism.
According to the Food and Drug Administration, if a child receives multiple
thimerosal containing vaccinations, he may be exposed to mercury in excess of
the federal safety guidelines (139). Although the association is not proven, most
infant vaccines are now made without thiomerosal.
The U.S. Institute of Medicine and the American Academy of Pediatrics
have both concluded that there is little evidence that MMR vaccination causes
regressive autism (140,141). Similarly, multiple vaccinations, whether given as
multiple injections or as tetra- or pentavaccines, do not increase the risk of autism.
VII. INFECTIOUS FACTORS
Cases of autism have been described in children who had intrauterine rubella
(142,143) and cytomegalovirus infection (144). Autism has also been described
after perinatal and postnatal herpes simplex encephalitis (145). Most of these
cases have clear evidence of brain damage with additional manifestations such as

mental retardation and seizures. Besides damaging the brain directly, viruses can
damage the brain indirectly by triggering an autoimmune response against the
neural elements of the host. Investigations are ongoing into the possibility of
previously unrecognized viruses specifically causing the syndrome of autism
without producing recognizable cytopathic effects. Hornig and Lipkin have
produced symptoms suggestive of autism in newborn Lewis rats by infecting
them with Borna virus (146). These rats have been noted to have abnormalities in
cerebellum and hippocampus that resemble the lesions reported in autism. Thus it
is biologically plausible for a viral infection occurring at a critical time of
development to result in neurodevelopmental disability with no overt signs of
encephalitis at the time of infection. Persistent viral infections can, theoretically,
cause neurotransmitter dysfunction without causing inflammation, histological
injury, or cytopathic effect and may not be detected by traditional neurological
investigations (147). Thus a viral infection at a key time in early stages of
neurological development can predispose an individual to autism, but no specific
viral cause of autism has been confirmed so far.
VIII. PERINATAL FACTORS
Perinatal and obstetric factors have not emerged as important in the etiology of
autism. Several case control studies have found no association between obstetric
factors and autism. Others have reported weak associations between various
obstetric factors and autism, but no single obstetric event has emerged as a
preeminent antecedent of autism. Higher incidence of second- or third-trimester
uterine bleeding and prolonged labor have been reported in several studies (148 –
151). Hyperbilirubinemia was noted more often in autistic children in three
studies (148 –151). Other complications that have been reported inconsistently
include induction of labor, prolonged and precipitous labor, and oxygen
requirement at birth. Data on vaginal infections during pregnancy are conflicting
and may be confounded by socioeconomic status and number of sexual partners,
factors not controlled for in the studies. Prematurity is not associated with autism.
Overall the complications that have been reported have been mild and none have
emerged as necessary or sufficient to cause autism (152).
Studies that have used the optimality approach to assess the obstetric
factors in autism have also reported mixed to negative results. This approach
looks at obstetric and neonatal risk as a composite score. Deb et al. found no
significant difference in the scores of obstetric optimality between the overall
group of autistic children and their siblings, but among children with severe
autism there was a significant correlation between severity of autism and
obstetric and neonatal complication scores. This observation supports the notion
of two types of autism: low-functioning, which is secondary to some known

56 Gupta
obstetric and other etiological factor, and high-functioning, which is idiopathic

(153). Cryan et al., on the other hand, did not find any association between autism
and obstetric complications score (154). Because some of the variance in
obstetric adversity may be due to birth order, Piven et al. studied the association
between perinatal factors and autism, correcting for birth order. They did not find
any association between perinatal factors and autism (155).
In summary, obstetric and perinatal complications do not, by themselves,
cause autism but may occur because the fetus and pregnancy are compromised by
the primary cause of autism. Alternatively, common risk factors may cause both
autism and the obstetric complication (149,152).
IX. METABOLIC FACTORS
Features of autism have been described in a few children with metabolic

conditions such as D-glyceric aciduria, phenylketonuria, histidinemia, adenylo-
succinate lyase deficiency, dihydropyrimidine dehydrogenase deficiency, 50 -
nucleotidase superactivity, and phosphoribosylpyrophosphate synthetase
deficiency (156,157). Although hyperuricosuria has been described in a few
children with autism, defects of purine metabolism such as adenylosuccinate
lyase deficiency are infrequent (158). Metabolic defects of detoxification, such as
a defect of sulfation, have also been suggested (159). Other metabolic disorders,
such as mitochondrial respiratory complex defects, fatty acid oxidation defects,
carnitine deficiency, and organic acidopathies, are being explored, but, at present,
there is little evidence to support the notion that autism is a metabolic disorder or
that metabolic defects are common in autism.
X. SUMMARY
It seems from the foregoing that the etiology of autism is still elusive. Many
hypotheses have been proposed, some based on empirical observations, some by
analogy, and some by deductive reasoning. Only the salient hypotheses have been
presented in this chapter. Because autism is such a disheartening condition, there
is a tendency to say “eureka” whenever any association is observed. Explosion in
the prevalence of autism has made it a political disease. And the media smells for
rats, ready to sensationalize any anecdote, any suggestion, and any insinuation as
a potential cause. In this charged environment it is the responsibility of the
professionals to be rational while keeping an open mind. Instead of rushing to
judgment, the professionals should measure every association with Hill’s criteria
and plan and inform accordingly. Because of the fervor with which the scientific
community and the society at large are responding to this apparent epidemic of

autism, it is likely that we shall find the etiological factors associated with autism
in the near future and be able to stall the tide of autism.
ACKNOWLEDGMENTS
I wish to acknowledge the help of Rohit Kohli, M.D., in the section on gastro-
intestinal factors and of Divya Aggarwal, M.D., in the section on teratogenic
factors.
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4
Neurological Basis of Autism
Vidya Bhushan Gupta
New York, U.S.A.
I. INTRODUCTION
Brain is the final pathway to which all the etiological factors discussed in the last
chapter lead. There is sufficient evidence in the neuroscience literature that
autistic symptoms occur because of functional or structural abnormalities of the
brain. About 15 – 30% of children with autism have macrocephaly (1 –5), due to
larger brain volume (6,7), with increases in both gray and white matter (8). While
autistic individuals continue to have a larger head circumference throughout their
life, their brain volume decreases after increasing for a few years after birth
(8 – 10), suggesting a neuropathological process that begins before birth but
continues postnatally. Increased head circumference in autism is not correlated
with IQ, verbal ability, seizure disorder, or autistic symptoms.
Despite a litany of studies pointing to the neurogenic origin of autistic
symptoms, the core areas of the brain that are involved and the specifics of their
dysfunction are unknown. The attempts to find a single source of autistic
symptoms in the brain have been unsuccessful and it is likely that this syndrome
is neurologically heterogeneous with different symptoms originating from
different structures of the brain. Perhaps autism occurs due to an insult to the
developing nervous system at an earlier stage when a localized insult branches off
to other areas of the brain because of the “interdependent nature of early brain
development” (11). Depending on sensory inputs and other factors during
subsequent maturation, this “branching off” takes its unique course in every
individual, giving rise to unique pathology in every individual. Reported

68 Gupta
abnormalities in the key brain structures that have been incriminated as the
“home of autism in the brain” (12) are described below.
II. CEREBELLUM
Several neuropathological studies have found low Purkinje and granular cell
count in the cerebellar hemispheres of individuals with autism (13 – 15). Smaller
Purkinje cells have been reported. Fatemi et al. attributed small this reduction in
the size of Purkinje cells to reduction in Reelin and Bcl-2 proteins in the
cerebellum (16,17). Proton magnetic resonance studies have found lower
concentration of N-acetyl aspartate (NAA) in the cerebellum, suggesting reduced
activity of Purkinje cells (18,19).
Hypoplasia of cerebellar vermal lobules VI and VII was reported as the
“eureka” of autism in 1988 by Courchesne et al. (20), but since then other
findings, such as hypoplasia of vermal lobuli VIII –X (21,22), hypoplasia of
vermal lobuli I– V (23), and a combination of vermal hypo- and hyperplasia, have
been described (24). A report of pervasive developmental disorder in two
children with Joubert’s syndrome, a condition characterized by the agenesis of
cerebellar vermis, provided some support to the cerebellar hypothesis of autism
(25), but a later study refuted this association (26). Not all individuals with autism
have vermal hypoplasia (27,28) and vermal hypoplasia has been described in
individuals without autism, such as acute lymphoblastic leukemia survivors
(29,30). According to Ciesielski and Knight, involvement of the cerebellum in
such diverse conditions may be due to its prolonged course of maturation, making
it vulnerable to injury (30).
Morphometric studies of cerebellum have also shown inconsistent and
contradictory results. Both small (31) and large (32) cerebella have been
described, and in studies that report large cerebella, increase in cerebellar size out
of proportion to the overall brain size (32) as well as increase in cerebellar size
proportional to the overall brain size has been reported (27,33).
Limited support for the cerebellar hypothesis of autism comes from an
animal model in which exposure to valproic acid early during gestation damages
the brainstem cranial nerve nuclei and reduces the number of neurons in the
deep cerebellar nuclei, changes analogous to thalidomide embryopathy with
autism (34).
Although it is difficult to conclude from the inconsistent and contradictory
data presented above that cerebellar abnormalities are the source of autistic
symptoms in every person with autism, they may be responsible for some
symptoms of autism in a subset of patients. The cerebellum plays an important
role in language, emotion, and motor-attentional systems through its connections
with frontal lobe, thalamus, olivary nuclei, and other areas of the brain. It is

Neurological Basis of Autism 69
plausible that abnormalities of the cerebellum or a disruption of its neural

networks with the other areas of the brain contributes to symptoms pertaining to
these domains (35,36).
III. LIMBIC SYSTEM
The limbic system includes subcallosal, cingulate, orbitofrontal and para-

hippocampal gyri, underlying hippocampal formation, dentate nucleus, amyg-
daloid complex, anterior thalamus, mamillary bodies, fornix, and septal nuclei.
The limbic system is believed to be the socio-emotional brain, and is, thus, a
plausible candidate for the source of social symptoms in autism (37). Citing a
functional MRI (fMRI) study in which patients with autism or Asperger’s
syndrome did not activate their amygdala when judging what that other person
might be thinking or feeling by looking at his face, Baron-Cohen et al. proposed
an “amygdale theory of autism” (38). Howard et al. showed that people with
high-functioning autism have a neuropsychological profile characteristic of
amygdala damage, in particular impairment in recognizing faces and facial
expressions. Using quantitative magnetic resonance (MR) images analysis
techniques, they demonstrated bilateral enlargement of the amygdala in these
individuals (39). Bitemporal ablation of the hippocampus and amygdala in
monkeys was reported to produce behavioral effects suggestive of autism (40),
but this finding has been recently refuted by Amaral and Corbett (41).
Limbic system involvement is suggested by the findings of smaller anterior
cingulate gyrus (42) and area dentata in MRIs of brains of individuals with autism
(43). Functional neuroimaging has shown reduced glucose metabolism in cingulate
gyrus of individuals with autism (44). Autopsy studies have revealed small, sparsely
branched, but tightly packed, neurons in hippocampus and amygdala of the brains of
individuals with autism (45,46), suggesting arrested maturation of the limbic system.
However, other studies have not confirmed these findings (13).
As in the case of cerebellum, the data on the involvement of limbic system
in autism are inconsistent and contradictory (13,47). It seems that structural or
functional abnormalities of the limbic system may be responsible for social-
cognitive deficits (theory of mind deficits) in a subset of individuals with autism,
but are by no means universal.
IV. BRAINSTEM
Association between autism and Möbius sequence suggests that brainstem may
be involved in a few cases of autism (48,49). Möbius sequence is characterized by
hypoplasia of cranial nerve nuclei resulting in congenital palsy of the sixth and

70 Gupta
seventh cranial nerves. Rodier et al. found cellular abnormalities of the facial and
other brainstem nuclei in the brain of a woman with autism. The association
between cranial nerve involvement and autism has also been seen in thalidomide
embryopathy (50). Rodier et al. reproduced the lesion seen in thalidomide
embryopathy in rats by exposing them to valproic acid at the time of neural
tube closure (50). Autopsy studies have revealed smaller pons, midbrain, and
medulla oblongata (51 – 53) and abnormalities of inferior olivary nucleus in the
brains of individuals with autism (54). It has been suggested that autism occurs
because of the persistence of a transitional zone (lamina desiccans) beneath the
Purkinje cells where the climbing olivary fibres synapse until 24 –30 weeks of
gestation. The lesions in brainstem at an early stage of embryogenesis perhaps
damage the cerebral-cerebellar connections that are necessary for the
development of higher cognitive functions (55). Such brainstem-cerebellar
dysfunction was suggested by the finding of abnormal oculomotor movements
and brainstem potentials in children with autism in a study (56). However, the
evidence for brainstem involvement in autism is far from conclusive. Studies of
auditory brainstem responses of autistic probands and their relatives report
contradictory results including prolongation, shortening (57,58), and no
abnormalities of transmission latencies (59). Few children with autism have
cranial nerve palsies.
The brainstem plays a role in arousal and shifting of attention, and
modulates both general sensory input and motor response to it. Ornitz et al. found
abnormal responses to vestibular stimulation in autistic children (60). Therefore,
it is plausible that brainstem dysfunction can cause some symptoms of autism
such as transitioning from one activity to another, vestibular dysfunction, and
abnormal sensory processing.
V. BASAL GANGLIA
Basal ganglia include caudate nucleus, putamen, globus pallidus, nucleus

accumbens, and substantia nigra. An increase in the volume of the caudate nuclei,
proportional to the increased total brain volume, was found to be associated with
compulsions and rituals, complex motor mannerisms, and resistance to change in
autism in an MRI study of the brain (61). The caudate may be part of the
abnormal neural networks that are responsible for the ritualistic-repetitive
behaviors of the autism (61). Enhanced activity of basal ganglia cells has been
incriminated in stereotyped movements of Rett’s syndrome (62). A boy with right
putamen infarct showed sterotypies similar to those seen in autism (63). Animal
models have localized behavioral stereotypies and self-injurious behavior to
basal ganglia (64). Although direct evidence of basal ganglia involvement in
autism is meager, circumstantial evidence is compelling that structural or

chemical abnormalities of the basal ganglia cause stereotypic and repetitive

behavior in autism. According to Thong, stereotypic and ritualistic behavior in
autism occurs due to injury to the more primitive striatal complex, mammalian
counterpart of the brain of reptiles (65).
VI. CEREBRAL CORTEX
Cognitive and communication deficits in autism make cerebral cortex a plausible

“home for autism.” Findings in structural MRIs of the brains of individuals with
autism have included changes in the size of anterior horns of lateral ventricles and
right lenticular nucleus (66), smaller parietal lobes (67), and findings suggestive
of abnormal neuronal migration, such as polymicrogyria, schizencephaly, and
macrogyria (68).
Functional neuroimaging of the brain of autistic individuals suggests
involvement of cerebral cortex but no particular region emerges as the
preeminent source of autistic behaviors. Many studies have reported involvement
of temporal lobes and auditory cortex in autism (69,70). Chugani et al. showed
reduced bitemporal hypometabolism on positron emission tomography (69).
George et al. reported reduction in total brain as well as frontal and right temporal
lobe perfusion, but this finding was not confirmed in another study (70,71). Using
functional MRI during a theory of mind task, Baron-Cohen et al. showed less
activation of the superior temporal gyrus, an area that is usually activated in such
tasks in normal individuals (72). The role of the temporal lobe in autism is
suggested by the association between autistic symptoms and temporal tubers and
temporal lobe epileptiform discharges in tuberous sclerosis (73), and focal EEG
abnormalities in the temporal region in West syndrome (74). DeLong has
proposed that low-functioning autism occurs due to bitemporal, especially mesial
temporal, involvement, while higher-functioning autism occurs due to left
hemispheric dysfunction with sparing and even better functioning of the right
hemisphere (75). Reversed hemispheric dominance with decreased blood flow to
the left cortical areas devoted to language and handedness in children has been
reported by others as well (76,77).
Abnormalities of other cortical areas have also been reported in autism.
Prefrontal dysfunction is suggested by abnormalities in voluntary suppression of
oculomotor responses to visual targets (78). Delayed metabolic maturation of
frontal lobes causing functional deficits in object permanence and theory of mind
has been reported (79).
Electrophysiological studies, like electro- and magnetoencephalography,
nonspecifically suggest that there is cortical dysfunction in autism but do not help
in clinical diagnosis or explain the neurological source of autistic behaviors.
Traditional EEG of individuals with autism shows paroxysmal activity in

72 Gupta
20 – 70% of cases while magnetoencephalography shows epileptiform activity in

as many as 82% of cases (80,81). Epileptiform activity is mostly focal
or multifocal with centrotemporal spikes, with occipital spikes in a minority of
patients (82). Although epileptiform activity is more common in children with
regression, it is not certain if this activity causes regression and whether
anticonvulsants can stall regression (83,84). The effects of the epileptiform
discharge on cognitive functioning may be due to the extension of epileptic
activity in temporal or parietal lobes, but this has not been confirmed.
Epilepsy has been reported in as many as 4 – 30% of children with autism
and pervasive developmental disorders, providing additional support for the
neurogenic basis of autism. Clinical seizures, usually partial, occur more often in
infancy and adolescence (86 – 90).
In the absence of a core deficit area in autism, abnormality of neural
networks has been proposed to be the primary problem in autism (35). Damage to
the developing neural networks can result in secondary problems in the regions
interconnected by these networks. Recent finding of small and less compact
minicolumns in key frontal and temporal lobe gyri of the brains of individuals
with autism supports this view (91). Because of environmental vulnerability and
neural plasticity of the networks, each child may have a unique neurological and
symptomatic profile. Other mechanisms that have been incriminated in autistic
neuropathology are listed in Table 1.
It is likely that dysfunction of different areas of the brain contributes to
different aspects of autistic symptomatology (Table 2). For example, attentional
deficits and inflexibility may be caused by prefrontal dysfunction, communi-
cation abnormalities due to temporal lobe dysfunction, theory of mind deficits
due to dysfunction of the orbitofrontal cortex and limbic system, and stereotypies
due to dysfunction of the basal ganglia.
Table 1 Possible Neuropathological Processes in Autism
Delayed maturation
Maturational arrest with persistence of fetal circuitry
Abnormal development of neuropil (reduced dendritic pruning or abnormal proliferation)
Early damage to neural circuits/networks
Abnormal neuronal migration
Abnormal differentiation (microcolumnar changes)
Early degeneration (neurofibrillay tangles)
Abnormal apoptosis
Disconnect between various areas of the brain
Abnormalities of cerebral regional blood flow

Table 2 Possible Sources of Autistic Symptoms in the Brain
Source in
Symptom complex the brain Reported associations
Impairment in social interaction Limbic Enlargement of amygdala

system
Theory of mind tasks Tightly packed small neurons
Impairments in communication Temporal Bitemporal hypometabolism
cortex Temporal lobe
epileptiform discharges
Cognitive impairment Cerebral Abnormal neuronal
cortex migration
Inattention, hyperactivity, Prefrontal Abnormalities in voluntary
impulsivity, and inflexibility cortex suppression of oculomotor
responses to visual targets
Restricted and stereotyped Basal Larger caudate nuclei
behaviors ganglia
Fine-tuning of communicative, Cerebellum Low Purkinje cell count
emotional, attentional, and Vermal hypoplasia
motor responses to the context
Difficulties in transitioning from Brainstem Smaller brainstem structures
one activity to another, Cranial nerve nuclear
vestibular and sensory hypoplasia
dysfunction Abnormalities of inferior olivary
nuclei
Inability to discriminate Frontal and Small, less compact,
between competing temporal numerous minicolumns
sensory information cortex
VII. NEUROCHEMICAL FACTORS
Because the symptoms of autism originate in multiple areas of the brain,

abnormal chemical neurotransmission among these areas may be the root cause
of autism. There is some evidence to support the neurochemical basis of autism,
but like neuroimaging, neurochemical findings in autism are inconsistent and
contradictory. While many studies have reported increased serotonin levels in
whole blood and platelets in individuals with autism (92 – 94), a few have
reported low whole-blood serotonin levels in children with autism (95). Based on
the finding of autoantibodies to brain serotonin receptors (96), it has been
suggested that serotonin-blocking antibodies inhibit the specific binding of
serotonin to its receptor in autistic children, causing serotonergic dysfunction
(97), but research support for this hypothesis is lacking (98,99).

74 Gupta
The finding of increased serotonin in blood platelets generated interest in

the role of serotonin transporter gene (5-HTT) in increasing 5-HT uptake in
platelets, but the findings have been inconclusive. While some studies have
suggested an association between the serotonin transporter gene and autistic
disorder (100,101), others have not (102,103). Serotonin transporter promoter
alleles have also been examined, because they can modify the severity of
autistic behaviors in the social and communication domains, without increasing
the risk for autism (104,105). Clinical pharmacological evidence about
serotonergic dysfunction in autism is contradictory, because clinical improve-
ment occurs with agents that enhance its transmission, such as clomipramine
(106), fluoxetine, and paroxetine (107), and those that deplete serotonin, such as
fenfluramine (108), or block its transmission, such as risperidone (109).
Serotonin is involved in perception and sensory filtration of stimuli and in social
attachment (110) and its dysfunction can plausibly cause autistic symptoms; the
exact nature of serotonergic dysfunction in autism is still unknown despite a
litany of studies.
Improvement in behavioral symptoms of autism by haloperidol, a
dopamine antagonist, suggests that dopaminergic systems are involved in autism
(111). Risperidone, an atypical neuroleptic and a potent antagonist of the
postsynaptic dopamine D2 receptor, is effective in controlling some symptoms of
autism, such as tantrums, aggression, and self-injurious behavior (109). Higher
levels of homovanillic acid, a metabolite of dopamine, have been reported in low-
functioning autistic children (112). The dopaminergic system influences selective
attention and motor behavior (113). Dysfunction of dopaminergic transmission in
the prefrontal cortex may cause symptoms of inattention and hyperactivity in
autism, while in the basal ganglia it may cause motor stereotypies (114). The role
of dopamine in autism is, however, inconclusive, because drugs that antagonize
dopamine, such as risperidone, as well as those that enhance its transmission,
such as methylphenidate, are helpful in children with autism.
Opioid overactivity in the brain has been proposed to be the cause of poor
socialization, decreased sensitivity to pain, and self-injurious behaviour in autism
(115). The limbic system, which is implicated in the causation of socio-emotional
and theory of mind problems of autism, is rich in endogenous opioid receptors
(116). But drug trials with the opiate antagonist naltrexone and direct
measurement of blood or spinal fluid levels of endorphins have not demonstrated
strong evidence of opiate excess being responsible for the core symptoms of
autistic spectrum disorder (117 –121).
An unsubstantiated theory about the role of exogenous opioids in autism is
in vogue in the alternative medicine camp. According to this theory, an excess of
opioids enter the bloodstream from the gut through a defective mucosal barrier.
Opioids are produced in the gut from incompletely digested gluten and/or casein
due to the failure of intestinal peptidases to convert opioids to innocuous

metabolites (122,123). The results of two systematic trials of dietary exclusion of

gluten and casein have been equivocal (124,125).
Dysfunction of other neurotransmitter systems, such as catecholamines,
glutamate, g-amino butyric acid (GABA), neuropeptides (126), and nicotine
(127), has been proposed to cause symptoms of autism. Catecholamines are
plausible candidates for involvement in autism because noradrenergic cells in
the locus ceruleus regulate attention, behavioral flexibility, filtering of
irrelevant stimuli, arousal, anxiety, and learning, which are impaired in autistic
individuals (128). Plasma norepinephrine has been reported to be elevated
in some children with autism (129). Increased levels of neuroexcitatory
neurotransmitters, such as glutamate and upregulation of their receptors, can
damage neural pathways, resulting in symptoms of autism. Reduced levels of
gluatamic acid decarboxylase have been reported in the brains of autistic
children. This can theoretically result in elevated levels of glutamate in
blood and platelets (130). Evidence for both these neurotransmitters is weak
and unreliable. Hormones such as oxytocin, insulin-like growth factor, and
testosterone have also been suggested to have or affect neurotransmitter
function (131).
It seems that no single neurotransmitter has a monopoly on the
symptoms of autism, but they modulate one another’s actions to cause a unique
mix of symptoms in each patient. Because of the unique pattern of
neurochemical dysfunction in each patient, no single drug works in all the
patients. Various neurotransmitters putatively involved in autism are presented
in Table 3.
Table 3 Neurotransmitters Involved in Autism
Neurotransmitter Symptom Evidence
Serotonin Social orientation, attunement, Increased serotonin levels in

and cognition whole blood and platelets
Autoantibodies to brain
serotonin receptors
Dopamine Inattention, hyperactivity, Higher levels of
In prefrontal cortex behavioral flexibility, homovanillic acid
Basal ganglia stereotypies, mannerisms
Norepinephrine Hyper- or hypoarousal Elevated plasma
Regulation of attention, norepinephrine
anxiety
Others Opioids, glutamate, g-amino butyric acid (GABA),
neuropeptides, and nicotine

76 Gupta
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5
Early Clinical Characteristics
of Children with Autism
Chris Plauché Johnson

University of Texas Health Science Center at San Antonio, San Antonio,
Texas, U.S.A.
I. INTRODUCTION
Most neurodevelopmental disorders are recognized either by their phenotype

(physical appearance) and/or by their genotype (chromosomal and/or molecular
appearance). Unfortunately, there is neither a specific phenotype nor a consistent
genotype that reliably defines autism spectrum disorder (ASD). Relatively new to
the field of neurodevelopmental disorders is the recognition of “behavioral”
phenotypes. Although the characteristic behaviors of some “syndromes” have
been recognized for quite some time, it has only been in the recent past that
sophisticated genetic diagnostic techniques [e.g., fluorescent in situ hybridization
(FISH)] have provided the corresponding genetic characteristics allowing the two
to be reliably linked to one another. Examples of such behavioral phenotypes
(and their corresponding genotype) include, but are not limited to: hand-wringing
and hyperventilation characteristic of Rett’s syndrome (MECP2), self-hugging in
Smith-Magenis (l7p11.2 deletion), excessive smiling and wide-based puppet-like
gait in Angelman’s syndrome (15 q11– 13 deletion of maternal origin), extreme
hyperphagia in Prader-Willi syndrome (15 q11– 13 deletion of paternal origin),
and self-biting and tissue destruction of lips and hands in Lesch-Nyhan
(X q26 –27).
In addition to the absence of a defining genotype or characteristic physical
phenotype, ASD also does not have a specific behavioral phenotype. For many
years ASD was conceptualized as primarily a communication disorder. In 1991,

86 Johnson
Rogers and Pennington (1) proposed a novel developmental model, suggesting

that an abnormal developmental cascade resulted in sequential deficits in joint
attention, social referencing, communication, symbolic play, and repetitive
restricted behaviors. The model accounted for deficits in all three main symptom
areas: social relatedness, communication, and restricted, repetitive behaviors, and
fostered recognition of children with ASD at much younger ages (2). Also
contributing to the de-emphasis of communication skills as the defining
characteristic of autism was the recent recognition of the full spectrum of autism
in which some children with high-functioning autism, or Asperger’s syndrome,
have relatively minor language deficits during early development (but later
demonstrate significant pragmatic deficits). Moreover, abnormalities in language
development are not specific to ASD and, in fact, are more commonly seen in
children with mental retardation, hearing loss, and communication disorders.
Although delayed echolalia, advanced expressive language skills relative to
receptive ones, and pragmatic deficits are somewhat unique to ASD, not all
children demonstrate these abnormalities. Although stereotypies may be obvious
and will readily alert the clinician to a problem, they often do not become
apparent until after 3 years of age. These are also seen in children with severe or
profound mental retardation or severe visual impairment. Thus, language deficits
and stereotypies do not distinguish ASD from other childhood disorders. All
children with ASD, however, do demonstrate unique deficits in social skills.
Although not pathognomonic, a few of the early recognizable social deficits are
very characteristic and considered by some to quite possibly be specific for ASD.
Currently, the DSM-IV (discussed in Chapter 6) is the gold standard in regard
to diagnostic criteria (3–5). Unfortunately, DSM-IV criteria are not as reliable in
children less than 3 years of age since, due to the natural evolution of developmental
skills, many of the defining criteria may not be present in very young children later
diagnosed with autism. For example, “failure to form age-appropriate peer
relationships” is really not applicable in very young children. Additionally, in a
preverbal child, it is difficult to demonstrate abnormal conversational skills and
stereotypic language. Ritualistic behaviors, a need for routines, and stereotypies are
often not found in children less than 3. Thus, even children appearing to have severe
autism may not meet full criteria at very young ages. Instead, they usually receive
the “threshold” provisional diagnosis of PDD-NOS. Later, if additional signs
appear, full criteria may be met and the diagnosis of autistic disorder is then made.
Realizing this diagnostic dilemma, especially now that earlier diagnosis is
emphasized, modified DSM criteria have been suggested for children less than 3
years of age (6):
A1: Decreased use of nonverbal behavior (eye-to-eye gaze, facial

expression, body posture, gestures)
A2: Lack of social and emotional reciprocity

Early Clinical Characteristics 87
A4: Lack of seeking to share enjoyment, interests, or achievements with

other people (absent showing, bringing, or pointing to objects of
interest)
B1: Delayed or absent language skills
The authors state that all four criteria should be present to make the provisional
diagnosis of ASD in the very young child. It is important to note that three of the
four are social skill criteria. Recognizing the importance of social skills in
defining and detecting ASD in very young children, this chapter will focus on
social skill deficits and how they impact later development of language and play
skills. A short discussion of additional DSM criteria in the language and
restricted, repetitive play domains, as well as brief discussions regarding physical
characteristics, motor development, savant skills, and autism regression variant,
will follow.
“Social skills” as discussed in this chapter are defined more loosely than
in the DSM-IV. Indeed, behaviors described in this chapter overlap with some
of the DSM-IV criteria listed in the language and repetitive/restricted play
domains. Additionally, deficits in social skills negatively impact the later deve-
lopment of language and cognitive skills. Whereas very early social skills
depend on facial and gestural interactions, later ones depend on the child’s
ability to verbalize. Social development parallels cognitive development in
normal or globally delayed children; in children with ASD, the development of
social skills is characteristically “out of sync” with the child’s overall level of
functioning. This discrepancy between social and general levels of functioning
is one of the most important defining criteria of ASD. The discrepancy can be
first noted in infants aged 8 – 12 months, but it becomes more evident as the
child approaches 18 – 24 months. The purpose of this chapter is not to discuss
the social skills as strictly defined by the DSM-IV, but rather to discuss a
more inclusive set of social-emotional characteristics that impact not only
social skill development but also language, cognitive, and play development.
Ultimately, the goal is to help the clinician recognize the expanded range of
social deficits to raise the index of suspicion for ASD at an earlier age than
would occur if one focuses only on failure to achieve later-occurring language
milestones. This is extremely important as recent literature has demonstrated
that children with ASD, who are recognized early and referred to an appro-
priate and intensive intervention program, improve and demonstrate decreased
symptomatology (7 –9).
In the past, the definitive diagnosis of autistic disorder has usually not
been made until after 3 years of age, more likely between 4 and 6 years of age.
Howlin (10,11) demonstrated that parents usually become concerned by 18
months, but do not present to the child’s primary care provider with these
concerns until 6 months later. In one study published in 1997, over 50% of

88 Johnson
parents were reassured and told “not to worry.” The usual interval between first
parental concern and the final definitive diagnosis was approximately 4 years.
Denial, lack of familiarity with the spectrum of distinguishing characteristics
that define ASD, and scarce subspecialty resources, among other reasons,
contributed to late diagnosis.
Parents usually first become concerned when they realize that their child’s
expressive language is delayed. Indeed, this has been the historical hallmark of
the disorder and will likely continue to be so as these deficits are easily
recognized. Although earlier social skill deficits are now better known in
professional circles, they are not as easily recognized by parents. There is one
exception. In families where there are two children with ASD, parents often
recognize the early social signs in the younger child prior to any concerns about
language. Indeed, now that experts in the field have begun to focus on these
earlier social deficits, often by the use of screening (e.g., the CHAT) or diagnostic
(e.g., the ADOS) tools that target such skills, the average age of diagnosis has
decreased. These instruments have facilitated a “provisional,” if not definitive,
diagnosis of ASD much earlier. In Europe, it has been reported that these
techniques have resulted in decreasing the average age of diagnosis from 4 years
to 30 months (12). The recent emphasis on social skill deficits has also led to
better ascertainment of children who are high functioning with few language
deficits, i.e., children with Asperger’s syndrome. Indeed, it is both the earlier
recognition of ASD and the recognition of additional children with ASD who are
high-functioning and/or more mildly affected that has been responsible, at least
in part, for the apparent rise in prevalence.
The recognition of the importance of deficits in social skills as defining
characteristics of ASD will not likely represent our final stage in the evolution of
our understanding of this disorder (Table 1). Our understanding of autism has
“come a long way,” especially during the 1990s. It has moved away from the
belief that most children with autism are nonverbal, make no eye contact, sit in
the corner, and engage in bizarre stereotypies. It is now known that more subtle
deficits in social skills, particularly in joint attention, may indicate a disorder
somewhere “on the spectrum.” But the journey is not yet over. At the time of this
publication, a multicenter study designed to evaluate signs in even younger
infants is in progress, but results are not available. The “Baby Sibs Project” has
been expanded from its original study site in Canada under the leadership of
Lonnie Zwaigenbaum to a multicenter project with international funding (l3).
The goal of this project is to identify ASD in siblings (between the ages of 3 and 6
months) of children with known ASD. Siblings have an increased incidence of
ASD—3– 9% when there is one older sibling with ASD (l4) and up to 25% when
there are two (15). The study infants will be prospectively observed for the above
distinguishing early social deficits as well as for new, potentially unknown early
behavioral signs of ASD.

II. DEFICITS IN SOCIAL SKILLS
As noted above, abnormalities in social relatedness are now the sine qua non of
autism; however, these are rarely defined (16). Rogers and Benneto suggest that it
is a kind of “interpersonal synchrony of bodies, voices, movements, expressions
and . . . complementary feeling states. It is the interpersonal coordination that
people feel, see and hear through the matching of their movements (face, body,
voice) with those of their social partners.” Infants with other disabilities, for
example cerebral palsy or blindness, may have difficulties with this synchrony
due to their respective motor and visual deficits; however, they do manage to
maintain social connectedness by using compensatory strategies. Infants who are
blind use voice, touch, and language through which emotions can be shared and
connectedness experienced. Those with severe cerebral palsy establish social
relatedness through eye contact, facial expressions, sounds, and conversations.
With time both partners ignore the asynchronies and attend to whatever
interpersonal coordinations are indeed present. Children with autism make no (or
very few) such attempts to compensate.
A. Joint Attention
The single most distinguishing characteristic of very young children with ASD is
a deficit in “joint attention.” Currently it is thought to be associated with
abnormalities in the amygdala. It is a core feature of the DSM-IV and includes a
limited inclination to share enjoyment, interests, or achievements with other
people. Joint attention is the triadic ability to coordinate one’s own attention
between an object and another person. It is dependent on four developmental
components: 1) orienting and attending to a social partner, 2) coordinating
attention between people and objects, 3) sharing affect or emotional states with
people, and 4) ultimately being able to draw others’ attention to objects or events
for the purpose of indicating a need of sharing experiences. Children with autism
may have difficulty with all of these components. Mastery of joint attention
reflects a child’s ability and motivation to share in mental states of others.
Joint attention serves both a communicative and a social function. In its
purely communicative function, it may be used to regulate the behavior of others
to get them to do something (request) or to stop doing something (protest).
Although children with ASD may occasionally use gestures to accomplish this,
they rarely alternate eye gaze between the object and the person’s face. When
they do happen to look at the adult’s face, they neither follow his/her gaze nor
use the adult’s facial expressions to influence their own behavior (see “Social
Orienting,” below). Even more rare is the use of joint attention for the pure social
function of drawing another’s attention to an object or event out of mere interest
(as in to comment or label).

90 Johnson
Just like other developmental skills, joint attention appears to develop in

graduated stages. Very early skills include true reciprocal smiling at the mere
sight of a caregiver’s smile. At approximately 8 months of age, a typically
developing infant may demonstrate an early form of joint attention called “gaze
monitoring.” For example, an infant sitting on his mother’s lap and facing her is
engaged and making eye contact with her while she sings to him. At some point,
something catches the mother’s visual attention causing her to look away from
the child and toward the object of interest. The child in turn will follow mother’s
gaze and also look in the same direction. It is the loss of mother’s eye contact that
stimulates the child to jointly look in the same direction . . . not the stimulus itself
as it is visualized later in time. If the environmental stimulus catches the child’s
attention first (as in an auditory stimulus that is heard by both mother and baby
simultaneously), then the spontaneous head turning is not an indication of joint
attention, but instead marks the child’s ability to “localize to sound” (a receptive
language milestone, not a social one).
At about 10 – 12 months of age, the child will “follow a point.” In this
situation, the child is engaged in some activity without particular regard for the
parent. The parent sees something of interest, points in its direction, and says, for
example, “Oh look! The kitty cat has come inside.” The child intuitively will look
in the direction that the parent is pointing. Upon seeing the object of interest he
may smile or look back at the parent to reassure himself. If he does not see the
object, he may even look back quizzically at the parent. This joint attention
milestone can easily be elicited during a clinic visit in a typically developing
10-month-old. However, a child with autism may appear oblivious to the
examiner’s request to look at the targeted object. If there is no response, one may
need to increase the intensity of the stimulus by calling louder, adding the child’s
name, or touching his shoulder first to get his attention, and then pointing and
exclaiming. Finally, if this still does not elicit a response, a familiar caregiver
may be asked to repeat the maneuvers. Often, no degree of intensity is successful
in getting the child to look at the desired stimulus.
Unlike these passive or reactive joint-attention milestones, the next ones to
emerge are “active” where the child, not the caregiver, initiates the interaction. At
approximately 12 –14 months of age, the child begins to point. At first he may
point to a desired object that is out of reach. Typically, a child will verbalize
during the act of pointing. Depending on his language level, the verbalizations
may not be recognizable words, but instead any vocalization used to solicit the
caregiver’s attention. The typically developing child will look back and forth
from the object to the caregiver in an effort to make the caregiver understand that
he desires the object. Here, pointing is used as a “command” and is often called
“protoimperative” pointing. The object is the goal; the caregiver is the means by
which the child can obtain that goal. Alternating eye contact between the object
and the caregiver is critical in designating this as a joint-attention skill. A child

with ASD rarely masters this skill at the usual time. Instead he is more likely to
take the caregiver’s hand and lead him to the object, for example, to the
refrigerator if he is hungry or thirsty. At that point the caregiver must open the
refrigerator door and guess what the child wants by offering him various items
and asking, “Is this what you want?” The child will then grasp the desired object.
Some children develop certain self-help skills (such as opening a refrigerator
door, climbing onto cabinets) at an advanced rate to circumvent the need to solicit
help. Another possibility might involve a more primitive pointing stage whereby
the child opens and closes his hand in repetitive grasping motion in the direction
of the refrigerator and cries or whines. There is little or no eye contact with the
caregiver. Some consider this to be a transitional skill leading to later more
mature protoimperative pointing.
At 14– 16 months of age, in a typically developing child, pointing and
accompanying verbalization may take on a new function. Instead of being used as
a “command,” pointing is used to “comment” or to point out an object/event of
interest. This type of gesturing is more social in nature and is often called
“protodeclarative pointing.” The same triad exists (child, caregiver, object), but
the goal is reversed. The child sees something of interest, perhaps a helicopter
flying overhead. He points to the sky and may vocalize to some degree
(depending on his language level) to get the caregiver’s attention. He will then
alternatively look at the object and the caregiver to make sure the caregiver has
seen the object of interest. The reward is the caregiver’s approval either by
smiling at the child or through some type of verbalization that acknowledges the
object of interest. Children with autism consistently fail to demonstrate
protodeclarative pointing skills at age-appropriate times. If and when these skills
finally emerge, there is often a qualitative difference in that the child is less likely
to show positive affect during acts of joint attention. Also around 14– 16 months,
children should master the social skill of “showing.” This occurs when the
child has found something or made something (a scribble on a piece of paper) and
holds it out to the parent as if to say, “Look at this!” This act is to be distinguished
from bringing an item to the parent to get help, for example, bringing a bottle of
bubbles to the parent and putting his/her hand on the lid to indicate that he wants
it opened. Although this skill is also often delayed in children with ASD, it is not
a pure joint-attention milestone. Instead, it is a “reenactment.” Reenactments can
be motor, as just described, or verbal (see discussion of echolalia, below). In
reenactment attempts, the child repeats an event to make it happen again. It may
serve as a building block and actually herald the emergence of joint-attention
skills in some children (17).
The ability to communicate using gestural joint attention (showing or
pointing to direct attention) emerges before words in typical development and
appears to be a core deficit in autism that impedes later functional language
development. Joint-attention skills (but not global social skills) appear to be

Table 1 Evolution of Clinical Characteristics of Autism Spectrum Disorder with Age
Signs in infancy (,18 months)
Motor Perceptual Socioemotional Language Mental representation

Inactive hypoactive Unusual mix of Temperament swings from Delayed or absent cooing Decreased visual pursuit of
Flaccid muscle tone hyper- and hypo- good to inconsolable and/or expressive objects or people
Rarely cries sensitivities to sensory Crying and unpredictable vocalization Poor shifting of attention
Decreased facial stimuli, i.e., sensory mood Failure to respond to name between:
expression integration deficits Late, rare or absent Failure to imitate words, Novel and familiar stimuli
Irritable Auditory social smile sounds Human and object stimuli
Hyperactive, restless Appears deaf to voice Decreased looking at faces Little communicative use of Delayed object permanence—
Only soothed when in but jolts or panics to Avoids eye contact when held gestures early sign of possible
constant motion environmental sounds Doesn’t recognize Absent to-fro babbling in comorbid cognitive deficits
Rigid when held Tactile parent’s face response to parent’s voice Delayed ability to solve glass
Arches away from close Tactile defensiveness Lack of anticipatory response Lack of usual progression frustration test—early sign
physical contact Refuses food with to being picked up from monotone babbling to of possible comorbid
rough texture Fails to show stranger anxiety immature jargoning with cognitive deficits
Adverse reaction to wool Lack of gaze monitoring inflection/animation Decreased facial expression—
fabrics and seams Does not follow a point Decreased protoimperative masked faces
Prefers smooth or rough Seems to dislike being held pointing; instead leads Persistent sensory motor play
surfaces Seems content to be left alone adult to desired object Delayed functional play
Visual Fails to visually follow Regression of language and
Sensitive to light coming and going of parent social skills between 12– 18
May panic at change in Doesn’t play peek-a-boo, months in some (25%)
illumination patty cake, or wave bye-bye
Preoccupied with observing Delayed attachment in some
own hand and finger Poor social referencing
movements Decreased “showing” parents
interesting objects

Table 1 Continued
Signs beyond infancy (.18 months)

Toe-walking Withdraws from Uses adult’s hand like a tool Regression may also Primitive (re-enactment)
Rocking environmental stimulation Lack of or delayed joint occur after 18 months pretend/representational
Head banging Engages in self-stimulation attention Immediate echolalia play; good constructional play
Whirling without dizziness Preoccupied with spinning Insists on sameness and Delayed echolalia unrelated to Little appropriate play of typical
Finger-flicking objects ritualized routines social context popular toys
Sensory stereotypies— May suddenly cease activity Unable to identify with Pronoun reversal Hard comfort items
sniffing and licking and stare into space, often another’s feelings Voice atonal, hollow, Delayed matching novel items
Proto-SIB with true SIB with neck hyper-extended or point of view rhythmic on demand, but advanced rote
.5 yr of age May crave deep pressure or Failure to make friends Lack of pointing for naming matching of shapes, colors,
Hypo- or hyperactivity stroking Lack of proto-declarative Neologisms letters and/or numbers
Perseverative movements pointing (to direct another’s Idiosyncratic language Inability to solve “false
Apraxia/dyspraxia attention to interesting Precocious counting, ABCs belief” problems (Sally and
Clumsiness object/event) Fails to use previously learned Anne test at 4 yr of age)
words Absent or weak ToM skills
Oral motor dyspraxia Poor executive functioning
Poor pragmatics Poor central coherence
Dissociation between form Inability to understand idioms,
and function of language metaphors, and humor
Hyperlexia
ToM, theory-of-mind.

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proportionate to language skills including the correct use of I and you pronouns
(18,19). In one longitudinal study, its emergence was shown to be a significant
predictor of functional language development approximately 1 year later (9,20).
In this regard, many researchers consider joint attention a “pivotal skill”; that is,
its mastery leads to collateral changes in a broader range of deficits within the
autism phenotype. This recognition has led to important advances in early
intervention strategies. Several groups are developing intervention strategies that
target the development of joint attention and prelinguistic communication skills
(21). In one study (22), interventionists presented children with unpredictable or
predictable social stimulation. In the unpredictable condition, the teacher played
with toys that did not match the toy play activities of the child. In the predictable
condition, the teacher imitated the toy play of the child. Children with ASD
displayed more joint attention in the predictable (imitated) condition than in the
unpredictable condition. Another study (23) revealed that children with ASD are
more likely to learn new words when the parent “tunes in” to (or joins attention
with) what the child is looking at than when parents attempt to direct the child’s
gaze to an object that the parent is focusing on and labels. Said differently,
language comprehension seemed to be proportional to the frequency of maternal
follow-in and not to maternal-directed language (24). Once language is
established, the older child is able to maintain joint attention with pure
conversation regardless of visual or gestural cues (e.g., telling a parent about
what happened in school) (25). The importance of joint attention as a core deficit
in ASD was further substantiated in a larger study that demonstrated limitations
in joint attention as linked to not only communication but also to deficits in play,
emotional responsiveness, and peer interactions (26). Other studies have shown
that joint attention is a necessary precursor for the development of theory of mind
(see below) (27). Joint-attention deficits also appear to be specific to ASD. In one
study, joint-attention skills were evaluated in children with Down syndrome and
autism (matched for nonverbal cognitive ages of 18 months). Children with
Down syndrome performed normally (as predicted by their mental age); those
with autism did not. Joint-attention deficits reliably differentiate children with
ASD from children with other neurodevelopmental disorders (28) and is a core
DSM-IV criteria for autism. Currently deficits in joint attention is believed to be
associated with abnormalities in the amygdala.
B. Social Orienting
Social orienting is the ability to orient to social stimuli, in particular, turning to
respond to one’s own name (29,30). Although it was recognized as a core deficit
in ASD somewhat later than joint attention, social orienting emerges earlier in
typical development and may actually influence the emergence of gestural joint
attention (31). Most children will turn preferentially when their name is called at

about 8– 10 months of age. Although some children with ASD might sporadically
respond, most do not do so consistently. In fact, one of the early concerns of
parents of children with ASD is a potential hearing impairment. They are puzzled
because their child seems to hear quite well in some situations but not in others.
This dichotomy occurs because children with ASD often attend to environmental
sounds extremely well but tend to ignore sounds generated by humans such as
calling the child’s name and other speech utterances (32). Again, using children
with Down syndrome as a control group, it was found that children with ASD
more often failed to orient to both social (name being called) and nonsocial
stimuli (a musical jack-in-the-box being played or rattle being shaken); however,
the difference was significantly more extreme for social stimuli. Furthermore, it
was found that social orienting, but not object orienting, was significantly related
to joint attention among the children with autism (33).
Several studies have evaluated infant behavior, especially in regard to
responding to name. These have involved the retrospective evaluation of 1-year-
old birthday videos in children later diagnosed as having ASD.
The original study demonstrated that blinded viewers could retrospectively

diagnosis ASD with 91% accuracy (34). The symptoms identified by
professionals had not caused parental concerns at the time of filming.
Normally developing children without ASD comprised the control
group. The distinguishing characteristics were decreased: (1) orienting to
name, (2) looking at the faces of others, (3) showing objects, and (4)
pointing. The single best distinguishing factor at 8– 10 months of age was
failure to orient to name since showing and pointing skills may not yet be
universally present in typically developing children at 1 year. A later
study (35) added a second control group consisting of children with
mental retardation. Although less dramatic, responding to name still
differentiated the two groups. The two groups were similar in that they
both used gestures less and repetitive motor actions more than the normal
group.
However, another study that also used blinded observers and home videos
filmed at 9 –12 months of age (36) failed to demonstrate that children
with ASD could be reliably distinguished from children with other types
of developmental delays based on such characteristic behaviors. This
study did, however, document that parents of autistic children called their
child’s name more frequently, which is actually an indirect measure of
orienting to name.
Finally, Maestro et al. (37) used blinded professionals to view home videos
from the first 6 months of life of children later diagnosed with ASD and
normal controls. They identified several behaviors that were
discriminating. These included all items regarding social attention

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(looking, smiling, and vocalizing to people), especially orienting to

human voices. The common thread that weaves these behaviors together
was the seeking of or response to “attention.” All nonsocial attention
measures were equal in both groups.
Although these studies demonstrated that trained professionals recognized
deficits in “responding to name” in videos, asking parents whether or not their
child consistently responds to his name has not been found to be as reliable.
Instead, a more distinguishing question for parents is asking them whether their
child responds to neutral statements, such as, “Oh no, it’s raining again!” without
specific prompting or calling the child’s name first (38).
C. Pretend (Symbolic) Play

Although pretend play is significantly correlated to receptive and expressive
language (39), facilitates and requires communication, and is listed as one of the
communication criteria in the DSM-IV, it is also a social skill. Lack of or very
delayed pretend play (using pretend actions with objects) appears to discriminate
children with autism from other children matched for mental age. In a typically
developing child, play evolves in a predictable manner. Once the child can grasp
objects (about 4 months), his play (exploration) is sensorimotor in nature. He
mouths and manipulates objects. The 8– 10-month-old will throw them, bang
them on the table, or, with one in each hand, bang them together. This evolves
into a more functional type of play as he becomes aware, usually through
observation, of the actual intended use of the object. At about 12 –14 months,
using this new understanding plus his imitation skills, he attempts to build a tower
with them.
Pretend play begins with simple and, later, more complex play scenarios.
“Simple pretend play” usually begins at approximately 16 –18 months, when
children begin to use miniature representative items, for example, a plastic bottle
or brush, to feed the doll or brush her hair, or a toy telephone to talk into. Very
soon after this skill is mastered, the child begins to engage in “complex pretend
play.” There are two types of complex pretend play: (a) the use of a generic item
to represent another or (b) two-step pretend play that is spontaneous. In the first
situation, the child might be given a miniature plastic telephone and encouraged
to “talk to grandma” (simple pretend play). Once this is accomplished, one might
then take the plastic phone away and give the child a wooden dowel. Again the
child is encouraged to “talk to grandma.” Most typically developing children will
use a generic object to pretend at approximately 18– 20 months of age. Two-step
play may be implemented with either miniatures or generic items or a com-
bination of items. Use of generic items, however, represents a more mature form
of play. In this situation, the child might feed the doll with a miniature plastic

bottle and then, spontaneously, lie the doll down and cover her with a cloth.
Depending on the child’s language level, she might even say, “all done,” “night
night” (examples of giant words), or “baby tired” (true two-word phrase). Both
types of complex pretend play represent a higher order of play that is consistently
absent in 18-month-old children with ASD. When one evaluates a child’s ability
to engage in pretend play, using tiny pieces of real food or a play bottle
containing an outer layer of milky liquid that appears to pour is discouraged since
this might not represent true symbolic play. Additionally, some children already
in intervention might have been “taught” to engage in certain pretend play
“routines.” These activities might be done repetitiously during daily therapy
sessions. However, until a “pretend play routine” can be generalized to other
situations, it should not be scored as “mastered.” Although, children with ASD
can be taught to imitate pretend play, no 20-month-old with ASD in at least one
study produced spontaneous pretend play (40). Novelty is important when
assessing a child’s skills, especially when he or she is already receiving formal
intervention services.
Imaginative play is the next level of play and is more sophisticated. True
imaginative play is not usually evident until well after the second birthday.
Emergence of this stage of play is more variable. When evaluating a child’s
ability to engage in imaginative play, no concrete representative or generic object
is used to engage the child. For example, as described in one evaluation tool
(ADOS), the child is asked to pretend to brush his teeth (41). The examiner draws
an imaginary circle with her finger on the tabletop to represent a sink. She then
points to an imaginary toothbrush and tube of toothpaste and says to the child,
“Show me how you would brush your teeth.” The typically developing child
would then “pretend” to pick up the imaginary brush and the tube of toothpaste,
open the lid, squeeze the paste out onto the brush, turn the water on, and brush his
teeth. Although some children with high-functioning ASD eventually master this
skill, albeit at a later age, many children with ASD never do.
Many children with severe autism never progress past the sensorimotor
play stage. They mouth and manipulate objects in stereotypic ways. They may
also twirl, bang, and throw objects. Often their favorite play toys are not typical
popular toys, but are instead string, sticks, rocks, ballpoint pens, books (for
carrying around, not reading), etc. Perhaps the only popular real toy is the puzzle,
especially shape-matching puzzles. Some children with ASD are quite proficient
in constructive play (e.g., using objects in combination to create a product, such
as stacking blocks, nesting cups, putting puzzles together, or solving computer
“puzzle” games) (42). Constructive play mastery depends on trial-and-error
problem solving and not imitation or observation of others. Children with ASD
excel at behaviors that do not depend on social interaction but can be instead
learned through trial and error. It is not uncommon for parents to state that the
child is an unusually “good” child, content to play by himself for hours, requiring

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little or no attention from the parent. Often this “play” is either constructive
(puzzles, computer games, blocks), ritualistic (lining objects up or sorting/
matching shapes or colors), or sensorimotor in nature.
In addition to classifying play according to its developmental level, play
can be described in several other ways that are helpful in differentiating children
with ASD:
Play logistics: Is the child’s play ritualistic, functional, or creative?
Communicative aspects of play: Through play, is the child attempting to
communicate in some way?
Social characteristics of play: Is the play done in isolation, parallel to other
children, or is it interactive?
Children with autism often engage in ritualistic play with little or no
communicative or social intent. It is carried out in isolation of other children or in
parallel (side-by-side another child) with little interaction. However, these
children often do like (and may appear to even be interactive during) chase games
and roughhousing. It is the sensorimotor aspects of these active games that are
appealing to the child and not the interactive or social aspects.
D. Additional Social Deficits

Although there are some additional deficits, the following are not as dis-
criminating as the deficits in joint attention, social orienting, and pretend play. No
single theory explains all types of dysfunction; they are often interrelated and
there is much overlap. Some seem to be cognitive-dependent and involve the
frontal cortex. Others seem to be functions of the limbic system, specifically the
amygdala, the cerebellum, and/or the brainstem. Although cognitive develop-
ment may somewhat influence emergence of skills, there is often a discrepancy
between social (and usually language) development and development of skills in
other domains. Of the following deficits described below, the first five appear to
be more specific to persons with ASD. Some of the following deficits,
particularly theory of mind, may not be recognizable or measurable until later
childhood and are, therefore, not helpful in the early recognition of ASD.
1. Poor Social Referencing

Social referencing (17) is the ability to recognize the emotional significance of
stimuli and includes the earlier-appearing ability to orient toward social stimuli
(see above). Persons with ASD have a poor understanding of and a decreased
responsiveness to the feeling of others. They rarely use an adult’s facial
expressions to influence their own behavior with novel objects or events (43).
When faced with a novel situation, a normal infant might look to his mother for

an indication of fear in her facial expression. His facial expression will usually
mimic hers although he may not understand the full implication of the situation.
A child with ASD often fails to look at his mother’s facial expression and even so,
if he does, he engages in less imitation. Children with ASD are less likely to
imitate social behaviors of others overall. Such deficits in social referencing and
orienting have been found to correlate with measured deficits in joint attention.
Children who display a greater capacity to coordinate and imitate affect (social
referencing) are more likely to communicate for social reasons (44).
2. Poor Shifting of Attention

The ability to shift one’s focus of attention from one stimulus to a competing one is a
very basic skill that can be measured in normally developing 4-month-olds. In the
late 1980s Courchesne and his colleagues (45–48) developed a model that views
attention as a critical and basic deficit in autism. Attention deficits are hypothesized
to be present from early development and to contribute to the atypical development
of social skills, particularly deficits in joint attention. Joint social attention relies on
the ability to shift attention from the object to the partner and back again. As noted
above, significant deficits exist and are thought to be responsible, in turn, for
perseverative symptoms and later-developing language and social abnormalities.
Functional MRI and PET studies have demonstrated that the cerebellum, particularly
the vermis, is activated during attention-shifting tasks (49). Additionally, hypoplasia
of these same areas has been correlated with functional deficits. Individuals with
acquired cerebellar damage demonstrate similar abnormalities. These studies, along
with others using normal subjects, have uncovered the relatively new role of the
cerebellum in behavior, sensory processing, and cognition (50).
In one form or another, shifting of attention has been used as the basis for
tests of visual acuity and nonverbal intelligence for many years. When presented
with two stimuli of differing resolution (thickness of alternating black and white
lines), the infant will shift his attention to the stimulus that is within the range of
his visual capability. It is well known that infants prefer novel stimuli and will
predictably shift their attention from a familiar image to a novel one. This
assumption has been used in numerous study paradigms to measure infant
intelligence and predict mental deficiency at very early ages. Such testing
paradigms were used in the mid-1980s in the development of the revised Bayley
Scales of Infant Development II.
Studies involving children with ASD examined two related behaviors:
spontaneous shifting of attention and structured, investigator-provoked attention
shifting. Children with ASD demonstrated distinct patterns in both conditions:
Spontaneous shifting of attention (51): In this study, observations were
made regarding the quantity and quality of spontaneous shifts in attention

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in 20-month-old children who were autistic, developmentally delayed, or

developmentally normal. Three types of shifting were studied: between
two objects, between an object and a person, and between two persons.
Whereas the two control groups shifted attention between an object and a
person most often, the autistic group more often shifted attention
between two objects. The autistic group spent less overall time looking at
people and when they did look, they did so only briefly. They looked at
objects longer than did controls.
Structured investigator stimulated shifting of attention (52): In a novel
stimulus paradigm, children matched for mental age faced screens
where one, two, or three stimuli could be projected simultaneously.
When presented with stimulus (A), children with autism, Down
syndrome, and controls attended to it equally well. In the next
situation stimulus (A) is turned off at the same time a new stimulus
(B) is projected onto a screen adjacent to where (A) had been. All
three groups shifted their attention to (B) equally well. Finally, in the
third situation, (A) is shown for a period of time before stimulus (C)
is shown. This time (A) remains on the screen and (C) is projected
side by side simultaneously. Normal controls and children with Down
syndrome both shifted their attention to the novel (C) stimulus;
children with ASD did not. The authors state that adults with ASD
also demonstrated difficulty with this task.
Since shifting of attention to a novel stimulus can be observed in very young
infants (4 – 7 months of age), it has been postulated that this test paradigm might
be used to detect early signs of ASD. As was discovered in the pilot testing of
the revised Bayley, measuring eye movement is fraught with logistical
challenges. Additionally, infants with severe cognitive delays who are not
autistic may have difficulty in detecting novel stimuli. Nevertheless, it seems
promising.
3. Decreased Facial Recognition

Even at a very young age, normal infants appear to recognize familiar faces. This
has been confirmed with PET studies. However, both younger and older
individuals with ASD have difficulty recognizing faces. Dawson (53) studied this
phenomenon with event-related brain potentials (ERP) in 3-year-old children
with and without ASD. Four stimuli were used in the testing paradigm: photo of
mom’s face, photo of a stranger, photo of the child’s favorite toy, and photo of an
unfamiliar toy. Control children showed differential ERPs to both photos of
mom and his/her favorite toy. Autistic children showed differential ERPs only
to his/her favorite toy. Furthermore, the degree of abnormality in ERPs during

face-looking was correlated with the degree of deficit in joint-attention skills.

Thus ability to recognize faces might yet be another skill that is contingent on
joint-attention skills. It is not presently known whether the deficit is congenital or
acquired. Children with ASD might primarily lack the neural components
necessary to recognize faces or, on the other hand, these synapses and circuitry
may not develop as a secondary consequence of their failure to attend to such
stimuli. If secondary, then it is hypothesized that early stimulation might promote
growth of neural pathways and result in some improvement. Curricula have been
developed using a tangible reward system that may be effective in motivating
children to look at and attend to faces.
4. Weak Central Coherence

Although not a true social skill, impairment in central coherence can lead to
atypical social interactions. Central coherence is the ability to interpret stimuli
in a relatively global way, taking context into account (54 –56). Persons with
ASD tend to make less use of context and to focus on parts rather than wholes;
processing is piecemeal. These persons have difficulty integrating component
features into a cohesive unit and seeing the “big picture.” Consider this
analogy. One enters a dark room, turns on the light switch, and scans the room
taking in its contents. Within seconds, one is able to form a mental image of
the entire room. On the other hand, one might enter a dark room, shine a
flashlight on the different areas of the room, and store these images separately.
When trying to form a composite image of the entire room, difficulty is
encountered if a deficit in central coherence exists. In computer lingo, it is as if
the child with ASD has multiple files on a topic but is unable to merge them.
Their exceptional ability to attend to the details rather than the gestalt results in
exceptional abilities in finding hidden figures embedded in a larger, more
naturalistic picture (57). Their focus on detail also makes them less suscep-
tible to visual illusions and may account for inflated block design scores on the
WISC. It is felt by some that this splinter skill might reflect a deficit in corpus
callosum functioning. PET studies have demonstrated reduction in coordinated
brain activity that may require an intact corpus callosum. However, this skill in
not specific to ASD and some studies have actually failed to demonstrate
problems in central coherence (58).
5. Theory-of-Mind (ToM) Deficits

The theory-of-mind (ToM) skill (59,60) enables one to take the perspective of
another and is based on the realization that others have thoughts and emotions
that are independent from one’s own. Because ToM ability is basic to perspective

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taking, children with ASD have difficulties with social emotional behaviors such
as empathy, sharing, and comforting. ToM is important in achieving acceptable
social functioning to maintain social relationships. Prior to the 1990s, it was felt
that children were largely unaware of the existence of states of mind until they
achieved a mental age of approximately 7 years; however, now it is generally
accepted that children have some beginning awareness of the mental states of
others around 3– 4 years of age (61). Although some feel it is one of the core
deficits defining ASD, its late appearance cannot explain the earlier deficits in
joint attention, social orienting, social referencing, etc. Instead these deficits
seem to be primary and likely contribute to subsequent impairments in ToM (62).
Its late appearance also prevents it from being helpful in the diagnosis of
ASD in the very young child, but may indeed be helpful, even critical, in the
diagnosis of the later-appearing Asperger’s syndrome. Besides being dependent
on the development of cognitive skills at approximately a 4-year-old level,
demonstration of intact ToM skills requires some language.
Hypothetically, ToM skills are dependent on a special type of cognition
called metarepresentation. Metarepresentational ability allows one to mentally
depict the psychosocial status of others: it involves the capacity of one individual
to mentally represent the mental representations of another individual. According
to the ToM theory, a disturbance in this metarepresentational thought process
gives rise to pragmatic language deficits seen in persons with ASD. This is also
linked to difficulties with understanding figures of speech (idioms like “two heads
are better than one”) and/or the communicative intent of an author who might
write headlines stating, “Iraqi Head Seeks Arms.” Without mastery of ToM, one
would also have difficulty gauging the constraints of discourse and perceiving the
informational needs of others. The fact that ToM skills are closely linked to
pragmatic functioning is also evident in very early prelinguistic gestural language
development. Whereas normal children develop requesting and commenting
skills concurrently, children with ASD develop the more social commenting
pointing skills significantly later than requesting ones (63). Commenting skills
are dependent on the ability to attribute attention to others.
ToM deficits are not specific to children with ASD. They have also been
found to be delayed in children with severe hearing impairment and in some
children with Down syndrome (64). However, it is important to note that neither
group demonstrated deficits in joint attention or social referencing. Unlike
persons with hearing impairment or Down syndrome, who eventually develop
some degree of ToM as their social experiences and mental age increase, adults
with autism and intelligence in the average range retain their inability to decouple
or segregate their own thoughts from others. Because ToM is the ability to infer
states of mind based on external behavior, Baron-Cohen (65) coined the term
“mindblindedness” to represent the most severe level of ToM deficit as seen in
persons with ASD.

Numerous experimental studies support the hypothesis that children with

autism have difficulty on ToM measures. Several mental-age-specific test
paradigms have been used to measure stages of ToM development:
False belief paradigms: One of the most popular test paradigms for 4– 5-
year-olds is the Sally-Anne Disbelief Test (Fig. 1). In this test situation, a
child is asked to watch “Sally” hide a toy in a box. Sally then leaves the
room, and Anne enters. She then moves the toy from the box and puts it
in a different covered container. Sally is then asked to return and the child
Figure 1 Sally-Anne Disbelief Test.

104 Johnson
is asked, “Where will Sally look for the object?” To answer this question
correctly, the child must be able to disregard or set aside his own
knowledge about where the toy really is and think about where Sally
thinks the toy is. People with ASD manifest robust difficulty with false
belief and related ToM tasks as compared to language- and IQ-matched
controls (65). An alternative false belief task simply requires a Band-Aid
box, Band-Aids, and wrapped strips of chewing gum. It is logistically
less complex and does not require a “Sally” or “Anne,” which makes it
easier to implement in clinical practice. The clinician asks the parents to
leave the room momentarily. He/she then shows the box containing
Band-Aids to the child. He removes the Band-Aids, substitutes them with
strips of gum, and closes the lid. He gives the box to the child and says,
“Let’s bring the box to your parents and ask them what’s inside the box!
What do you think they will say?” Whereas most typically developing
4-year-old children will realize that their parents would expect to find
Band-Aids, the child with ASD is more likely to say “gum.”
Strange stories: Individuals are read short stories depicting each of the
following: pretend, joke, lie, white lie, double bluff, figure of speech,
irony persuasion, and a control (physical story). Afterward one is asked if
the story is true and why the person said what he/she did (66). Persons
with ASD often give quite different answers than other populations
owing to their inability to understand humor or idioms. A mental age of
at least 6 years is required.
Faux pas vignettes: A series of stories have been developed for children
with mental ages of 9 years and above. For example, one story describes
a mother and her daughter making an apple pie as a gift to welcome a
new neighbor. When it is baked, they box it and visit the neighbor. The
neighbor very graciously accepts the gift, saying, “A pie, how very
thoughtful of you. I just love pies, all except apple pies that is.” A set of
questions follows each vignette to determine whether or not the listener
understood the faux pas (67).
Judging mental states: One is asked to interpret the mental or emotional state of
others by observing their facial expression in photos of pairs of eyes. He/she
must choose the word from a list of four that most accurately describes the
person’s emotional state (i.e., angry, serious, happy, afraid) (68).
Using single-photon-emission computerized tomography data, it has been

demonstrated that solving ToM vignettes involves cortical activity in the left
medial frontal gyrus (Brodmann area 8) (69). Although these testing paradigms
may be helpful in differentiating children with ASD, adequate performance on
them does not necessarily mean that persons with high-functioning autism are
able to always use this skill functionally in real-life situations (70).

6. Decreased Facial Expression and/or Animation

Often children with ASD are described as having a “flat affect” or “masked
facies.” Their facial expression is rather bland and monotonous and lacks the
animation commonly seen in typically developing children during joint-attention
activities when the child presents something that is interesting or that he is proud
of to his parent in the act of “showing.” Such functional deficits are similar to the
neurological abnormalities seen in Möbius syndrome. Although an autopsy study
revealed a hypoplastic cranial nerve VII nucleus in the brain of one adult with
autism (52), this deficit seems to be more often psychophysiological and possibly
associated with abnormal functioning of the amygdala.
7. Attachment
Attachment does not seem to be primarily impaired in children with ASD, though
at one time it was thought to be a core feature. Occasionally children with
primary attachment disorders are confused with those having ASD. In a study of a
Romanian orphanage where children received less than optional attention from
multiple-shiftwork caregivers, several children demonstrated quasi-autistic
features and actually met full criteria based on the ADOS (71). However,
symptoms improved once the child was adopted into a nurturing family
environment. In an Ainsworth Strange Situations paradigm, it was demonstrated
that children with ASD seek proximity and contact with their mothers as often as
normal children matched by mental age (72).
8. Summary
The above discussion provides a broad overview of the social deficits in ASD.
Some of these deficits are consistently seen in young children with ASD; others
are not. The goal of this chapter is to help raise the clinician’s awareness of these
characteristics since they are more subtle and/or more difficult to evaluate than
failure to attain language milestones. Hopefully, a better understanding will allow
the clinician to recognize ASD at a younger age and to refer the child to an
appropriate intervention program earlier. It is thought that earlier intervention
utilizing strategies that address these social deficits as well as the more obvious
language deficits and behavior problems will result in better functional outcomes.
Recent outcome studies support this approach (7– 9).
III. DEFICITS IN LANGUAGE DEVELOPMENT
Traditionally, delays and deviancies in language development have been the

presenting sign in children heretofore diagnosed with ASD. Although studies
during the past two decades revealed that approximately 50% of children with

106 Johnson
autism are nonverbal, the remainder have some degree of speech, and in a few,
speech may “appear” to be advanced due to echolalia. Children with Asperger’s
syndrome may not demonstrate obvious speech delays but instead have more
subtle abnormalities in language pragmatics. As more and more children are
being diagnosed with milder conditions on the spectrum, those with speech
represent a growing proportion of children with ASD. For a much more in-depth
discussion of language development in children with ASD, the reader is referred
to Chapter 6 in Autism Spectrum Disorders, edited by Amy Wetherby and Barry
Prizant (73).
A. Absent or Delayed Speech

Delayed or absent speech is the most common presenting concern of parents.
Although most parents will admit that they sensed something was wrong by 18
months of age, they often do not share these concerns with the clinician until after
the child turns 2 years old (73,74). They may delay raising a concern about absent
or delayed speech because they rationalize that the delays are due to the child’s
temperament (shy, slow to warm up), or that the child may be spoiled because
either they themselves or older siblings have overanticipated the child’s needs
thereby eliminating any reason to speak. When the child is an “only child,”
parents may rationalize that the delays are due to the absence of peers to stimulate
speech. The gravity of the problem is often not realized until a younger sibling
“passes the child up” or a Sunday school or preschool teacher raises a concern.
However, delay in recognition and diagnosis of ASD may also be due to the
lack of realization on the physician’s part that the parental concerns are
significant and merit further evaluation and/or intervention. Parents commonly
complain that in response to verbalizing their concerns about speech delays, their
physician gave false reassurance and took a “wait and see” approach. This is
often followed by resentment when the parents learn about the availability of
early intervention and its possible impact on prognosis. Indeed, several national
parent-directed organizations have embraced the challenge to educate physicians
in an effort to prevent ongoing delays in diagnosis and referral. Their fervent and
intense advocacy activity has also been directed at various state and federal
governing bodies and, if successful, may eventually effect changes in physician
practices and increase funding for infant and school-age educational programs.
B. Loss of or Inconsistent Use of Previously Acquired Words

Approximately 25 –30% of children with ASD lose previously mastered words
between the ages of 18 and 24 months. However, the loss of language skills is not
pathognomonic of ASD; it occurs in Rett’s syndrome and other neurodegen-
erative disorders as well. Loss of speech associated with seizures is characteristic
of Landau-Kleffner syndrome; however, onset is later, and the language

regression is typically not associated with parallel regression in social skills.

In other children with ASD, previously learned words seem to lose their
communicative function and appear to “pop up” for no apparent reason. The
words are said inconsistently and out of context. These “pop-up words” should be
distinguished from meaningful words that are consistently said with intention
(not merely parroted), are functional, and are used in appropriate contexts for at
least a month (73,75). Sometimes a particular “pop-up word” is said frequently
for a short period of time before it disappears. Occasionally the utterances may be
phrases or entire sentences, also said out of context. Parents might report these
words and sentences as mastered skills when, in fact, they have little or no
communicative intent. On the other hand, the words and phrases might indeed be
prompted by some yet unrecognizable motive. Although generally more obvious
than speech delays, loss of skills may also be rationalized. Such regression is
sometimes attributed to a family event such as the birth of a new sibling or a
move to a new house.
C. Echolalia
The vast majority of children with ASD who eventually demonstrate functional
symbolic language go through a period of using echolalia. Echolalia is classified
as immediate (child’s parroting occurs immediately after the partner’s
vocalization) or delayed (child’s parroting occurs at a time remote from the
original vocalization). Although a child with ASD may demonstrate both kinds of
echolalia, the delayed form is more distinguishing. Most typically developing
children go through a stage where they imitate other’s speech, particularly the last
one or two words of a sentence. It is usually immediate and occurs when children
are rapidly gaining new words during the “vocabulary burst stage” (73). Autistic
echolalia should be differentiated from normal imitation that occurs during this
period of rapid language acquisition. The echolalia is more exact, has a monotone
quality, and includes larger “chunks” of verbal utterances. It is also associated
with reversal of I and you pronouns since the child repeats the phrase or sentence
exactly as he himself hears it. For example, he may say, “Do you want a drink?”
when he actually is requesting a drink for himself. Additionally delayed echolalia
in children with ASD may include recitation of songs, advertisement jingles,
ABCs, etc. to a degree that far exceeds the child’s functional language ability.
These abilities are sometimes viewed as an indication of genius on the part of
parents and observers.
Echolalia may serve as a verbal type of reenactment (see discussion above
in the section on joint attention) whereby the child repeats a phrase or sentence to
make the event happen again. For example (73): “A 4-year old boy with ASD
repeatedly approached his teacher and stated, ‘Do ahhh’ while opening his
mouth. It was clear by his nonverbal behavior that he was trying to communicate

108 Johnson
something, but his teacher was at a loss to understand his meaning. After school,
the teacher called the boy’s mother and explained the dilemma. Without
hesitation, his mother explained that when her son is not feeling well, she tells
him to open his mouth and ‘Do ahhh’ so that she can observe whether his throat is
inflamed. Recently, he had begun to initiate interactions with her using this same
phrase to ‘tell’ her that he was not feeling well. Thus, he used this rather
unconventional gestalt language form that he had come to associate with feeling
ill.” Often these and other reenactments might not be understood if the listener
does not know the history of how the behavior evolved. Reenactments are
performed with some sense of anticipation and may serve as building blocks to
symbolic communication.
In the past, echolalia was considered deviant and not to play a role in the
development of functional language. It is now recognized that most verbal
children with ASD go through a stage of using both immediate and delayed
echolalia. It may be a necessary first step for children with ASD in their unique
journey to meaningful language; they use echolalia to communicate rather than
just parrot. Parents are now encouraged to acknowledge it and help functional
language development by providing context and meaning to echolalic phrases
and sentences. Transforming seemingly meaningless echolalia into functional
language appears to take place in five stages (76):
First the child simply repeats the phrase spontaneously without
understanding its meaning or use.
Then, the child gradually learns the meaning of the phrases by using them
repeatedly and finding out how they “work.” In the example above, once
the parent deduces that “Do you want a drink?” might actually mean that
the child wants a drink, he/she may stop answering “no” and, instead
offers the child a drink while saying, Oh, so [name], you want a drink.
Here is a drink for you, [name], and here is a drink for me, too.
This, in turn, reinforces the utterance and the child begins to use the
sentence/phrase purposefully, yet the pronoun reversal persists since he
can only repeat it as he has heard it.
Next the child starts to break the sentence down into chunks . . . smaller
meaningful units that he might mix and match in various contexts.
Finally he transforms it into a rule-governed language system and he is able to
substitute I for you and make it a personal request: “Can I have a drink?”
Children with ASD who eventually develop functional language tend to develop
grammatical skills in the same general progression as normal children. However,
they lag far behind and, in fact, may never develop an understanding of the social
rules, how to take turns in conversation or how to “read” the listener’s interest or
response to what is being said. These are all aspects of pragmatic language (see
below).

D. Preoccupation with Labeling

Some children are quite obsessed with labeling colors, shapes, numbers, and
letters of the alphabet, yet they are unable to use these in functional language or
point to them upon request. Unlike typically developing children, they
demonstrate less interest in common everyday objects or pictures in books and
rarely point to them to request new words from the listener. In recognizing their
child’s advanced interest in letters and numbers, parents will sometimes purchase
flashcards and other educational materials to promote spelling and written word
recognition. This may lead to hyperlexia or advanced oral reading without
accompanying comprehension skills. Such skills are out of sync with the child’s
functional use of symbolic language. However, since written words are coded and
processed in a different manner than verbal words, these splinter skills are
sometimes used in an effort to bridge the gap in oral-verbal abilities (73).
E. Idiosyncratic Use of Language

Children with ASD may utter unique words that have meaning only to them
(neologisms). They may use these words in a series of utterances that represents a
unique form of jargoning. Unlike typically developing children this jargoning
does not eventually evolve into a more mature jargoning style whereby
recognizable words are sporadically inserted and provide some meaning to the
listener. Additionally the intonation, inflection, rate, and rhythm may be
idiosyncratic and unlike more typical jargoning. It appears that the child has
developed a unique language schema that is uttered without any attempt to make
the listener understand. Finally, it may be associated with laughing out loud for
no apparent reason, at least to the observer. In the higher-functioning child with
some degree of fluent, symbolic language, recognizable words may be used in
very unique ways. For example, one high-functioning 6-year-old (nonverbal IQ
of 143, verbal IQ of 86, and a seventh-grade reading level) in a conversation with
his 12-year-old sister who was complaining about how hard her homework was,
said in reply, “That isn’t so hard, it’s just medium.”
F. Advanced Expressive Language Relative

to Receptive Language
It has been said, “Comprehension is the power that fuels expression” (77).
Comprehension is basic to and a building block for expressive communication.
In a child learning his first language or in an older individual learning an
additional language, expressive language development usually trails behind
receptive. Some children with ASD and exceptionally good memory and
articulation skills may demonstrate advanced speech relative to comprehen-

110 Johnson
sion. This results in an apparent disconnect from the typical receptive-

expressive relationship just described. However, their word combinations
(giant words or multiword echolalic utterances) really function as single words
and thoughts rather than as a true phrase or sentence. Comprehension at the
one-word stage on testing should confirm this observation. The rather
sophisticated long utterances actually function as single words and thoughts
and should be scored as such. In so doing the more typical receptive-
expressive relationship is preserved (73).
G. Preverbal Language Abnormalities

The language deficits described above are those that are more typical of older
children with ASD. To facilitate earlier diagnosis of children with ASD, the
clinician must also be familiar with the earlier-appearing prelinguistic lan-
guage deficits that characterize the disorder. These are often more subtle
receptive milestones, include gestural deficits, and go unnoticed by parents.
Some are communicative manifestations of joint attention or other social deficits
described above. It takes an astute clinician to probe with pointed questions to
determine if these earlier signs are present. Some of these include:
Lack of the usual alternating to-and-fro pattern of vocalizations between
baby and parent that usually occurs at approximately 5 months (i.e.,
vocalizations continue to overlap without regard for the partner’s
vocalization)
Lack of recognition of mother’s (or father’s or consistent caregiver’s)
voice
Disregard for vocalizations, yet keen awareness for nonlanguage or
environmental sounds
Lack of interest in babbling to and/or patting one’s own reflection in a
mirror
Delayed onset of babbling past 9 months of age
Decreased or absent use of prelinguistic gestures (pointing, showing,
waving, nodding head)
Lack of expressions such as “oh oh,” “huh,” etc.
Lack of interest or response to neutral statements (e.g., “Oh no, it’s raining
again!”)
Lack of any attempt to compensate for lack of language
Often the parent is unaware of these deficits, and may not be able to answer the
clinician’s questions decisively. However, once brought to their attention, parents
often become very vigilant and later notice them.

H. Pragmatic Deficits
Some high-functioning children with ASD may have mild or very limited speech
delays and actually demonstrate rather fluent symbolic speech patterns. The only
defining abnormality may be in speech delivery and/or in the social use of
language (pragmatics). Their language may seem odd and not listener-
responsive. Early diagnosis of (later-appearing) Asperger’s syndrome might be
missed unless the clinician and parents have a good understanding of language
pragmatics. The description of the pragmatic components of language came
relatively late to the accumulated fund of knowledge on language development
(78). First described by Bates in 1976, the study of pragmatics revolutionized
language-learning literature (79). (For a comprehensive discussion of pragmatics,
the reader is referred to Chapter 10, in Autism Spectrum Disorders, edited by
Amy Wetherby and Barry Prizant (78). Pragmatics rest on three premises:
1. Speech acts have function; they express intentionality to accomplish a
given purpose. Simple functions might include making requests or
protests; more complex functions include negotiating and expressing
opinions. Although verbal children with ASD may learn to use
language for simple functions, they have much more difficulty with
more complex ones, especially those that require abstract reasoning
and discussion of thoughts and opinions of others.
2. Competent communication requires the speaker to make judgments
about what the listeners already know and what new facts they need to
be given in order to comprehend the intentions of the speaker. For most
people this is automatic and effortless. For those with ASD it is not. For
example, one teen with ASD simply exclaimed, “Florida!” Not
knowing what he meant, his teacher approached him and discovered he
was concerned about a lesion on his leg. It looked like a map of
Florida. Persons without pragmatic deficits would intuitively know that
they needed to provide more information to the listener than simply
“Florida” (80).
3. To engage in cooperative conversational exchanges, one must speak
according to the “rules of discourse.” This may include such things as:
how to choose a topic of conversation, understanding and producing
appropriate facial expression and body language during conversation,
politeness, recognizing when the partner has lost interest in a topic,
knowing when to start, sustain, and end a conversation based on
listener cues, knowing when and how to repair a communication
breakdown, and appropriate tempo and turn taking (78). For example,
a teen with Asperger’s syndrome suffered a minor injury at a fund-
raising event. The physician on duty approached him to inquire of his
status. Instead of answering the inquiries regarding the injury, the teen

112 Johnson
delivered a monotone oration comparing and contrasting different

makes of automobile motors (his particular obsession at the time). The
doctor attempted repeatedly to redirect his interest to the presumed
injury. After each attempt, the boy stopped briefly, momentarily
looked bewildered, and then resumed his oration. Finally, he said,
“That will be all. You are dismissed.”
In these children there appears to be dissociation between the form and the
function of language. Whereas the form (syntax, tense, grammar, articulation, and
vocabulary) is intact, function (pragmatics and semantics or word meaning) is
significantly impaired. This disconnect may not be helpful in the early diagnosis
of classic autism but it can be very helpful in the early recognition of Asperger’s
syndrome.
Mastery of pragmatic skills depends on competence in ToM and executive
function. ToM ability allows one to mentalize or understand the intent of the
speaker so that one, in turn, can understand metaphors, irony, lies, jokes, faux
pas, and deception (59,65). Individuals with ASD and deficient ToM abilities will
have difficulty with statements like “Put your money where your mouth is,”
“Eyes on the board,” “Two heads are better than one,” or a news caption such as
“Iraqi Head Seeks Arms” (78). Finally, fluent children with ASD may
demonstrate unique delivery of speech in regard to intonation, volume, rhythm,
and pitch that also tend to disregard listener needs.
IV. STEREOTYPIES AND REPETITIVE,

RESTRICTIVE PLAYS
Children with ASD often demonstrate little interest in the usual popular childhood
toys, often preferring everyday items such as string, rocks, dirt, feathers, and
chains. They may play with them in a stereotypic, sensorimotor manner for hours
at a time without seeking attention. Sometimes parents will state that the child is
exceptionally “good” and can entertain himself indefinitely, requiring little or no
supervision. Depending on the child’s developmental stage, he may line objects
up, put objects in and out of containers, complete board puzzles, turn pages of
books, or play for hours with constructive toys or computer games. Sometimes
children with ASD are, indeed, interested in typical toys but in unusual ways or in
only their parts. For example, rather than playing with a miniature truck in the
typical way, they instead turn it upside down and spin the wheels repeatedly. Still
others are intensely interested, even obsessed, with certain unusual items such as
fans, light switches, electric cords, etc. Although most children, at some time
during their early development, form attachments with a stuffed animal, a special
pillow, or a “blankee,” children with ASD often prefer hard items (ballpoint pens,

chains, fast-food giveaway toys, etc.). Moreover, the attachment is much more
robust; they may even insist on holding the object most of the day, even during
meals, and protest violently when the object is removed. Children may violently
protest other types of transitions as well, insisting on “sameness” in regard to
events and routines. When forced to change to a different activity or toy, they may
become extremely angry and quickly escalate to a prolonged temper tantrum
characterized by aggression or self-injurious behaviors.
Many children with ASD develop stereotypies (e.g., hand flapping,
twirling, finger movements, rocking, head nodding etc.). Although stereotypies
are often very distinctive and obvious, they are not specific to children with ASD.
They often do not occur until after 3 years of age and thus they are not helpful in
the early diagnosis of ASD. Normal toddlers, especially prior to the onset of
fluent language, sometimes flap briefly when they are excited or frustrated and
children with profound mental retardation and/or severe visual deficits also
demonstrate stereotypies. Somewhat unique to children with ASD, however, is
the demonstration of habitual toe walking and/or sensory stereotypies such as
persistent sniffing and licking of nonfood items.
V. SELF-INJURIOUS BEHAVIOR
It is estimated that 5– 17% of persons with ASD, especially those with comorbid
mental retardation, demonstrate some form of self-injurious behavior (SIB). SIB
is a symptom expressed in many different syndromes and in various forms. It is
also thought to have several etiologies: operant, metabolic, neurochemical (dopa,
serotonin, opioid, and GABA neural transmitter systems have all been
implicated), or anatomical. True SIB usually does not appear until after 5
years of age. A proto-SIB (head banging that is not injurious and, occasionally,
self-biting without breaking skin) occurs prior to 5 years. Reasons for SIB include
(81):
Frustration with skill deficits, primarily in language, whereby the SIB
serves a social-communication function.
Reaction to a stimulus where SIB is used to obtain a tangible, to cope with
an under- or overstimulating environment, to escape from an anxiety-
provoking situation (encroachment on one’s personal space or a
requirement to transition from one activity/toy to another); an
endogenous neurochemical abnormality in dopa, serotonin, opioid, or
GABA neural transmitter systems.
A trait that makes up the behavioral phenotype in specific genetically
determined syndromes (self-picking in Prader-Willi and self-hugging in
Smith-Magenis syndromes).
A chronic health problem: pain, illness, pruritus, sleep deprivation, etc.

114 Johnson
SIB is often the most challenging behavior that caregivers encounter.

Management is best accomplished with a functional analysis of behavior to
determine the stimulus for the SIB. The stimulus may be obvious when it
immediately precedes the behavior and is consistent (e.g., hand biting each time a
transition is attempted). However, it is more elusive when the stimulus does not
consistently produce the SIB, when it is rarely considered noxious by nonautistic
persons, or when it occurs well in advance of the SIB (e.g., a delayed response to
running water in a distant bathroom). Additionally, the antecedent may not be
readily evident when it is associated with an ongoing condition (sleep
deprivation, illness, pain).
VI. COGNITIVE AND EXECUTIVE

FUNCTION DEFICITS
In the past, cognitive deficits were thought to be extremely common in

children with ASD. Most studies published prior to 1990 report a prevalence
of mental retardation in 90% or more of individuals. More recently, the
prevalence has been commonly reported as 75%. This figure continues to drop
and, in one study, was as low as 26% (82). Better ascertainment of children
with milder disorders, more effective strategies for evaluating cognitive
abilities in children with ASD, and early intense intervention in integrated
settings have all been cited as possible reasons for the decreasing prevalence
of comorbid mental retardation. The presence or absence of mental retardation
in a child with ASD may be the most important factor in determining long-
term functional prognosis (83).
EF abilities have been traditionally “housed” in the frontal lobe and enable
one: to process information, plan, organize, and regulate one’s behavior; to
monitor one’s own performance and make use of feedback; and to think about
and organize one’s own thoughts. It was not until the mid-1980s that empirical
work directly assessing executive function (EF) in persons with high-functioning
autism were conducted, some with conflicting results. Until that time the main
cognitive deficits known to be associated with persons with ASD included
difficulties with abstract thinking, tendencies toward preservative response
patterns, and stimulus overselectivity. EF skills also include the ability to
disengage from external context to inhibit an inappropriate response and to
disregard a false literal meaning in favor of a correct nonliteral inference.
Although many children with ASD are unable to understand humor, jokes,
sarcasm, and figurative speech (e.g., “Two heads are better than one”), these are
not specific to ASD. One longitudinal study of high-functioning children with
autism demonstrated consistent deficits in EF performance with little
improvement over time, thus indicating a possible developmental ceiling on
this type of ability (84).

VII. ABNORMAL SENSORY PROCESSING
Although not at all specific for ASD, “sensory integration” problems have
received much attention in the recent years. [For a comprehensive review of
sensory and motor processing in ASD, the reader is referred to Chapter 6 in this
book and/or Chapter 7 (Understanding the Nature of Communication and
Language Impairments) in Autism Spectrum Disorders, edited by Amy
Wetherby and Barry Prizant (85).] Children with ASD tend to demonstrate
simultaneous hyposensitivities and hypersensitivities for different stimuli even
within the same sensory modality. For example, the slightest sound of water
dripping may provoke a negative response, yet the child seems oblivious to his
mother calling his name loudly. Although part of the explanation may be rooted
to the tendency of children with ASD to selectively tune out social (human)
sounds (see above discussion of social orienting), some degree of physiological
deficit might also be responsible. As noted earlier in this chapter, often one of
the first concerns the parents have is the possibility of deafness. Yet they
eventually deny that the child has a hearing problem since he seems to hear
environmental sounds exceptionally well. Vision does not seem to be as
problematic, but parents will often report that their child explores toys visually
in unusual ways. He may hold the object very close to his eyes, look at the
object out of the corners of his eye, or demonstrate an unusual head tilt (which
would typically raise concerns about visual impairment and/or strabismus).
Additionally, some children seem annoyed with fluorescent lights and if verbal,
they might complain that the light makes things “jump around.” Although motor
stereotypies are seen in other disabilities, particularly severe mental retardation
and blindness, children with ASD demonstrate somewhat unique sniffing and
licking stereotypies. On the other hand, children with ASD may have oral
aversions and intolerance to certain textures that contribute to self-imposed
restricted diets. In addition to oral aversions, many children demonstrate “tactile
defensiveness” and are intolerant of soft touch and various clothing textures.
Conversely, they may be indifferent to significant injuries and other noxious
stimuli that would typically be quite painful to children without ASD. The
dichotomy is puzzling, but most experts feel that it is due to an abnormal arousal
level or sensory gating system in the cerebellum and/or brainstem. Recently, the
frontal cortex has been the focus of attention for its abnormal minicolumns
possibly resulting in less “insulation” of neural transmissions thus causing
overstimulation (86). Abnormalities in the gating of stimuli are thought to
account for two patterns of children with autism: (a) the hyporeactive child with
a high sensory threshold requiring excessive sensory input to achieve activation
of the system and (b) the hyperreactive child with a low sensory threshold who
is often overly focused on detail. Understanding these patterns has implications
for medical intervention, with SSRIs possibly being more helpful in the former
and stimulants in the latter (87).

116 Johnson
VIII. MOTOR ABNORMALITIES
One isolated video study of very young infants who were later diagnosed with
ASD (88) demonstrated unusual movement abnormalities of the mouth, trunk,
and extremities. Some investigators feel that these abnormalities may herald
the praxic deficits noted to be present in many older children with ASD.
Praxis refers to the planning, execution, and sequencing of movements (89).
Apraxia (severe deficits) and dyspraxia (milder deficits) are linked to deficits in
imitation and cannot be linked to neuromotor pathology. Praxic deficits affect
the imitation of speech, facial expressions, play, and/or motor patterns of
the extremities. Most children with ASD exhibit less imitation. In those
children with comorbid praxic deficits, imitation quality as well as quantity is
impaired; the movements appear awkward and inaccurate. The children are
often labeled as clumsy and uncoordinated, which seems to contradict earlier
reports that children with ASD usually had advanced gross motor skills.
Dyspraxia is not unique to ASD; oral-motor dyspraxia has long been known
to be a contributing factor to speech delay in children without ASD. Both
groups have difficulties imitating sequenced oral-motor movements (e.g.,
imitating “da-pa-ka” rapidly) necessary for fluent speech in spite of intact
neurological and oral cavity exams. Praxis problems also prevent automatic,
smooth synchronous, continuous motor matching of a partner and result in
problems in timing, speed, and grading of movements (90). Praxia has been
conceptualized as encompassing three steps: (l) ideation (formulating the
goal), (2) motor planning (figuring out how to accomplish the goal), and (3)
execution (the actual carrying out of the planned action) (85). Deficits can
occur at any step and result in failure. For example, when faced with the task
of playing in a carpeted play tunnel, a child must first develop some concept
that it is possible to crawl through a tunnel. Children with ASD often had
difficulty with this first step, ideation. They have little idea of the goal for
play in a tunnel. Others may have a deficit in the next step, motor planning;
although they desire to go through the tunnel, they cannot figure out how to
accomplish the task owing to a poor sensorimotor awareness. Still others will
be unable to execute the activity owing to poor motor control and
coordination. These children may also demonstrate gross and fine motor
delays.
In addition to abnormal quality of motor actions, children with ASD may
demonstrate abnormal amounts of activity. Some may appear to be “hyperactive”
and motor-driven with an exterior focus of attention. Others may be hypoactive,
move little, seem to have an interior focus of attention, and are withdrawn. This
may impact decisions regarding medication management at a later time. Whereas
the former may respond to stimulants, the latter may more likely respond to a
selective serotonin reuptake inhibitor.

IX. PHYSICAL CHARACTERISTICS
As noted in the introduction to this chapter, ASD is not associated with a classic
physical phenotype. Fewer than 25% of children will have a comorbid genetic
syndrome and thus will manifest the physical signs that are characteristic for that
syndrome (91) (see Chapter 6). Most children have idiopathic autism and are
not dysmorphic. Approximately 25 –30% of children develop postnatal-onset
macrocephaly that is not associated with ventricular pathology (92). A few
studies have reported children with slightly posterior rotated ears.
X. AUTISM REGRESSION SYNDROME
Although the majority of children with ASD present with abnormalities as

described above, 25 – 35% will appear to develop normally until 12 –24 months at
which point they regress in both language and social skills (93). Parents report
that the children were smiling, waving “bye-bye,” and saying a few words, when
they either suddenly or gradually stopped speaking and “withdrew into a shell.”
Although the underlying mechanism is unknown, several hypotheses, such as
immune dysfunction and stress, have been proposed (94,95). A detailed
discussion of these hypotheses is beyond the scope of this chapter. Home videos
recorded prior to the onset of regression have revealed that, in at least some
children, subtle early signs were present before the apparent regression (35 – 38).
Some investigators have reported an increased incidence of seizures and/or
abnormal EEG in regressive form; otherwise, physical, medical, or neurological
characteristics appear to be very similar (93).
XI. CONCLUSION
If the pediatrician is to be successful in detecting the early signs of ASD, he/she

must be knowledgeable and extremely vigilant. Owing to the increased
prevalence of ASD and its broader phenotype, an even higher degree of vigilance
is warranted in the younger siblings of children already diagnosed with ASD.
Ascertainment of deficits in very early social skills and in preverbal language
skills is critical. Although a variety of screening tools target these skills, no
current one can be singled out as superior (see Chapter 6). Newer tools, as well as
modifications of the current, are being studied to improve sensitivity and
specificity. Hopefully, the ideal tool will emerge soon. In the meantime,
pediatricians are encouraged to have a high index of suspicion, use one of the
tools (realizing its limitations), and, most important, listen to the parents. Again
most parents become concerned by 18 months. At that point, if the clinician does

118 Johnson
not feel qualified to conduct a comprehensive evaluation, he/she should

immediately refer to a specialist or, ideally, to an autism team. Additionally, the
pediatrician should refer the child to the local early-intervention program. It is not
necessary to have a definitive diagnosis, or an etiological one, for the child to
qualify for early-intervention services. Most programs have multidisciplinary
teams that can conduct a developmental evaluation and provide a profile of the
child’s strengths and weaknesses. This developmental profile can then assist the
physician in making a diagnosis especially if it demonstrates language and social
skills that are significantly below the child’s overall level of functioning.
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6
Screening and Diagnosis for Autistic
Spectrum Disorders
Pasquale J. Accardo
Virginia Commonwealth University, Richmond, Virginia, U.S.A.
I. INTRODUCTION
Several clinical practice guidelines for the screening and diagnosis of autism and
autistic spectrum disorders are fairly similar in their components, and any variations
in the process reflect their target audience. Guidelines drafted by the American
Academy of Pediatrics (1) are intended for pediatricians; those by the American
Academy of Neurology (2,3), for child neurologists; those by the American Academy
of Child and Adolescent Psychiatry (4), for child psychiatrists; and those by the
New York State Department of Health (5), for professionals from diverse disciplines
as well as for parents. The present chapter will assume some familiarity with such
protocols and attempt to provide a rationale for the major steps in this clinical process.
Familiarity with the more traditional components of routine pediatric health care
provision as well as with child developmental surveillance will also be assumed. The
emphasis will be on how the medical practitioner can most effectively contribute.
The American Psychiatric Association’s DSM-IVTR (6) and the American
Academy of Pediatrics DSM-PC (7) place autism within the category of pervasive
developmental disorders (PDD). This category includes five separate conditions:
Autism occurs when the child displays significant impairment in all of three
separate areas of functioning: communication, socialization, and
repetitive, self-stimulatory, and restrictive behaviors, and these
impairments have their onset before the age of 3 years (Table 1).

126 Accardo
Table 1 DSM-IVTR/DSM-PC Criteria for Autism
Six of the following 12 items with onset prior to 3 years:

Socialization—at least two of the following four behaviors:
1. Impaired nonverbal interactive behaviors (e.g., eye contact, facial expression)
2. Poor peer relationships
3. No spontaneous sharing (e.g., joint attention)
4. No social reciprocity
Communication—at least one of the following four behaviors:
5. Delayed language (including nonverbal communication): the communication
delay may be part of a more generalized delay in developmental competency;
since children with autism may have mental retardation, children who present
with global cognitive delay should be assessed for the presence of autism.
6. Conversational (pragmatic) difficulties
7. Stereotyped (echolalia) or idiosyncratic use of language
8. Lack of symbolic or social imitative play
Repetitive, stereotypic, restrictive behaviors—at least one of the following four behaviors:
9. Intense or narrowed focus of interest
10. Rigidity with regard to routines or schedules
11. Stereotypic and repetitive mannerisms (e.g., hand flapping or hand regarding)
12. Preoccupation with parts of objects
Children with autism may present with signs and symptoms of developmental delay,
developmental coordination disorder, expressive and receptive language delay
(5), impulsive/hyperactive or inattentive behaviors, obsessive, compulsive behaviors
(9,11,12), sleep disorders, constipation, restrictive diets or extreme sensitivity to food
texture/odors (10), self-stimulatory behaviors (11), and social interaction behavior problems
(1–4,6,8). Difficulties with social interaction can present as variations (overly sensitive to
social interaction such as the slow-to-warm-up child), problems (shy and solitary), and
autistic disorders (absence of most basic interactional behaviors such as eye contact).
The numbers in the last paragraph do not refer to footnotes but to the table.
Source: Refs. 6, 7.
Pervasive developmental disorder – not otherwise specified (PDD-NOS)

occurs when the child exhibits many of the features of autism but is not
severely impaired in all three areas of functioning. Age of onset may be later
than 3 years of age. PDD-NOS is sometimes referred to as atypical autism. It
is not necessarily accurate to describe it as a milder form of autism since
associated developmental problems (such as intellectual deficiency) may
render a child with PDD-NOS and severe global cognitive impairment more
severely involved than a child with autism but without any intellectual
disability. The lower boundary for PDD-NOS remains unclear: how few
autistic-like symptoms will qualify for a diagnosis of PDD-NOS?

Screening and Diagnosis 127
Asperger’s syndrome occurs when the child exhibits typical

communication skills development up to 3 years of age but later in life
is found to have autistic-like behaviors in addition to significant
problems with pragmatic language. (This behavioral pattern can be
mimicked by right-brain-deficit learning disabilities.) Outcome research
is finding it increasingly difficult to distinguish between Asperger’s
syndrome and high-functioning autism. The presence/absence of
language difficulties prior to age 3 years seems to have little impact on
prognosis in high-functioning autism.
Rett’s syndrome occurs only in girls who exhibit a dramatic regression
in language, motor, and social skills before the age of 2 years. This
regression is fairly permanent and accompanied by an acquired
microcephaly and two strikingly autistic-like behaviors: hand wringing
and severe gaze aversion. Since Rett’s syndrome has now been identified
as a specific genetic defect (an MECP2 mutation), it will probably be
removed from the PDD category in the next DSM revision.
Childhood disintegrative disorder (Heller’s syndrome) has its typical onset
in children between 5 and 10 years of age when they undergo a severe
generalized deterioration in cognitive functioning so that they go from
normal intellectual functioning to moderate mental retardation. The
presence of several autistic-like features does not strongly support the
placement of disintegrative disorder within the PDD classification; it is
more properly conceptualized as a neurodegenerative disorder that needs
a comprehensive neurological assessment rather than educational and
behavioral services appropriate to children with autism.
To streamline an approach to this family of neurodevelopmental disorders,

(1) the last two conditions (Rett’s syndrome and disintegrative disorder) will be
removed from the PDD category, (2) Asperger’s syndrome will be considered to
be the equivalent of high-functioning autism (the person with autism with normal
to superior intellectual capabilities and relatively intact language skills), and (3)
the distinction between autism and PDD-NOS will be considered essentially
irrelevant for the purposes both of diagnostic-biomedical assessment and of
educational-behavioral intervention in infants and young children (5). PDD can
then be condensed to autism—PDD-NOS—high-functioning autism with this
new triad being referred to as autistic spectrum disorders (ASD).
Since early identification is imperative, any discussion of the diagnostic
process must focus on 18 –36 months of age, or younger. There can be no
acceptable approach to late diagnosis. When some variant of ASD presents
outside this age window, it should not be difficult for the clinician to extend the
following rationale to older age groups and analogous presentations.

128 Accardo
II. SCREENING IN THE PRIMARY CARE SETTING
All children who are receiving well-child health care have their developmental
progress routinely evaluated at each visit. The physician is less concerned to be
intimately familiar with all aspects of a given child’s developmental progress
than to identify significant developmental delays and neurological diagnoses that
warrant biomedical assessment and both general and specific intervention
strategies. From this perspective, screening procedures can be situated within a
larger framework that rationally delineates their use.
Focusing on which conditions can be diagnosed at specific ages can help
further to limit the investment of time needed to screen for different conditions.
With the partial effectiveness of early (prior to age 60 months) intensive
behavioral intervention strategies in the treatment of ASD (8), the importance of
early identification is increasingly recognized. Nevertheless, it is not unusual still
to encounter a child with developmental problems in whom the diagnosis of ASD
was not considered or confirmed until after the age of 60 months (9). Parents
usually become concerned by 18 months of age, but do not present to the primary
care provider with these concerns until 6 months later and considerable time
lapses between first parental concern and the final definitive diagnosis (10). In the
current state of knowledge, failure to diagnose ASD earlier is unacceptable.
While researchers pursue the diagnosis of ASD into the age group prior to 18
months (see Chapter 5), the clinician needs to be comfortably familiar with the
presentation of ASD between the ages of 18 and 36 months. Most children who
will qualify for a diagnosis of ASD will actually develop sufficient signs and
symptoms between 18 and 24 months, and the remainder will do so between 24
and 36 months of age. Eager to initiate therapy by 24 months of age, there is
concern that the age for diagnosis be lowered to 24 months. The average age of
diagnosis in Europe has, indeed, decreased to 30 months from 4 years (11). It has
been suggested that DSM criteria be modified for younger children to include
social skills deficits, such as decreased use of nonverbal behaviors, lack of social
and emotional reciprocity, and lack of seeking to share enjoyment, to account for
unreliability of some DSM criteria in children less than 3 years of age (12).
However, some children with ASD will simply not be diagnosable until closer to
age 36 months, the upper age limit as defined by DSM-IVTR.
Until the development of a screening tool based on the early social signs of
autism (see Chapter 5), it is acceptable for a working approach to screening for
this group of conditions to rely on the DSM system’s characterization of ASD as
disorders with significant impairments in communication, socialization, and
repetitive, stereotypic behaviors. Since the specific and often striking stereotypies
are not pathognomonic, and social interaction is difficult to assess in the pediatric
office setting, the screening process can best start with universal prospective
surveillance of communication skills in children.

III. SCREENING COMMUNICATION IN INFANTS

AND YOUNG CHILDREN
Some degree or type of communication disorder occurs in 20 –25% of all

children (13). With such a high incidence of problems in communication, routine
detailed surveillance of language development in infants and young children can
and should be universal. There are many different tools for screening language in
children. It is less important which instrument is used than that an instrument
be used, be used routinely, and be interpreted consistently in accordance with the
specific developmental diagnoses under consideration. Thus although the
physician may routinely ask about the child’s acquisition of language milestones,
if any reported delays are then attributed to willfulness, personality (shy, quiet
child), older siblings talking for the child, grandparental spoiling, or even genius
(“Einstein didn’t talk until he was 5 years old”), then the whole purpose of the
screening process will be vitiated. Significant delays need to be taken seriously
and considered as markers for potentially treatable developmental problems.
Three early language instruments are appropriate for the pediatric office
setting: the MacArthur Communicative Developmental Inventories (CDI, with
Infant and Toddler versions), Early Language Milestone Scale—Second Edition
(ELMS-2), and the Clinical and Linguistic Milestone Scale (CLAMS). The
CLAMS, the language component of the Capute Scales, is an assessment instrument
specifically devised for use by the physician in the medical office setting (Table 2).
Using such instruments, children with ASD will be found to present around age 24
months with impaired communication according to one of three patterns:
1. Mute: The child has no expressive spoken language—no words.

Technically, any child at 18 months who has no words should be
evaluated further or immediately referred for in-depth assessment of a
developmental problem. Some children with ASD will have had
several (or more) words at 18 months but will then have regressed and
lost them by 24 months of age or later (one component of “autistic
regression”). While not diagnostic, such loss of previously acquired
expressive language skills is highly suggestive of ASD.
2. Delayed expressive language milestones: The child has a less-than-50-
word vocabulary and no two-word combinations at 2 years of age.
These two milestones are associated or linked; they occur or fail to
occur together. If a child has more than 50 words, he will almost
certainly be putting two words together; if a child is putting two words
together, his vocabulary is almost certainly greater than 50 words. If a
parent reports the presence of one of these milestones without the
other, there is usually an error in the reporting. Thus the child with a
10-word vocabulary and several two-word phrases will often have

130 Accardo
Table 2 Selected CLAMS Milestones
Expressive Receptive
12 mo 1 word One-step command
with gesture
14 mo 3 words
Immature jargoning
16 mo 4 words One-step command
without gesture
18 mo 6 words Points to one picture
Points to one body part
Vocabulary explosion
22 mo 2 word phrases
24 mo 50 words Points to a half-dozen
body parts
2 – 3-word sentences Two-step command
30 mo Pronouns Points to a half-dozen
pictures
“bye-bye” and “ice cream” as examples of the “two-word phrases.” The

child with valid two-word phrases and a vocabulary of only 30 or so words
will be found actually to have a larger vocabulary when the parent is asked
to record all the child’s different words as used over a 2-week period.
3. Typical expressive language milestones: Occasionally children who
might qualify for a diagnosis of ASD will present at around 24 months
of age with a greater-than-50-word vocabulary and several two-word
phrases. If, however, an additional question is used to supplement the
CLAMS language milestones, the artificiality of this attainment can be
discovered: “Is any . . ., how much of your child’s spoken language is
merely being repeated (echoed, parroted, either immediately or
delayed) rather than being spontaneous to the situation and with
relatively novel combinations?” If a significant percentage (.20%) of
the child’s spoken utterances are echolalic, then the child’s language
achievement needs to be adjusted to whatever part is not just repeated.
Expressive language delay will then often be recognized. Although
echolalia is often both prominent and prolonged in children with ASD,
it is neither diagnostic nor pathognomonic. Many children with other
(and much more common) communication disorders along with some
children with mental retardation will also exhibit significant echolalia.
Along with the expressive language delay, this specific finding merely
invites further investigation.

With the identification of expressive language delay, the primary care

physician can either refer the child on for more detailed developmental
assessment or utilize further screening steps to narrow the range of diagnostic
possibilities. Caution should be observed if the child is to be referred to a state
early-intervention program. In some state programs there is a reluctance to
diagnose ASD, so that children who when assessed are found to exhibit significant
delays in communication and socialization as well as stereotypic and repetitive
behaviors will have designed for them an intervention program that addresses
each and every area of delay and problematic behavior without ever grouping the
findings into a specific “diagnosis” of an ASD. The recommended treatment for
the specific ASD diagnosis is often much more intense than the proposed
intervention strategies for the separate parts that comprise the syndrome.
Even if the child is being referred for more in-depth assessment elsewhere,
it is often helpful and productive for the primary care physician to take steps to
remain an integral component of the diagnostic and evaluation process that
follows. Any differential diagnosis achieved at this stage will be subject to
clarification and refinement (but not contradiction) according to more detailed
discipline assessments. Further developmental assessment gives the primary care
physician “hands on” experience with the strengths and weaknesses of the child
that will be the subject of future assessment and intervention, and a baseline from
which to measure later progress in response to various interventions.
IV. DIFFERENTIAL DIAGNOSIS OF EXPRESSIVE

LANGUAGE DELAY
Children who present with delayed expressive language delay will typically fall
into one of the following broad diagnostic categories:
1. Isolated expressive language delay, slow talkers
2. Communication disorder with delays in both expressive and receptive
language
3. Global cognitive impairment (intellectual deficiency, mental retar-
dation)
4. Hearing impairment
5. ASD
There are a number of clinical observations by which these conditions might be
distinguished in the primary care setting (14). Although such clinical clues might
seem to adequately differentiate one condition from another, it is generally
accepted that any child who presents with some variant of expressive language
delay needs to have a formal audiological assessment and never just a hearing
screening.

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Isolated expressive language delay is the single most common

developmental problem in children. It can be distinguished from all the other
items in the above differential diagnosis list by the presence of intact receptive
language abilities. The child who is not talking at an age-appropriate level but
who understands what is said to him at an age-appropriate level cannot have
global communicative or cognitive impairment and is unlikely to have a
significant hearing problem. The child who demonstrates age-appropriate
receptive language abilities is also very unlikely to have ASD.
The problem in the primary care setting is to effectively assess receptive
language skills. Even in a formal speech/language evaluation, receptive language
is considered rather difficult to assess adequately in the second year of life.
Typically one expects 12-month-old children to begin to follow single-step
commands (with accompanying gesture by 12 months and without an
accompanying gesture by 16 months of age), and 24-month-old children to
respond to two-step commands. Obtaining such cooperation in the pediatric office
setting is, however, quite difficult, and even parent history for the child’s ability to
follow two-step instructions at home is fraught with difficulties. Typically
developing 2-year-old children are frequently very much into a negativistic or “no”
phase (15) and are rarely very cooperative in routinely doing what they otherwise
might be able to do.
Table 2, however, presents several alternative receptive milestones that are
more easily elicited either in the office setting or by parental history. Between 12
and 18 months of age, children begin to point to what they want; between 18 and
24 months of age they begin to point in order to identify things. Protodeclarative
pointing (pointing to elicit shared interest) also comes in between 18 and 24
months of age. Starting at around 18 months of age most children can point to one
or more body parts as well as one or more pictures in a book. By 24 months of age
a number of pictures and body parts should be in the child’s receptive (with
pointing responses) repertoire. These pointing milestones provide a very useful
probe for tapping receptive language.
When the child has both expressive and receptive language delays, then
global developmental delay (cognitive impairment, intellectual deficiency,
mental retardation) and ASD must be specifically ruled in or out.
V. SCREENING FOR AUTISM VERSUS GLOBAL

COGNITIVE IMPAIRMENT
The child with delayed expressive but intact receptive language milestones has
some version of isolated expressive language disorder. The child with expressive
and receptive language delays may have a more severe combined communication
disorder, global cognitive impairment such as mental retardation, or ASD.

To differentiate communication disorder from cognitive impairment requires

some measure of nonverbal intelligence. The Clinical Adaptive Test (CAT)
component of the Capute Scales or formal psychometric testing by a child
psychologist [using the Bayley Scales of Infant Development, Second Edition
(BSID-II) or the Stanford-Binet Intelligence Scale, Fourth Edition (SB-FE)]
might be used for this purpose (16).
Alternatively, clinical observation and history can be used to ascertain the
child’s major or preferred ways of interacting with toys and other objects in
the environment. This preference can be converted to an approximate mental
age level (Table 3). The child who is significantly delayed in expressive
language, receptive language, and problem-solving abilities probably has global
cognitive delay rather than just a communication disorder. However, whether or
not the child appears to have global cognitive impairment does not appreciably
help to decide the presence or absence of ASD since the latter may occur along
with global cognitive delay. In other words, nonverbal-problem-solving abilities
will be in the normal range in a significant percentage of children with ASD while
a significant percentage of children with ASD will exhibit delayed nonverbal-
problem-solving abilities and will also be mentally retarded. (The issue of exactly
what these percentages might be is under active discussion.) If global cognitive
limitation is present (with or without ASD), then the appropriate biomedical
assessment will focus on that neurodevelopmental disorder (17).
Suspected because of the presence of language delay, the diagnosis of ASD
will now depend on the additional presence of atypical features of the language
delay (such as echolalia and pronominal [“I/me”—“you”] reversal), impairment
in socialization (out of proportion to the language or other developmental delays),
and stereotypical or repetitive behaviors. Whenever a child is shown to have a
severe communication disorder, behavioral screening for ASD should follow.
The DSM-IVTR criteria can be used. Various listings of specific behaviors
associated with each of the deficit areas can be helpful (Table 4). One of the
problems in listing autistic-like behaviors is deciding exactly how to classify a
Table 3 Patterns of Object Interaction
Visual tracking 0 – 3 months

Reaching/grasping 3 – 6 months
Mouthing 6 – 9 months
Banging/noisemaking 9 – 12 months
Throwing/receptacle play 12– 15 months
Stacking blocks 15– 18 months
Puzzle/shape fitting 18– 21 months
Scribbling with pencil 21– 24 months

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Table 4 Autism Features
Qualitative impairment in Qualitative impairment in Deviant (restrictive,

social interaction communication repetitive) behaviors
No/poor eye contact Language delay Water play
In own little world Echolalia, immediate and Lines up/groups toys
No peer interaction delayed Perseverative
No reciprocity or sharing Equinus gait (toe walking) Preservation of sameness
Doesn’t read faces Acts as if deaf Stereotypies
Treats people like No protodeclarative Rocking
furniture pointing (“joint Spinning/twirling
Laughs for no reason attention”) Likes fans
Language regression Stiff/noncuddly baby
(18– 24 months) Splinter skills
Refers to self in third Inflexible routines/rituals
person Tone abnormalities
Pronominal reversal Arching
Good rote memory Flapping
Poor pragmatic language Absence of pretend play
No communicative intent/ Preoccupation with parts
lack of frustration over of objects
failure to communicate Insensitivity to pain
Olfactory
Hyperactivity (ADHD)
specific behavior. Thus, is poor eye contact a communicative or socialization

item? Is toe-walking a communicative or stereotypical behavior?
It is interesting to note that children with ASD exhibit several
communicative behaviors that are not typically found in other children with
severe communication disorders. These more specific behaviors all seem to relate
to a failure in the development of the desire to communicate (communicative
intent). Although children with ASD will tantrum when their wants are not met,
they rarely get upset when other communicative efforts fail—usually because
there are no other communicative efforts. Children with other types of
communication disorder and those with hearing impairments frequently grow
increasingly frustrated as they approach the age of 24 months because they
recognize that others are trying to verbally interact with them and they want to
respond—but cannot. This failure of communicative intent characterizes children
with ASD and some with severe to profound mental retardation.
There are no physical findings specific to ASD (18). If an equine gait
(persistent toe walking) is present, the child should be checked for heel-cord
tightness (shortened tendo Achillis). Even with a persistent equinus gait, the heel

cords usually reduce past neutral (19). While global cognitive limitation and most
other neurodevelopmental disabilities are frequently associated with some degree
of microcephaly, ASD is more often found with macrocephaly (20,21).
One screening test for ASD that has been proposed is the CHAT (22).
While statistics do not support its general usage, it does highlight several key
behaviors that can be used to help diagnose ASD (Table 5). An obvious weakness
in the construction of the CHAT is simply that many of the items are not specific
to ASD but rather are common to global cognitive impairment or mental
retardation. As the percentage of ASD children with mental retardation
decreases, so does the utility of the test. The CHAT behaviors more specific to
ASD are those that involve pretend play and joint attention (protodeclarative
pointing). (For a more detailed discussion of these behaviors see Chapter 5.) The
use of these markers can help discriminate ASD from other types of
communication disorders. Apart from issues with sensitivity and specificity,
the CHAT may be too long for routine use in the primary-care office setting,
particularly in the American managed-care setting.
Table 5 Checklist for Autism in Toddlers (CHAT)
Parent questions
1. Does your child enjoy being swung, bounced on your knee, etc.?
2. Does your child take an interest in other children?
3. Does your child like climbing on things such as up stairs?
4. Does your child enjoy playing peek-a-boo/hide-and-seek?
5. Does your child ever pretend, e.g., to make a cup of tea using a toy cup and
teapot, or pretend other things?
6. Does your child ever use his/her index finger to point, to ask for something?
7. Does your child ever use his/her index finger to point, to indicate interest in
something?
8. Can your child play properly with small toys without just mouthing, fiddling,
or dropping them?
9. Does your child ever bring objects over to you to show you something?
Professional observations
1. Has the child made eye contact with you?
2. Get the child’s attention, then point across the room at an interesting object and say,
“Oh look! There’s a. . .!” Watch the child’s face. Does the child look across to
see what you are pointing at? [and not just at your finger]
3. Get the child’s attention, then give a miniature toy cup/teapot, and say, “Can
you make a cup of tea?” Does the child pretend to pour out tea, drink it, etc.?
4. Say to child, “Where’s the light?” or “Show me the light.” Does the child point [with
his/her index finger] to the light?
5. Can the child build a tower of bricks? (If yes, of how many bricks?)

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VI. FORMAL DIAGNOSTIC EVALUATION
There is no single accepted diagnostic evaluation process for ASD. To answer the
question as to what such a battery should contain, the specific goal of the
diagnostic evaluation must be clarified. Specialists are often looking to answer
questions of little concern to the parents, while parents are often asking questions
that the most extensive test batteries do not address. There are four separate
questions that a diagnostic assessment might attempt to address:
1. Does this child have ASD or not?
2. If the child has ASD, how severe is the condition?
3. What tests are appropriate to investigate possible etiologies for the
ASD?
4. What are the interventions appropriate to this specific child?
1. The response to the first question is a straightforward clinical one. The
clinician familiar with the diagnostic criteria for ASD can usually answer it with
reasonable certainty after a developmental history and a period of observation
and interaction taking something on the order of 1 –2 hr. Not infrequently in more
classic cases the diagnosis can be strongly entertained after only several minutes
of observation. Needless to say, the diagnosis should never be based on such a
quick glance but rather such an initial impression needs to be supported by a
developmental history that confirms such behaviors to be pervasive across
settings and chronic in duration—in other words, that this atypical behavior is
actually typical for this child.
A number of formal ASD screening tools exist: Autism Behavior Checklist
(ABC), Autism Screening Questionnaire (ASQ), Checklist for Autism in
Toddlers (CHAT), Pervasive Developmental Disorder Screening Test (PDDST)
Stage 1, Social Communication Questionnaire (SCQ), and Screening Tool for
Autism in Two-year-olds (STAT) (Table 6). Since it is usually not practical to
screen the general population of young children for autism using a specific autism
screening test, it is recommended instead to look for clinical clues (5). The
clinical decision tree outlined here does not allow a major role to the routine
employment of screening instruments.
Formal diagnostic instruments include: Autism Diagnostic Interview –
Revised (ADI-R), Autism Diagnostic Observation Schedule– Generic (ADOS-
G), Behavioral Summarized Evaluation (BSE), Childhood Autism Rating Scale
(CARS), Diagnostic Instrument for Social and Communicative Disorders
(DISCO), Gilliam Autism Rating Scale (GARS), Parent Interview for Autism
(PIA), Pervasive Developmental Disorder Screening Test (PDDST) Stages 2 and 3,
Pre-Linguistic Autism Diagnostic Observation Schedule (PL-ADOS) (Table 7).
The ADI-R and ADOS-G are considered the “gold standard” for such diagnostic
instruments and the CARS has the longest history and the widest use. No single

Table 6 Autism Screening Instruments
Autism Behavior Checklist (ABC): Originally intended more for designing

educational placement and monitoring progress as part of a broader tool, the Autism
Screening Instrument for Educational Planning (ASIEP), rather than for diagnosis, the
ABC is sometimes used for screening. 57 dichotomous items are scored across five
domains (sensory, relating, body and object use, language, social and self-help). Total
scores .67 indicate a high probability of autism, between 53 and 67 are questionable
for autism, and ,53 make autism unlikely.
Autism Screening Questionnaire (ASQ, formerly Social Communication
Questionnaire, SCQ): A brief 40-item dichotomous behavioral questionnaire that
addresses reciprocal social interaction, language and communication, and repetitive,
stereotypical behaviors. One version is for children under age 6, and another version
is for children 6 and older.
Checklist for Autism in Toddlers (CHAT): A screening test for autism in children from
18 to 36 months of age; it contains 9 parent questions and 5 behavioral observation items.
Absence of three items is considered critical: protodeclarative pointing, gaze monitoring,
and pretend play (administration time: 15 min). MCHAT: A revision of the CHAT with
23 parent questions and no behavioral observation items.
Pervasive Developmental Disorder Screening Test (PDDST) Stage 1: A parent
questionnaire for use in the primary care setting; 3 affirmative answers support further
diagnostic consideration for autism.
Screening Tool for Autism in Two-Year-Olds (STAT): An interactive play
instrument designed for children 24– 25 months old. Failure in 2 of 3 areas (play,
motor imitation, and nonverbal communication) differentiates autism from other
developmental problems (administration time: 20 min).
instrument should be used as the sole basis for diagnosing ASD (5). On the one
hand, the better formal instruments require extensive training and experience; on
the other hand, the instruments are intended for use by practitioners not clinically
experienced in the diagnosis of ASD (3).
The confirmation of the clinical diagnosis of ASD by a formal instrument is
strongly recommended but will be subject to the reasonable availability of
professionals with the requisite training in the administration of such scales.
Reasonable availability can also refer to the fact that a diagnostic medical
evaluation by a child neurologist, child psychiatrist, or developmental pediatrician
may be covered by the family’s health insurance, but the performance of an ASD
rating scale by a child psychologist or other certified professional is rarely
covered. Neither is the requisite training expertise universally available through
either early-intervention programs or the public school system.

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Table 7 Autism Diagnostic Instruments
Autism Diagnostic Interview – Revised (ADI-R): A comprehensive semistructured

parent interview with behavioral items scored on a 0 (none) to 4 (extreme) point Likert
scale. Three domains (communication and language, reciprocal social interaction, and
restrictive, perseverative, and stereotypical behaviors) have different cutoffs
(administration time: 60 min).
Autism Diagnostic Observation Schedule – Generic (ADOS-G): Four modules (for use
in persons with different developmental levels: preverbal/single words, phrased speech,
fluent speech child-adolescent, fluent speech adolescent-adult) administer structured
standardized situations to assess communication, social interaction, and play/
imaginative use of objects (30 – 45 min). The Pre-Linguistic Autism Diagnostic
Observation Schedule (PL-ADOS) is derived from the ADOS to be used with
nonverbal children under the age of 6 years (administration time: 30– 45 min).
Behavioral Summarized Evaluation (BSE): A set of French instruments that includes
the 20-item BSE Likert scale, the 29-item BSE-R scale, and the 23-item IBSE (Infant
Behavioral Summarized Scale).
Childhood Autism Rating Scale (CARS): In the most widely used autism
diagnostic instrument, 15 items are scored on a 7-point Likert scale. It combines parent
report with direct observation. Scores ,30 make autism unlikely; scores between
30 and 36 suggest mild to moderate autism, and scores .36 suggest moderate to
severe autism (administration time: 30 min).
Gilliam Autism Rating Scale (GARS): A behavioral checklist to estimate the
severity of autistic symptoms in persons aged 3 years to adult.
Parent Interview for Autism (PIA): A semistructured parent interview with 118
items grouped into 11 domains and scored on a Likert scale from 1 (almost never) to 5
(almost always) to assess autism in preschool children (administration time: 45 min).
Pervasive Developmental Disorder Screening Test (PDDST) Stage 2 and 3:
A parent questionnaire in which 4 or more affirmative answers on Stage 2
(Developmental Disorders Clinics version) or 6 or more affirmative answers on Stage 3
(Autism/PDD Clinic version) indicate further diagnostic consideration for autism.
Pre-Linguistic Autism Diagnostic Observation Schedule (PL-ADOS): A version
of the Autism Diagnostic Schedule (ADOS) that uses a semistructured assessment
of play, interaction, and social communication to diagnose autism in children under 6 years
of age. 12 brief play activities are scored on a Likert scale from 0 (no abnormality
consistent with autism) to 2 (response consistent with autism) and generate
17 individual and 31 overall ratings (administration time: 30 min).

While the usefulness of formal scales to help confirm a diagnosis of ASD is

readily conceded, the ability of such instruments to discriminate ASD from
whatever borders on the milder end of the autistic spectrum remains
controversial. Such difficulty resembles the quite similar problem that occurs
when attempting to discriminate a slow learner from a person with mild mental
retardation by the use of an intelligence test score alone. The psychometric
properties of the test can be excellent, but is the instrument being used to discover
or to create a cutoff? Psychometric instruments are similar to blood tests in that
quantitative results are always subject to clinical interpretation. There is no
perfect test that will obviate the need for clinical judgment.
2. The severity of the ASD does not necessarily relate to the incidence or
frequency of various autistic-like behaviors but rather to the degree to which
these behaviors interfere with more typical functioning. Thus children with many
striking autistic behaviors may sometimes be able to be easily drawn out to interact
with others. The presence of associated dysfunctions such as cognitive limitation
may render a child with milder autistic-like features much more impaired. Scores
on formal autism rating scales may be used to quantitate the degree of severity
and to provide a baseline for treatment efficacy. Nevertheless, with the exception
of the degree of associated mental retardation, degrees of severity of autistic-like
symptoms have not been shown to correlate with the long-term responsiveness to
intervention. Measuring global cognitive impairment in ASD, however, presents
its own set of assessment problems.
A measure of general intellectual level should always be attempted in the
assessment of children with ASD. Since it is not unusual to find such children
very difficult to engage in the testing situation, the evaluation should be
performed by a professional skilled in working with children with ASD.
Although many children with ASD will test out in the intellectually deficient
range, significant dissociation is often observed. Thus, while the overall IQ may
be in the retarded range, there is often a verbal-performance discrepancy such
that verbal skills are much more delayed than nonverbal skills. ASD performance
on the verbal or communication sections of various intelligence tests is often
impaired by limitations in language usage or by deviance in communicative and
social interaction. On the other hand, selected verbal items or subtests may be
inflated by their rote language or sometimes excellent memory skills.
Most children with ASD will perform much better on the nonverbal
sections of intelligence tests or on those items that are defined as more classically
right brain (nonlanguage or nondominant hemisphere) dependent. It is therefore
not surprising to find that whenever these children exhibit savant skills (isolated
isles of superior ability), these are almost always derived from right-brain skill
areas such as mathematics, numerical calculation, music, memory, and graphic
art. Similarly, when one groups genetic syndromes associated with different
learning disability patterns, those syndromes with the strongest association with

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ASD are all found within the syndrome group with verbal skills more impaired
than nonverbal skills. Therefore, any attempt to measure general intellectual
ability in ASD children should always use instruments with a strong nonverbal
component such as the Leiter International Performance Scale –Revised (Leiter-
R), the Griffiths Mental Development Scale, the Raven’s Progressive Coloured
Matrices, the Seguin Formboard, and the Clinical Adaptive Test (CAT) of the
Capute Scales. The finding of nonverbal-problem-solving superior to verbal
abilities (e.g., a CAT score above the CLAMS score) should be considered
typical for ASD.
When a child with ASD tests out globally delayed with low scores in both
the verbal and nonverbal areas, the problem will be to differentiate an associated
mental retardation from difficulties in obtaining the cooperation of a child who is
not socially reciprocating. How can one differentiate superior nonverbal skills
that equate with overall better nonverbal intelligence from an isolated “splinter
skill” or two? Sometimes the examiner can note test behaviors that make one of
these two interpretations more probable, but it will often take time for the picture
to sort itself out. The difficulties in interpreting such data should not dissuade one
from obtaining such baseline information. Sometimes the use of the Vineland
Adaptive Behavior Scales can help in this differential diagnosis by providing
developmental age levels for several other functional areas. Modifications in the
use of the Vineland with ASD persons have been published, and this population
will be specifically addressed in the next revision of the instrument. Rating scales
for repetitive, obsessive compulsive, stereotypic, and tic behaviors (23) are less
diagnostic than treatment oriented by providing baseline measures for targeted
behaviors.
3. The pediatric medical evaluation for ASD should review and explore
all those prenatal, perinatal, and postnatal factors associated with the entire
spectrum of neurodevelopmental disabilities.
Since the incidence of seizures is increased in children with ASD (and
tends to increase further with age), electroencephalography needs to be
considered in the diagnostic medical assessment. Children with obvious or
suspicious seizure episodes should receive an electroencephalogram (EEG). This
recommendation does not support the routine use of the EEG.
Concern remains that even in the absence of overt seizure activity,
epileptiform discharges might represent a deleterious influence on certain brain
areas. The classic example of such an association is the Landau-Kleffner
syndrome (or acquired epileptic aphasia) (24). In this syndrome, children develop
a seizure focus directly over the language areas of the brain and lose previously
acquired speech (they develop aphasia). Most cases of Landau-Kleffner
syndrome occur later than the upper age limit for the onset of ASD (3 years),
and most have obvious clinical seizures. There are, however, some cases of
Landau-Kleffner syndrome with only electric discharges and no clinical seizure

activity. A key distinction between the regression that typically occurs in ASD and
the regression that occurs in acquired epileptic aphasia relates to the
accompanying impairment of social interaction and relatedness. In children
who are developing some form of ASD, the language loss is contemporaneous
with the onset of social withdrawal. In children with an acquired epileptic
aphasia, the emotional withdrawal will occur only after the language impairment
has had time to exert a secondary impact on socialization. In this latter case, the
effect and its time course are similar to the socialization difficulties that occur
with significant hearing impairment.
No consistent neuroimaging findings are associated with ASD. The criteria
for obtaining an MRI or CT scan should be the same as with children without
ASD: abnormalities of the head (other than mild macrocephaly), facial
dysmorphology (e.g., midface hypoplasia), positive or localizing findings on
neurological examination, or significant global developmental delay (mental
retardation) (17,25). The last reflects the importance of attempting an assessment
of general intelligence in ASD. Otherwise neuroimaging cannot be considered
routine in ASD.
ASD has been associated with a number of genetic syndromes (Table 8).
Often such syndromes will have been identified prior to the development
and diagnosis of the ASD. For a long time ASD was thought to be relatively
uncommon in children with Down syndrome (trisomy 21). Recent research supports
an incidence of ASD in Down syndrome on the order of magnitude of 10% (26,27).
Sometimes the diagnosis of ASD will lead the clinician to search more
closely for a genetic etiology (Table 9). The most common genetic disorder
associated with autism is fragile X syndrome. In fact it would be more correct to say
that fragile X syndrome is strongly associated with the presence of autistic-like
features and less so with ASD. And more importantly, the primary developmental
association of fragile X syndrome is with mental retardation and not with ASD. A
child who qualifies for a diagnosis of ASD but who is not mentally retarded rarely
needs to be screened for fragile X syndrome. Using a checklist in which each of six
items (mental retardation, family history of mental retardation, ADHD, large ears,
elongated face, autistic-like behaviors) is scored 0 (absent), 1 (borderline), or 2
(present), scores of 5 or more will identify all cases of fragile X syndrome (28,29).
The accumulation of various trace elements and heavy metals in the body
has been claimed to be associated with ASD, and attempts have been made
sometimes to measure their levels in hair, blood, and urine for the purpose of
recommending chelation therapy. With the exception of lead, there is no
scientific support for either the validity of these measures, their association with
ASD, or any responsiveness to the proposed therapy.
Lead poisoning (plumbism) is a disorder most commonly found in children
who engage in pica in settings where interior lead-based paint is flaking from the
walls or ceiling. Children with ASD often engage in pica and are therefore at

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Table 8 Genetic Syndromes Associated with Autism
Angelman
Bardet-Biedl
Coffin-Siris
Cornelia de Lange
Down
Duchenne muscular dystrophy
Fragile X
Gilles de la Tourette
Goldenhar
Hurler
Hypomelanosis of Ito
Joubert
Laurence-Moon-Biedl
Lugan-Fryns (X-linked mental
retardation with marfinoid habitus)
Möbius
Myotonic dystrophy
Neurofibromatosis I
Noonan
Oculocutaneous albinism
Phenylketonuria
Prader-Willi
Rett
Rubella, congenital
Sanfillippo
Smith-Magenis
Tuberous sclerosis*
Velocardiofacial syndrome*
Williams
XYY
These syndromes have all had several case reports of their

occurrence with autism; those with an asterisk (*) have had data
to support more than an incidental association with autism.
Syndromes with a strong association with ASD are detailed in
Table 9. Sites on more than half a dozen genes have been
reported to have some association with autism.
greater risk of developing lead poisoning. Generally the relationship with lead is
considered to be secondary rather than causative, but the possibility remains that
some cases of ASD might be caused or (more likely) exacerbated by toxic levels
of lead (30). Lead screening should be entertained in any medical assessment for
ASD in children with pica and possible exposure to lead-based paint. In addition,
such lead screening may need to be periodically repeated in ASD children with
persistent pica.
Table 9 Genetic Syndromes Strongly Associated with Autism
Cornelia de Lange syndrome: A syndrome of severe mental retardation,

hirsutism, microcephaly, prenatal-onset short stature, micromelia, thin downturning
upper lip, small nose with anteverted nostrils. The hirsutism is especially prominent
in the synophrys (bushy eyebrows that tend to meet in the middle).
Down syndrome (trisomy 21): A chromosomal disorder with mental retardation,
hypotonia, short stature, flat facial profile, microcephaly, epicanthal folds, upslanting
palpebral fissures, small ears, simian creases, and cardiac and duodenal defects.
Duchenne muscular dystrophy: An X-linked muscular disorder that typically presents
with motor loss progressing from around 4 years of age until death by respiratory
compromise.
Fragile X syndrome: A form of X-linked mental retardation caused by an
increased number of trinucleotide repeats at the fragile site on the X chromosome. It
includes mild to profound mental retardation, macrocephaly, large, prominent ears,
prognathism, and (postpubertal) large testes. The typical behavioral pattern comprises
hyperactivity, poor eye contact, and autistic-like features.
Neurofibromatosis I: An autosomal dominant (chromosome 17) neurocutaneous
syndrome with café au lait spots, axillary freckling, neurofibromata (tumors of the skin,
brain, optic and auditory nerves), with mental retardation in only 10% of cases.
Phenylketonuria (PKU): An autosomal recessive inborn error of metabolism resulting
in elevated blood phenylalanine levels. Untreated PKU causes microcephaly, mental
retardation, seizures, and atypical behaviors.
Tuberous sclerosis: A hereditary neurocutaneous syndrome with mental retardation,
a facial rash, and seizures.
Velocardiofacial syndrome: Shprintzen syndrome, or 22q deletion syndrome, is
comprised of cleft palate and structural heart defects, and associated with learning
disabilities, psychiatric disturbances, and mild mental retardation.
A wide variety of immunoglobulin abnormalities have been reported in

ASD. The patterns have been inconsistent and unrelated to any clinical symptoms
of either the ASD or any diagnosable immunological disorder.
There have been inconsistent reports of an increased rate of
gastroenterological symptoms in children with ASD. These symptoms include
diarrhea, constipation, and stomach cramps. While such symptoms should be
inquired after, no routine gastroenterological work-up is indicated. Many
children with ASD are placed on dairy-free or gluten-free diets on the basis of a
supposed association between ASD and some variant of a gastroenterological
disorder such as celiac disease. Recent reports of an association between various

144 Accardo
neurological and neurodevelopmental disorders in children with celiac disease

(31,32) have supported the possibility of an atypical central nervous system
response to gluten. The presence of diarrhea or constipation in a child with ASD
who also has growth parameters (height and weight) below the tenth percentile
for age would represent a reasonable indication to test for celiac disease.
Serological screening should include total IgA, antigliadin IgA, tissue
transglutaminase, and antiendomyseal IgA. In the presence of ASD one’s
index of suspicion for celiac disease should be heightened, and the criteria for
further investigation loosened. A diagnosis of celiac disease and the prolonged
commitment to the use of a gluten-free diet should not, however, be undertaken
without confirmation of the diagnosis by an intestinal biopsy.
Biochemical studies of serum and urine amino acids and organic acids as
well as other metabolic and endocrine tests should be considered in the presence
of relevant family history, atypical growth pattern, specific physical findings,
fluctuating symptoms of lethargy, episodic vomiting, or severe global cognitive
delay. In other words, the indication for such studies is similar to their indication
in the medical assessment of mental retardation (17).
4. There is no definite listing of disciplines that need to be involved in the
diagnostic and evaluation process for a child with suspected autism. A number of
different professionals from a variety of disciplines may be appropriate to help in
assessing the strengths and weaknesses of any given child. Which would be
appropriate for this child may depend on the specific behavioral pattern and
problems presented by the child as well as the expertise and experience of the
various professionals with children with ASD. There should be no routine
assessment process but rather the process should be tailored to the needs of each
individual child and family. Assessments and tests should be performed to
answer specific questions of diagnosis, differential diagnosis, and treatment
planning, and to obtain baselines for follow-up measures used to monitor
progress. Parents should be informed whenever more extended testing is being
administered predominantly to complete research databases.
A medical assessment by a specialist (child neurologist, child psychiatrist,
developmental or behavioral pediatrician) should be performed and can help
decide whether any further medical assessments (such as genetics) are warranted.
A child psychologist with experience with ASD should confirm the diagnosis
with a formal autism rating scale, attempt a measure of general intelligence, and
perhaps review problem behaviors and possible interventions.
Speech language assessments can provide detailed levels for commu-
nicative abilities, verbal, nonverbal, and pragmatic language. These levels of
functioning can be used to plan intervention strategies and to serve as baselines
for measuring treatment progress.
In those children with ASD who also exhibit problems with sensory
processing, an assessment of sensory-integration dysfunction may be indicated.

Feeding selectivity and tactile aversion are specific behaviors for which
desensitization procedures may be helpful.
VII. CASE EXAMPLE
At his 18-month well-child checkup a boy has a vocabulary of six words, is

following one-step commands, and is beginning to point to body parts;
additionally mother has no concerns about the child’s social relatedness. At his
2-year visit mother reports that in the interval he has lost all his vocabulary and
has withdrawn socially so that he is no longer making eye contact or even
seeming to want to communicate. He no longer responds to his name or to
commands and often appears deaf. She also notes, however, that his interest and
skill in solving puzzles have increased significantly. The pediatrician asks about
several other autistic behaviors (including perseverative and reciprocal social
interaction items), strongly suspects autism, and refers the child to a local child
psychiatrist with expertise in ASD and to the state’s early-intervention (EI)
program. Using DSM-IVTR criteria, the child psychiatrist clinically confirms a
diagnosis of autism and refers the child to a geneticist for a medical investigation.
The EI program team assessment includes formal audiological testing (hearing
intact), a speech language assessment (expressive and receptive language delays
and communicative deviance), and psychological testing (Bayley Scales of Infant
Development – II, Childhood Autism Rating Scale, and Vineland Adaptive
Behavior Scales). A diagnosis of mild developmental delay with moderate autism
is confirmed, and the child is placed in an ABA program with the intensity
scheduled to increase over the next year. The geneticist screens the child for
fragile X (negative) but does not consider further biomedical tests warranted. The
EI case manager links the family to a parent support group and maintains close
contact with them through the initial stages of adjustment to the diagnosis and
treatment.
VIII. CONCLUSION
Because of the many uncertainties that cloud the field of autism, there is a
tendency to rush to conclude that the latest research finding, instrument, test,
suspected cause, or even risk factor is the final key to having it all make sense.
The vast amount of clinical data that needs to be restructured by new
interpretations cannot yet be jettisoned by an oversimplification of the complex
phenomena that can present as ASD.
Despite the wide prevalence of out-of-home caregiving settings for infants
and young children (e.g., nursery, day care, preschool), the primary-health-care

146 Accardo
provider remains the mainstay for early diagnosis of ASD. Given the importance
of early diagnosis for early intervention, the primary-care physician should
specifically rule out ASD at the 18– 36-month checkups. Expressive language
screening accompanied by several probes into social reciprocity can effectively
rule out most cases of ASD and alternately identify those children who need to be
referred for more in-depth assessment. It would also be appropriate for the
primary care physician to raise the possibility of autism with those patients
otherwise identified with various communication disorders or other patterns of
nonspecific developmental delay since it is not unusual for children with ASD to
be identified with neurodevelopmental problems but incorrectly categorized.
Although ASD is a serious neurodevelopmental disorder, the only formal
assessment that is routinely indicated in every case is a careful and
comprehensive audiological assessment. Every other possible medical test and
procedure needs some other specific indication. ASD by itself is not sufficient to
justify an expensive battery of biomedical and behavioral tests. When
accompanied by significant global developmental delay (mental retardation),
ASD becomes open to a much larger range of biomedical considerations.
Measured clinical judgment needs to collaborate with informed parents to select
the best approach to a comprehensive diagnosis.
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pediatrician’s role in the diagnosis and management of autistic spectrum disorder in
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Johnson CP, Kallen RJ, Levy SE, Minshew NJ, Prizant BM, Rapin I, Rogers SJ,
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autistic spectrum disorders. J Autism Dev Disord 1999; 29:437 – 482.
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parameter: screening and diagnosis of autism: report of the Quality Standards
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4. Volkmar F, Cook EH Jr, Pomeroy J, Realmunto G, Tanguay P. Practice parameters
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(DSM-PC), Child and Adolescent Version. Elk Grove, IL: American Academy of
Pediatrics, 1996.
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autism be diagnosed accurately in children under 3 years? J Child Psychol Psychiatry
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Rogers BT, Capute AJ, eds. Disorders of Language Development. Baltimore: York
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International Universities Press, 1957.
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Developmental Medicine Number 126. London: MacKeith Press, 1992.
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25. Filipek PA. Neuroimaging in the developmental disorders: the state of the art. J Child
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item checklist for screening for fragile X syndrome in the pediatric population.
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ataxia, even in childhood. Dev Med Child Neurol 2000; 42:283– 286.

7
Informing, Educating,
and Supporting the Family
Alfred L. Scherzer
Joan and Sanford I. Weill Medical College, Cornell University, New York,
New York, U.S.A.
I. THE FAMILY AS THE FOCUS OF TREATMENT
While the family plays an important role in the subsequent development of all
children with developmental disabilities, it has a unique and multifaceted
position when the child has autism. The interactive relationship involving
communication and behavior between the family and child is fundamental and
unique in the autistic spectrum disorders (ASD). It serves both as a basis for
alerting the family that something is awry, and an opportunity for involvement in
treatment and management. That a special kind of relationship exists between the
family and the child with ASD is apparent in the literature. Comparison with
family references to other major developmental disabilities from the National
Library of Medicine (PubMed) indicates that only mental retardation approaches
the frequency of ASD entries (Table 1).
The special relationship between a child with ASD and his or her family
has led to the widespread practice of direct parental involvement in the treatment
and management of ASD. The family is specifically an integral part of all the
currently described model treatment programs for children with autistic spectrum
disorder (1,2).
The unique interactive parent involvement in the subsequent development of
the child with ASD can greatly influence outcome. For example, there is a relation
between the development of communication skills of the child and parents’ ability
to synchronize interaction with the child’s attention and activity (3). At the same
time, the greater severity of the child with autism may have considerable impact on

150 Scherzer
Table 1 References to Family and Disability in PubMed
Developmental disability Frequency of citations

Autism 6928
Mental retardation 5270
Learning disabilities 1186
Down syndrome 1185
ADHD 1174
Cerebral palsy 515
Spina bifida 443
parental stress (4). In turn, this can be related to less social responsiveness as the
child develops. On the other hand, more mutual play and positive feedback by the
parent is seen with more highly communicative children who have ASD (5).
The parents, therefore, are in a pivotal position with respect to the child with
autism. They are involved early because of the fundamental deviations in
behavior and communication, and have a role in identification by bringing their
concerns to the primary care provider. They have a major team role in the very
nature of the therapy and treatment processes that have evolved. At the same time,
it is clear that their interaction with the child in itself may significantly influence
the treatment process and ultimate development. Finally, parental coping ability,
stress, and mental health are all intimately intertwined in the process.
II. COMMUNICATING THE DIAGNOSIS
Regardless of whether a family has preexisting concerns about their child’s

development, how they are told about the diagnosis will have profound effects on
their emotional adjustment, interaction with the child, and subsequent relation-
ships with professionals (6). Estimates of satisfaction with the informing process
by parents of children with developmental disabilities vary greatly (7– 10). Many
factors have been identified that influence its effectiveness, including: medical
versus educational setting (11); availability of both parents or caregivers (12);
giving appropriate attention to cultural considerations (13); language and
technical terms used and amount of information given (9); provision of a written
report for later reference (14,15); as well as the tone and empathy of the physician
(16,17).
Communicating the diagnosis is an active, highly charged process (18).
Either through direct discussion or more subtle body language, there is often a
seesaw effect in discussions. Professionals generally use labels rather than
emphasizing function, whereas the parent wants to know how the child will be

Informing, Educating, Supporting the Family 151
able to perform now and in the future. The process can be a kind of unstated
active negotiation about pessimism versus optimism, on either side, out of which
evolves a jointly constructed diagnosis. Though the physician or other pro-
fessional controls the interaction, there is great need to allow parents to freely
express feelings, doubts, and concerns during this informing process and at any
subsequent meetings (16). Parental dissatisfaction with how the diagnosis is dis-
closed is not inevitable (19 –21). Success requires appropriate understanding,
sensitivity, and technical skill on the part of the physician (9).
Training in “breaking the news” needs to be given much more emphasis in
the medical curriculum, and is increasingly essential in continuing medical
education programs (CME) (7,8). Targeted communication training programs
can be effective in changing physician attitudes (22,23).
In general, the broad steps to guide planning for a successful informing
experience include the following:
1. Planning the setting
2. Assessing the family’s background knowledge and experience
3. Individualizing the strategy of informing
4. Evaluating the family’s understanding
From a consensus of several studies, Table 2 summarizes specific guide-
lines to follow in developing optimum conditions to achieve an effective parent/
professional communication process for discussing the child’s diagnosis.
Table 2 Guidelines for Communicating the Diagnosis
1. Arrange for a private setting to ensure confidentiality and

reduce distraction;
2. Include both parents or caregivers together;
3. Have a colleague present if possible;
4. Individualize the information given, specifically related to the
particular child;
5. Use simple, direct language;
6. Be open and sympathetic;
7. Avoid medical jargon;
8. Be sensitive to cross-cultural, and language considerations;
9. Discuss both strengths and weaknesses of the child;
10. Provide professional empathy and support;
11. Share one’s own anxiety in the situation;
12. Allow time for questions;
13. Provide a written report for later parental reference;
14. Arrange for follow-up sessions for ongoing parental questions
or concerns.

152 Scherzer
Of course, these guidelines should also provide the basis for all subsequent
communication with parents, and can help to develop the kind of rapport
necessary for long-term care. Remember that initial disclosure represents but the
first of many opportunities for communicating with parents. Subsequent contacts
will need to keep in mind the strategies outlined above, particularly when further
clinical contacts with the child may result in revisions in prognosis concerning
degree of involvement, functional capability, the presence of comorbidity, or
even the diagnosis itself.
III. FAMILY STRESS AND COPING
Once the diagnosis of autism is confirmed, irrespective of the effectiveness of

initial communication, there is bound to be initial stress in the family, and some
degree of mourning for the loss of a normal child that was anticipated (24). Guilt
and blame are common feelings, especially in the mother (25), and often a source
of later poor adaptation (26). Other factors that may affect initial stress include
race and ethnicity, as well as lower socio-economic status (27).
Family stress can be expected to continue in every subsequent stage of the
child’s development. Data suggest that stress is significantly greater in families of
children with any type of developmental disability compared to normal (26,28),
but is more frequent in autism than in mental retardation (29), Down syndrome
(30,31), or cystic fibrosis (32).
Factors influencing ongoing family stress include severity, especially of
communication problems, and changes or limitations that become apparent as the
child ages (33). However, the availability of resources and support in managing
the child, and positive personality beliefs of the parent, seem to be more pre-
dictive of positive adaptation than severity alone (34,35).
Greater stress is found in mothers than fathers (36), and is related to more
responsibilities in management, and perceived position of dependency (37).
Moreover, preexisting psychopathology is seen more frequently in the mother
and may be an important factor in adjustment (38).
Siblings may be equally affected. More stress is suggested in the ASD
group compared to children with mental retardation or the nondisabled. Siblings
with autism were seen as a burden; there were more peer problems, concerns
about the future, and feelings of loneliness (39). However, sibling adjustment
appears to be strongly influenced by degree of understanding of the disorder (40).
It should also be noted that preexisting stress and psychopathology might
be seen in some parents of children with ASD. However, it is essential to
emphasize that there is no evidence to indicate that parental mental health is
causally related to autism, or that the parent is responsible for the autistic
condition of the child. (For discussion see Section IV, “Mental Health Issues.”)

The wide range of strategies used by parents for coping with the child and
dealing with stress includes: authoritarian versus permissive discipline (31),
variable sharing of responsibility with spouse and siblings (41), partnering with
the professional team (42), and even becoming a community advocate (43).
Heightened anxiety relating to unanticipated or delayed changes as the child
develops can also greatly affect both parents and professionals as the child develops
(6). Open exchange on each side is needed when this occurs. The clinician must be
sensitive to the tensions that appear and encourage expression of concerns by
the parent, yet be able to share his own feelings of uncertainty and anxiety. Where
there is need for emotional assistance or treatment of existing psychopathology,
counseling or psychiatric intervention should be strongly recommended.
Periodic respite care also provides an important alternative to ease the
constant demands of daily management, and can greatly relieve the stress to
which many families are often subjected (44).
IV. MENTAL HEALTH ISSUES
To begin with, the stress of adjusting to life with a child who has autism, and
coping with long-term care and management, may be associated with significant
psychopathology in some families (38). Compared to normal populations and those
with Down syndrome, mothers of children with autism show depression (36%),
anxiety (46%), or both (9%) (25). Established maternal coping styles, attitudes, and
philosophy are found to be important determinants in later adjustment (26).
On the other hand, fathers are said to show relatively good adaptation,
comparable to those raising children with Down syndrome, but are frequently
under significant stress as well (45). Both parents of children with autism are
reported to experience significantly lower marital intimacy, associated with greater
stress and depression, than those with Down syndrome, or normal children (46).
Siblings, likewise, are at greater risk for emotional and behavioral problems
(47). In addition, preexisting personality abnormality and even psychopathology
is reported in some parents and families of children with autism (48 –50). Parents
have been noted to be more aloof, untactful, and less responsive than those with
children who have Down syndrome (51). Fathers are considered to have more
schizoid and intellectual traits (52,53). Compared to a normal population,
mothers of children with autism showed a greater degree of family problems
during the pregnancy (54). Lifetime prevalence rates for anxiety disorder and
major depressive disorder were likewise found to be greater in the group whose
children have autism (55).
These findings are reported in an effort to alert and sensitize professionals
to potential family mental health issues, rather than in any way to suggest an
etiological relation to autism. In fact, it is concluded in studies reported that there

154 Scherzer
is no evidence of an association between preexisting family mental health and

autism (49). Indeed, parents must be constantly reassured that neither their own
prior or current mental health is the cause for the condition of their child. This
must be emphasized wherever professionals come into contact with the family.
With these mental health concerns in mind, it is essential that the pro-
fessional be sensitive to and identify early any emotional problems and psychiatric
disorders in parents and siblings of children with autism, and help provide the
necessary timely intervention. Management of the child with autism requires
addressing the needs of the family as a whole, and not simply targeting the
affected child.
Emotional needs should be brought to the attention of the family at any
point in the course of professional contact. In early-intervention programs for
children up to age 3, for example, the staff can help the family build an awareness
of the need for emotional support in the course of developing the individual
family service plan (IFSP). At whatever point providers identify emotional issues,
the family should be informed tactfully so that parents do not feel responsible for
the condition of their child, and are enabled to recognize the need for assistance.
All professionals who deal with children who have autism should be involved
with the entire family. If they suspect significant stress, adjustment and coping
problems, or overt psychopathology, they must take the responsibility for timely
referral of the family for counseling, networking, support groups, or direct
psychiatric care. Follow-up is equally essential to determine ongoing needs and
assure adequate provision of appropriate services.
V. PARENTAL EDUCATION AND TRAINING
Children with ASD have fundamental needs in the areas of communication,

socialization, and behavior that set them apart from those with other deve-
lopmental disabilities. The home is obviously the primary setting in which
development and change in these areas is routinely influenced on a daily basis by
parents, siblings, and other caregivers. In addition, the home environment is
essential for follow-through and transfer of the communication skills training,
social maturation activities, and behavior change treatment programs in which
the child is participating. Recognition of the important place of the home and the
parental role led to a strong partnering relationship with professionals in the early
design of treatment programs (56). Today, all of the existing and most frequently
used educational and behavioral treatment programs offer training to parents
either in direct involvement or in follow-up at home, including a major role in
management (57). Available information concerning training methods of parents
showed that skills were obtained equally through the use of professionals or peers
(58). Studies involving training of parents to participate in treatment programs for

their children indicate a favorable attitude to involvement, but many expressed

difficulty with the responsibilities required (59).
Data have generally confirmed positive effects of parent involvement in
school/education programs conducted outside the home (60 – 64). Participation
of parents in the treatment process itself has also shown reduction in stress (63),
and more positive parent-child interaction (65).
Specific benefits from a totally home-based program provided by parents
with outside professional assistance appear to be mixed. On the one hand, higher
posttreatment IQ scores are reported using ABA methodology at home compared
to those receiving conventional school-based interventions (66). In contrast, the
results obtained when families used methods from various consultants were not
comparable to professionally directed programs (67). Significant gaps exist in the
available data, with the need for better documentation of family interaction, use
of training materials, change in attitudes and practice, and research design using
control groups (68). Effectiveness of primary parent leadership in a home-based
program clearly needs further and more uniform evaluation (69).
VI. INFLUENCE OF THE MEDIA
The universal availability of information (and misinformation) has powerful

effects on conceptualization of the entire field of autism, its etiology,
pathogenesis, management, and treatment (70). Much of the information can
be completely accurate and helpful. However, a barrage of stories and theories
often surround both the lay public and professionals with quasi-scientific
breakthroughs that may confuse, misinform, and misdirect. The print media
frequently give daily access to sensationalist articles and case histories without
objective review. The Internet places at the fingertips a vast amount of
information that is but a click away (71). This swirling amount of data and ideas
has a profound effect on how families deal with professionals, and with
interrelationships among professionals themselves. Add to this the impact of
“secondhand” information, advice, and recommendations gleaned from the
media by relatives and friends, which is imparted to families with the best of
intentions.
The public information that is constantly being accessed may have an
adverse effect on families that can influence acceptance of the diagnosis, increase
stress, reduce coping ability, and possibly heighten the presence of anxiety and
depression. Witness the media flurry concerning secretin as a treatment
alternative (72), or the continuing controversy about immunizations (73 –75).
Conflicting views expressed with scientific certainty and conveyed by
articles in the press on these topics, for example, present continuous challenges to
the clinician both to keep up with relevant scientific data and to maintain

156 Scherzer
sensitivity to the background of information to which parents are exposed.

At every level of professional contact, it is essential to enquire directly about
parental information and attitudes in an open and candid manner. This approach
can set the stage for a mutual interchange of ideas and help separate out the
factual from the hearsay. It is this kind of interaction that is especially relevant in
the field of autism, where etiology, pathogenesis, and treatment are in an active
evolving stage, and where there is no cure for this lifelong chronic condition.
Without such an approach, the rapidly increasing flight to poorly established, or
even harmful, alternative medical protocols will continue (76).
A special case exists with the media influence on coprofessionals. There is
a wide and varying range of understanding and acceptance among physicians,
educators, and therapists concerning the field of developmental disabilities in
general, and autism in particular. Many pediatricians, for example, have limited
interest or background and may respond subjectively to media prejudice or
misinformation. How they deal with parents who turn to them for guidance
about what they have been told by specialists in the field may greatly affect all
of the issues of accepting the diagnosis, family stress, coping ability, and mental
health. The clinician in this field needs to reach out to coprofessionals at
all levels of contact to engage in dialogue about information in the media, to
answer concerns on the basis of current knowledge, and to allay prejudicial
ideas that may not have a basis in established fact. It is an important educational
task that falls to those of us dealing with this condition in its present state of
rapid change.
VII. THE ATTRACTION OF ALTERNATIVE TREATMENTS
Discussion elsewhere (see Chapter 12) reviews the major issue of complementary/
alternative medicine (CAM). The use of CAM has been increasing in the United
States over the past 50 years, and today is said to involve more than one-third of
the population (77). A burgeoning number of websites now provide extensive
information on CAM, and are easily accessible (78). The use of CAM is common
and significant among pediatric patients with acute illness seen in primary care
practices, and includes herbs/homeopathic medicines, prayer healing, high-dose
vitamin therapy, nutritional supplements, folk/home remedies, massage therapy,
chiropractic care, biofeedback, self-help groups, relaxation, hypnosis, and
acupuncture or acupressure (79–81). It is estimated that up to 50% of families of
children with autism are using CAM (82). Among the family factors identified in
this practice is maternal age over 31, foreign-born caretakers, religious affiliation,
and the use of CAM by parents (79). And more than 50% of pediatricians in
practice also reported using CAM (83). The extent to which caretakers inform
physicians about their use of CAM is estimated variously (80,84).

While there are many theories concerning the widespread use of CAM in
autism, the clinical basis of the (sometimes changing) diagnosis, massive
amounts and diverse quality of available information, and influence of well-
meaning person-to-person and family contacts are all factors in play. Perhaps
most important is inadequate or failed communication between physician and
family. In one respect it goes back to the initial diagnostic interview when trust,
sharing, and mutual acceptance form the basis for an ongoing relationship. If
successful it will help to shield the family effectively from turning to alter-
natives that either may be of little value or are possibly expensive and even
harmful.
Particularly with the child who has autism, there needs to be a medical
home setting that provides compassionate, family-centered care. An atmosphere
of mutual participation is essential between clinician and family, in which the
range of options for care is mutually explored, and a collaborative decision about
management is based on informed consent (84). This has been termed “shared
decision making and relationship-centered care” (85).
One principle to keep in mind is that the family has the right to choose
CAM, yet it is the physician’s obligation to be aware of any untoward effects and
to communicate them effectively (86). There may not be complete agreement, but
such discussions and how they are handled provide opportunities for developing
positive relationships (87).
Another principle is that coincidental use of both traditional medicine and
CAM may be acceptable provided the risks and benefits are well understood. The
bottom line is not whether one or the other is used exclusively, but rather finding a
solution acceptable to the family that is best for the child. The process of arriving
at such a plan is the essence of truly good medicine (85).
VIII. THE PARENT AS ADVOCATE
Assuming a major parental role as advocate at many levels flows naturally from
the unique involvement and relationship of the family with a child who has
autism. This often initially begins with the discussions and negotiations
concerning services for the infant under age 2, when the IFSP is formulated
(88,89). At that point the parent has the opportunity to express concerns regarding
available treatment and support services, and to press for additional or more
targeted programs. The process continues into the preschool level with the
parent-professional team preparation of the individual education plan (IEP).
Opportunities for parental involvement in influencing awareness of the unique
needs of their child, and the provision of relevant services, continues throughout
the entire subsequent school experience during periodic updating of the IEP.
In the course of participating in the school setting, many parents become

158 Scherzer
knowledgeable about their legal rights and are better able to initiate requests for
special services or a Section 504 Plan that will better meet their child’s needs.
Parents may also become involved when there are concerns about
availability and adequacy of medical, social, and mental health services. Either
individually or through the efforts of support groups, parents may bring their
concerns to government at various levels, help in fund raising, and work
toward changing or adopting needed legislation. This can result in stimulating the
community to influence legislation, organizing advocacy groups to educate the
public, and heighten awareness of the medical profession to the needs of children
with autism (90,91).
One area of special concern is the transition from school to employment,
and eventual integration into the adult world. For those children who will remain
totally dependent, parents will be stimulated to work for residential and day-care
services in a group setting where dignified and compassionate management is
available at a community level. The more challenging advocacy issue relates to
integration into the workplace, changing attitudes of employers, and ensuring fair
and equitable employment practices. Mobilization of parents to achieve these
goals will take on more immediacy as children with autism increasingly age into
the workforce.
The extent to which parents become personally involved in advocacy issues
will depend on many variables: education, socioeconomic status, gender, religion,
perceived local needs, and mental health status. Fostering a partnership with
professionals as a team member in caring for the child with autism will greatly
assist in developing a more realistic and productive advocacy role. Much-needed
research is essential to better understand parental involvement in advocacy, and
Table 3 Potential Opportunities for Parental Advocacy
1. During the initial disclosure diagnostic interview;

2. At subsequent contacts with clinicians and other professionals;
3. At early-intervention individual family service plan (IFSP) conferences;
4. As a team member at the annual (or more frequent) school individual
education plan (IEP) review;
5. Organizing and participating in parent support groups, local, state, and
national voluntary organizations;
6. Developing and participating in speakers’ bureaus for education of the lay
public and as a means of informing professionals;
7. Partnering with local business groups, industry, chambers of commerce for
employment opportunities for adults with autism;
8. Helping raise funds for services and research;
9. Campaigning for legislation to improve services and facilities;
10. Working in the political process on behalf of candidates for elective office.

how best to channel and educate to achieve maximum effectiveness. Table 3

summarizes some potential opportunities for parental involvement in advocacy.
IX. SUMMARY
Children with autism differ from those with other developmental disabilities in
that they have aberrations in the basic, fundamental areas of communication,
behavior, and social interaction that affect their function. These are the areas
normally nurtured within the family context from the earliest age, and when
they have gone awry place both burdens and opportunities on the family for
resolution. For this reason it was early recognized that the family should have
a pivotal place in treatment programs and strategies as they evolved. No
wonder, then, that the family of the child with autism is perhaps more at the
center of early diagnosis and management than all the other major childhood
disabilities.
At the same time, there is likely to be a unique sensibility of the family
when their child is diagnosed with autism. Disclosure can greatly influence their
subsequent relationship with the child, other family members, and siblings, as
well as caregivers. The procedure for communicating the diagnosis, therefore,
requires careful planning and a sensitive, caring process.
Since the disabilities in autism are so basic to development, it is not sur-
prising that the family is likely to experience significant stress when the diag-
nosis is confirmed, and subsequently as daily care and treatment progress. In
addition, data currently available indicate that in some cases parents of children
with autism have preexisting personality abnormalities and emotional disorders.
Sensitive professional caregivers must assure families that their emotional or
psychiatric status is not a cause of the child’s condition, and help to provide
necessary mental health services where indicated. Management of the child with
autism must focus on family needs as a whole, and not simply target the affected
child.
The vast amount of information on autism through news media and the
Internet to which families are exposed can greatly affect their involvement
with the child, participation in treatment programs, as well as their use of
complementary/alternative therapies. This places great responsibility on pro-
fessionals to maintain close communication with families to help interpret
information and develop a partnership relationship in which there is shared
decision making in care of the child.
Finally, families that initially work to improve facilities and services for
their own affected child may go on to assist other parents through discussion
groups, attempt to educate professionals, work toward improving employment
opportunities for adults with autism, campaign for needed funds and legislation,

160 Scherzer
or even become involved in the political process itself. The opportunities are
extensive; the challenges are great, for there is much more yet to be learned about
this family-centered condition.
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8
Behavioral and Educational
Interventions for Young Children
with Autism
John M. Suozzi
I. INTRODUCTION
Behavioral and educational interventions are the mainstay of management of

individuals with autism (1 – 7). A wide array of such “treatments” is available for
young children with autism. While there is empirical evidence for the efficacy
and effectiveness of some of these interventions, many have gained support in the
absence of empirical data to verify their effectiveness and utility. Behavioral and
educational interventions, both proven and unproven, are discussed here, because
the absence of a research-based demonstration of efficacy does not mean that a
treatment is ineffective, only that its efficacy has not been demonstrated through
objective means (8).
II. BEHAVIORAL INTERVENTIONS

A. Applied Behavior Analysis and Discrete
Trial Training
Broadly defined, the body of knowledge known as applied behavior analysis
(ABA) focuses on what people say and do (behavior), and utilizes experimental
analyses of environmental influences on behavior to derive techniques for

166 Suozzi
behavior change. The origin of the experimental analysis of behavior is credited

to B.F. Skinner (9). Based on his extensive data from observation, manipulation,
and analysis of animal and human behavior, Skinner hypothesized that behavior
is a function of its consequences. He believed that there are rules or laws that
govern all behavior, and he developed procedures from these laws that were used
to produce significant changes in a number of different types of behavior. Many
years of experimental research by a number of prominent psychologists of a
behavioral orientation have given credence and support to Skinner’s original
theories.
Although skeptics feel that it is too simplistic to posit that behavior is solely
a function of its consequences, and that human behavior can be controlled or
changed in much the same way as animal behavior, there are enough research and
clinical data to support the use of the principles and practices of applied behavior
analysis in the treatment of individuals with autism. ABA techniques advise the
simultaneous strengthening of adaptive behaviors and the reduction of
challenging behaviors. The characteristics of individuals with autism, such as
idiosyncratic behavior patterns, lack of responsiveness to social reinforcers,
difficulty anticipating and/or delaying reinforcement, poor communication
skills, and the presence of competing behaviors, necessitate the use of structure,
repetition, and dense reinforcement schedules (all of which are advised by ABA).
Moreover, ABA relies on the collection of copious data about the impact of
various environmental manipulations on behavior, and provides a record of
therapeutic progress to guide future treatment. Finally, ongoing inquiry and
research into the factors that influence rate of behavior and the effectiveness of
reinforcers (such as establishing operations, motivation, and response effort)
ensure that the most effective strategies are being employed. (See Table 1.)
In ABA, the focus is on observable behavior, that is, on what the individual
says and does. ABA helps us to understand how people access reinforcement for
different behaviors and effectively “learn” the behaviors that provide reinforcers.
Children with autism often obtain reinforcement through the display of
inappropriate behavior (for a variety of reasons). To teach newer, more adaptive
behaviors, reinforcement principles are utilized in a manner that increases the
value of performing the newer more adaptive behaviors relative to the value of
performing inappropriate behavior. To increase the value of newer, more
adaptive behaviors, reinforcement must be contacted quickly, easily (i.e., with
little effort), and, at first, frequently.
The first to “package” ABA principles as a treatment for individuals with
autism was O. Ivar Lovaas. His “UCLA Young Autism Project” (10) is perhaps
the most widely cited treatment study of individuals with autism. Lovaas reported
that a percentage of his subjects achieved “normal” intellectual and educational
functioning. This was popularly interpreted as a “cure” for autism. The more
realistic interpretation of Lovaas’ findings is that he has formulated an

Behavioral and Educational Interventions 167
Table 1 Basic Applied Behavior Principles
Reinforcement: The procedure used to increase the likelihood that a behavior will occur
or to increase the rate of a behavior.
Reinforcer: The event that follows the occurrence of a behavior and increases the
probability or rate of that behavior. Generally, a reinforcer is most effective if delivered
immediately after the behavior occurs (immediacy) or if access to that reinforcer has
been limited or denied for some time (deprivation).
Schedules of reinforcement:
Continuous reinforcement: A behavior is reinforced every time it occurs.
Ratio schedule: A behavior is reinforced after the occurrence of a number of fixed
or variable responses.
Interval schedule: A reinforcer is administered after a fixed or variable period of time
and after the occurrence of a response. Variable ratio schedule builds behavior most
resistant to extinction.
Punishment: A procedure used to decrease the likelihood that a behavior will occur again
in the future (or to decrease the rate of the behavior).
Punisher: The event that follows the occurrence of a behavior and decreases the
probability or rate of that behavior. There are fixed and variable ratio and interval
schedules of punishment. Forms of punishment include contingent punishment,
extinction, time out, and overcorrection. Overapplication of punishments can create
conditions of aversion for the learner.
Establishing operation (EO): Refers to a condition that establishes the power of a
reinforcer and that evokes particular behavior(s). The effect of an EO is to change the
reinforcing effectiveness of some stimulus and to change the frequency of all behavior
that has been reinforced by that stimulus.
Motivation: A state of willingness to perform an action or a set of actions.
Response effort: The amount of effort that must be spent to perform a task. Familiar
tasks with fewer steps require less response effort than novel tasks with several steps.
Generalization: The occurrence of a behavior in the presence of a novel stimulus. A
behavior should be reinforced in different stimulus situations, such as across instructors
and settings until it generalizes to other related stimuli.
Shaping: A method of teaching successive approximations of behavior by reinforcing a
portion of a desired response or a behavior that approximates a desired response.
Chaining: The process of creating a sequence of two or more behaviors in which each
behavior produces a result that acts as a stimulus for the next behavior to occur and in
which the last behavior is reinforced.
Prompting: A process of providing an added stimulus to increase the likelihood of a
correct response.
Fading: Withdrawing a prompt quickly to avoid creating a condition under which
behavior occurs only when prompted. Prompts must be faded quickly from most to least
restrictive in order to build behavior that occurs when environmental conditions call for
its use.
Discriminative stimulus (or SD): A stimulus associated with reinforcement of a
particular behavior. Refers to the conditions under which a behavior is taught and/or is
expected to occur.

168 Suozzi
intervention that is highly effective in some and less so in other cases of autism.
Importantly, Lovaas’ specific results have not been replicated universally. While
the method of intensive one-to-one instruction that Lovaas described is the
mainstay of several highly effective programs, some aspects of his instruction,
such as the use of prompts and punishments, remain unclear. Moreover,
methodological weaknesses in the design of Lovaas’ study have been identified,
such as nonrandom assignment of subjects to treatment groups and no indication
of whether children in the treatment group received other kinds of treatment
simultaneously (11).
Lovaas’ method of intensive one-to-one instruction is known as discrete
trial training. A discrete trial follows the basic format of presentation of an
instruction or request (called a “discriminative stimulus”), an expected response
from the learner, and a consequence delivered by the instructor. If required, a
prompt (an additional stimulus that helps the learner to make the correct response)
may be administered as well. This general format allows for several interpre-
tations of how antecedents, learner responses, and consequents are to be rendered.
Proper training and education of individuals who provide ABA is essential
because a few inappropriate and unproven applications of the format, such as the
use of the “no-no” prompt, have found their way into widespread popular
application. The “no-no” prompt consists of the instructor providing the verbal
consequent “no” contingent on the learner giving an incorrect response, and then
informing the learner that “no” reinforcement will be provided. While there are
no data that support the use of the “no-no” prompt (12), research does support the
use of errorless learning approaches (13) for response acquisition. In the errorless
approach, the learner is prompted to make swift and correct responses that always
end with delivery of a reinforcer, as opposed to the “traditional” discrete trials in
which the learner obtains reinforcement only when a correct and independent
response is made. A clear distinction must be made between “behavioral” and
“educational” techniques that involve some element of reinforcement and those
that are truly grounded in ABA. There are several effective techniques that fall
under the latter category, such as discrete trial training, functional behavior
assessment (FBA), functional communication training (FCT), applied verbal
behavior (AVB), the picture exchange communication system (PECS), and
pivotal response training (PRT). Other behavioral interventions that have shown
promise include social stories and programs devoted to social skills training
(including modeling strategies).
B. Applied Verbal Behavior

Skinner (14) broke down communication into seven functionally independent
categories. A word and its meaning are categorized according to the conditions
under which a person was taught to use them: a single word could be categorized

Table 2 Applied Verbal Behavior Communication Categories
Tact A label, or the name of an object, an

action, or an event
Mand A request for something
Echo Repeating what is heard
Receptive language Following instructions
Receptive by feature, function, and class Being able to respond to items when given
some information about them
Intraverbal Answer to “wh” question
Text Symbolic representation of a word
(e.g., written or signed)
as tact, mand, echo, receptive, intraverbal, receptive by feature, function, and

class, or text. (See Table 2.)
For truly functional communication to develop, the meaning of a word
needs to be taught across all categories of verbal behavior.
Verbal behavior is thus not limited to speech. It consists of vocalizations,
signs, gestures, and even the use of augmentative systems for communication.
Analyses of the verbal behavior of children with autism suggest that they often
possess large receptive repertoires and many labels, but very few spontaneous
requests and almost no conversational speech (15). Assessment of the verbal
behavior of individuals with autism is typically accomplished via tools such as
the Assessment of Basic Learning and Language Skills (ABLLS) (16). Although
verbal behaviorists provide direct instruction to individuals with autism in
accordance with the core principles of ABA—appropriate use of prompting
procedures, fading, shaping, and the use of errorless learning techniques, verbal
behaviorists are careful to distinguish the appearance and results of their mode of
instruction from the appearance and results of “traditional discrete trial training.”
From the verbal behavior perspective, all of these distinctions from discrete trials
are central to effective instruction of individuals with autism.
Traditional discrete trials may achieve little in the way of functional skills,
because the emphasis is largely on imitation and labeling. A verbal behavior
approach usually begins by pairing the instructor with reinforcement so that the
child comes to see the instructor as a very powerful source of reinforcers. This is
done in the absence of demands or contingencies for expected behavior. Once the
child consistently approaches the instructor to obtain reinforcers, he is then taught
to request reinforcing items directly. Demands for learning new tasks are
increased slowly by number and by amount of effort required to complete them.
Again, there is clear intent to teach across categories of verbal behavior. While
instruction through traditional discrete trials appears structured because it begins

170 Suozzi
by setting up response requirements to obtain reinforcement, instruction based on

verbal behavior has a “natural” look to it, because careful attention is paid to
build foundational skills that help the child with autism to become an effective
learner. In a verbal behavior approach, the instructor is also responsible for
maintaining a high rate of response from the learner, by being mindful of the rate
at which the learner obtains reinforcement, the number of demands placed on the
learner, and the amount of effort required of the learner to complete demands.
Empirical research supports teaching verbal behavior to individuals with autism
using these principles of functional and applied behavior analysis (17).
C. Functional Behavior Assessment

FBA provides a framework for investigating functional relationships between
aberrant behavior and specific environmental events (18). As typically applied to
developmentally disabled populations, the method promotes careful experimen-
tal manipulation of environmental events (i.e., sources of reinforcement) that
apparently maintain the challenging behavior. FBA is generally directed toward
determining an appropriate intervention for specific behavioral issues, rather than
toward skill building. The goal is to identify antecedent conditions and the
sources of reinforcement that produce and maintain behavior problems. This can
be accomplished by anecdotal reports, checklists, and most effectively, analog
procedure (19). In the analog procedure, first hypotheses are made about the
source(s) of reinforcement that may maintain aberrant behavior (such as escape,
attention, or automatic reinforcement), and real-life conditions are set up to test
these hypotheses. For example, if aggressive behavior displayed by an individual
is thought to be maintained by attention, then an analog condition to test that
hypothesis would consist of attention being delivered after each instance of
aggressive behavior. Data about the frequency of aggression would be collected
during that condition. Next, data from the “attention” condition could be
compared to data from a condition in which there is no consequence for
aggression, and to data from a condition in which escape is permitted contingent
on the display of aggression. In this way, possible conclusions can be reached
about the factor that maintains aggression, and a treatment can be developed that
addresses that specific factor.
D. Functional Communication Training

FCT involves teaching adaptive (“functionally equivalent”) responses that serve
the same purpose as the problem behavior (20). In other words, communicative
responses are taught so that the individual can request and obtain the specific
reinforcers that serve to maintain aberrant behavior instead of acting out. There is
some evidence for the effectiveness of this technique in reducing problem

behaviors such as aggression, self-injury, disruptive behavior, stereotypy, and

communication problems. For example, if FBA determines that a child exhibits
aggressive behavior when presented with a task because it results in the removal
of demands (“escape”), an intervention advised by FCT would be to teach a
communicative response that would also result in removal of demands. An FCT
intervention would teach the child to request a “break,” by a sign, vocalization, or
other augmentative strategy that would achieve the same end as the aggressive
behavior, that is, the removal of demands. The greatest advantage of FCT is that it
results in a relatively rapid reduction of the problem behavior owing to the
specificity of the intervention. A thorough FBA to determine the purpose of the
problem behavior is a prerequisite for FCT.
A criticism of FCT is that it teaches additional behaviors that achieve the
same end as the challenging behavior. To use the example above, the learner now
has another behavior in his repertoire that can be used to remove demands.
However, in the case of aggressive behavior (especially if the aggression is
directed toward other people), it is critical to achieve a rapid reduction so that
other more functional skills can be taught.
E. Picture Exchange Communication System

PECS was intended to provide nonverbal individuals with a mode of expressive
communication (21). Specifically, line drawings are used to represent everyday
objects, foods, and activities, and the PECS protocol begins with building simple
requests. The learner delivers the picture representation of the object, food, or
activity to the instructor and then receives what is represented in the picture.
As the learner becomes more proficient in requesting preferred items, carrier
phrases are added, such as “I want ———.” Teaching the child to make a request
reduces the demands associated with receptive tasks. This practice is consistent
with what is observed in typical development, in which the skill of requesting is
the first expressive skill to emerge. Later, more advanced skills are taught through
PECS, such as calling attention to what one observes (e.g., “I see”) and what one
possesses (e.g., “I have”). PECS requires the child to approach a listener and
initiate interaction before “communicating.” The PECS system is grounded in
basic behavioral principles such as shaping, differential reinforcement, and
transfer of stimulus control.
Charlop-Christy et al. (22) were the first to present an empirical assessment
of the efficacy of PECS in a multiple baseline design involving three children.
Vocal communication and social-communicative behaviors emerged in all the
three and a reduction in problem behavior was observed after they mastered the
use of PECS. Some limitations of picture systems relate to problems with
portability of the system, problems displaying complex words in symbol form,

172 Suozzi
the lack of a natural community that uses pictures, and difficulty in emitting the
appropriate communicative response exactly when it is needed (23).
F. Pivotal Response Training

PRT was developed by Robert L. Koegel and Laura Schreibman (24,25). This
technique is related to incidental teaching and includes didactic instruction,
modeling, role playing, and feedback. The instructor capitalizes on the learner’s
interests, motivation, and needs, using naturally occurring opportunities as the
basis for instruction. PRT is less contrived than discrete trials, which emphasize
the use of instructor-controlled reinforcers, a very highly structured environment,
and repetition. It uses both naturally occurring and formally structured
opportunities to teach new behaviors. The core considerations in PRT are
motivation and the ability to respond to multiple cues, both of which are
considered “pivotal” behaviors. Motivation is a pivotal behavior because it leads
to concomitant changes in other related behaviors (24). Reinforcement is direct,
and is specifically related to the behavior being taught. The behaviors most likely
to change through this technique are speech and language, social behavior, and
disruptive responses (25). As a more natural (or social-pragmatic) form of
intervention, PRT may be more appealing to parents and educators because it
does not involve the withholding of reinforcers and the structure or repetition of
structured interventions that characterize discrete trials.
G. Social Stories
Social stories (26) are intended to provide individuals with autism with
information about what can be expected in various social situations. Social stories
can provide information about what the physical setting may look like, what other
people in that setting might say and do, and offers suggestions about the
behavior(s) that may be expected in that setting. Stories normally consist of
words and pictures, and are rendered in a simple fashion without extraneous
detail. Social stories can be written to address virtually any social situation that
may arise, based on a basic “formula” that is offered. Social stories are used
prophylactically or preventively; that is, they are reviewed prior to entering social
situations in which the individual with autism encounters some difficulty, in an
attempt to prevent the difficulty. The use of social stories is supplemented with
modeling and role playing of appropriate behavior as well as corrective feedback.
Through the use of social stories, individuals with autism have the opportunity to
experience elements of a number of different problem settings, from a “safe”
environment in which they can practice responses to social situations without
negative consequences. However, social stories may not be able to capture the
nuances of all social situations and environmental settings.

H. Social Skills Training

Because socialization is a core area of deficit in autism, training in social skills is
of great importance in the treatment of autism. Social skills training usually
entails modeling, feedback, and direct reinforcement for appropriate behavior.
Very recently, a good deal of attention has been paid to the effects of video
modeling on the acquisition of play and social skills. Research has revealed that
children with autism are capable of acquiring complex sets of play and social
skills, including verbal language, from watching videos of other individuals
performing various acts (27). Video modeling has some excellent advantages,
such as not requiring the learner to interact with another person during
instruction, and presenting the behavior to be learned the same way each time it
is viewed.
III. EDUCATIONAL INTERVENTIONS
Most educational programs for children with autism are based to varying degrees
on the principles of ABA (28,29). Few educational programs have empirical
support for their efficacy based on properly controlled studies. Methodological
flaws in outcome studies of educational programs for children with autism often
make it impossible to determine with certainty if the intervention (or some
component of the intervention) truly contributed to the putative outcome.
Therefore, the interventions below can strictly be considered as “unproven” (30).
A. Rutgers Autism Program

“Based upon a broad spectrum of methods derived from the principles of applied
behavior analysis,” the Rutgers Autism Program is geared toward helping
families to develop home-based programs (31). Parents are considered an integral
part of the team and have to be committed to an intensive and “pure” behavior
analysis intervention. Additionally, the Rutgers Autism Program consults with
schools to develop educational and behavioral programs for children with autism,
and provides intensive and ongoing staff training. The primary method of
instruction is through discrete trial training. Children receive 30 –40 h/week of
one-to-one, individualized ABA instruction.
B. UCLA Young Autism Project

This program is “based on research by Ivar Lovaas and colleagues, as well as
studies from other ABA treatment programs worldwide” (32). Instruction is
through discrete trials. Although Lovaas (10) claimed to normalize about 40% of

174 Suozzi
his subjects, the study has been criticized for the punishment procedures.
Currently more positive approaches are emphasized.
C. Children’s Unit for Treatment and Evaluation

(SUNY Binghamton)
This program individually selects goals for each participant, based on an
individualized goal selection curriculum (IGS), and provides instruction
primarily through discrete trials (33). Curriculum items are chosen from
approximately 2000 individual tasks in 18 “areas” of development. The program
provides a “comprehensive, integrated, and state-of-the-art behavioral model of
service delivery” for children from 10 months to 11 years of age (34). Although
the proponents claim that their “philosophy is derived from empirical research
rather than a philosophy in search of research support,” program outcomes have
been reported only in non-peer-reviewed publications (35,36).
D. Denver Model
This program is based on a developmental model of autism first described by
Rogers and Pennington (37). Since autism is a social disorder, building social
relationships should be the core of treatment. This is done by providing
opportunities for social interaction and play at home, in an integrated preschool,
and during one-to-one teaching. The program is geared toward children from
ages 2 to 5 years. More than 20 h/week of systematic instruction is provided with
preplanned objectives and ongoing data collection. Instructional approach in this
program is interdisciplinary and eclectic, including relationship-based, develop-
mental, sensory, and discrete trials-based approaches. Curriculum emphasizes
building communication, play, sensory, and motor skills, and promotes personal
independence and participation in social routines. The Denver Model is a
comprehensive “best practices” model without a narrow theoretical
underpinning.
E. Alpine Learning Group, Paramus, NJ

This program is rooted in the teachings of ABA, and instruction is mostly given
through discrete trials, although incidental teaching is also mentioned as an
instructional strategy. Individualized programs are created for each student, with
clearly defined and measurable objectives for learning. The initial focus of
instruction is on teaching attending, imitation, receptive language, expressive
language, and play skills, with additional emphasis placed on reducing
challenging behavior through the use of differential reinforcement. With a very
small class size (i.e., two to four children), the environment is highly structured
and there is ample opportunity for individual instruction (38). Moreover, the

Alpine Learning Group utilizes visual supports in the form of daily activity
schedules, a strategy made popular within Treatment and Education of Autistic
and Related Communication Handicapped Children (TEACCH). Initially the
program is strictly 1:1, but after mastering some prerequisite skills, the child is
allowed to participate in regular education programs with typically developing
peers through a supported inclusion program.
F. The Walden Early Childhood Programs

The Walden Early Childhood Programs provides “a continuum of early
instruction,” through a comprehensive incidental teaching approach (39).
Incidental strategies derived from ABA are the only mode of instruction.
Programming consists of at least 30 h/week of planned instruction to provide an
inclusive experience for the young learner to develop his/her language and social
skills. For the youngest learners, the initial focus is on improving social
responsiveness, and overall engagement with classroom materials and activities.
Development of verbal language through incidental strategies is considered a
priority. The Walden Program professes that high levels of social engagement
represent the surest means of avoiding challenging behaviors. Family programs
and overall family involvement are considered critical to maximizing a child’s
potential.
G. Princeton Child Development Institute

The Princeton Child Development Institute offers a broad range of services,
including early intervention for children younger than age 3, a preschool and a
primary school program, family services, group homes, and career services. All
services are provided through individualized programming based on applied
behavior analysis (40). Teaching new learners to follow simple directions is often
the starting point for instruction, because this foundational skill is a prerequisite
for building other skills. Picture schedules are utilized to promote independence
in navigating the events of the day, as well as to generalize skills from preschool
and home to community settings. Children with autism are integrated with
typically developing peers, and foundational skills that are prerequisites for
integration, such as the ability to follow instructions, sustain interest and
engagement with leisure materials, and generalization of skills to new settings,
are developed.
H. Treatment and Education of Autistic and Related

Communication Handicapped Children (TEACCH)
The basis for education at TEACCH is structured teaching, which combines
cognitive and behavioral strategies to minimize problem behaviors associated

176 Suozzi
with autism (41). The emphasis is on reinforcement-based procedures for

behavior change, and to address skill deficits that underlie challenging behavior.
Developed in the early 1970s by Eric Schopler at the University of North
Carolina at Chapel Hill, TEACCH emphasizes the culture of autism, the concept
that children with autism have learning and social interaction characteristics that
are different from, but not necessarily inferior to, those of typically developing
children. Understanding those differences allows the construction of programs
and teaching tasks to optimize learning potential. Thus learning environments are
structured in such a way as to capitalize on the visual-perceptual strengths of
individuals with autism. The program attempts to build on the child’s strengths
and interests rather than drilling deficit areas. TEACCH may be categorized as an
eclectic program because of its both developmental and behavioral under-
pinnings (42). It is one of the most frequently replicated models for autism
intervention and is especially popular among public school special education
programs.
I. Douglass Developmental Disabilities

Center Programs
The center-based Douglass School and outreach home-based preschool programs
rely on the principles of ABA such as discrete trials, functional assessments,
functional communication training, and incidental teaching strategies. The
curriculum addresses domains of attention, speech and language, cognition,
fine and gross motor skills, socialization, self-help, and appropriate behavior.
The Douglass Center Programs believe that intensive individual work is needed
before large-group integration with typically developing peers is possible.
Parents are an integral part of the team and are involved in the creation of routines
and strategies for use in the home setting (43).
J. Developmental, Individual Differences,

Relationship (DIR) Model
This model was pioneered at the George Washington University School of
Medicine. Relationship-based, the “Greenspan” approach emphasizes affect and
relationships, developmental levels, and individual differences in motoric,
sensory, affective, cognitive, and language functioning by targeting six
developmental skills through intensive floor-time work, which is also known
as “DIR” (44). These six skills include shared attention and regulation,
engagement, affective reciprocity and gestural communication, social communi-
cation and problem solving, symbolic use of ideas, and logical and abstract use of
ideas. There is an extensive home-based component in this program in which
parents are taught to follow the lead of the child in play and other interactions for

3 –5 h/day. In the data supporting DIR (45), the composition of the “comparison
group” raised the possibility of a significant placebo effect. The DIR approach
might better be considered more a theoretical framework for intervention rather
than a specific intervention: this framework incorporates a variety of approaches,
each adjusted to the individual child’s specific needs rather than to theoretical
needs. To varying degrees the application of DIR to a specific child might
therefore overlap with any number of other intervention approaches.
K. LEAP Preschool at the University of Colorado

School of Education
The Learning Experiences and Alternatives for Preschoolers and Their Parents
(LEAP) preschool was one of the first programs in the United States to include
children with autism with typical children. It provides a preschool program for
children from ages three to five, with typically developing and children with
autism in a ratio of 2:1. The program also provides behavioral skill training for
the parents. The curriculum at LEAP is best known for its peer-mediated social
skill interventions. The individualized curriculum also targets goals in domains
of social, emotional, language, adaptive behavior, cognitive, and physical skill
development. LEAP blends a behavioral approach with developmentally
appropriate practices (46). The model has now been replicated at several other
sites but there are no efficacy studies.
L. Pivotal Response Model at the University

of California at Santa Barbara
The aim of pivotal response training is to effect change in “pivotal” areas such as
responsivity to multiple cues, motivation, self-management, and self-initiation.
These domains are considered central or pivotal because improvements in these
areas often bring about positive changes in other areas of adaptive behavior. The
program provides individuals with autism with the social and educational skills
necessary to participate in inclusive settings. Curriculum goals are targeted in
domains of communication, self-help, academics, and social and recreational
skills (47). In the beginning phase of the program, children are taught through
discrete trials, and as proficiency is gained, there is a shift toward more
naturalistic behavioral interventions. Also critical is a parent education
component. Currently, the intervention consists of in-clinic and one-on-one
home teaching. Children enrolled in the program also participate concurrently in
special education services in the schools.

178 Suozzi
Table 3 Parent Questions for Treatment Programs
1. What kinds of services do you provide?

2. What is your philosophy or approach to working with children with autism?
3. How many hours of service per week are included in the program?
4. How many of those hours are one-on-one?
5. Can you describe a typical day?
6. What are the teachers’/therapists’ qualifications/experience?
7. What is the parent role in this therapeutic program?
8. How do you manage difficult behaviors?
9. What communication system/approach do you use?
10. Is there an integration/inclusion component with typically developing children?
11. How do you measure progress?
12. Are there arrangements for transitioning to the next school/educational level?
Source: Modified from Ref. 55.
M. Higashi School (Boston, MA)

Five principles are espoused by daily life therapy at the Higashi School: group-
oriented instruction, highly structured routine activities, learning through
imitation, rigorous physical exercise, and a curriculum that is based on
movement, music, and art (48). To date, there are no outcome studies to examine
the effectiveness of this program.
IV. CONCLUSION
On the one hand, there appear to be a wide variety of intervention approaches and
programs for children with autism. On the other hand, the presence of more than a
few (if any) options within a given community is rare. Theoretically, many of
these approaches differ significantly from one another. Practically, many
programs tend to be more eclectic and diverse in content. The components
common to effective programs could be derived from the above review of
available approaches. Research supports the early (prior to age 5 years)
application of a program with a significant component of applied behavioral
analysis (49 – 53). A recent study found that the specific nature of the intervention
is more important than merely the intensity (54). Table 3 presents a number of
questions that parents might use to assess specific programs.
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(Age 0 – 3 Years). Albany: New York State Department of Health Early Intervention
Program, 1999:IV – 12.

9
Communication Disorders
in Children with Autism:
Characteristics, Assessment,
Treatment
Elaine Dolgin Schneider

Pediatric Neurological Associates, White Plains, New York, U.S.A.
I. ROLE OF THE SPEECH PATHOLOGIST

IN TREATING CHILDREN WITH ASD
The field of speech language pathology encompasses the diagnosis and treatment
of communication disorders in a population ranging from infancy to geriatrics.
A pediatric speech pathologist has extensive training in the evaluation of speech
production and language development. Speech production is characterized as the
way one forms the sounds of one’s language (articulation), the rhythm and
inflection (prosody), the fluency of the production, and the vocal quality. These
qualities have a significant impact on a child’s ability to communicate effectively
and intelligibly.
Language is the meaningful use of words that are symbols that enable us to
convey our ideas and express our needs and wants. Language development
includes receptive and expressive language. Receptive language is the ability to
understand the meaning of verbal language. Expressive language is the ability to
use verbal behaviors.
Pragmatic language is the ability to use language in a social setting. This
skill develops in infancy as children use eye gaze to interact with their caregivers.

184 Schneider
Children instinctively use nonverbal and verbal language to regulate the behavior
of others through protesting (No, don’t touch) and requesting objects (i.e., I want
cookie) and actions (i.e., Tie my shoe). Young children may socially interact by
greeting, showing off (i.e., Did you see that red fire truck?), requesting assistance
(i.e., Help me), answering questions, and posing questions to seek information.
Finally, children establish joint attention, which is defined as the ability to share
attention. Deficits in joint attention are considered by many researchers to be an
early predictor of childhood autism (1) and are considered to be pivotal to deficits
in language, play, and social development in the autism spectrum disorder (ASD)
population.
A. Speech Characteristics of Children with ASD

Delay and abnormality in development of speech are very common in children
with ASD. The difficulties vary and can range from the absence of speech, to
repetitive use of language, to the emergence of novel and creative speech with
mistakes in grammar and word meaning. Children with Asperger’s syndrome
(AS) may develop normal speech without any differences in grammar and
vocabulary. However, closer analysis reveals subtle and, often, less than subtle
differences in the use of language. These children may speak very little, speak at
length about a particular subject, or use language that is repetitive, rather than
conversational. They have difficulty transitioning from one event to another and
have weakness in social judgment. The inability to use language to share social
interaction is among the core characteristics of individuals with ASD.
Children with autism have impaired social interactions, repetitive
behavior and restricted play, and differences in communication. The speech
pathologist working with children with autism must be sensitive to the
communication disorders associated with this disorder. These characteristics
occur in children with language delays exclusive of autism; however, the severity
of disorder in autism is far greater than observed in the nonautistic population.
II. MUTISM
It is reported that up to 40% of children with ASD are nonverbal, that is, make
few sounds or words. Nonverbal children with ASD do not spontaneously
develop gestural or other nonverbal means of conveying complex messages as
nonverbal children with hearing impairment do. A nonverbal child who acquires
language prior to 5 years of age has a better prognosis.
Some nonverbal children with ASD cannot communicate due to verbal
apraxia. Children with verbal apraxia have difficulty coordinating and/or
initiating the sequential movements for speech in the absence of weakness or

Communication Disorders in Autism 185
paralysis of the speech musculature. Verbal dyspraxia is different from oral motor
apraxia in which the coordination of the movement of the articulators is
compromised for nonspeech (i.e., tongue movements) and feeding (i.e., chewing)
skills. Children with verbal apraxia, without ASD, possess intact comprehension
and acquire linguistic concepts consistent with their chronological age. Children
with verbal apraxia tend to be quiet as babies, with limited vocal play or babbling.
Depending on the severity of the apraxia, a child’s imitation skills are impaired.
Despite a model, children with severe verbal apraxia may not be able to imitate
oral movements, vowels, consonants, or consonant-vowel combinations. If the
child does possess speech, the most salient characteristic of apraxia is
the inconsistent production from one attempt to another. The prosody of speech,
including inflection, stress, and pitch, is often affected, particularly as the child’s
language skills increase. Children with ASD may have speech apraxia in addition
to the pragmatic language deficits, which will hamper speech development (2).
III. ECHOLALIA
Children normally acquire language through single words. By 19 –21 months of

age, children will progress from single words to two-word utterances. By 24 – 30
months, three-word combinations are noted and grammatical morphemes
(smallest units of language: i.e., plural /s/, present progressive verb ending:
walking) emerge. Language is productive, creative, and increases in complexity.
Along with this “analytical mode” of language development, in the early
stages of development (through 18 –24 months), children learn language through
imitation. The children will repeat a parent’s verbalizations in chunks that are
specific to the situation. This is the “gestalt” mode of learning. For example, the
children may generalize the phrase “go out,” previously learned from the parent
to now mean “Let’s go outside” or “Let’s go to visit Grandma.” For children who
develop language normally, analytical and gestalt modes may co-occur in very
early stages with rapid movements to a primarily analytical mode.
Children with ASD become masters at echoing the content of what others
say, without the vocal inflection and rhythm (prosody). Children with ASD may
rely on or be limited to a gestalt mode for extended periods of time (3). Children
with ASD who are echoic have not progressed in their language development.
Their language acquisition reflects their “gestalt” thinking process (4).
Prizant (3) described two types of echolalia. Immediate echolalia is defined
as “the repetition of a word or phrase just spoken by another person.” Immediate
echolalia can serve a communicative purpose to initiate or maintain an
interaction. When asked if the child wants a cookie, the child may request the
cookie by repeating the last word produced, i.e., “cookie.” Immediate echolalia

186 Schneider
may also be noninteractive and serve as an aid to process the information to

facilitate understanding or to help the children move through an activity.
Delayed echolalia is defined as “echoing of a phrase after some delay or
lapse of time.” People who use delayed echolalia have been observed to repeat
scripts from television shows, movies, or videos, or even parental reprimands
(i.e., “Don’t do that.”). Prizant identified 14 possible functions of delayed
echolalia (3). As noted in immediate echolalia, delayed echolalia can be
purposeful or noninteractive. The key to understanding the purpose of delayed
echolalia lies in the listener’s familiarity with the child’s idiosyncratic use of
verbalizations and past experience with the child’s language patterns.
IV. LANGUAGE DISTURBANCES
As children with ASD acquire novel language, their comprehension remains

concrete and their expressive language may be limited to single words.
Regulation of behavior is often achieved by naming or labeling objects as a form
of request. If a child wants milk, then a child with emergent language may
communicate through a single utterance: “milk.” The listener has the burden of
interpreting the child’s intent. The young child may advance to spontaneous
sentences, with frequent mistakes in grammar and vocabulary.
Children with ASD often confuse pronouns. They generally substitute
“You” for “I.” An individual with ASD may say, “You want train,” instead
of “I want the toy train.” Pronoun reversal is one of the most difficult errors to
correct. Children with ASD may avoid using pronouns altogether and refer to
themselves by their proper name.
Semantic weakness is evident. Children communicating at the single-word
level may confuse words (i.e., brush/comb), while children who are at a higher
language level have difficulty understanding and using words with multiple
meanings (i.e., There is a fork in the road). Pivot words (i.e., the, in, on, before,
because) do not have meaning for these children and they may leave them
out altogether, resulting in messages that sound telegraphic (i.e., Matthew go
store).
Children with semantic and grammatical weakness often process
information partially. They have a tendency to reply to one or two words in
the question or direction and ignore the rest of the statement. When asked, “Bring
mom the book on the chair in the kitchen,” a child with processing deficits may
bring a chair rather than the book.
A major characteristic of children with ASD is their literal interpretation of
language. These children may respond seriously to teasing as they have little to
no understanding of jokes or sarcasm. Verbal children with autism may be
excessively verbose, posing the same question over and over again. They have a

preoccupation with the verbal exchange rather than the content of the
conversation and insensitivity to the nonverbal cues of boredom displayed by
the listener. They lack role taking and have poor perception of the listener and the
listener’s needs.
V. NONVERBAL COMMUNICATION
Children who are acquiring language normally understand gestures, facial

expressions, and bodily movements that accompany the speech of those with
whom they interact. Children who immigrate to a new country will rely on
nonverbal cues rather than the content of the unfamiliar language to make sense
of the communicative intent. Even children with a language disorder will be able
to recognize the emotions expressed by a person or understand the intent of a
finger pointing into the distance.
Children with high-functioning autism or AS do not readily acknowledge
or understand the nonverbal clues. Children with AS have difficulty recognizing
emotions and may not be able to interpret the meaning and clues that come from
facial expressions or natural gestures.
Expressively, individuals with ASD may use unconventional forms of
nonverbal communication. They may grab, pull, or reach to gain desired objects.
Their ability to point to a desired object is delayed, if present at all. Simple
gestures that are noted in children under the age of 18 months, including nodding
and shaking the head, may or may not develop in children with autism.
VI. DISORDERED PROSODY
Many children with ASD have odd intonation, characterized by monotonous or

inappropriate inflection. Monotone speech is described as an utterance consisting
of successive words, without change in pitch or key. It has been reported that
infants who are later diagnosed with ASD often babble without inflection. Speech
differences also include atypical use of loudness. While many children tend to
speak too loud, there are others who communicate in barely audible speech. Their
voices sound mechanical and have a robot-like quality. In addition, they may
self-stimulate through vocalizations (high-frequency sounds, glottal Fry, buccal
sounds).
Shriberg et al. studied children with high-functioning autism and AS. From
their findings they concluded that children with ASD displayed differences
in articulation and inappropriate prosody in the areas of phrasing, stress, and
resonance (5).

188 Schneider
VII. FEEDING DISORDERS
Parents of children with ASD often complain that their children are very picky
eaters. These children are overly selective in their choice of foods and will not
taste foods shared by other members of the family. Idiosyncratic differences in
processing of tactile, auditory, olfactory, proprioceptive, and visual information
are common in children with ASD and may be the basis of food selectivity.
Children who are hypersensitive to touch may react negatively and emotionally
when offered food. They may be unable to tolerate the food inside their mouth,
where touch may trigger a tonic bite reflex or a hypersensitive gag response.
These children may develop feeding aversions as a way of protecting themselves
from the negative feelings. Aversions include negative responses to specific
textures, tastes, smells, and temperatures of foods, and the children may avoid
eating. Ahearn et al. evaluated 30 individuals with ASD or PDD-NOS who had a
history of aberrant feeding patterns (6). More than half of the participants
exhibited low overall levels of food acceptance, while several individuals refused
all food presented.
VIII. ASSESSMENT
The Quality Standards Subcommittee of the American Academy of Neurology

and the Child Neurology Society issued a report outlining the parameters for both
the screening and diagnosis of ASD (7). While it is recommended that every child
have a comprehensive hearing evaluation, a speech and language evaluation is
recommended if babbling and gesturing have not emerged by 12 months, if there
is a loss of language or social skills, if true words do not emerge by 15 months,
and if two-word combinations are not observed by 24 months. The American
Academy of Pediatrics (AAP) issued a technical report on the pediatrician’s role
in the diagnosis and management of ASD children (8). Their recommendations
included the need to monitor developmental milestones, especially in the areas of
speech, language, and social skills, and to elicit parental concerns.
Once the early signs of ASD have been recognized, the speech pathologist
should be asked to evaluate the core deficits associated with ASD—social
interaction, communication and play, and behaviors—in detail. In addition to a
hearing evaluation, an oral motor speech assessment, feeding evaluation, and
speech/phonological assessment should be included in the battery of tests. Rating
scales and checklists such as Autism Diagnostic Interview –revised (ADI-R)
(9) and the Communication and Symbolic Behavior Scales (CSBS) (10) can
be incorporated into a comprehensive assessment. The former is for use in both
children and adults, while the latter was specifically designed to meet the

assessment needs of children with ASD. Each of these tools requires considerable
training to ensure reliability.
Direct observation of social behavior, communication, and play in children
suspected of having autism may be made using standardized tools such as the
Autism Diagnostic Observation Schedule (ADOS) (11), the Pre-Linguistic
Autism Diagnostic Observation Schedule (PL-ADOS) (12), and the ADOS-G
(13). ADOS and ADOS-G are observational scales used for children and adults,
while the PL-ADOS (12) serves as a downward extension of the ADOS to
evaluate nonverbal young children. The ADOS-G is a semistructured assessment
of social interaction, communication, play, and imaginative use of materials to
evaluate individuals with ASD across their life span.
The CSBS model (10) evaluates children in seven areas of pragmatic
function. It looks at a child’s ability to respond with emotion and establish eye
contact during interactions. It examines a child’s ability to use language to
regulate the behavior of others, to interact socially, and to establish joint
attention. Use of natural gestures, sounds, words, and objects is evaluated, along
with a child’s understanding of words.
A. Background Information
Prior to an assessment, it is necessary to obtain as much background information
as possible. Parents serve as the primary source of information about a child’s
communication, play, and behavior in the first 2 years of life. Parent recollections
can be enhanced with a review of videotapes taken over the course of the 2 years.
Information pertaining to use of natural gestures, social eye gaze, understanding
of the spoken word, and vocalizations may be analyzed prior to an assessment.
B. Social Communication
Evaluation of a child’s social use of language is central to an assessment of
communication in ASD. Informal and formal tools are available to evaluate a
child’s conversational skills, ability to share information, and ability to
understand contextual cues.
The Test of Pragmatic Language (TOPL) is the only evaluation devoted
specifically to the assessment of language pragmatics. It is used for children 5 – 13
years of age (14).
The Prutting Pragmatic Protocol is a descriptive taxonomy of 30 pragmatic
parameters (i.e., variety of speech acts, topic selection, topic introduction, topic
maintenance) rated according to whether they are used “appropriately” or
“inappropriately” or “not observed” (15).
The Checklist of Communicative Function and Means is an evaluation of a
child’s intent gained through a natural play setting (16). Wetherby and Prizant

190 Schneider
identified communicative functions that a child uses to interact, especially when

language is limited (17). A child’s earliest use of language is to regulate the behavior
of others. Conventional means of protest would include shaking the head “no” or
stating “no.” A child may gesture his intention by pushing an object away or averting
eye gaze. Nonconventional means include loud vocalizations, having tantrums, and
aggressive behaviors. Social interaction is a higher communicative behavior. A child
will use social interactions to call attention by stating “look.” The child may seek
information by asking “what’s that,” interact through greeting, request permission by
stating “please,” and show off. The most defining area of social communication is
the establishment of joint attention. Children use joint attention to comment, request
information, and provide information about past events.
C. Receptive and Expressive Language Testing

A number of published measures are available to evaluate the children’s
understanding and use of language. These evaluate either receptive and/or
expressive language development, but do not rule in or rule out a diagnosis of
autistic spectrum disorder. The results will give specific information as to the
level of language comprehension and use that the child possesses.
Language skills are measured by tasks of increasing complexity within the
receptive and expressive domains. These tests assess specific aspects of a child’s
understanding and use of vocabulary, grammar, and syntax. These published
assessments are merely a sampling of testing available.
The Infant/Toddler Checklist for Communication and Language
Development is a checklist designed to identify different aspects of development
in children and in toddlers (15). This checklist was designed for a caregiver to
complete for children between the ages of 6 and 24 months to determine whether
or not a referral for a comprehensive assessment is needed.
The Infant Toddler Language Scale is a criterion-referenced evaluation
designed to assess receptive and expressive language development, play, natural
gestures, and pragmatics of children from birth through 36 months (18).
The Reynell Developmental Language Scale (RDLS) is a measure of a
child’s development in receptive and expressive language areas. The scale
evaluates children from 1 to 7 years of age. It provides qualitative and quantitative
information into expressive language and verbal comprehension. This test was
developed to evaluate children suspected of having a language delay (19).
The Preschool Language Scale– Fourth Edition (PLS-4) (English and
Spanish) evaluates children from birth to 6 years, 11 months of age. The PLS-4 is
comprised of two subscales assessing receptive and expressive language. The
assessment includes the precursors to language development, comprehension,
and use of vocabulary and grammar. It assesses the child’s ability to process
complex sentences and communicate over successive statements (20).

The Oral and Written Language Scales is a standardized tool designed to

evaluate children ranging from 3.0 to 21.11 years of age. This assessment,
accompanied by visual cues, was designed to evaluate an individual’s under-
standing and use of spoken language (21).
The Expressive One-Word Picture Vocabulary Test is a picture-naming test
that evaluates a children’s vocabulary on the single-word level. This evaluation was
developed to assess the word retrieval skills of children aged 2.0–18.11 years (22).
D. Play
A child’s cognitive, nonlinguistic abilities are often evaluated through play. The
goal of the play assessment is to determine whether the child is able to use objects
for truly imaginative play or is just preoccupied by unusual aspects of objects.
Is the play repetitive and stereotyped?
Westby described 10 stages in the development of symbolic play abilities.
The Symbolic Play Scale evolved from a Piagetian model (23).
Between the ages of 9 and 12 months (Stage I), the child is developing
object permanence and will find a toy if it is hidden under a scarf.
Between 13 and 17 months (Stage II), the child explores a toy, operates it
by pulling levers and strings, and will attempt to act upon it by pushing,
pulling, turning, and pounding. The child will hand a toy to an adult if
unable to operate independently.
Between 17 and 19 months (Stage III), Westby identified the emergence of
pretend skills. The child may pretend to go to sleep, drink from a cup, or
eat from a spoon. At this age level, true language is emerging and a
marked growth occurs in the number of words that a child uses.
By 19 –22 months (Stage IV), the child extends the symbolism beyond him
or herself to include the caregiver or a doll. The child may feed the doll,
brush the doll’s hair, or put the doll in the bed.
By 24 months (Stage V), the child will represent his daily experiences
through play. The child plays house and takes on roles. A true sequence
of events has not emerged.
By 21⁄2 years (Stage VI), the child begins to represent events less frequently
experienced. The child may pretend to be the doctor and take care of a
sick child. The child continues to play alongside his peers; however,
associative play appears.
By the age of 3 (Stage VII), the child’s actions have a sequence (i.e., the doctor
checks the patient, calls the ambulance, takes the patient to the hospital).
By 31⁄2 years (Stage VIII), the child is less dependent on realistic toys such
as a dollhouse, farm, parking garage. He is more interested in using
blocks for building and will use one object to represent another.

192 Schneider
At approximately 4 years of age (Stage IX), the child is able to hypothesize

about future events and problem-solve events he has not experienced.
Dolls and puppet play becomes more elaborate and is used to resolve
issues regarding “what would happen if.”
By the final stage of play at age 5 (Stage X) reflects the child’s ability to
plan out pretend situations in advance. The child gives roles to himself
and to the other children and full cooperative play emerges.
E. Articulation and Oral-Motor Skills

Difficulties with articulation or specific oral-motor difficulties should be assessed
when appropriate. An oral-motor-sensory feeding assessment ought to be completed
if the child is nonverbal or if the child’s speech production is highly unintelligible.
This evaluation ought to determine whether or not the speech difficulties are
associated with a verbal dyspraxia, a motor planning speech disorder often noted in
children with ASD. A number of published evaluations are available to evaluate
a child’s speech production on the single-word and sentence levels based on a
phonological, articulation, or motor planning approaches to assessment.
IX. INTERVENTION
A. Play
Play is a free-choice activity that is self-motivated, enjoyable, process-oriented,
and not literal. The materials, time, and roles of the “players” are made up by the
children. Children play because they like it. They do not play for praise, food,
money, or rewards.
Motor play helps the brain to develop gross and fine muscles, nerves, and
brain functions.
Social play encourages learning to give and take, cooperation, and sharing.
The children use play to learn to use moral reasoning and values.
Constructive play encourages children to manipulate their environment.
Building cities with blocks and making castles in the sand are forms of
constructive play.
Fantasy play helps the children to try out new roles, rehearse a variety of
possible situations, and experience language and emotions.
Teaching a child to play games with rules is helpful in addressing turn
taking, social interaction, and learning to play by the rules imposed by
another. Games with rules teach children a very important concept—we
all must follow rules.

B. Social Language
Children with ASD benefit from intervention that teaches specific social goals.
The role of the speech pathologist is to identify the complex social behavior (i.e.,
conversation) and analyze the prerequisite behaviors and rules that can be
memorized and practiced in a variety of settings. Several models and inter-
ventions have proven to be quite effective in addressing the social communi-
cation and language needs of young and older children with ASD.
1. SCERTS Model
The social communication, emotional regulation, and transactional support
(SCERTS) model was developed by Wetherby and Prizant as a tool to enhance
the communication and social emotional development in young children on the
autistic spectrum (24). This model addresses the challenges and issues at each
level of language development—including prelinguistic, emergent language, early
language, and the more advanced language stage—through an individualized and
developmental approach.
2. Social Stories
Social stories, developed by Gray and Garand, is a technique used to teach a
critical component of social interactions (25). Its development was based on the
understanding that children and adults with ASD are impaired in their ability to
consider the perspective of others. The intention of the social stories is to help the
person with ASD to learn strategies to interact in a variety of social situations.
These stories can be tailored to meet the individual needs of the person for whom
the story is written. The stories can be used to teach children social routines (i.e.,
greeting a new person), how to ask for help, and how to respond to their feelings.
Social stories are considered an effective tool to teach children social skills and
how to make sense of social situations.
3. Teach Me Language
Teach Me Language, by Freeman and Dake, identifies and helps to teach speech
and language concepts to children on the autistic spectrum, including AS (26).
This book was designed to meet the specific needs of children with ASD with
ABA teaching techniques. It is most effective for children who perceive visually
presented information better than orally presented information. The children
must be able to communicate in some way, either verbally or through total
communication.

194 Schneider
C. Speech Production
Therapy to address speech production is dependent on the diagnosis of the speech
disorder, whether the problem is due to an apraxia (motor planning disorder) or a
dysarthria (speech disorder), or even a phonological disorder (linguistic basis).
Many children with ASD experience motor planning speech disorders.
Traditional articulation therapy is useful for teaching a child to produce one
sound at a time in isolation until he or she can master this sound. Once the child
masters the sound, the therapist will increase the complexity of the word until the
child can produce this sound on the sentence and conversational levels. However,
this approach does not address the significant obstacles presented by a child with
a motor planning disorder/apraxia or muscular weakness/dysarthria.
The preferred approach for treating children with verbal apraxia is to focus
on the motor movements in sequence for the production of a meaningful word.
The therapy will start with sounds already in the child’s phonemic repertoire and
use these sounds to increase the consistency of sound production in a variety of
syllables and words. For example, a child with apraxia may have learned to
produce the “o” sound; however, the child will state “apa” instead of “open.” The
goal of the therapy is to patiently repeat the sound in varying words and word
combinations and provide the child the opportunity to practice and repractice
until the new sounds are integrated.
Tactile cueing is an essential technique in working with children with
motor planning disorders. PROMPT (prompts for restructuring oral muscular
phonetic targets) is a cueing technique developed by Hayden (27). Using
tactile-kinesthetic-proprioceptive cues, a speech pathologist using the PROMPT
method would restructure the speech production output of children and adults
with speech disorders. The input presented to the individual helps the individual
achieve voluntary control of the motor speech system as he or she begins
to integrate the motor, cognitive-linguistic, and social-emotional aspects of
communication. The cues, which are applied externally to the muscles of the
face and the mylohyoid muscle under the chin, nose, and jaw, help to reshape
sounds on the individual (i.e., “a”), syllable (i.e., “ma”), word (i.e., mom,
mommy), phrase (i.e., my mommy), and sentence levels. As the length of the
word increases, the child who has an emergent speech system benefits from the
hands-on cues to stimulate the articulatory movements. As the child integrates
the correct sequence of movements to achieve speech sound production, the hand
cues are faded.
Speech disorders due to muscular involvement are best addressed through
an oral motor program. The children with a dysarthria will demonstrate weakness
through the jaw, tongue, lips, cheeks, and soft palate. This weakness will affect
all motor speech processes, including breathing, sound production, articulation,
resonance, and the prosody (melody) of speech.

D. Feeding Issues
Feeding issues tend to have both a motor and sensory basis. As noted, children
with feeding issues often have hypersensitivities and specific food preferences.
A team approach is recommended, comprised of the parent, teacher, occupational
therapist, and speech pathologist. A physical therapist may be part of the team
in the case of children with a neuromuscular disorder.
Interventions utilize techniques to normalize sensory defensiveness and
aversive responses to tactile, auditory, and olfactory stimulation. Calming music,
oral stimulation of the tongue, lips, and facial region, an explanation of
expectations, and graded modifications in texture and temperature can be pre-
sented as techniques to help reduce oral hypersensitivity.
E. Total Communication
A total communication approach with children with ASD would provide a range
of effective and accessible means available to communicate including alternative
and augmentative systems. Speech, when available, provides an effective and
accessible means for children to communicate, but augmentative systems may be
necessary for children who are preverbal and are experiencing difficulty in
acquiring speech. These systems encourage the children to communicate without
precluding the acquisition of verbalizations. Research suggests that the use of
alternative communication systems actually promotes the development of more
complex skills (28).
Augmentative and alternative communication (AAC) and assistive tech-
nology (AT) are used to provide new communication possibilities for the children
who are nonverbal and when speech is not an effective means of communication.
A wide variety of products are available, ranging from a device that has a few
words to more sophisticated devices that are programmable to include an
individualized vocabulary of pictures and/or written words.
The picture exchange communication system (PECS) developed by Frost
and Bondy, uses drawing to help young children with severe speech disorders to
communicate. PECS uses pictures to convey words and concepts (29).
Sign language is a viable intervention when working with nonverbal or
apraxic/dysarthric children until language emerges. It involves introducing
natural gestures along with oral language to build communication skills.
X. CONCLUSION
On November 12, 2002, Ms. Polly Morrice wrote about her struggle with autism
in The New York Times (30). Her son, who was 11 years at the time of this

196 Schneider
op-ed article, was diagnosed with ASD and enrolled in a specialized preschool
program at the age of 3. She described autism as a “window-of-opportunity
disorder,” which she elaborated by stating that “the earlier in a child’s life you
intervene to adjust the faulty neural wiring that causes it, the better the outcome.”
According to many clinical practice guidelines developed by experts, such as the
Clinical Practice Guideline – Autism/Pervasive Developmental Disorders:
Assessment and Intervention for Young Children (Ages 0– 3 years) supported
by the New York State Early Intervention Program, treatment is most effective
when intensive training is provided to young children (31). Although the
applied behavioral analysis program, similar to the intervention developed
by Lovaas, has been endorsed by some of these guidelines, including the
New York State guidelines, other models, such as Greenspan’s floor time (32)
may be effective if applied early and intensely. Each of these interventions
encourages the integration of a speech pathology component in a comprehensive
program.
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3. Prizant BM. Language acquisition and communicative behavior in autism: toward an
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10
Sensory Integration and
Occupational Therapy Intervention
for Autistic Spectrum Disorders
Patricia M. Stevens, Sallie Tidman, and Kari A. Glasgow
I. INTRODUCTION
I was destructive as a child. I drew all over the walls not once or twice, but
anytime I got my hands on a pencil or crayon. I remember really “catching” it
for peeing on the carpet. So the next time I had to go, instead of peeing on the
carpet, I put the drape between my legs. I thought it would dry quickly and
Mother wouldn’t notice. Normal children use clay for modeling; I used my
feces and then spread my creations all over the room. I chewed up puzzles
and spit the cardboard mush out on the floor. I had a violent temper, and when
thwarted, I’d throw anything handy—a museum quality vase or left-over
feces. I screamed continually, responded violently to noise and yet appeared
deaf on some occasions. (1)
The above quote graphically depicts the chaotic and overwhelming world of
individuals with autism. The overt behaviors that occur because of this inner
chaos can be daunting and overwhelming for parents, physicians, teachers, and
all who come in contact with them. Occupational therapists believe that much of
this behavioral chaos occurs because of a failure of individuals with autism to
organize their sensory experiences, or sensory integration dysfunction (DSI).
Sensory integration theory was developed over 50 years ago by a pioneering
occupational therapist, A. Jean Ayres, while she was working with children with
perceptual, learning, and behavioral problems of unknown etiology. She set out

200 Stevens et al.
to examine how the brain processed sensations, not just sensations of the eyes and
ears but other parts of the body as well (2). Ayers referred to sensory integration
(SI) as “the organization of sensory input for use, through sensory integration,
[of] the many parts of the nervous system [that] work together so that a person
can interact with the environment effectively and experience appropriate
satisfaction” (2). Carol Kranowitz broke down SI into four sequential steps:
receiving, organizing, and using sensory information, and reacting to sensory
information (3). Sensory information is picked up peripherally, and travels to the
CNS for organization and planning. The reaction and execution is then carried
out in the motor system. DSI occurs when sensory information is not processed,
integrated, or organized properly in the brain, resulting in dysfunction of
information processing, behavior, and the ability to meet the demands of the
environment (3). DSI makes it hard for the child to learn from his/her
experiences.
II. MAKING SENSE OF THE WORLD THROUGH THE SENSES
The five senses obtained via the sense organs of eyes, ears, mouth, hands, and
nose are vision, auditory, gustatory, touch, and olfactory, respectively. These are
often referred to as “far senses” because the input comes from outside one’s body.
SI also adds three “near senses,” or hidden senses. These are tactile, vestibular,
and proprioceptive. They are called hidden because the information comes from
within one’s body (3).
Tactile includes the sensations of touch, pressure, vibration, pain, and
temperature, which we obtain through the skin all over the body. These
sensations determine: Does the person like to be hugged, or shies away from a
hugging, kissing relative? Does the person like to walk in the surf at the beach
getting wet and sandy? Does the person have the label in the back of a shirt cut
out because it is bothersome? What is the person’s pain tolerance?
Vestibular is the sense that receives and responds to input from movement
of the body and from changes in the head position. This information is received in
the inner ear (3). Vestibular sense tells a person that he or she is moving—
forward, backward, upward, or downward. It tells one how fast he or she is
moving, or how slow he or she is moving. Vestibular sense tells one whether he or
she is upright or upside down. It also tells one when his or her head is tilted or
rotated looking at the horizon. The vestibular sense determines if a person is an
amusement park thrill-ride seeker or the thought of a roller coaster makes him
nauseous.
The last hidden sense is proprioception, or the internal “position sense.” It
tells us how the body and the body parts are positioned. This information comes
from the muscles, ligaments, and joints. The brain registers when muscles are

Sensory Integration and Occupational Therapy 201
contracted or elongated; it also registers when the joints flex, extend, or when
joint traction occurs (2). This sense determines if a child maintains an upright
sitting posture at the table or shifts constantly, falling out of the chair.
The three basic senses, vestibular, proprioceptive, and tactile, are integral in
developing a child’s body perception, coordination of the two sides of the body,
motor planning, activity level, attention span, and emotional stability. Along with
the far senses, particularly vision and auditory, a child learns to make sense of his
or her world (2). Children with autism fail to organize their sensory information.
The inability to organize this information often leaves a person with autism appear
highly reactive to sensory information. Temple Grandin’s description of riding a
spinning amusement ride is an excellent example of sensory organization:
Frightened but dared, I bought a ticket for the ride and with trembling legs,
walked up the few steps to enter the barrel. My heart in my mouth, I leaned
against the side. The sound of the motor starting up sent a chill skittering
down my spine. Then the “rotor” picked up speed and the motor sounded like
a giant’s hum. The colors of the blue sky, the white clouds, the yellow sun
blended together like a spinning top. The smell of cotton candy, Karmel Corn
and tacos swirled around individually until they too, combined into the
carnival smell. Glued to the side of the barrel, I waited for the floor to drop
out. Fear tasted bitter in my mouth and I tried to press harder against the side.
With a creak on the hinges the floor opened to the ground below but now my
senses were so overwhelmed with stimulation that I didn’t react with anxiety
or fear. I felt only the sensation of comfort and relaxation. (1)
III. PROCESS OF SENSORIMOTOR INTEGRATION
The process of sensorimotor integration includes the following elements.
A. Sensory Modulation
In a review of recent research literature, Wilbarger and Stackhouse (4) define
modulation as “the intake of sensation via typical sensory processing mechanisms
such that the intensity and quality of response are graded to match environmental
demand and so that a range of optimal performance/adaptation is maintained.”
The human organism seeks to maintain a state of homeostasis, or sensory
balance. Typical children can modulate their level of arousal and alertness to be
able to attend to stimuli. They can regulate themselves to achieve, monitor, and
change a state of attention that matches the demands of the environment. They
can modulate a response in relation to the task required. They can discriminate
and attend to selected stimuli (sensitization) and accommodate to the constant
bombardment of stimuli in daily life (habituation). Modulation states can vary

202 Stevens et al.
widely during a typical day in both the neurotypical and atypical child, depending
on environment, stresses, and physiological needs (hunger, sleep).
Children with autistic spectrum disorder (ASD) demonstrate deficits of
sensory modulation. As they function through the day, their regulation states may
not match the level of intensity in a given situation. For example, the child may
have completed the morning routine of waking, eating, dressing, and trans-
itioning to school in a highly aroused state with very poor ability to focus on a
visual motor activity requiring attending and inhibition of extraneous stimuli
(auditory and tactile as well as emotional arousal). For this child to participate, he
or she will need to modulate or bring his or her arousal state to a level of matching
the environment. For the neurotypical child, this can be accomplished through
following a set of routines and verbal and social cues to “settle down” and sit at a
desk in the classroom. For the atypical child, the requirement to “settle down” has
no context or strategy to accomplish. This child may need sensorimotor cues to
ease the transition. It might well start with waking up with a deep pressure
massage and followed by clothing that is less irritating to the skin. A breakfast
with textures that provide proprioceptive input such as a chewy bagel and
drinking through a straw may assist in regulating the arousal level. Once the child
arrives at school, having a structured task involving controlled movement may
again assist in regulation of activity level. The modulation problems include low
registration of stimuli, hypo- and hyperresponse to stimuli, and sensory
avoidance.
B. Sensory Discrimination
Sensory discrimination is the ability to differentiate between incoming stimuli
based on prior experience to make meaningful adaptive responses. It provides the
foundation for sorting and classifying information. It allows the individual to
prioritize what information is important and what is not necessary at the moment.
At the sensory level, this happens unconsciously. An easy example is all the
auditory information received constantly (hums of electrical equipment, people
talking, background music, etc.), and the ability to screen it all out, yet still
be able to discern something unusual or important. Discrimination is necessary
for both habituation and sensitization. It allows the individual to put multiple
attributes to a sensory experience and integrate the information for further
learning.
C. Motor Planning
Praxis, or motor planning, is the ability to conceive, organize, and execute an
unfamiliar motor activity (2). It involves physically or mentally constructing the
movement in a goal-directed manner. Adequate movement skills require proper

postural mechanisms such as adequate muscle tone, balance, strength, and

development of normal gross and fine motor skills. Motor planning itself involves
ideation or generating an idea of the new movement and then executing it based
on sensory information. The child with DSI will frequently demonstrate deficit in
both the planning and execution of a movement.
IV. SENSORY ISSUES IN AUTISM
A child can rarely describe his sensory experiences to others, for he has no
internal baseline with which to compare them.—T. Berry Brazelton
A. Problems of Sensory Modulation

Lack of sensory modulation or inability to regulate arousal is a common
observation in autism. Children with ASD are frequently in states of under- or
overarousal in regard to incoming sensory input and reactivity to the demands of
the environment. The various problems of sensory modulation are as follows.
1. Low Registration
The child appears to show dull affect with little interest in the external
environment and requires a significant amount of stimulation to achieve an
alerting response. Threshold or the amount or quality of stimulus required to have
a CNS reaction is high (5).
2. Underresponsive
The child has a diminished perception of self as moving and interacting within his
environment. He seeks sensations to remain alert, but has difficulty reaching an
alert status because of impaired processing. He may appear to be very active and
disorganized as he attempts to gain enough sensory input to organize self and
respond; threshold is high.
3. Increased Registration
This results in poor ability to discriminate or select sensation to respond or
process to habituate. A child demonstrates defensive behaviors to protect from
incoming sensory information from the environment and may typically display
“fight, fright, or flight” behaviors in response to environmental demands;
threshold is low.

204 Stevens et al.
4. Hyperresponsive
Children with this behavior demonstrate overreaction or defensiveness to sensory
input. Their motor responses are fearful, cautious, withdrawing, or aggressive
and they may appear negative and angry.
B. Sensory Avoidance
The child avoids sensory input that is perceived as painful and overwhelming to
the nervous system and develops routines and rituals to avoid external stimuli.
Threshold is low (5).
C. Sensory Seeking
Self-stimulatory and self-injurious behaviors and constant motion fall into this
category. Within the concept of threshold and habituation, the self-stimulating
child may be seeking to meet the sensory need, but the arousal/threshold is not
met and the behavior recurs. The child may also be seeking to extinguish
unpleasant sensory or environmental stimuli by blocking them with stimuli that
turn his or her attention inwardly. Extremes of seeking proprioceptive or
vestibular stimulation may be observed with repeated pounding with the
extremities, head banging, pushing, and seeking of deep pressure or “squeezing”
(6). Temple Grandin and several others have reported relief with the “squeeze
machine.” Spinning and rocking are commonly seen as both alerting and calming
for the child. Through the visual-vestibular connection, the child may also engage
in seeking out the same sensory information through spinning toys and objects.
D. Sensory Defensiveness
This is a sensory disorder characterized by a “fight, flight, or fright” reaction to
sensory stimulation most individuals would consider harmless. The nervous
system does not adequately discriminate different sensory stimuli and responds in
a survival mode: aggressive response, withdrawal from stimuli, rigid routines to
avoid stimuli and maintain control over the environment, and other nonfunctional
responses to the environment.
E. Tactile Defensiveness
This is commonly seen in DSI. The child may be irritated by clothes and may
refuse to wear certain clothes. He or she may not like the texture of certain foods
and may refuse to eat them. Socially the child may be seen as aggressive when he
or she avoids contact with others or responds aggressively when touched

unexpectedly. Self-care may be affected in terms of bathing, haircuts, and other

grooming activities.
F. Auditory Defensiveness
This is an aversive reaction to sounds, common and unexpected. Sounds, such as
a vacuum cleaner, a telephone ringing, or a timer on a stove, may be enough to
disrupt the child, eliciting flight or withdrawal. Both sound intensity and pitch
may disturb the child.
G. Visual Defensiveness
This includes hypersensitivity to light or avoidance of gaze. Busy visual
environments may be overwhelming because of poor figure ground
discrimination. The child may have difficulty in transitioning from indoor to
outdoor because of the light sensitivity.
H. Oral Defensiveness
This child with ASD may refuse many foods because of oral defensiveness and
may become more selective as he or she gets older instead of using a broad
selection of foods. It may be difficult to clean the child’s face after eating,
creating a problem of hygiene. Olfactory defensiveness may also be present.
Food selections in oral sensitivity may be based on taste and/or texture and it is
important to note the taste and texture of preferred foods.
I. Gravitational Insecurity
This is a form of hyperresponsivity to vestibular sensations, particularly
sensations from the otolith organs, which detect linear movement through space
and the pull of gravity (2). The child may show an excessive fear to ordinary
movement and is challenged by changes in head position and movement,
particularly with head tilted back or up and down. The child may demonstrate
intolerance to movement imposed or on an unstable surface. Movement through
the environment is difficult and confusing for the child. The fear that the child
feels is very real and impacts movement and balance.
J. Decreased Imitation
Children with autism have difficulty in imitating others. Imitation and develop-
ment of praxis require adequate development of body awareness and kinesthetic
processing. The sensory inputs from the tactile, proprioceptive, and vestibular

206 Stevens et al.
systems all contribute to support motor skills. When the child is unable to plan a
movement through imitation or receives faulty feedback from the movement he
completes, his motor coordination is affected. Children with autism frequently
have difficulty with initiating movements and performing goal-directed motor
complex activities.
V. IMPACT OF SENSORY ISSUES
Here’s your hat, Temple. . . My ears felt as if they were being squashed
together into one giant ear. The band of the hat pressed tightly around my
head. I jerked the hat off and screamed. Screaming was the only way of
telling Mother that I didn’t want to wear the hat. It hurt. It smothered my
hair.—Temple Grandin
Tasks of daily living can be very challenging for a child with ASD and his
caregivers. Sensory processing and modulation disorder combined with language
impairment make the routines of daily living a constant challenge. Frequently,
the child falls into patterns of routines and unchanging rituals to self-regulate his
day. By controlling the environment in this manner, the child can have an
internalized set of expectations and outcomes with each activity. But when a new
challenge or change in routine is introduced, the child lacks the ability to plan,
compensate, or react in a meaningful manner to it.
Dressing can be a major issue for children with autism, especially as it
relates to tactile processing. Abnormal reactions may relate to hypersensitivity or
hyposensitivity. The hypersensitive child may refuse clothing altogether, or be
very selective in terms of textures, tags, or clothing that is loosely touching the
skin. The child does not become habituated to his perceived source of irritation
and seeks constant relief from it. The hypersensitive child may also demonstrate a
need to be covered on all extremities and body parts by layering of clothing. By
layering and wrapping clothing tightly, the child is self-regulating and providing
not only a protective barrier from touch, but deep pressure to inhibit irritating
stimuli and calm him. The hyposensitive child requires significant amounts of
stimuli for arousal and attention and seeks sensation. This child may tightly wrap
clothing on his or her body and extremities or may not want to wear clothing to
maximize the sensory input being received by the CNS.
Mealtimes also present significant issues in regard to sensory processing.
Environmentally, the modulation required to regulate sounds, smells, and body
position to stay at the table may present as a challenge. Decreased proprioceptive
awareness in the hands to hold a utensil may result in finger feeding or passively
waiting to be fed. The motor plan to scoop the spoon and bring it to the
mouth, while maintaining the grasp, is a challenge for many of the children.

Visual as well as tactile food aversions are commonly seen. Children with autism
may prefer certain food textures, may avoid foods that are multitextural
(casseroles, cereal in milk, salads, or oranges, for example), may select foods that
are all of similar textures (smooth, least resistive, less taste), and frequently may
prefer foods that are savory and sharp over sweet (barbeque flavor, bacon, etc.).
Sensory processing and modulation impact daily routines and require-
ments. Transitions in arousal states begin with waking in the morning and
progress throughout the day. Modulation is often on the high end of arousal and a
small amount of sensory input can cause the child to react strongly and
emotionally. From a sensory point of view, the child with autism seeks out the
routine and ritual to decrease the amount of input and novelty the system needs to
accommodate and act upon. Always walking against a wall and limiting food and
clothing preferences decrease tactile input. Vestibular dysfunction is character-
ized by gravitational insecurity and decreased movement from place to place. The
child may show extreme distress at a diaper change because of the head tilt and
body movement imposed by lying the child down. Toilet training may become
difficult as the child is perceiving fear of feet off the ground and the tactile and
auditory sensations of the bathroom are overwhelming to the nervous system.
Rearranged furniture in a familiar room may cause an extreme reaction, as
if the child has “lost” the visual motor plan of the room and is unable to recognize
the room out of context. Without the ability to “reorganize” internally, the point
of control becomes restoring the room to the familiar state.
Self-stimulatory and self-injurious behaviors may serve a sensory function
to the child with autism (6). The behaviors frequently center on tactile,
proprioceptive, and or vestibular input. The child may use these behaviors to alert
and arouse or to assist with calming and blocking other, more aversive stimuli.
Children are frequently noted to engage in oral stimulation by mouthing
nonfood items and hands, as well as extraoral stimulation with fabrics and light
touch. Hands are frequently engaged in light touch patting and rubbing preferred
textures and favorite items to hold. The self-seeking stimulation of this type often
appears with the tactile defensive child, yet that is the child that who refuses
touch imposed upon him or her. Once again, it appears to be an issue of
controlling the sensory input. This child may also seek to rub and hug against a
caregiver, but refuse reciprocation as a defensive measure. The extremes of this
behavior may be seen in biting, hair pulling, and slapping. The hyporesponsive
child may engage in extreme sensory-seeking behavior when in actuality, the
child may be trying to produce sensation that he or she can perceive.
Proprioceptive self-stimulatory behaviors are seen in a variety of ways.
Compressing and stretching the muscles over a joint gives the strong
proprioceptive feedback the body is seeking to assist with muscle tone, body
image, and regulation of movement effort. Flapping, jumping, slapping, and other
movements that involve jarring of the joints give intense proprioceptive

208 Stevens et al.
stimulation. Toe walking stretches the leg muscles, also giving the deep
proprioceptive input. Frequently, oral behaviors such as hitting against the face,
pulling against resistance with teeth, clenching teeth, and even guttural sounds
are providing proprioceptive input to the child. The chewing gum industry
has been aware of how people seek out this type of stimulation. The extremes of
this sensation seeking may be seen in head butting and hitting against walls,
biting oneself, and slapping and hitting oneself.
The focus of vestibular self-stimulation is responsively to head movement.
Rocking the body, isolating head movements in linear movements, twirling, and
spinning are all movements related to vestibular stimulation. The close
association of visual-vestibular processing gives rise to the concept of using
visual stimulation (watching spinning objects, finger flickering in the periphery)
to arouse the vestibular system.
VI. ASSESSMENTS OF SENSORY ISSUES
SI issues are assessed by an occupational therapist through interviews and

questionnaires, standardized tests, and formal and informal clinical observations.
A. Interviews and Questionnaires

During an evaluation the therapist will ask the caregiver about the child’s
difficulties to decide if the problems are sensory-related. For example, the child
may have difficulty with tolerating a certain clothing fabric owing to tactile
defensiveness. Interviewing the family provides the therapist with important
medical history.
The Sensory Profile, developed by Dunn in 1999, is a standardized
caregiver questionnaire, which assists therapists in measuring the sensory-
processing abilities of children. The original profile was designed for ages 5– 10.
There are now, however, additional profiles available for infants, adolescents,
and adults. The profile consists of 125 questions and is grouped into three
categories: sensory processing, modulation, and behavioral and emotional
responses. The caregiver fills in the questionnaire according to how often the
behaviors occur (always, frequently, occasionally, seldom, never). The profile
assists therapists in targeting the sensory processing issues affecting daily life (5).
Another questionnaire is the Sensory Integration Inventory – Revised: For
Individuals with Developmental Disabilities. This questionnaire provides the
same information for children and adults with developmental delays and
disabilities and is based on observations of behavior patterns. It is divided into
tactile, vestibular, proprioceptive, and general reactions. Information is gathered
through interviewing familiar caregivers and uses clinical observations. Yes and

no questions are asked and scored to provide the therapist with a profile as to the
areas where there are difficulties that need to be targeted (6). Other questionnaires
available include the Touch Inventory for Elementary School-aged Children
(TIE) and behavior checklists for families and teachers.
B. Standardized Tests
Only a few standardized tests have been developed to test sensory integration
specifically. It is important to evaluate fine motor, visual motor, and activities of
daily living (ADL) skills because sensory issues affect everyday life and skills.
The following section will comment on several of the available tests.
The Sensory Integration Praxis Tests (SIPT) is one of the main
standardized tests used to evaluate sensory dysfunction. It contains 17 subtests,
which measure tactile, vestibular, and proprioceptive sensory processing;
visuomotor perception (including position in space); motor planning; and
bilateral and sequencing skills. This test takes 21⁄2 hr to administer and score but it
can be broken into sections and administered separately (7).
A sensory test for younger children is the Test of Sensory Functions in
Infants (TSFI). It can be administered in 20 min. It is for ages 4 – 18 months and
will assist with children who are at risk for developing sensory issues later.
DeGangi-Berk and Berk also developed the TSI, which is the DeGangi-Berk Test
of Sensory Integration, and is for children 3– 5 years of age. This test requires
30 min to administer.
Testing of fine motor skills can be completed using the Peabody
Developmental Motor Scales –Second Edition (PDMS-2) or the Bruninks-
Oseretsky Test of Motor Proficiency, depending on the age of the child. The
PDMS-2 tests children from birth to 72 months of age in gross motor (reflexes,
locomotion, bilateral coordination) and fine motor skills (grasping and visual
motor integration). It requires approximately an hour for administration and
scoring (8). The Bruninks test is for ages 4– 17, and tests gross motor and fine
motor skills (response speed, bilateral coordination, upper-limb speed and
dexterity, and visual motor coordination). This test requires 11⁄2 hours, but can be
broken into sections (9).
Other tests include the Beery-Buktenica Developmental Test of Visual-
Motor Integration (VMI). This test is administered quickly and can be interpreted
in three components: visual motor integration, visual integration, and motor
skills. The age range is 3– 18 years and a short form is available that can be used
with children up to 8 years (10). The Developmental Test of Visual Perception – 2
(DVPT-2) is for ages 4– 10 years. It measures visual perceptual skills through
eight subtests (eye-hand coordination, position in space, copying, figure-ground,
spatial relations, visual closure, visual-motor speed, form constancy). It can be
administered in sections and the time frame can range from 30 min to 1 hr (11).

210 Stevens et al.
Evaluation of ADL skills is mostly completed through clinical observation

and interview. Areas addressed include: grooming, dressing of the upper and
lower body, and toileting. A therapist will want to know how much assistance is
needed in each area and will determine if the abilities of the child are age-
appropriate.
C. Clinical Observations
Clinical observations can be completed in several settings including the home, a
clinic, or any other natural environment for the child. Observations include play
skills and interactions with objects in the environment, muscle tone, reflex
integration, and strength.
VII. INTERVENTIONS
i want to go on with the therapy as long as planned

and i want to go on with the music
it is calming and smoothes my nerves
it is a feeling of gentle peace internal warmth and a place
free of anxiety like i never knew before.—Berger Sellin (12)
Guiding principles of sensory integration therapy include:
Controlled sensory input can be used to elicit an adaptive response.
Registration of meaningful sensory input is necessary before an adaptive
response can be made.
An adaptive response contributes to the development of sensory
integration.
More mature and complex patterns of behavior are composed of
consolidations of more primitive behaviors.
The more inner-directed a child’s activities are, the greater the potential
of the activities for improving neural organization (4).
Occupational therapy intervention often involves activities that incorporate
sensory activities based on proprioceptive and vestibular input. Use of suspended
equipment such as swings and trapeze can provide a variety of movement
experiences in the different planes of movement. Vestibular input is a strong
sensory input that has potential to affect arousal states (2), as the receptors are
located in the inner ear. For the child who needs intense stimulation secondary to
low registration and high threshold, engaging in movement on a circular or
orbital plane may assist in arousing. Conversely, moving in a linear, slow plane of
movement may calm and focus the child who is operating at an increased arousal

level. But not all intervention requires swings or other suspended equipment.
Assisting the child to move using scooter boards, changing running speed, and
movement through complex motor skills can also assist with integration of
sensation.
A key concept in therapy is providing structured input to organize the
nervous system. Proprioceptive input has a strong effect on modulation.
Trampolines and other equipment that provide deep pressure to the joints are
frequently used to provide input to promote sensory stimulation. Many of the
repetitive or self-stimulatory behaviors seen in autism have a basis in
proprioception-seeking behaviors. By increasing the amount and duration of
varied input, the need for this type of behavior can be decreased.
To provide a program of vestibular-proprioceptive input, the program must
be structured to meet the child’s sensory needs and be flexible to meet the child’s
changing status. Occupational therapy begins with finding the child’s arousal
state and establishing the child’s sensory responsiveness. Challenge to motor
skills and modulation is ongoing and toward the goal of increasing tolerance for
the changing environment and the child’s ability to make an adaptive response. A
“sensory diet” is frequently set up with the family. This refers to evaluating a
child’s day and keying into those times and activities that appear to be most
disruptive for the child. Evaluating whether incorporating a sensory component
into that activity would assist with completion, as well as increase the learning
potential for the child, is one of the roles of the occupational therapist. As an
example, a bedtime routine is frequently a challenge for families. The child may
be in a state of overarousal and unable to stay in bed or sleep. The sequence of
events prior to bedtime may be examined and evaluated with the parents. A
typical experience may be that the child has been free-playing until bedtime. The
parent tries to make the child brush his teeth, wash, change into nightclothes, and
settle with a book to sleep. However, the child is not at a place where transition to
sleep can be easily accomplished. Changing the routines to have a time to brush
teeth (a high-arousal activity), then providing deep proprioceptive input, slow
vestibular input (slow movement in a glider-rocker chair, wrapup in bath towels),
and evaluating the sleep area (use of weighted blanket or sleeping bag) may assist
with the transition. A sensory diet is an ongoing evaluation of the child’s status
and must be flexible. It requires task analysis from the therapist and the family for
it to be successful.
Other interventions focus on tactile and oral processing. The defensive
behaviors discussed previously are responsive to touch pressure as well as
increasing discrimination. Slow exposure to tactile experience and acceptance of
input is often the focus of therapy. Setting up the environment to support the
child’s ability to integrate sensory experience is essential for a successful
experience. Oral motor and feeding issues involve motor planning. A child with
ASD may not be able to plan the movements of bringing food to the mouth,

212 Stevens et al.
chewing, and swallowing. Tactile and visual aversions to food may be present. To
be successful in promoting good nutrition, the therapist requires a good
understanding of the child’s sensory status and needs to use a sensory model
within the context of a behavioral model.
Interventions include providing the opportunity to increase body awareness
and giving proprioceptive and tactile inputs for the body to recognize where it is
in relation to position in space. Incorporating sensory motor stimulation in a
directed manner assists in the development of motor skills, because successful
motor planning requires adequate sensory processing. The therapist teaches
motor planning and sequential motor skills so that the child is able to perform
complex motor skills and react in a functional manner to novel motor
requirements.
VIII. TIPS FOR PARENTS
Tables 1 – 6 were developed by occupational therapists from Children’s Hospital

in Richmond, Virginia to give ideas for sensory activities for children with
autism. For the best results, these should be tailored to a child’s individual needs
by a therapist and should be incorporated into home and school routines. The
tables include various supports and activities in areas such as proprioceptive,
tactile, vestibular, visual, auditory, and oral-motor sensory. Proprioceptive
sensory support involves using sustained moderate to deep pressure on total body
or major joints for calming. Tactile sensory support includes using slow,
moderate to deep skin depression for calming influence, as well as using a variety
of various textured and temperature items or substances to engage a child in
activities. Vestibular sensory support involves the use of slow, predictable linear
movement in horizontal or vertical direction as a calming influence. Visual
sensory support entails using visual input as a calming influence or to engage a
child in activities. Auditory sensory supports include the use of low-volume and
low-frequency rhythmic sounds as a calming influence. Finally, oral-motor
sensory support can be used to calm or alert.
IX. INTEGRATING OCCUPATIONAL THERAPY

AND SENSORY INTEGRATION THERAPY
INTO A LARGER AUTISM PROGRAM
Integrating an occupational therapy and sensory integration therapy program into

a larger autism program can take many forms. A child can receive occupational
therapy services on a regular basis: weekly, twice weekly, or monthly. Or the
child may receive regular weekly therapy for a few months, then carry over at

Table 1 Proprioceptive Activities
Alerting Calming Other

Perform large body Push-and-pull activities: Swaddling activities: wrap
movements, such as push and pull partner on up in futon mattress like
climbing, pushing, swings, push and pull a taco, use foam mats,
pulling, and crossing large objects around comforters, or futon
obstacles, before sitting house and school, push mattresses as tunnels or
down to do hand and pull while both people sandwiches
activities people are sitting facing To release energy:
each other holding jumping on trampoline,
hands with arms bed mattress, into piles
extended, push and pull of pillows, or beanbag
balls, hula hoops chairs, and bouncing on
Playing “Simon Says” to inflated balls
walk like animals (bear
walk on all fours, rabbit
hop), or to push floor
with arms, or push feet
against wall
Wearing a weighted vest,
hat, shoes, or put
weights in pants/jacket
pockets, wearing heavy
clothes, wearing a
weighted backpack or
fanny pack
Napping or sleeping with
heavy comforters or a
weighted blanket
Before school or during
transitions provide deep
pressure to joints by
pushing on joints in a
steady firm manner
5 – 10 times (shoulders,
elbows, wrists, hips,
knees, ankles, fingers,
feet)

214 Stevens et al.
Table 2 Tactile Activities

Use vibrating toys, Slow massage with deep Use weighted crayons,
Vibrating Bugs, or pressure touch: can use pencils, or vibrating
electric toothbrushes, calming scented lotions toys to draw in resistive
and attach small (lavender, sandalwood; clay, putty, sand, Ziploc
vibrators to other to include olfactory bag filled with hair-
objects you want the sensory input) styling gel, or
child to play with Use a brushing program construction paper.
Use a loofah sponge before transitioning to Let the child play in a
during bathtime and new or potentially sandbox
include different- stressful activities Finger painting with
textured toys in bath (dressing, bathing) and pudding, shaving
Use non-see-through box then give deep pressure cream, nontoxic
with small opening to to joints (get paints, etc.
feel and find various instructions concerning
textured objects: keys, brushing program from
macaroni, koosh balls, an occupational
car, truck, ball, etc. therapist)
Firm hugs, avoid light
touch or tickling
At bedtime use heavy
blankets, fill bed with
stuffed animals, make
huge pillows by sewing
sheets together with
foam filling
Use weighted lap drapes
when seated for
activities
home and school, and then come back when new developmental or sensory issues
arise. Regular therapy services should include a home and school carryover
program and instructions should be provided to the parents and teachers. Therapy
performance and goals should be shared with the medical and instructional team
for optimal outcomes. Occupational therapy services with a sensory integration
focus could also occur via a consultation mode with the therapist observing the
child monthly in a school or home setting and provide ideas, activities, and
suggestions to be incorporated into regular daily activities. For children with
moderate to severe impairment, the occupational therapists should work closely

Table 3 Vestibular Activities

Circular movements Slow rocking in lap or in rocking chair
on swings Slow swinging on various suspended swings
(tire swings, regular swings, wide-
platform swings, net hammocks)
Attach bungee cords to swings for an
up-and-down movement (be careful not to
excite the child with fast bouncing)
Table 4 Visual Activities

Use carpet to teach Work in a cubby or a Use computer games with
boundaries in play hideout area, such as added sounds for
For transitioning from one ball pit or tent to auditory input
activity to another, use decrease visual Use Touch Window or
“Simon Says” or colored distraction Big Keys to direct
and laminated feet Make the environment visual attention to the
pictures as a roadmap to predictable and computer
the next activity; or uncluttered by arranging Use grids to decrease the
make the child carry toys in the room in a visual field of choice
objects or pictures that consistent way
Use red to yellow shades,
represent the next Use deep colors with low bright-colored lights,
activity; picture contrast and black-and-white
exchange
Keep the space peripheral visual input
communication system
uncluttered
is good for transitioning
Table 5 Auditory Activities

When trying to engage in Use headphones with soft Use short and simple
activities, include toys lyrical music verbal messages when
that make sound (music Use a slow and soft voice giving directions
boxes, whistles, toy Transition to new activities
Present activities in a
cars/blocks/utensils by reciting children’s
room with a rug or
that make noises) songs or by listening
carpet to decrease
extraneous noises with headphones

216 Stevens et al.
Table 6 Oral-Motor Activities

Use sour, spicy, Use sweet, warm, and Before mealtime,
bitter, and hard smooth-textured foods apply deep pressure
or chewy-textured Sucking activities: hard in and around the
foods candy, imitate smacking child’s mouth and
sounds and raspberries; use straws, on the body
aquarium or therapy tubing, crazy Prepare mouth with
straws to suck up liquid, pudding, deep pressure
Jell-O, milkshakes, etc., to promote before
strong sucking; introduce strong or toothbrushing, and
intense citrus flavors (Cran-mixes, use electric
etc.); choose food that is about the toothbrush if
diameter of the mouth to promote a tolerated
good suck seal, sports bottles, Use weighted
lollipops, Popsicles utensils and dishes,
Blowing activities: musical and nonslip
toys, whistles, party favors, visual surfaces (place
action toys (blow and something pops setting, Dycem
up); blow out candles, blow cotton mats)
balls, blow bubbles at bathtime;
blowing activities in many positions:
sitting, on stomach, on back
Biting, chewing, and
crunching activities: crunchy food
like carrots, celery, crunchy peanut
butter, potato chips, chewing on
therapy tubing, licorice, taffy, etc.;
food textures that encourage biting
and crunching (bread sticks, apples,
crackers, Cheetos); use food that is
heavily textured not thin and slimy
(peanut butter, Cheetos, pretzels, etc.)
with educators and speech pathologists as a team. For children with mild
impairment, the therapists should work with the families to evaluate how sensory
issues impact functional performance and develop strategies to assist the child in
activities of daily living.
As with most forms of intervention, the earlier the child receives therapy,
the more effect it will have on learning and functional performance.

REFERENCES
1. Grandin T, Scariano MM. Emergence: Labeled Autistic. Novato, CA: Arena Press,
1986:20, 76.
2. Ayres AJ. Sensory Integration and the Child. Los Angeles, CA: Western
Psychological Services, 1979:5, 14, 59 – 66, 69 – 75, 82 – 83, 83 – 88, 91 – 101.
3. Kranowitz CS. The Out-of-Sync Child: Recognizing and Coping with Sensory
Integration Dysfunction. New York: Berkley Publishing Group, 1998:8, 40 – 42,
42 – 47, 95 –101.
4. www.ot-innovations.com/jerry.html
5. Dunn W. Sensory Profile User’s Manual. San Antonio, Texas: Psychological
Corporation, 1999:1– 5, 33– 36, 35.
6. Reisman JE, Hanschu B. Sensory Integration Inventory –Revised: For Individuals
with Developmental Disabilities. Hugo, MN: PDP Press, 1999:2 – 5, 8 – 9, 20–22.
7. Case-Smith J. Occupational Therapy for Children. 4th ed. St. Louis: Mosby,
2001:359.
8. Folio MR, Fewell RR. Peabody Developmental Motor Scales Examiner’s Manual.
2nd ed. Austin, TX: Pro-Ed, 2000:3, 4, 10.
9. Bruininks RH. Bruininks-Oseretsky Test of Motor Proficiency Examiner’s Manual.
Circle Pines, MN: American Guidance Service, 1978:11, 43.
10. Beery KE. The Beery-Buktenica Developmental Test of Visual-Motor Integration:
Administration Scoring and Teaching Manual. 4th ed. Parsippany, NJ: Modern
Curriculum Press, 1997:21 – 22.
11. Hammill DD, Pearson NA, Voress JK. Developmental Test of Visual Perception
Examiner’s Manual. 2nd ed. Austin, TX: Pro-Ed, 1993:5.
12. Sellin B. I Don’t Want to Be Inside Me Anymore: Messages from an Autistic Mind.
New York: Basic Books, 1995.
13. Berk RA, DeGang GA. Test of Sensory Function in Infants (TSFI). Los Angeles,
CA: Western Psychological Services, 1990:1, 7.

11
Drug Therapy (Pharmacotherapy)
of Autistic Spectrum Disorders
Vidya Bhushan Gupta

New York Medical College and Columbia University,
I. INTRODUCTION
Lack of understanding of the origins of abnormal behaviors in autism has

impeded the development of rational drug therapies. Treatment is further
complicated by a tremendous range of syndrome expression, perhaps due to the
involvement of many neurotransmitters (1). There is no specific drug to cure
autism or to treat its core symptoms of poor social relatedness and com-
munication skills deficit. Therefore, the goal of drug treatment of autism is, at
present, to decrease the frequency of maladaptive behaviors, such as hyper-
activity, aggression, self-abusive behavior, temper tantrums, lability of mood,
irritability, social withdrawal, anxiety, repetitive compulsive behaviors, and
stereotypies. Atypical behaviors should be examined for their antecedents and
contexts in which they occur and treatment should be considered only if the
behaviors are maladaptive, interfere with programming, or impair the quality of
life. For example, if a child flaps his hands when he is overaroused, but is still
responsive to programming, his behavior may not require treatment. On the
contrary, if a child turns an electric switch off and on repeatedly, and throws a
tantrum when removed from the switch, his behavior is maladaptive and requires
treatment. If a behavior occurs to avoid a socially threatening situation or a
distressing sensory stimulus, behavioral interventions should be tried before drug
treatment is initiated. An embarrassing behavior that occurs in public may be

220 Gupta
considered for treatment earlier than if it occurs in private. In other words, a

proper behavioral diagnosis should be made before initiating treatment. Even if a
decision is made to treat a behavior, drug treatment or pharmacotherapy should
not be the sole treatment, but should be part of an overall management plan that
includes other therapeutic and educational interventions. Some guidelines for
drug treatment of target behaviors are given in Table 1. Although, in this chapter,
medications have been grouped under the predominant symptom for which
they are used, they often have effects on other symptoms as well. In other words,
there are no specific drugs for target symptoms in autism and hit and trial is
the rule.
II. HYPERACTIVITY, IMPULSIVITY, INATTENTION,

AND DISTRACTIBILITY
The underlying basis of hyperactivity, inattention, distractibility, and impulsivity

may be different in autism from that in attention deficit hyperactivity disorder
Table 1 Guidelines for the Management of Maladaptive Behaviors in Autism
1. Monitor behaviors for a period of time at home and in the school.

Observe the frequency, setting, and antecedents of behaviors.
Record the behaviors objectively using behavior checklists.
Rule out medical causes of abnormal behavior (those who cannot talk act out).
Assess if behaviors impair family’s quality of life and cause parental stress.
2. Decide which behaviors are maladaptive and require intervention (target behaviors).
3. Try behavioral and environmental changes; involve therapists, teachers, and parents.
4. Once it is decided to try a medication, develop a multidisciplinary management plan for
target behaviors including therapeutic and pharmacological interventions.
Choose a medication, its dose and formulation—“start low and go slow.”
Have patience and be ready for unexpected reactions, avoid polypharmacy.
Set realistic expectations and support parents in tolerating “bad” behavior.
Set up goals of management (the end point).
Plan how therapeutic response and side effects will be monitored.
Use a behavioral checklist or a global impression scale, such as CGIa or CGASb.
Develop a follow-up plan—how often the dose will be adjusted, when the trial will be
called a failure or success, how long the drug will be continued after the acceptable
response has been obtained, and the game plan for drug failure.
4. Discuss the plan with the parents, inform them about the limitations of drug therapy in
autism and potential side effects of the medications, and obtain their verbal or written
consent.
a
Clinical global impressions.
b
Clinical global assessment scale (children and adolescents).

Drug Therapy of Autism 221
(ADHD), because the response to psychostimulants is not as robust in autism as in

ADHD. DSM-IV excludes the diagnosis of ADHD if the child has autism or PDD.
Some children with autism are overfocused on a particular object, activity, or
stimulus. Others may be hyperactive, but work within a narrow range of interests.
A. Psychostimulants
Although psychostimulants, such as methylphenidate and dextroamphetamine,
have shown modest effects in reducing overactivity (2– 4), the effects on
attention and distractibility are not so obvious. Side effects of psychostimulants,
such as irritability, anxiety, agitation, insomnia, aggression, delusions, and
worsening of social withdrawal and stereotypies, have been reported more often
in individuals with autism (5). Handen et al. reported positive response in 8/13
subjects but adverse effects, such as social withdrawal and irritability, were noted
at higher doses (6). Others have reported therapeutic benefits without adverse side
effects (4). Stimulants are more useful in children with Asperger’s syndrome and
PDD-NOS than in autism, and are not so helpful in patients who persevere within
a narrow range of activities (6). Theoretically stimulants have the potential to
increase stereotypic behaviors.
B. a2 -Adrenergic Agonists
Clonidine, an a2 -adrenergic agonist, has a modest effect in reducing hyperactivity,
overarousal, and irritability, but has little effect on the social and communication
abnormalities (7,8). Fankhauser et al. reported improvement in stereotyped body
movements, self-stimulation, hypervigilance, and hyperactivity with weekly
clonidine patch treatment in a double-blind, placebo-crossover study, but side
effects such as sedation and fatigue occurred during the first 2 weeks of clonidine
treatment (7). Clonidine was modestly effective in the short-term treatment of
irritability and hyperactivity in children with autism in another study (8).
C. Antipsychotics (Neuroleptics)
Although older antipsychotics (neuroleptics), such as haloperidol, were effective
in treating hyperactivity and aggression (9), they resulted in significant adverse
effects, particularly tardive dyskinesia (10). Newer or atypical neuroleptics, such
as risperidone and olanzapine, hold more promise in reducing hyperactivity,
impulsivity, perseverative behaviors, and aggression with much less risk of
tardive dyskinesia. Risperidone, an HT2A and dopamine D2 antagonist, has been
studied the most frequently (11 – 14). Besides open-label trials (12,13), a multi-
center, double-blind, placebo-controlled study has indicated that risperidone may
be effective in children and adolescents in reducing temper tantrums, aggression,

222 Gupta
and self-injurious behavior (15). It may also increase socialization in some

children. The major side effect of risperidone has been increased appetite causing
weight gain. Olanzapine, another atypical neuroleptic, was also found beneficial
in a small open-label trial in reducing the symptoms of hyperactivity, repetitive
behaviors, self-injurious behaviors, and even social relatedness in individuals
with autism, but it, too, causes weight gain (16,17). Ziprasidone (Geodon)
improved the symptoms of aggression, irritability, and agitation without
significant weight gain in an open-label study (18). Clozapine (Clozaril) showed
some positive effect in two case reports in older subjects but its tendency to cause
agranulocytosis limits its use in autism and PDD (19,20). Quetiapine (Seroquel)
was not tolerated well in an open-label trial because it caused sedation,
behavioral activation, and weight gain (21). Atypical or newer neuroleptics used
in autism are described in Table 2.
Other drugs that may be potentially used to treat hyperactivity in children
with autism include opiate blockers, such as naltrexone, cyclic antidepressants,
and anxiolytics (5). Among the antidepressants, clomipramine (Anfranil), desi-
pramine (22), and mirtazapine have been found to decrease hyperactivity in small
samples of individuals with autism (23). Mirtazapine (Remeron), a tetracyclic
drug with both serotonergic and adrenergic properties, showed modest effec-
tiveness for treating the symptoms of hyperactivity, aggression, self-injury,
Table 2 Newer Neuroleptics Used in Autism
Name Side effects Dose and formulation

Risperidone (Risperdal) Weight gain, drowsiness, Starting dose: 0.25 mg twice
(11 – 14): blocks D2 and tardive and withdrawal a day, to be increased by
5HT2a, a1 - and a2 - dyskinesia 0.25 mg weekly
adrenergic receptors; Tablets: 0.25, 0.5, 1, 2,
off-label in children 3, 4 mg
Oral solution: 1 mg/mL
Olanzapine (Zyprexa) Weight gain, drowsiness, Starting dose: 2.5 mg once
(16,17): blocks D1, D2, orthostatic hypotension, a day, to be increased
D4, and 5HT1, 5HT2, dry mouth, dizziness by 2.5 mg weekly
adrenergic, cholinergic, Tablets: 2.5, 5, 7.5,
histaminergic receptors; 10, 15, 20 mg
off-label in children Orally disintegrating tablets
(Zyprexa ZYDIS): 5, 10
Ziprasidone (Geodon) (18): No weight gain, less change Dose: 20–80 mg twice a
higher HT2 to D2 in blood pressure, less day
binding; off-label in anticholinergic effects, Capsules: 20, 40, 60,
children and transient sedation, 80 mg
QT "

irritability, anxiety, depression, and insomnia in autistic disorder and other

pervasive developmental disorders. Adverse effects were minimal and included
increased appetite, irritability, and transient sedation (23). Serotonin reuptake
inhibitors have not been particularly helpful in reducing hyperactivity and may, in
fact, may cause behavioral activation and hyperactivity (24).
Traditional anxiolytics, such as benzodiazepines, are not helpful in the
treatment of hyperactivity in autism. In fact, these might cause paradoxical
hyperactivity. Buspirone (BuSpar), on the other hand, has shown some promise
in reducing hyperactivity (25), but the underlying basis of hyperactivity in
buspirone-responsive individuals may be anxiety. Opioid receptor blocker nal-
trexone (ReVia) has been noted to have modest effects on hyperactivity, but it is
not clear if it decreases motor activity due to its sedative effect (26 – 29). Its use in
children below 18 years is off-label. The starting dose is 50 mg once a day. It has
a low side effect profile. Levetiracetam, a nootropic medication, decreased
hyperactivity in 10 autistic children in an open-label trial (30).
In summary, drug treatment of hyperactivity in autism is, at present,
unsatisfactory and additional studies of drug treatment of hyperactivity in autism
are needed. For a detailed review see Aman and Langworthy (5).
III. REPETITIVE, RITUALISTIC,

AND STEREOTYPIC BEHAVIORS
Some children with autism have stereotypic or repetitive motor behaviors, such
as body rocking and spinning, flicking hands in front of the face, twisting of
hands, twirling an object, and gesticulations. They also repeat motor sequences or
scripts such as lining up toys, breaking the line, and lining them up again. Some
indulge in repetitive self-stimulatory behavior such as rocking, swaying, and
lying on the floor. Some repetitive behaviors, such head banging and hand biting,
cause injury but perpetuate themselves, perhaps because of endorphin release.
Other children with autism have compulsive behaviors such as hording or tearing
paper or turning the faucet on and off. The underlying basis of repetitive
behaviors in autism is unclear. Unlike typical obsessive compulsive disorder
(OCD), these are not due to uncontrollable and distressing obsessions, but
perhaps due to inflexibility, immaturity, or cognitive limitation. They might even
have some adaptive value like stress reduction, sensory stimulation, and social
attention, and escape from demands (31). Therefore, repetitive behaviors should
be treated only if they are maladaptive; that is, they interfere with programming,
worsen the quality of life, or are potentially harmful to the child.
Serotonin reuptake inhibitors (SRIs) and atypical neuroleptics are the
major drug groups that have been used to treat repetitive, ritualistic, and
stereoptypic behaviors in individuals with autism.

224 Gupta
A. Serotonin Reuptake Inhibitors

Studies of SSRIs in autism suggest that they decrease the symptoms of repetitive
behaviors, anxiety, social withdrawal, and behavioral rigidity with few side
effects when used in doses smaller than used in depression or OCD (32). Higher
doses of these medications, on the other hand, cause disinhibition syndrome
characterized by increased restlessness, activity, agitation, and aggression. SRIs
are less well tolerated and are less effective in younger autistic subjects compared
with autistic adolescents and adults.
1. Nonselective Serotonin Reuptake Inhibitors

Clomipramine (Anafranil). Several trials of this tricyclic, nonselective
SRI have shown that it reduces stereotypy, self-injurious behavior, and repetitive
behaviors and improves social interaction in individuals with autism (33 – 36), but
often causes serious side effects (37). Although clomipramine is approved for use
in children at and above the age of 10 years for OCD, children tolerate
clomipramine worse than adolescents and adults. Several side effects, such
as prolongation of corrected QT interval, tachycardia, constipation, rash, enuresis,
increased seizure frequency, agitation, aggression, and serotonin syndrome—
myoclonus, muscle rigidity, fever, chills, diaphoresis, restlessness, tremor,
agitation, irritability, confusion, and coma—have been reported (38). An open-
label study of clomipramine in children had to be discontinued because of side
effects (39).
2. Selective Serotonin Reuptake Inhibitors (SSRIs)

Fluvoxamine (Luvox). Fluvoxamine, a selective SSRI, was found to be
effective in reducing repetitive behaviors and aggression in adults with autistic
disorder in a controlled trial (40). Although controlled trials of fluvoxamine have
not been done in children, case reports suggest improvement in stereotypical,
repetitive behaviors with fluvoxamine in children with autism (41). Fluvoxamine
is approved for use in children age 8 years and older for OCD.
Fluoxetine (Prozac). Several open-label trials of fluoxetine have reported

improvement in perseverative behaviors, aggression, and self-injurious
behaviors, in a quarter to third of the patients with autism and PDD, but
several subjects had drug-induced behavioral activation. Side effects such as
hyperactivity, agitation, decreased appetite, insomnia, and hypomania have been
reported with fluoxetine (42 – 44). Recently, DeLong et al. have reported better
results with fluoxetine in a subset of children with “unusual intellectual
achievement” and family history of affective disorder (45).

Paroxetine (Paxil). Paroxetine is a serotonin and norepinephrine uptake

inhibitor. There are a few reports of paroxetine use in autism and results have
been similar to fluoxetine with improvement in a quarter of patients with low
doses but behavioral activation at higher doses (44,46).
Sertraline (Zoloft). Sertraline is a serotonin and dopamine reuptake

inhibitor. A few open-label trials of sertraline in individuals with autism have
shown that it decreases self-injurious behavior, aggression, and anxiety with
minimal side effects (47,48).
In summary, it seems that SRIs and SSRIs are modestly effective in

adolescents and adults with autism in the management of repetitive, ritualistic,
and stereotypic behaviors. These are also useful in mood disorders in individuals
with autism. Their role in younger children is uncertain because of less efficacy
and more side effects. There is a need for further research with controlled trials,
because the current information is from case reports or open-label trials in small
samples of heterogeneous subjects (49). For doses and formulations, see Table 3.
IV. AGGRESSION
Aggressive behavior in children with autism is not premeditated or predatory as

in conduct disorder, but impulsive, often as a reaction to frustration and fear.
Children with autism may also act aggressively to seek attention or to escape
Table 3 Serotonin Reuptake Inhibitors Useful in Autism
Name Dose and formulation

Fluvoxamine (Luvox) 50– 200 mg
Approved for use in children for OCD Tablets: 25, 50, 100 mg
Fluoxetine (Prozac) 10– 80 mg
Approved for children .7 years for Tablet: 10 mg, pulvule: 10, 20, 40
OCD and .8 for depression Solution 20 mg/5 mL
Sertraline (Zoloft) 25– 200 mg
Approved for children .6 years Tablets: 25, 50, 100 mg
Paroxetine (Paxil) 20– 80 mg
Off-label in pediatrics Tablets: 10, 20, 30, 40 mg
Oral suspension: 10 mg/5 mL
Clomipramine (Anafranil) 75– 200 mg
Approved for children .10 years Tablets: 10, 25, 40 mg
Capsules: 25, 50, 75 mg

226 Gupta
unacceptable demands. Alternatively, they may encroach upon others or attack

others if the latter are in their way. At the neurochemical level, aggression is,
perhaps, mediated by many neurotransmitters, including various excitatory and
inhibitory amino acids, long-acting steroids, serotonin, noradrenaline, and
dopamine (50 –53).
Because the etiology of aggressive behaviors is diverse, many medications
have been used to target this symptom, including antipsychotics, SSRIs,
anticonvulsants, opioid antagonists, and lithium (54,55).
A. Antipsychotics (Neuroleptics)
Increased dopaminergic activity has been postulated to be a cause of
aggression in animals (56). Extrapolating from the animal data, antipsychotics
that block dopaminergic receptors, such as haloperidol, have been the mainstay
of treatment of aggressive behavior in psychiatry. Campbell et al. conducted
several controlled drug trials of haloperidol in autism reporting beneficial
effects. Combination of haloperidol with behavior treatments resulted in
acquisition of imitative speech and social skills. Haloperidol also decreased
fidgetiness, withdrawal, and stereotypies and improved relatedness to the
examiner. However, on long-term follow-up, 34% of children developed
tardive or withdrawal dyskinesias, involving the face and mouth. Most of these
movements were reversible in the long run (57). The newer antipsychotics,
such as risperidone and olanzapine, cause fewer side effects and are replacing
haloperidol as medications of choice. Risperidone, a 5-HT2 receptor and
D2-receptor antagonist, has been found to reduce behavioral symptoms such as
aggression, self-injurious repetitive movements, and hyperactivity in many
studies, both controlled and uncontrolled. Adverse side effects include weight
gain, sedation, and galactorrhea (58). Olanzapine was found to be comparable
to haloperidol in an open-label trial (59). Quetiapine, on the other hand, was
not well tolerated by children with PDD (60), and side effects of clonazepine,
particularly agranulocytosis, preclude its use in autism, except as a last
resort (61).
B. Serotonin Reuptake Inhibitors

Disturbed central serotonergic function has been suggested to play a role in
problems with frustration tolerance and has been correlated with increased
aggression in adults, hyperactive children, children with OCD, and nonhuman
primates (62,63). For a detailed discussion of SRIs, see above. Citalopram
has been found to be particularly useful for impulsive aggression in
children and adolescents in an open-label study (64), but has not been studied
in autism.

C. Anticonvulsants
Theoretically anticonvulsants may improve the behavior of individuals with autism
by controlling epilepsy and underlying bipolar disorder (65). There are case reports
of individuals with autism whose behavior and language and social skills improved
after anticonvulsant therapy (66–68). Many of these had epileptiform discharge on
EEG with or without epilepsy. It has been suggested that some children with autism
may respond to anticonvulsants because of shared neuropathology, such as
abnormal electric activity in the amygdale (65). According to Rapin, although
epilepsy may play a minor role in a few children with regressive autism, it is
uncertain if anticonvulsants can stall autistic regression (69,70).
Affective anticonvulsants, valproic acid (VPA) and carbamazepine, are
used to treat aggression, irritability, and bipolar disorder in individuals with
mental retardation, with or without autism. A study of VPA in the treatment of
patients with intellectual disability and aggressive or self-injurious behavior
found a moderate to marked improvement in 71% of subjects. In 82% of the
subjects there was a significant reduction in aggression and self-injurious
behavior, in 46% other psychotropic medications could be discontinued, and in
39% the dose of other (71) psychotropic medication could be reduced. Although
it is difficult to diagnose bipolar disorder in individuals with autism, it is likely
that aggressive and irritability in some individuals with autism may be a
manifestation of underlying affective disorder. This view is strengthened by the
finding of higher prevalence of affective disorders in families of individuals with
autism (72). However, anticonvulsants can have serious side effects (73,74) and
should be used after careful risk-benefit analysis in individuals with autism also
who have epilepsy, epileptiform discharge on EEG, cyclic aggression and
irritability (75).
D. Trazodone (Desyrel)
Trazodone, an antidepressant that is neither tri- nor tetracyclic, has been
mentioned as treatment of aggression and violence in autistic children (76). The
response rate is 25– 30% and side effects, such as orthostatic hypotension and leg
swelling and pain, can occur. In males it can cause priapism.
E. Lithium
Lithium maybe used in individuals who are aggressive, agitated, and overaroused,
and have cycles of overarousal and withdrawal. But its side effects and the need
to draw blood for levels and tests limit its use in individuals with autism.
Buspirone and beta-blockers have also been used to treat aggressive
behavior in autism. These have been discussed in other sections.

228 Gupta
V. ANXIETY
Children with autistic spectrum disorder often have symptoms of anxiety (77),
particularly in unfamiliar environments, when exposed to certain environmental
stimuli, when the familiar order in their environment is changed, or when their
rigidity and repetitive behavior is challenged (78). Buspirone, a 5-HT1A receptor
agonist, has been found to be safe and effective in controlling the symptoms of
anxiety in autism in double-blind, placebo-controlled crossover study (79). It
belongs to the azipirone group of medications, does not affect mental alertness as
other anxiolytics do, and is not addictive. At higher doses it inhibits 5-HT 2A
receptors, and decreases striatal levels of serotonin and its metabolites. Buspirone
has effects on dopamine, norepinephrine, and the GABA systems as well. It takes
about 2 – 4 weeks for its full effects, although mild effects are seen within 1 week
(80). In an open-label trial buspirone resulted in marked improvement in the
target symptoms of anxiety and irritability in children with autism (81). It has also
been found to decrease aggression, hyperactivity, stereotypies, and self-injurious
behavior (82). Others have shown mixed results (83,84). In an open-label study,
there was worsening of aggression with buspirone (84). Rarely increase in
agitation and aggression and involuntary movements of the mouth have also been
reported (85).
VI. SELF-INJURIOUS BEHAVIOR
Children with autism, especially the low-functioning children, indulge in self-

injurious behaviors, such as self-biting, self-hitting, head banging, eye poking,
and skin picking. Reduced pain sensitivity, “addiction” to endorphins, and
abnormalities of opioid and dopaminergic neurotransmission in the brain have
been suggested as the possible causes of self-injurious behavior in autism (86).
A. Opioid Antagonists
Positive results for self-injurious behavior have been reported with naltrexone, a
long-acting narcotic antagonist (87 –89). Naltrexone has been reported to
decrease hyperactivity, irritability, and withdrawal, and to increase verbal output
and attentiveness (90 – 93). Despite its initial promise, several double-blind
control trials have either failed to show significant effects of naltrexone on
behavioral symptoms of autism or have found rather small effects, particularly
on the core symptoms of social withdrawal and communication deficits
(94 –96). Others have argued that only those individuals who have evidence
of dysregulation of the propiomelanocortin system with elevated levels of
C-terminal b-endorphin and serotonin benefit from naltrexone (95,97).

Nevertheless, naltrexone has some role in the management of hyperactivity,

irritability, and self-injurious behavior in autism, because of its low side effect
profile. It is given in the dose of 0.5 – 1.0 mg/kg body weight with an average
dose of 1 mg/kg/day. Side effects, such as rash, sedation, and unsteady gait, can
occur (96).
B. b-Adrenergic Blockers
b-Adrenergic blockers, such as propranolol and nadolol, have been reported to
decrease aggressive outbursts and self-injurious and stereotypic behavior in a few
open-label studies and case reports of individuals with mental retardation and
autism. Secondary improvement in attention (98–100), language, and social skills
was also reported in the one study. Nadolol was reported to be better than
propranolol in a case report (101).
The use of b-adrenergic blockers is limited by their side effects of
hypotension, bradycardia, exacerbation of asthma, and nightmares. For a detailed
review of b-adrenergic blockers in aggression see Haspel (102).
VII. SLEEP PROBLEMS IN CHILDREN WITH AUTISM
Individuals with autism often have sleep problems, such as difficulties in settling
down, frequent and prolonged nighttime awakenings, night terrors, and distur-
bances of sleep-wake cycle (103). Sleep disturbances may be due to disturbance
of the sleep-wake cycle, underlying medical conditions, anxiety, or psychosocial
stress. Disturbances of nighttime sleep affect daytime behavior and also cause
parental stress (104). While behavioral interventions are the mainstay of manage-
ment of sleep problems, medications are sometimes necessary. Short-acting
benzodiazepines, such as triazolam (Halcion) and flurazepam (Dalmane), may
have a short-term role in the treatment of pediatric insomnia but are not approved
for use in children in the United States. However, tachyphylaxis and risk of
misuse preclude the long-term use of benzodiazepines for the treatment of
insomnia in children. Alimemazine (trimeprazine), a phenothiazine, has been
shown to be effective in the short-term treatment of insomnia in young children,
but does not have U.S. Food and Drug Administration approval for pediatric
insomnia (105). Niaprazine, a histamine H1-receptor antagonist with sedative
properties, was found to treat insomnia in an open-label study of 25 children and
young people with autism and a range of severity of mental retardation (age range
2 –20 years) (106). Individuals with mild-to-moderate mental retardation were
selectively better responders. Newer hypnotics, such as zolpidem (Ambien),
zopiclone (Imovane), and Zaleplon (Sonata), which appear better tolerated and

230 Gupta
less habit-forming than the benzodiazepines in studies of adults, may have a role
when combined with psychosocial treatments for pediatric insomnia (107,108).
Melatonin, a pineal gland hormone, was found to be effective in treating
insomnia in a recent uncontrolled study of 50 children and young adults with
developmental disorders (age range 3– 28 years) (109). The results in people with
mental retardation have been mixed (110). Side effects, such as residual
drowsiness the next morning, awakening in the middle of the night, and excite-
ment after awakening and before going to bed, can occur but are usually mild.
There is no consensus about dosage and the mode of administration. It is
uncertain if melatonin needs to be given continuously or can be phased out after
sleep pattern has improved (111). The recommended dose is 0.5– 3 mg/day.
VIII. SUMMARY
Table 4 summarizes the major drug groups and their indications in autism. The
number of medications that have been or are being tried for autism is too large to
be discussed in this volume. Some, such as fenfluramine, have become history.
It was withdrawn from the market because of side effects. Others, such as
lofexidine, amantadine, cyproheptadine, famotidine, and donepezil, have been
tried in individual cases, with mixed results. Unless the neurochemical basis of
autism is discovered, a specific drug in unlikely to be available for autism. Until
then drug therapy will remain, at best, an adjunct to behavioral and educational
interventions.
Table 4 Summary of the Use of Various Drug Groups in Autism
Anxiety/
Repetitive Hyperactivity Aggression, affective
behavior impulsivity self-injury symptoms
SSRI X
Atypical X X X X
antipsychotics
Stimulants X
Naltrexone X
Clonidine X X X
Lithium X
b-blockers X
Anticonvulsants X
Buspirone X
Source: Adapted from Williemsen-Swinkels SHN, Buitelaar JK. The autistic spectrum: subgroups,
boundaries, and treatment. Psychiatr Clin North Am 2002; 25:811–836.

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Open trial effects of beta-blockers on speech and social behaviors in 8 autistic
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12
Complementary and Alternative
Treatments for Autism
Vidya Bhushan Gupta

New York Medical College and Columbia University,
I. INTRODUCTION
Complementary and alternative medicine (CAM) has been defined as “a broad

domain of healing resources that encompasses all health systems, modalities, and
practices and their accompanying theories and beliefs, other than those intrinsic
to the politically dominant health system of a particular society or culture in a
given historic period” (1). Although complementary and alternative treatments
are not commonly prescribed by the practitioners of conventional medicine, their
use has increased in the United States in the last decade (2). Owing to the lack of
satisfactory treatments, CAM use is particularly common in children with
developmental disabilities (3,4). About 50% of children with autism are treated
with CAM (5). Parents feel a sense of autonomy when they make therapeutic
decisions for their children based on their own research. Usually a significant
component of this research involves the Internet, where a lot of unauthenticated
and unscrupulous information exists along with useful information. The
information in this chapter is not an endorsement of CAM but an
acknowledgment that it is widely used by individuals with autism, and the
physicians and others who take care of children with autism should know about it
so that they can counsel the families judiciously (6).

240 Gupta
II. BIOLOGICALLY BASED THERAPIES
This category includes natural and biologically based practices, interventions,

and products, including the following: phytotherapy or herbalism; special diet
therapies; orthomolecular medicine; and unconventional pharmacological,
biological, and instrumental interventions.
A. Dietary Manipulation
Proponents of the gastrointestinal theory of autism posit that autism occurs
because of the absorption of toxic peptides from the gut and, therefore, can be
treated by eliminating the source of these toxins from the diet. See Chapter 2 for
details.
1. Casein- and Gluten-Free Diet (CFGF)

According to the gut theory of autism, casein and gluten are digested
incompletely in children with autism. Autism is putatively caused by the end
products of this incomplete digestion—amino acid polymers with opioid
characteristics, called exorphins. Removal of casein-containing foods, such as
cow’s milk and dairy products, and gluten- and gliadin-containing foods, such as
wheat, barley, rye, and oats, from the diet is supposed to improve the behavior of
children with autism by reducing exorphins. Maximum improvement after
elimination can take up to 2 years. A Medline search revealed two poorly done
studies of CFGF diet and both reported positive results (7,8). In one study, skin
tests for food allergy were positive in many of the subjects and many had high
levels of antibodies against casein in their blood (7). Proponents recommend
testing the urine for toxic peptides in their personal laboratories, but recommend
eliminating casein and gluten even if the levels of urinary peptide are normal (9).
For a review see Ref. 10.
2. Sugar- and Additive-Free Diet

There is no empirical evidence that sugar and food additives, such as colorings,
sweeteners, and preservatives, can cause the symptoms or that eliminating them
from the diet improves the behavior of children with autism. Children with
autism often have preferences for particular foods and textures, but these are due
to perceptual and sensorimotor reasons and do not reflect food intolerance or
sensitivity.
Elimination diets increase the burden of care on the parents, exclude the
child from many pleasures of life, and can cause nutritional deficiencies (11).
Instead of eliminating casein and gluten from the diet of every child, a more

Complementary and Alternative Treatments 241
selective approach may be taken. Take a history of food allergies, food

intolerance, and gastrointestinal (GI) symptoms in every child with PDD and
refer those with a history or symptoms of food allergy to an allergist and those
with food intolerance and GI symptoms to a gastroenterologist. If a child has
diarrhea or constipation, and is not gaining weight or height, celiac disease may
be considered and tests such as total IgA, antigliadin IgA, tissue trans-
glutaminase, and antiendomyseal IgA antibodies may be ordered. Elimination
diets can be tried for children with positive test results.
If testing is normal, but the parents insist that symptoms become worse
when the child eats a particular food, eliminate the food item from the diet for 4
weeks and then reintroduce it, logging the foods eaten and the child’s behavior in
a diary. This selective approach is more benign and harmless than blanket
elimination of casein, gluten, gliadin, and soy products from the diet.
B. Dietary Supplementation
1. Megavitamin B6
In 1978, Rimland et al. reported that some autistic children responded favorably
to high doses of vitamin B6 (orthomolecular treatment) (12). In a subsequent trial,
Rimland observed that some children experienced increased irritability, sound
sensitivity, nausea, increased excitability, increased autistic symptoms, loose
stools, and upper respiratory infection when they were given large amounts of
vitamin B6 (pyridoxine), but these problems disappeared when increased
amounts of magnesium were added to the diet. Subsequent trials have, therefore,
used pyridoxine with magnesium. The advocates of this treatment claim that the
favorable changes in behavior are not due to general sedation but represent
improvement in symptoms associated with autism. Although vitamin B6
deficiency has not been documented in individuals with autism, according to the
proponents, subclinical deficiencies could be present in individuals with autism.
The effects could be mediated by neurotransmitters, because vitamin B6 is
involved in the formation of dopamine and other neurotransmitters (i.e.,
serotonin, g-aminobutyric acid, norepinephrine, and epinephrine) (13). Some
studies have, indeed, documented a tendency toward normalization of urinary
homovanillic acid levels and evoked potentials with pyridoxine and magnesium
(13,14).
Sensory neuropathy, a serious side effect, has been reported with very high
doses of pyridoxine in the literature at large (15), but in studies that use 1 g/
kg/day of vitamin B6, few participants reported adverse side effects and the
adverse effects were relatively minor and manageable. Once magnesium was
added to the megavitamin therapy, adverse effects were even less. In the trials,
dose of vitamin B6 ranged from 1 mg/kg to 30 mg/kg, and of magnesium, from

242 Gupta
10 to 15 mg/kg/day. Megavitamin B6 therapy may be a relatively harmless and

cheap adjunct for the treatment of autism (13,14,16). For a detailed discussion see
Chapter 14.
2. Other Vitamins
Supplementation with other vitamins, such as vitamin A, folic acid, vitamin E,
vitamin B1, vitamin B12, and vitamin C, is also recommended by some. As long
as the dose of vitamins is within the recommended dietary allowance or slightly
higher, the treatment may be harmless, but megadoses of vitamins, particularly
vitamin A, D, and C, can be toxic. Vitamin C in the dose of 8 g/70 kg/day in
divided dose was found to decrease stereotypic behaviors in a small sample of
individuals with autism spectrum disorder (ASD) and mental retardation in a
double-blind, placebo-controlled study. Except for a risk of renal stones this
therapy seems to be benign (17).
3. Minerals
Advocates of trace and other minerals claim that children with autism have low
levels of calcium, magnesium, copper, manganese, and chromium and higher
levels of lithium and mercury in their hair samples as compared to age-and-sex-
matched controls. Based on this premise, children with autism are given
supplements of common minerals (calcium, magnesium, copper, manganese,
zinc, chromium, and cobalt), and trace minerals (vanadium, germanium,
selenium, tungsten, molybdenum, and tin). Minerals, such as zinc, have
important functions in brain development and function, but dietary deficiencies
or metabolic abnormalities involving trace elements are rare and have not been
shown to cause autism. If the supplement contains doses within or slightly
beyond the recommended dietary allowance, the treatment is harmless.
4. Fatty Acids
Supplementation with long-chain fatty acids (especially omega-3 and omega-6)
has been alleged to improve the symptoms of autism in a few individuals, but
there is no empirical or theoretical proof of their efficacy. The proponents argue
that long-chain fatty acids restore the imbalance of prostaglandins and cytokines.
If the intervention consists of merely administering oils such as evening primrose
oil or borage seed oil, it is innocuous, but when the proponents recommend costly
analysis of fatty acids in their personal laboratories, it becomes exploitative.
5. Inositol
Inositol is a precursor in the second-messenger system of some serotonin
receptors. In animal studies and human trials, it has been found to improve

behavior in depression, panic disorder, and OCD, but not in schizophrenia,

ADHD, or autism (18,19). According to a controlled, double-blind, crossover
trial, inositol is not helpful in autism (20).
6. Dimethylglycine
Dimethylglycine, a tertiary amine, is claimed by some to be effective in about
50% of individuals with autism (21). It has antioxidant and immunomodulating
effects. In one study it was found to enhance humoral and cell-mediated
immunity (22). At one time it was considered to have anticonvulsant effect as
well, but controlled trials have failed to demonstrate its anticonvulsant effect
(23). Two placebo-controlled trials failed to demonstrate significant benefits of
dimethylglycine on behavior of patients with autistic disorder (24,25). One of
these studies was faulted for using a low dose of dimethylglycine. However,
dimethylglycine is a reasonably priced innocuous substance with few side effects.
The recommended dose is one to four 125-mg tablets for a child, and two to eight
tablets for an adult. It is also available as a liquid for younger children (26).
Other nutraceuticals, such as antioxidants, a-lipoic acid, peroxynitrate, and
urecholine, have also been suggested as potential treatments for autism, but do
not have any empirical or theoretical support.
Although physicians should be open to the idea of using neutraceuticals,
they should provide limited leadership to the families without compromising the
families’ autonomy. They should carefully check the neutraceuticals for harmful
ingredients because under the Dietary Supplement Health and Education Act of
1994 (DSHEA), ingredients used in dietary supplements are no longer subject to
the premarket safety evaluations by the Food and Drug Administration. They
should be vigilant about the side effects of neutraceuticals and should caution the
families about brand-name products that make tall claims, because there is
nothing unique in one concoction of minerals and vitamins over another.
C. Biologicals
1. Secretin
Fortuitous improvement in language and social behavior of three patients with
autism who received a single dose of porcine secretin during a GI procedure led
to an interest in secretin as a treatment for autism (27). It is a 27-amino-acid
polypeptide hormone released by the cells of upper intestinal tract in response to
a bolus of food to stimulate bicarbonate and bile production. Although it is widely
distributed in the brain, its role in the brain is unknown. Many well-done studies
have failed to demonstrate therapeutic benefits of single or multiple doses of
either synthetic human secretin (28 –31) or porcine secretin in individuals with
autism (32 – 34).

244 Gupta
At present, secretin is approved for diagnostic purposes only and its use
in autism is off-label. Recommended dose for autism is 2 clinical units (CU)/kg
or 0.2 –0.4 mg/kg body weight (35). A sensitivity test with a smaller dose is
recommended before the full bolus is given. Although the proponents claim that
secretin is safe, hyperactivity and a few cases of diarrhea, seizures, and apnea
have been reported. Secretin is neither innocuous nor inexpensive.
2. Antiyeast Therapy
Candida albicans, a yeast, is normally found in various parts of the body,
including the gut. Generally, the amount of yeast in the gut is kept under control
by other microbes that compete for the same nourishment. However, exposure to
antibiotics, especially repeated exposure, can destroy these microbes, resulting in
an overgrowth of C. albicans. According to the proponents of the yeast theory of
ADD and autism, when the yeast multiplies, it releases toxins, such as aldehyde,
alcohol, tartaric acid, and other organic acids, which, in turn, impair the central
nervous system and the immune system. Only one laboratory in the country,
owned by one of the proponents of the Candida theory, tests the urine for the
toxic metabolites of Candida. The promoters of this theory recommend that this
test, costing about $200, be done at the initiation of therapy and then periodically.
No other commercial laboratory tests for these substances and medical insurers
do not reimburse the cost.
Some of the behavior problems that have been linked to an overgrowth of
C. albicans include confusion, hyperactivity, short attention span, lethargy,
irritability, and aggression. Health problems, such as headaches, stomachaches,
constipation, gas pains, fatigue, and depression, have also been attributed to
Candida. Treatment is begun with an antifungal antibiotic, nystatin. If this does
not work, other antifungal antibiotics, amphotericin B, ketoconazole,
fluconazole, and terbinafine are tried. All are given orally. Additionally, the
gut is replenished with a rich culture of probiotic agents or good microbes such as
acidophilus. Avoiding sugar and other carbohydrate-rich foods on which yeast
thrives, such as fruits, prevents overgrowth of the yeast. Interestingly, the child is
supposed to become ill and to show negative behaviors for a few days after
receiving antifungal treatment, because the yeast is destroyed and the debris is
circulated through the body until it is excreted. A child who shows such
deterioration is believed to have a good prognosis.
All evidence is anecdotal, written up in well-marketed books (36). There is
no empirical evidence that there is overgrowth of Candida in individuals with
autism (37). Whereas nystatin is relatively safe with mild risk of anemia and
diarrhea, the other drugs are not so benign and may cause serious side effects,
such as liver function abnormalities, headache, and rash. This treatment has no
scientific basis.

3. Immunomodulator Therapy
a. Intravenous g-Globulins (IVIG). There are two contradictory reports
about the efficacy of IVIG. Gupta reported improvement in 10 children with
autism who had evidence of immunodeficiency with IVIG at 400 mg/kg every 4
weeks for 6 months (38). Plioplys, on the other hand, reported benefit in only one
of 10 children who did not have evidence of immunodeficiency with IVIG at
154 –375 mg/kg every 6 weeks (39). Doses up to 5 g/kg every other day have
been suggested without any empirical evidence. IVIG is costly and carries the
risk of blood-borne infections such as hepatitis and HIV. Renal dysfunction
ranging from increased blood urea nitrogen and creatinine to renal failure has
been reported. IVIG is contraindicated in individuals with IgA deficiency. Thus
IVIG is neither innocuous nor inexpensive.
b. Pentoxifylline. Pentoxifylline is a phosphodiesterase inhibitor with

immunomodulatory, hemorrheological, and serotonergic effects. Its immuno-
modulatory effect includes inhibition of tumor necrosis factor-a (40). It is
approved in the United States for the treatment of intermittent claudication
because of its effects on blood vessels, such as vasodilatation and increased blood
flow. Its effects in autism may be mediated by its immunomodulatory or
serotonergic properties. Most of the reports about its benefits in autism are either
anecdotal or open-label studies without comparison groups. Until a double-blind,
crossover trial confirms its benefits, it cannot be recommended.
4. Detoxification Therapies
Because the increased prevalence of autism has coincided with increasing
industrial pollution, there is a considerable interest in the xenobiotic theory of
autism. According to this theory, autism is caused by accumulation of heavy
metals such as mercury, lead, cadmium, arsenic, and antimony in the body. The
proponents use unconventional commercial panels of questionable validity to
measure the body burden of heavy metals in hair and urine samples and
recommend chelation if the tests are positive (41). If mercury poisoning is
suspected, a careful environmental history, including the frequency, amount, and
types of seafood consumed, should be taken followed by measurement of
mercury concentrations in blood and urine at a reliable laboratory that uses
reference values in general agreement with the published values. Blood mercury
is the best test for current methylmercury exposure, while a 24-h urine collection
is the best indicator of recent or chronic exposure to elemental or inorganic
mercury (42). Spot collections are usually adequate but must be adjusted for
creatinine concentration. Provocative chelation should not be used as a primary
diagnostic test (42,43). In most cases hair testing is not required and has limited

246 Gupta
utility (42). Unconventional commercial hair, urine, and other panels should not
be used (44).
Although no link has been found between patients’ symptoms and mercury
levels in individuals without known exposure (44), proponents of this theory
recommend chelating children with autism with DMSA (2,3-dimercaptosuccinic,
or Succimer) and DMPS ((2,3-dimercapto-1-propanesulfonic acid) even if there
is no clinical or laboratory evidence of mercury poisoning. Blood CBC, liver, and
kidney panels, and a sensitivity test are a prerequisite for this treatment. Succimer
is given in the dose of 10 mg/kg/day in three divided doses for a few days
followed by a rest period (45). Such cycles are repeated until heavy metals are
cleared from the urine.
The reports supporting this treatment are mainly anecdotal. The treatment
is neither innocuous, nor inexpensive. Both DMSA and DMPS can cause
adverse reactions, such as gastrointestinal (GI) symptoms, rashes, neutropenia,
and elevation of liver enzymes.
The proponents of the toxic theory also recommend supporting the
cytochrome 450 and sulfation system in the liver to promote metabolism of toxic
chemicals, but there is little theoretical or empirical support for such treatments.
Proponents recommend glutathione and its precursors, glutamine, N-acetylcys-
teine, glycine, a-lipoic acid. The list of substances that are mentioned, such as
methylsulfonylmethane, taurine, and molybdenum, is formidable and irrational.
Even probiotics, such as lactobacilli and bifidobacteria are recommended to assist
with mercury detoxification (46). The theory is pseudoscience in megawords and
can be intimidating for the families. The physician should assist the families in
researching the harmful effects of the ingredients offered in preparations sold on
the Internet or in health food stores.
5. Famotidine (Pepcid)
One double-blind, placebo-controlled study reported some behavioral improve-
ment in 9 children with ASD with 2 mg/kg of famotidine per day in divided
doses. Famotidine is a H2 (histamine) receptor antagonist used to treat
gastroesophageal reflux. H2 receptors in the brain are supposed to mediate
exploratory behavior in animals. Although more studies are needed, the treatment
is benign and worth a try (47).
III. MANIPULATIVE AND BODY-BASED SYSTEMS
This category refers to systems that use manipulation and/or movement

of the body, such as chiropractic medicine, massage and bodywork, and

unconventional physical and occupational therapies. There is no evidence that

chiropractic or craniosacral manipulation helps children with autism and it will
not be discussed further. A few controversial methods that fall in this realm of
CAM are presented in this chapter.
A. Deep Pressure
It has been suggested that deep lateral pressure can reduce arousal and anxiety in
autism. Occupational therapists often use deep pressure to decrease anxiety level
and to increase sensory awareness of their subjects, but specific advantage of
contraptions such as the Grandin Hug machine or Velvasoft Deep Pressure
Sensory Tops and Shorts is not proven (48,49). Medline search came up with only
one pilot study that suggested reduction in tension and anxiety for children with
autism who received deep pressure (50). However, the treatment is innocuous and
not very costly.
B. Auditory Integration Therapy (Tomatis Method)

This treatment is based on the premise that transmission of high-frequency
human voice and music to the brain through an “electronic” ear can promote
neuromaturation improving attention and behavior (51). Guy Berard introduced
this therapy in France as a treatment for autism. Sensitivity of a child with autism
to specific sound frequencies is tested with a detailed audiogram. The child then
listens to music from which troublesome sound frequencies have been
eliminated, in 20 half-hour sessions over a 10 – 12-day period. Although the
proponents claim that AIT improves attention, auditory processing, expressive
language, and auditory comprehension and decreases irritability and lethargy,
there is no scientific support for these claims (52). Objective electrophysiological
measures such as auditory-evoked brainstem responses fail to demonstrate
differences in hearing sensitivity between autistic and nonautistic children (53). It
is difficult to test children with autism. The sound level produced by the
equipment can be potentially harmful (54). According to Bettison, listening to
music in general may improve some aspects of autism, but there is no additional
benefit of manipulated music (55).
Children with autism often like music and vocal or instrumental music is
commonly used in the schools for autistic children to engage them. Music may
reduce their social anxiety and self-stimulatory behavior, and may even improve
their social responsiveness if participation in music is made contingent on
responding, but it is not certain that these behavioral changes generalize to other
settings or are curative.

248 Gupta
C. Touch and Massage Therapy

Like music, some children with autism may respond to gentle touch and massage
with calming and increased attention. Some parents even claim benefits such
as reduction in hyperactivity, stereotypical and off-task behavior, and better
sleep. Massage is innocuous if tolerated and certainly worth a try. There is
nothing esoteric about massage beyond total loving care (TLC) and if a massage
therapist asks the parents for exorbitant sums of money to use a special technique
or oil, beware.
Touch has also been used in an educational approach called “rapid prompt
method” in which the mother or an educator repeatedly touches, prods, and urges
a child with autism to write. This prompting method has been made popular by
the media, but is still awaiting scientific validation.
D. Facilitated Communication
Facilitated communication (FC) involves supporting a nonverbal individual’s
hand to make it easier for him/her to type out words on a typewriter, computer
keyboard, or other communication device (56). Several scientific studies have
suggested that facilitators may unintentionally influence the communication,
perhaps to the extent of actually selecting the words themselves. There are no
correct responses from the subject unless the facilitator knows the response
(57,58). Many controlled studies have reported negative findings, indicating that
the technique is neither reliable nor valid (59,60). The families should be aware
that FC has been used to obtain allegations of abuse, particularly sexual abuse,
from individuals with autism against third persons, causing negative
consequences for families (61). For a detailed review of FC, see Ref. 62.
IV. ALTERNATIVE MEDICAL SYSTEMS
These include medical systems that have been practiced in other parts of the
world from antiquity. Each of these systems has its unique explanation of how
diseases are caused and how they should be treated. Except for homeopathic
doses of secretin, there are few reports of alternative medical systems for the
treatment of autism.
V. LIFESTYLE CHANGES
Lifestyle changes are helpful, actually essential, in coping with and caring for a
child with autism. Parents should be encouraged to join parent support groups,
obtain respite services, and practice behavioral relaxation.

A. Mind-Body Medicine
Mind-body medicine involves behavioral, psychological, social, and spiritual
attempts to treat the body by exerting the influence of the mind over the body.
The mind is the sum total of our thoughts, feelings, and memories. Each of our
thoughts, feelings, and memories is a chemical or electrical wave in the brain that
has the potential of circulating through the entire body. Thus, mind and body are
intricately interlinked and constantly affect each other. Mind-body treatments,
such as behavioral relaxation training, yoga, and mediation, are not effective for
autism per se, but can help the parents in coping with the condition of their
children.
B. Art, Music, and Dance Therapy

Such therapy has been used to improve social skills of children with autism and to
enable them to engage in some acceptable activity instead of a maladaptive
behavior to self-stimulate themselves.
VI. SUMMARY
The number of CAM treatments that are being promoted for autism is too large to
be covered in this book. Physicians should be cautious about cynically rejecting
these treatments, because some may have a placebo effect. If a treatment is not
harmful, even if not useful, one should not dissuade the patents from trying it.
Parents feel more empowered and in control if they make therapeutic decisions
about their children, right or wrong. However, if a treatment is potentially
harmful, one should caution the parents without paternalistically forbidding its
use. The parents should decide for themselves what is good for their child and
their family. The physician can assist them in this process but should not usurp
their autonomy. A few examples of CAM are given in Table 1 and a clinical
approach to CAM is presented in Table 2.
Table 1 Some Examples of CAM for Autism
Biological Diet, vitamins, minerals, secretin, detoxification

Educational Rapid prompt method
Communication Facilitated communication
Sensory therapies Auditory integration therapy
Body manipulation Touch, massage, chiropractic

250 Gupta
Table 2 Guidelines for Professionals Who Counsel Families About CAM
1. Keep an open mind. Instead of being overcritical, support parents in their quest for a
cure for their child’s condition.
2. Respect the parents’ autonomy in making decisions about their child. Avoid
paternalism. Do not judge and treat the parents adversely if the parents choose to try
CAM along with conventional medicine.
3. Stay informed about CAM and be willing to provide guidance and assistance to the
family in obtaining and reviewing information when the family is considering
controversial or unproven treatments.
4. Discuss CAM options with the parents when a treatment plan is being developed. State
whatever is known about a CAM, including its side effects, objectively and neutrally.
5. Discuss with the parents how to decide if CAM is based on hearsay or credible
scientific research performed by a number of researchers working independently.
Word of mouth, multisyllabic words, testimonials, and sponsored programs that make
tall claims for a product are red flags. Counsel the parents about the importance of
blinded controlled research with a comparison group. Newspapers and radio or TV
talk shows cannot achieve the rigor of science. Tell the parents about reputed sources
of information such as Medline Plus, the National Institute of Mental Health, the
MIND Institute of the University of California, EBSCO, and ERIC.
6. Support the parents in choosing a reliable practitioner of CAM and a reliable product
if they decide to try CAM. Help them develop some objective criteria to assess the
efficacy of the CAM. Encourage them to use conventional treatments as well when
CAM is being tried. Check for drug interactions.
7. Ensure that the treatments are not harmful to the child’s health and safety.
8. Check for fraud. Check the National Health Fraud Unit, the FDA, the National Center
for Complementary and Alternative Medicine (NCCAM) at www.nccam.nih.gov, the
Federal Drug Administration (FDA) at www.fda.gov, and Alternative Medicine Alert,
a monthly newsletter published by the American Health Consultants, to find out if the
claims of the alternative provider are extravagant and fraudulent. If it is an herb, check
the webpage of the Duke Center for Integrative Medicine at www.dukehealth.org/
int_med for its efficacy and toxicity. The Federal Trade Commission has a free
consumer alert about fraudulent health advertising on the Internet, called “Virtual
Treatments Can Be Real-World Deceptions.” It can be obtained by writing to the
Federal Trade Commission, Consumer Response Center, 600 Pennsylvania Ave.,
N.W., Washington, DC 20580, or by calling 877-FTC-HELP. Another useful site is
www.quackwatch.com.
9. Check that the treatments are cost-effective and that the family’s financial and
emotional resources are not compromised by the use of these treatments. Check the
cost of the treatment and suggest to the parents that they check with the insurance
company to see if it will pay for the treatment.
10. When in doubt, acknowledge ignorance and be willing to refer for consultation.
11. Do not take away hope. Even if the positive effect of a CAM is a placebo effect, let the
parents savor it, and positively acknowledge it.
12. Suggest that parents read the FDA Guide to Choosing Medical Treatments at
www.stopgettingsick.com.

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13
Planning Education Programs
for Students with Autism Spectrum
Disorder
Catherine Trapani
Marcus Institute and Emory University, Atlanta,
Georgia, U.S.A.
I. INTRODUCTION
Twenty years ago, autism was considered to be a rare, hard-to-diagnose disorder

that was far from newsworthy. Students with autism did not typically receive an
education in public schools, or if they did, they were combined in self-contained
classes with students with severe retardation. The salient features of the disorder
include delays in language, social competence, and presence of stereotypic and
persevative behaviors. These characteristics are evidenced in children before the
age of 3. Currently, the number of children diagnosed with autism spectrum
disorder (ASD) is 1/500 (1). As a result of the availability of assessment
measures such as the Autism Diagnostic Interview Schedule –Revised (2) the
diagnosis can be made reliably by the age of 2 (3), and ASD is a “hot topic” in the
popular and scientific press. In 1990, autism became an educational classification
in the revision of Individuals with Disabilities Education Act (IDEA) (4); thus
entitling students with ASD to a free appropriate education designed to meet their
needs.
Despite the increasing student body and the increasing knowledge base, no
single effective “appropriate” curriculum has been isolated, and controversies
rage among professional and parent groups about methods of intervention [i.e.,
applied behavior analysis (ABA), treatment and education of autistic and related

256 Trapani
communication-handicapped children (TEACCH), floor time]. Additionally, the

amount of intervention time that should be provided (20 –40 hr/week) is widely
debated. Therefore, the provision of “appropriate” treatment and education for
students with ASD is highly charged involving multiple disciplines and the
realms of litigation and public policy.
In addition to the controversy in identifying appropriate interventions there
exists the daunting mission of accessing educational and intervention services.
Despite the fact that IDEA is a federal law, there is a lack of parity nationwide
(between and within the states) on what constitutes an “appropriate” education
for any student falling within the realm of special education (5), but this is
especially true with respect to children with ASD. The operational definition of
the word appropriate has itself been the topic of litigation (6), and rightly so. The
language in IDEA is broad and vague making parents and schools vulnerable to
the very problems the law was designed to solve. On one hand, all schools are
required to provide appropriate (but not optimal) education. On the other hand, it
is difficult for parents to understand why students in some states have access to
ABA or TEAACH through public education (because they are deemed
appropriate), while the same services in other states are deemed to be optimal and
beyond what is expected of the schools. This disparity is emotionally charged and
has contributed to the rapid and significant increase in litigation regarding
students with ASD (7).
The litigious climate that has been created between parents and schools
regarding the design and delivery of services is difficult at best. The onus of
responsibility is on the parent to prove that the services provided by the school are
inappropriate (8). Although the outcomes of litigation nationwide have been
mixed (9), typically, the courts defer to the schools to select the methodology to
be used in the individual education program (IEP) (10). Ironically, in some cases,
the money involved in settling a case that has been ruled in favor of the parents
could have provided “state of the art” services for a number of children (11). (For
an extensive review of the special education law see Ref. 12.)
Clinicians know that the level of sophistication that parents possess
regarding their rights to a free appropriate public education (FAPE) or how to
approach their insurance provider is as diverse as the spectrum of autism. Some
parents are well apprised of their rights and access information about the latest
interventions. Others have no idea of what they should be asking during IEP
meetings or how to be evaluating their children’s progress from one year to the
next. Clearly, all parents of children with ASD want what is appropriate for their
children and realize that the stakes are high. The literature documents that
receiving early intervention can circumvent many of the difficulties associated
with the disorder possibly resulting in successful placement in regular education
within the public schools (13). Other parents, whose children experience less
success from early intervention, continue to advocate for the receipt of

Planning Education Programs 257
interventions that may assist in decreasing aberrant behaviors and increasing

even a modicum of independence. They realize that gains in appropriate behavior
and self-help skills will translate directly into quality-of-life issues long after the
public schools are responsible for their children.
ABA has produced the largest number of controlled studies using single
subject-designs documenting the efficacy of the approach (14). Additionally, the
Surgeon General has noted that ABA is the most effective means of teaching
children with ASD (15). Nonetheless, case studies and some empirical research
have documented the positive effects of other approaches. In 2000, the National
Research Council formed a committee to empirically review the research in
education and public policy and to create a framework for evaluating the
scientific evidence regarding features and outcomes of educational interventions
(16).
The search for an effective curriculum addressing the needs of students
with ASD continues, but guidance for parents, teachers, and clinicians is needed
until a perfect intervention is identified. In reviewing all of the treatment
paradigms, Lord and McGee (16) isolated priorities for intervention receiving
consensus from all. The efficacy of the different approaches to intervention will
not be reviewed in this chapter. Rather, the chapter will focus on reviewing the
critical elements of instruction as identified by the National Research Council.
These elements should be considered in the design of an IEP for students with
autism: behavioral interventions, communication, play skills, social skills; and
acquisition of cognitive and functional academic skills. For a comprehensive and
critical review of the extant literature refer to the National Research Council
publication Educating Children with Autism (16,17).
II. BEHAVIORAL INTERVENTIONS
Behavior problems are prevalent among persons with autism. In early childhood
tantrums and disruptive behavior are displayed, whereas adolescents and young
adults often exhibit aggressive, stereotypic, and self-injurious behaviors (18).
Often parents, teachers, and other caregivers inadvertently enable children to
manipulate their environment by displaying inappropriate behaviors, thus
reinforcing and maintaining them. Persistent problem behaviors may, over time,
interfere with participating in school, developing functional skills, and engaging
in community activities. Additionally, placement options for young adults are
often dictated by the presence of aberrant behavior (19). Once established,
problem behaviors require direct intensive intervention before they are
diminished. Consequently, behavioral intervention is optimal in early childhood

258 Trapani
to circumvent escalation of behaviors and is essential in older students to

diminish aggression, disruption, and self-injury (20).
During the 1960s learning theorists utilizing behavioral principles
produced positive gains in behavioral and educational intervention in students
with autism (21,22). Over the course of 30 years, behavioral interventions have
been effective in addressing a wide array of problem behaviors.
A recent critical review of the literature utilizing behavioral interventions,
documented that more than half of the studies reported an 80 –90% reduction in
problem behaviors of students with disabilities (23). The efficacy of ABA has
also been recognized by the 1997 amendment of the IDEA (24). Functional
behavior assessment and a behavior intervention plan are now required in the
IEPs for students with disabilities who have comorbid problem behaviors (25).
Although this mandate is promising for children with ASD who exhibit problem
behaviors, it is challenging for school systems that do not have the expertise or
economic resources to conduct functional assessments. To meet the requirements
of IDEA in a viable manner, rating scales and interviews have been utilized.
Although such measures are user-friendly and inexpensive, their reliability and
validity are dubious. Thus, experimental functional analysis is the assessment
method that is considered to be best practice (26). Studies have documented the
relationship between the precision of assessment and the success of the
intervention (27). This issue is especially relevant for students who have complex
severe behaviors that present a danger to themselves or others.
The purpose of functional analysis is to isolate the function of behaviors
exhibited and to identify the extent to which the outcome or consequence of the
behavior predicts its probability. Functional analysis differs from other
assessments (e.g., interviews, standardized tests) in that the variables believed
to affect behavior are systematically manipulated (28). The antecedents and
consequences associated with the problem behavior are isolated during various
assessment conditions (i.e., attention, toy play, demand, or alone conditions) and
observed in a controlled setting. The child randomly encounters one of the
four conditions in a series of 15-min sessions presented in random order.
Documentation of the occurrence of high rates of a target behavior during an
assessment condition is indicative of the function of the behavior (29). This is a
critical process as a behavioral intervention cannot be successfully designed and
implemented without identifying the specific function of the behavior (30).
When target behaviors are isolated and their functions identified,
behavioral strategies can be employed to reduce the incidence of problem
behaviors. For treatment to be effective, further assessment to identify reinforcers
that are highly preferred (31,32) and punishers that are least preferred (33) is
conducted. Fisher et al. (34) documented that the forced-choice assessment (e.g.,
stimuli were presented in pairs and the student was instructed to choose one of the
pair) was most effective in predicting stimuli that would serve as a powerful

reinforcer. Likewise, Fisher et al. (34) employed a strategy for assessing effective
punishers. The punisher that produced the greatest reduction in target behaviors is
selected for inclusion in the treatment protocol (34).
Currently, many schools employ positive behavior interventions that do not
utilize punishers. However, some behaviors may require the inclusion of a
punisher in an intervention to rapidly produce behavior change (35).
A. Issues for Planning Educational Goals

Children with limited communication skills and/or poor social development are
at risk for developing problem behaviors. If aberrant behaviors develop, trained
professionals should conduct functional assessments to ensure the safety of the
child and the reliability of the results (36). Parents should inquire about the
credentials of professionals conducting functional assessments and interventions.
The information obtained from the functional analysis should direct the
design of the behavioral intervention and be reflected in the behavior intervention
plan contained within the IEP (37). Sometimes, behaviors can be so challenging
to parents and teachers that it is easier to give in to them than to persist in
demanding compliance or appropriate behavior. Although this is understandable,
it is essential that the rewards received for engaging in problem behavior are
minimal. Once problem behaviors are maintained over time, they are exceedingly
difficult to change. To minimize the need to engage in aberrant behavior, children
should be given ways to control their environment by making choices and
receiving reinforcers for appropriate behaviors (38). For behavioral interventions
to be effective over time, parents and schools must work collaboratively in
collecting data on target behaviors and in implementing the behavioral protocol.
The systematic use of reinforcers and consequences across settings is essential to
maintaining the positive effects of intervention.
III. LANGUAGE AND COMMUNICATION
Consistent with the variability present within the continuum of ASD, the
population displays a wide array of language and communication deficits. Some
children’s language skills display idiosyncratic language or echolalia (39).
Individuals who do acquire complex language encounter difficulties similar to
those of their counterparts with learning disabilities, regarding conversational
turn taking, shifting language levels to fit the situation and skills of their
conversation partner, and following the social protocols of pragmatic language
(40). Similarly, nonverbal language skills are also problematic for children with
ASD (41).

260 Trapani
Problems in joint attention and use of symbols have been isolated as core
deficits in communication in this population (42). Joint attention refers to
problems in coordinating attention between people and objects. It relates to skills
in orienting and attending to a social partner, shifting gaze, sharing affect and
experience, and following the gaze and point of another person. Symbol use
refers to learning conventional or shared meanings for symbols including
gestures and words. Many individuals with ASD are limited in learning symbols
and in using conventional gestures such as showing, waving, pointing, and head
nodding (43). These are target skills for intervention (44). A relationship seems to
exist between competence in communication and behavior and overall level of
outcome. Thus, language is a critical area for intervention (45).
A. Intervention
Language and communication skill interventions have utilized developmental
and behavioral approaches. Although behavioral approaches to intervention are
more widely represented in the research, it is one area of intervention where the
two paradigms intertwine. Interventions have centered on developing functional
communication, as well as verbal and nonverbal communication (46).
1. Functional Communication Training

This intervention is used when the results of a functional analysis indicate that
problem behaviors such as aggression, tantrums, and self-injury are maintained
because they enable individuals to manipulate the environment by gaining access
to attention or escaping demands (47). Utilizing the elements of functional
analysis described in the previous section, individuals are taught communication
skills that provide access to the desired reinforcer (i.e., a break from work,
attention, change in setting). Studies of functional communication training have
culminated in robust findings in the ability to reduce problem behaviors (48).
However, the efficacy of functional communication training is not limited to
reducing problem behaviors, but includes teaching new methods (e.g., card
exchange) of communicating requests for attention, preferred activities, and
reinforcers. Functional communication can enable students to fully participate in
community settings (49).
2. Verbal Communication
A vast literature documents the effects of speech and language intervention for
children with autism. Most of these studies have utilized discrete trial training or
more contemporary approaches of applied behavior analysis to develop verbal
language skills, which have ranged from developing single-word vocabulary to

describing objects and pictures and responding to questions. Perhaps the most
widely known techniques are the discrete trial training protocols addressing
labeling and naming skills designed by Lovaas. Limitations of discrete trial
training are failure to develop spontaneous use of language and to establish
generalization in natural contexts (50).
Recent discrete trial training approaches have successfully taught
responses to “wh” questions and elicited descriptions of objects and pictures
(51) and comprehension of prepositions (52). Other contemporary approaches
include, but are not limited to, incidental teaching (53) and pivotal response
training (54). Incidental teaching techniques utilize naturally occurring adult-
child interactions to teach the language skills and incorporated behavioral
techniques such as prompting, imitating, and requesting (55). Pivotal response
training centers on initiation of communication that is considered to be a pivotal
behavior. Child-initiated communication will be a catalyst for responses from
others, thus providing reinforcers for communication and facilitate the
development of language skills (56). It has been documented that self-initiated
communications have been taught to children with autism who possessed poor
spontaneous communication (57).
3. Nonverbal Communication
The use of augmentative and alternative communication systems enables persons
with severe communication disorders to compensate for their disabilities by
supporting existent speech or developing nonspeech symbol systems such as sign
language, visual symbols displayed on communication boards, and voice output
devices. The goal of these systems is to empower individuals to independently
communicate their wants and needs (58).
Sign language has been used with many special education populations. It is
widely documented that total communication (use of both sign language and oral
speech) is an effective method of teaching receptive and expressive vocabulary to
individuals with autism (59). Signing does not hinder the development of speech,
but research findings suggest that it may enhance the use of speech. Acquiring
skills in signing is especially important for students with limited communication
who may never acquire speech (60).
It is essential to provide independent functional communication systems to
students with autism. Visual symbols have been used successfully to facilitate
compliance, initiate communication, and minimize dependence on verbal cues
(61). Nonetheless, the efficacy of a system of visual symbols that is most widely
used in public schools (the picture exchange communication system) is not
empirically documented (62).

262 Trapani
B. Issues for Planning Educational Goals

Language and communication are essential to facilitate independence and to
circumvent the development of problem behaviors. Therefore, parents and
professionals must be meticulous in designing language assessments and
intervention. Comprehensive assessments of receptive, expressive, and
pragmatic language skills are an essential first step in understanding the nature
and scope of language deficits and in implementing intervention (63). Teaching
sign language is helpful in providing students with a means to communicate as is
functional communication training. Photographic activity schedules and
augmentative communication devices should be probed. The efficacy of the
intervention must be carefully evaluated so that critical time is not lost; “based
on the available research with this population, progress on language and
communication goals should be evident within 2 to 3 months, or different
approaches should be considered.” Progress should be evaluated using data
collection methods consistent with single-subject design (64).
It may be helpful for parents and professional to collaborate in formulating
a plan that would determine which language interventions will be implemented,
the length of the trial for the intervention approach, and the next step in isolating
an effective treatment. Similarly, language intervention and data collection
should be implemented across home and school settings (65).
IV. PLAY SKILLS
Play presents a vast array of opportunities to assist children in developing

essential skills. Appropriate play skills provide children the ability to interact
with others and formulate friendships that are critical to social development
throughout life. A vast literature addresses the play skills in children with autism.
Skills deficits range from lack of organized, independent, cooperative play to
engaging in repetitive, deviant, or aimless play (66). Studies have indicated that
deficits in these areas of play are more problematic for children with ASD than
for mentally retarded or normal children (67). Students experience increasing
levels of difficulty playing with others as they progress in school if they have not
developed the cooperative and rule-governed play skills needed for participation
in group play. Functional and symbolic play have been identified in the literature
as two skill deficits that are critical to the development of viable play skills (68).
Functional play involves using objects appropriately during play activities
in a manner that is consistent with their function. Young autistic children show
less appropriate functional play in unstructured situations (69). Symbolic play
refers to the ability to substitute one object with another (i.e., using a play needle
as a microphone). Difficulties in developing functional and symbolic play may be

indicative of other related developmental delays. For example, researchers have

identified a relationship between delayed receptive and expressive language skill
deficits and functional and symbolic play skills (70). Delays in related skills
impact on the ability to develop and demonstrate play skills; therefore, it is
essential that those collateral skills (i.e., language, cognition, social skills, and
motor skills) be assessed. Selecting play activities that are consistent with a
child’s level of development may facilitate learning (71). Therefore, intervention
should focus on addressing the needs of the child rather than on engaging in age-
appropriate activities demonstrated by same-age peers (72).
A. Play Skill Interventions

Interventions can provide opportunities to engage in developmentally appropriate
play while at the same time moving children forward to higher developmental
stages (i.e., zone of proximal distance) (73). Initially, adults can mediate play
activities and model the appropriate varied use of toys and other playthings.
Adult and child-directed play can provide exemplars to children with ASD about
purposeful play that has a logical beginning and end. Such activities may have the
added benefit of improving language, cognition, and social interaction (74).
In addition to teaching isolated play skills, other skills have been enhanced
by including the ability to make social initiations using script-training photo and
written activity schedules (75). Issues about the motivation to play have been
addressed using choice making in pivotal response training (76). Additionally,
integrated playgroups have created environments in which to play and provide
opportunities for guided and peer-mediated intervention (77).

Engaging in developmentally appropriate play can be a catalyst for positive gains
developmentally. Scheduling numerous daily structured play periods and
incorporating adult and child-directed play activities is critical. Children with
ASD need direct instruction and guided practice in selecting preferred playthings,
using toys purposefully, and transitioning appropriately from playtime to other
activities. When these skills have been obtained, children should participate in
organized playgroups. Play buddies or playgroups should be carefully selected on
the basis of children’s skills, needs, interests, and ages. It is essential that children
encounter pleasure and success from such experiences (78).
Play should be incorporated in interventions that address other critical
domains such as language, social competence, and acquisition of basic academic
skills. These activities can be utilized in both the school and home settings (79).
Therefore, developing play skills, utilizing play across the curriculum, and

264 Trapani
planning for generalization of skills across settings should be goals included in

IEPs.
The skills that are afforded by playing are foundations for abilities needed
later in life, such as recreation and leisure time activity. The ability to organize
free time constructively and engage in solitary or group play activities without
assistance has critical ramifications regarding placement in postsecondary
settings and quality of life. These issues affect all individuals with ASD, but are
especially pertinent for those with moderate to severe difficulties. Recreational
and leisure time skills enable individuals to access group home placements or
have greater options for admission to more restricted residential settings.
Likewise, these skills foster inclusion in family activities over the course of a
lifetime. The importance of this cannot be underestimated. Individuals who do
not initiate activities or possess interests require constant supervision and
programming. Such persons are considered to be “high maintenance” and are
extremely vulnerable to abuse and neglect.
V. SOCIAL SKILLS
The general literature in social competence suggests that the use of prosocial
behaviors may contribute to the social adjustment of individuals and influence
their interpersonal relationships. Positive as well as negative social behavior
tends to be reciprocal (80). For example, observations of nursery school
children’s social behavior have revealed that positive social behaviors, including
giving attention and affection, expressing approval and personal acceptance, and
giving objects to another, are related to peer acceptance. Conversely, negative
social behaviors, including noncompliance, interference, and attack, relate to
rejection by others (81). Socially competent individuals posses the components of
social behaviors (i.e., facial expressions, gestures, greetings), monitor those
behaviors through a system of rules, and utilize these skills to obtain desired goals
(82).
There are critical social skills that appear to foster friendship such as
demonstrating sensitivity to the needs and feelings of others, expressing warmth
and affection, and sharing goals and activities. Moreover, attitudes that
precipitate friendship include finding people to be sources of satisfaction and
enjoying the exchange of affection (83). Obtaining and using the skills required
for reciprocal social exchanges and making friends are challenges experienced by
individuals on the autism spectrum (84).
Deficits in social competence were included in the first descriptions of
autism (85) and remain salient features of the disorder. Children evidence
delayed or aberrant social behavior beginning in early childhood (86). Compared

to same-age peers, children with autism exhibit more sterotypies and self-
injurious behaviors and spend more time engaged in meaningless activity (87).
Research findings suggest that social interaction is not reinforcing to many
students diagnosed with ASD (88). Proximity to peers is avoided or the quality of
interactions is lacking when these students do engage with others (89). This is an
issue of concern as reciprocal peer exchanges are salient to the development of
social relationships (90).
People with autism have difficulty talking to others (91) and coordinating
joint attention (92). At higher skill levels interpreting nonverbal language (93)
and comprehending humor are difficult for students with ASD (94). Additionally,
demonstrating the capacity to extend beyond self is problematic in this
population. A section of the Autism Diagnostic Interview Schedule – Revised
(ADI-R) (95) focusing on the assessment of social development and play
investigates the ability to offer comfort, among other behaviors needed to
formulate relationships. Developing empathy is important, as it is a core
requirement for establishing social relationships with others (96). Analyzing the
parent responses in ADI-Rs can assist in formulating and sequencing appropriate
goals for social development.
A. Intervention
Bandura’s work in social learning theory (97) posited that specific identifiable
skills form the basis for socially competent behaviors and that interpersonal
difficulties may arise as a function of a faulty and/or incomplete behavioral
repertoire (98).
Interventions have focused predominantly on developing social skills
in young children with ASD using a variety of techniques. Social skills training
has addressed initiating social exchanges (99) using picture schedules to
initiate social exchanges (100) and prompting reciprocal interaction through
incidental teaching (101). Other studies aimed at improving social interactions
have used social scripts (102), and substantiated the power of peer-mediated
interventions (103). Social behaviors have been increased by using peers in
pivotal response training (104) and involving children in integrated play groups
(105).
While there are numerous models for social skills training, no one model
fits all needs. Social skills training models share common elements: social skills
change to correspond to the social setting (106); verbal and nonverbal learned
responses guide interpersonal skills (107); social competence is dependent upon
the receipt of reinforcers (108); and models are designed with assumption that
skills can be taught (109).

266 Trapani
B. Issues for Parents and Professionals in Setting

Educational Goals
Social skills should be assessed to determine skill deficits and identify target
skills for intervention. Social skills training conducted by a school psychologist,
speech and language therapist, or social worker should be incorporated into the
IEPs (110). The goals of social skills training should reflect the child’s cognitive
ability and communication skills. Children need to receive direct instruction in
this area, as they will not develop or model socially skilled behaviors merely from
being in proximity to typically developing peers. Skill acquisition should be
monitored so that a different intervention can be utilized if indicated. Although
children with ASD may initially appear to prefer being alone, the most powerful
intervention and reinforcer for using prosocial behavior comes from the natural
environment. Children should have opportunities to practice the skills they are
learning in settings such as the classroom, the community, and the home (111).
Children should participate in playgroups, friendship groups, or groups that focus
on their special interests.
VI. ACQUISITION OF BASIC SKILLS
Some students with ASD possess abilities that enable participation in a traditional
academic curriculum, while others experience cognitive delays that compromise
participation in a functional curriculum. Irrespective of ability level, generalizing
what has been learned across materials, settings, and times is challenging. To
teach toward generalization, a curriculum should plan for practicing skills in
natural settings with naturally occurring reinforcers from multiple sources such
as parents, teachers, and peers (112).
Consistent with other special education populations, comprehensive
assessment must drive the design of the “what, how, and where” of educational
programming. Consideration of issues presented in previous sections of the
chapter must be reflected in the selection of the curriculum and the design of an
instructional schedule. Similarly, other attributes affecting learning, such as
attention, impulsivity, motivation, and cue dependence, must also be considered
(113). Irrespective of the level of ability, the goal of an educational program
should be to assist students in developing independence and obtaining quality of
life to the greatest extent possible (114).
The infinite number of interventions aimed at improving outcomes for
students with ASD is overwhelming leaving parents and professionals vulner-
able to the latest fads in treatment. After completing a comprehensive critical
review of instructional treatment programs for students with autism, the state

of New York concluded that instruction utilizing ABA was the only one that had
empirical merit and substance (115).
Although the term “ABA” is frequently used, many parents and
professionals are uncertain about what ABA really is and its approach to
intervention. Green (116) provides a succinct explanation in the following
passage from her article on behavior analytic instruction.
Behavior analytic instruction begins with a comprehensive assessment of each
learner’s current skills and needs, accomplished by observing the learner
directly in a variety of situations and recording what she or he does and does
not do. Every skill that is selected for instruction (often called a target) is
defined in clear, observable terms and broken down into its component parts.
Each component response is taught by presenting or arranging one or more
specific antecedent stimuli, such as cues or instructions from another person,
and/or items of interest to the learner. (116)
ABA relies on data collection so that educational and behavioral

interventions can be formulated systematically. Thus, individual assessment is
directly correlated with individual design and evaluation of goals, objectives, and
overall curricula (117).
A. Intervention
Olley notes that the emphasis of the literature is on the method rather than the
content of instruction (118). Consequently, it is easy to select a strategy of “how”
to teach, but often difficult to isolate and sequence “what” should be taught.
Appropriate educational programs for students with ASD require utilizing the
technology of instruction in designing errorless learning and structuring
environments that facilitate learning (119).
1. Instructional Techniques
In ABA, the instructional unit is the learning trial, which is defined as a structured
opportunity for a response, in the presence of an antecedent, followed by a
consequence (SRS) (120). Instructional methodologies address the manner in
which lessons are organized and delivered and responses are evoked. Instruction
can be organized in massed, spaced, and collective teaching trials. Massed trials
elicit the same response from students in rapid succession. Spaced trials require
students to complete a task with intervening intervals of time. Collective trials are
presented sequentially to students in group instructional settings (121).
The demonstration of learning can be solicited by employing systematic
antecedent and response-prompting strategies. Response prompting includes
strategies such as time delay and least-to-most prompts. Time delay techniques

268 Trapani
present prompts and fade them in incremental time segments between the
direction and the response. The system of least-to-most prompts utilizes a
prompting hierarchy. Following the instructional cue, response prompts of
gradually increasing levels of assistance are provided until the student
demonstrates the correct response (122). The use of preference and reinforcer
assessments (as described earlier) can assist in motivating students to learn and
empowering them with choices (123).
2. Learning Environments
Students with ASD rely on external organizers embedded within the environment
to anticipate tasks and expectations for performance. Thus, organizing the
setting, the timing, and the sequencing of tasks and presenting materials that
motivate the child to learn are essential. Dedicated space for specific learning
tasks should be defined within the classroom (124). Ideally, student schedules
should be organized by referring to the student assessment. Tasks that are difficult
should be presented at optimal times for learning for the individual (125).
Similarly, preferred activities can be used as reinforcers alternating the
presentation of them with difficult, less preferred lessons.
The use of visual supports represents best practice for many students with
ASD (126). Visual activity schedules using photographs or symbols provide
students with advanced organizers for the daily schedule (127). Picture schedules
can assist students in anticipating transitions, and in comprehending the demands
of activities and social interactions (128). Recent work by Stromer et al.
successfully incorporates computer technology in constructing activity
schedules. Computerized activity schedules enable students to independently
execute the visual and auditory prompts embedded in the program. This area has
promising implications for individuals with ASD who are cue dependent (129).

Parents and professionals are desperate for solutions to the problems experienced
by children with ASD. Often, interventions that are not empirically based are
utilized at significant emotional and financial cost (130). To date, a cure for
autism has not been identified. It is critical to investigate interventions before
implementing them (131). Children are entitled to participate in a learning
program that is designed to meet the needs of learners with ASD and taught by
professionals who understand the disorder. Parents should refer to the guidelines
of the National Research Council (132), in advocating for appropriate
educational programs for their children. The recommendations regarding
instructional time include instruction for a minimum of 25 hr weekly, sustained
over the course of the entire calendar year. Programming should include low

student/teacher ratios and family components such as parent training (132).

Children should not aimlessly proceed through their years in school without
making progress in IEP goals.
VII. SUMMARY
Across the nation parents with children challenged by ASD seek the services of
professionals who are knowledgeable and empathic to their needs. This quest is
as frustrating as the deficits that their children present, often depleting the
emotional and financial resources of the family. At this time there are vast
numbers of children in need of appropriate, effective intervention. Many
interventions are available that produce positive outcomes. It is important for
parents and professionals to be vigilant about obtaining assessments and
interventions that address skills identified as priority areas of development as
discussed in this chapter. It is equally important to investigate the efficacy of
those interventions so that critical time is not wasted in fruitless endeavors.
Behavioral and educational gains should be well documented and changes should
be made in instructional strategies if progress is not demonstrated within a
reasonable time. Developing self-help and leisure time activities are also critical
skills for students with ASD. Obtaining assistance in securing appropriate service
and developing these skills will potentially optimize future placements and
enhance the quality of life for students with ASD and their families (132).
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16(2):68– 71.

14
Science as a Candle in the Dark:
Evidence-Based Approach
to Evaluating Interventions
Charlene Butler
Seattle School District, Seattle, Washington, U.S.A.
I. INTRODUCTION
At the heart of science is an essential balance between two seemingly

contradictory attitudes—an openness to new ideas, no matter how bizarre or
counterintuitive, and the most ruthlessly skeptical scrutiny of all ideas, old
and new. This is how deep truths are winnowed from deep nonsense. The
collective enterprise of creative thinking and skeptical thinking, working
together, keeps the field on track.
Carl Sagan, The Demon-Haunted World: Science as a Candle in the Dark
(1996)
The judicious mix of these two modes of thought is crucial to the success of
science in the pursuit of truth. Good scientists do both. They churn up many new
ideas and winnow the wheat from the chaff by critical experiment and analysis to
try to distinguish the promising ideas from the worthless ones.
Earlier chapters of this book have demonstrated that treatment of autism,
like diagnosing it and understanding its cause(s), is still in flux. With a sense of
urgency created by a growing prevalence of autism, the health care and
educational communities have risen to the task of creative thinking and continue
to produce a plethora of new and appealing ideas about interventions that may
benefit children with autism.

278 Butler
Treatment for autism remains a particular challenge because it is still a

phenomenological diagnosis, that is, a diagnosis based on the symptoms of a
disorder—the social and language impairments and stereotypical patterns of
behavior. This is in contrast to an etiological diagnosis, which is based on the
causes of a condition. An etiological diagnosis is superior to a phenomenological
diagnosis because knowing what has gone wrong can lead to more specific and
effective treatment. Unfortunately, the causes, or etiologies, of autism are still
unknown; therefore, interventions have been somewhat hit or miss—and
controversial. Many quasi-scientific interventions are being promoted for autism
through the Internet and print and broadcast media without an objective analysis of
their efficacy. The multidisciplinary nature of some interventions makes it difficult
for professionals to assess the evidence from other disciplines. Despite a logical
façade and popular usage, many interventions for autism have not been found to be
efficacious under scientific scrutiny. It was this growing realization in medicine
that created the new movement in medicine called evidence-based medicine.
The practice of evidence-based care requires individual practitioners to use
interventions whose efficacy has been proved scientifically rather than
interventions based on clinical intuition. New tools are, therefore, needed to
help busy practitioners to view and scientifically scrutinize evidence. It is the
purpose of this chapter to demonstrate a new tool, called evidence-based reports,
developed by the American Academy for Cerebral Palsy and Developmental
Medicine (AACPDM), for skeptical thinking that can be applied to old, new, and
yet-to-be-offered interventions.
II. TOOL FOR CRITICAL APPRAISAL OF INTERVENTIONS
Evidence reports aggregate disparate data produced by a multidisciplinary field to

produce an evidence table after a systematic review process. The objective of the
AACPDM evidence reports is to provide the current state of evidence about
various interventions for the management of developmental disabilities. These
reports can be read on its online Database of Evidence Reports. It is possible for
anyone to create an evidence report by following a step-by-step process outlined
in the online Methodology for Developing Evidence Tables and Reviewing
Treatment Outcome Research (1).
An evidence table conveniently summarizes research findings and makes it
easy to identify current “best evidence” to inform individual recommendations
and choices. Best evidence is represented by a study (or studies) in an evidence
table that most closely approximates the client characteristics of interest to the
clinician, that used a therapeutic regime most like the one the clinician is

Evidence-Based Interventions 279
considering and can provide, that investigated outcomes of greatest concern to

this client, and that provided the most convincing or valid results.
The AACPDM adopted a two-part framework for its evidence table that
uses: (1) a dimensions-of-disablement classification within which to gather and
interpret disparate research data in a meaningful way, and (2) a levels-of-
evidence classification that puts the quality of all available evidence in a
meaningful perspective.
A. Dimensions-of-Disablement Classification: What Kind

of Evidence Is There?
Dimensions-of-disablement is a concept and a classification system developed by
the World Health Organization (2) that facilitates the description, measurement,
and management of rehabilitation outcomes and minimizes the barriers between
medical and social models of rehabilitation. Central to the concept is the idea that
the consequences of a medical condition occur in and are mediated at four
different reference levels of human experience: impairment of body functions,
impairment of body structures, activity limitations and participation restriction,
and environmental factors. Just as the disablement of autism can be described
according to the different dimensions in which it manifests, interventions and
outcomes can also be categorized by this classification.
1. Impairment of Body Structures

The Autism Tissue Program, a brain tissue donation program for the study of
brain tissue, may help to discover impairments of body structures that, in turn,
may lead to appropriate intervention in that dimension. Gene therapy may be an
example of an intervention with potential to alter body structures.
2. Impairment of Body Function

Neuroleptic drugs or megavitamins represent intervention in this dimension
because the intervention is expected to improve brain function, and, in turn,
social behavior, by altering the concentration of neurotransmitters such as
dopamine and serotonin. Expected treatment effects of sensory integration
therapy also target impairment of function, in this case, of impaired sensations
and response to them. Similarly, speech and language therapy to stimulate more
normal language development intervenes at this level.

280 Butler
3. Activity Limitations and Participation Restriction

Specific pragmatic language training to improve social interactions, on the other
hand, targets the activity/participation dimension. The use of systematically
developed “social stories” to increase understanding and handling of specific
social situations also attempts to intervene at this level.
4. Environmental Factors
Influencing social policies, reducing architectural barriers, and making low-cost
drugs available represent interventions in this dimension. Parent counseling or
training to enhance their parenting or coping skills improves the microenviron-
ment of the child and belongs in this dimension.
B. Levels of Evidence Classification: How Good

Is the Evidence?
The actual effectiveness of an intervention can only be established through
empirical research, i.e., direct observation and comparison of outcomes under
systematic and controlled conditions. The purpose of research is to tease out
attribution. In other words, it seeks to establish the extent to which any change
observed to occur in the presence of an intervention can be attributed to the
intervention rather than to some other factor present during a research study. For
example, it is possible that an observed change could be attributed to natural
history; that is, people with the medical condition of interest are known to get
better over time. The change may be attributable to normal variation in
symptoms, including periods of complete remission. Greater improvement
observed in a treated group may be attributed to the fact that the treated group
contained fewer severely involved individuals than the control group. There may
be any number of differences between the treated and control circumstances of a
study that can account for change observed in the presence of an intervention.
These “threats to internal validity” must be systematically controlled for there to
be confidence that an observed outcome can be attributed to the intervention.
AACPDM evidence reports classify evidence into levels-of-evidence based
on (1) a hierarchy of research designs that range from the greatest to least
according to ability to reduce bias and error combined with (2) a means of
assessing the thoroughness with which the particular research study was
conducted including use of statistical calculations or other determinants of
probability. The five levels of evidence reflect the methodological strength of a
study. Stronger levels of evidence (Levels I and II) suggest that there are fewer
sources of error present in the study design so that greater confidence can be
placed in the results. The weakest level of evidence (Level V) can only hint at a
possible connection between an intervention and an outcome because it is not

evidence derived from research but from theory or simple description of an

outcome that was observed with exposure to, or subsequent to, an intervention.
The conduct of the study serves as a second gauge to a study’s rigor, since
even a Level I study can contain flaws that decrease confidence in its results.
Given the opportunities possible under the research design, the strength of the
evidence depends on the extent to which possible threats to validity within that
design were actually controlled. The AACPDM assessment of the conduct of the
study results in a rating of strong, moderate, or weak.
C. Internal Versus External Validity

Unlike some others, the AACPDM classification is confined to gauging only the
internal validity of a study. Internal validity is the ability of a study to
demonstrate that the intervention—and not other factors in that study—was
responsible for the observed outcomes. External validity is the confidence with
which a finding might be expected to be true for others outside the study. As yet,
the bodies of evidence in developmental disabilities are neither robust nor
comprehensive enough to allow confident generalization to groups of people-at-
large. Therefore, external validity is not reflected in the Academy level of
evidence. Instead, whether a finding can be expected to generalize is believed to
be more appropriately determined by individual users of the evidence reports
who will focus on only the specific aspects of similarity between a patient of
interest and the people who have been studied (e.g., their age, severity and type of
autistic behaviors, secondary medical conditions, circumstances of treatment).
D. Group Results Versus Uniformity of Effect Results

In a trial that compares one group with another, not all the participants will
respond in the same way. In a positive trial, not all will have benefited from
therapy; in a negative trial, there may have been a subgroup, but too small to be
reliably detected, who actually benefited. Some studies report only how the group
as a whole fared, i.e., the averaged effect in the experimental group compared to
the averaged effect in the control. Other studies report only the uniformity of
effect within the treated group, i.e., how many of the participants improved, were
unchanged, or were worse. Some studies report both. The AACPDM summary of
results and evidence tables accommodate both types of these important results.
III. USING AACPDM EVIDENCE REPORTS TO EXAMINE

TREATMENT OPTIONS IN AUTISM
Autism has a history of theories and treatments proposed in multiple disciplines.

This is a strength in the sense that new knowledge and approaches continually

282 Butler
press us to reconsider assumptions and strategies. On the other hand, in the

absence of a coherent focus based on widely accepted theory, general clinical
support, and systematic medical research, such a diversity of approaches can also
be divisive.
The numerous intervention options this situation has generated can be
mind-boggling to the initiate. The Autism Society of America (ASA) (3) has
attempted to organize the various approaches. This listing does not imply
endorsement, efficacy, or even general acceptance by the field, by the ASA, or by
this author. It represents the kind of information that parents may have when they
consult health care and education professionals.
To demonstrate the AACPDM evidence report strategy as a useful tool for
sorting the wheat from the chaff, three interventions have been chosen from the
ASA list and one from the Cure Autism Now website. Evidence reports will be
developed and, in one case, only a critically appraised topic is possible. This
exercise will reveal the surprising lack of scientific evidence in place to support
even the most accepted, noncontroversial intervention (TEACCH). It will then
describe the body of evidence for a well-established but still controversial
intervention (sensory integration therapy) as well as a less widely used, even
more controversial intervention (megavitamin B6 therapy). Finally, it will
demonstrate how the popular press/media “buzz” about an intervention can
create the appearance of much evidence when there is essentially none, scientific
or otherwise (rapid-prompt method).
All four of these interventions are based on theoretical assumptions that the
inappropriate behaviors observed in autism are related to a dysfunctional nervous
system that is typified by cognitive and sensory-processing problems. In
TEACCH, integration and organization of sensory inputs for learning is
externally applied to the child through a highly structured, visually based
teaching method. In the newly proposed rapid-prompt method, the intervention is
also external to the child, but there is no attempt to integrate simultaneous
sensory inputs. Rather, the lack of sensory integration is recognized, but focus is
placed on using the child’s primary learning channel while ignoring other
channels, on giving sufficient time for a child to switch from one sensory channel
to another when necessary to do so, and on providing constant verbal prompting
for children. On the other hand, sensory integration and megavitamin B6
therapies are attempts to internally correct sensory processing. In sensory
integration therapy, the nervous system is thought to permanently change with
better ability to modulate, organize, and integrate through increasingly
appropriate responses to therapeutically designed somatosensory and vestibular
activities. Likewise, megavitamin B6 therapy is expected to alter brain
neurochemistry and, thereby, correct faulty sensory processing. All four
interventions attempt to intervene in the dimension of impairment of body
function but at different reference levels: vitamin B6 attempts to alter function at

the cellular level (neurotransmitters), sensory integration attempts to alter

function at the organ system level (the central nervous system), and TEACCH
and rapid-prompt methods attempt to alter emotional, social, and language
function (developmental domains).
Searches for studies about each intervention were conducted as follows.
Electronic searches on MEDLINE and Clinical Trials.gov were conducted via
PubMed; on ERIC, via AskERIC; and on CINAHL, via ERLWebSPIRS. Further
trials were sought through examination of references in studies and in review
publications. Full text of English-language publications that were available
through the extensive University of Washington health sciences and other library
collections were examined. In addition to, or in the absence of, professionally
peer-reviewed publications, a search on the Internet was conducted, with
particular attention given to the websites of Cure Autism Now, ASA, and Autism
Research Institute.
A. Evidence for Effects of TEACCH (Structured Teaching)

for Individuals Diagnosed with Autism
1. What Is TEACCH?
Treatment and education of autistic and related communication-handicapped
children (TEACCH) has had a most profound and long-lasting impact on the
treatment and education of children with autism (4,5). It started as a research
project that fundamentally changed thinking about autism and grew into a
comprehensive program of services for children and their families in the state of
North Carolina, and of research and professional training. This system of clinics,
classrooms, training programs, social outreach, and materials research and
development is funded by the state but administered by Division TEACCH,
Department of Psychiatry, University of North Carolina School of Medicine.
TEACCH has been endorsed by a number of groups over the years including the
National Society for Autistic Children (1972), American Psychological
Association (1986), and the American Psychiatric Association (1972). It is
recognized nationally as a center of excellence in autism.
TEACCH began in 1966 with Eric Schopler, whose NIMH-funded Child
Research Project tested the assumption that parental pathology caused autism.
Autism was considered an emotional problem—a withdrawal from pathological
parenting. Current thinking was that children needed to be under psychiatric care
in psychodynamic play therapy, be removed from their parents to residential
treatment, and be educated in classrooms established on the assumption that
children’s emotional learning problems would improve through freedom and
unstructured self-expression. Schopler found that autism was not caused by
parental pathology but by some form of brain abnormality and that parents of

284 Butler
children with autism were no more or less pathological than the general
population. Autism was not a form of social withdrawal but a developmental
disability characterized by impairment in relationships and communication skills
from the beginning of life and by repetitive preoccupations and movements.
In the ensuing years, Division TEACCH became foremost in the field,
publishing over 50 books, chapters, and articles to promote its precepts, and
editing the Journal of Autism and Developmental Disorders to keep up-to-date on
other work in the field. One of its main ongoing contributions has been the
diagnostic instruments and many special curricula developed by its research unit
in collaboration with its clinical units with subsequent field trials in TEACCH
classrooms and centers before publication. The curricula include social skills,
communication skills, preschool programs, teacher training, family training,
behavior management, prevocational training, job advocacy and placement, and
family advocacy (6,7). The concepts introduced by TEACCH that were so novel
at its inception have become “best practice,” and often standard practice, in
special education, and even mandated by law. Individualized education plans
(IEPs), for example, are now required by federal law and are based on
individualized assessment with parents as integral members of IEP teams.
More recently, a new principle has evolved at Division TEACCH. This
posits that people with autism should be understood and worked with, not in the
context of “normalization,” but in the context of a “culture of autism” (7). This
holds that people with autism are part of a distinctive group with common
characteristics that are different from, but not necessarily inferior to “normal”
people. Indeed, the differences between people with autism and others may
sometimes favor people with autism. Their relative strengths in visual skills,
recognizing details, and memory, among other areas, may become the basis of
successful adult functioning, if properly promoted and nurtured. Therefore, the
goal for helping people with autism is not to make them more normal but to
cultivate and emphasize their strengths and interests. This is in direct contrast to
most programs for developmental disabilities; they emphasize remediation of
deficits with exclusive focus on that goal. Moreover, capitalizing on individual’s
interests, however unusual they may seem to the outside observer, increases
motivation of people with autism for engagement and learning. Focus on
strengths and interests can enhance efforts to work positively and productively
with people with autism, rather than coercing and forcing them in directions that
do not interest them and that they may not comprehend.
TEACCH was, initially, an approach to management of autism
characterized by a new interpretation of autism that vindicated families,
established the need for structured teaching for children, established a
multifaceted professional-parent relationship, and provided an organizational
structure with collaborative policies that provided service and support to families
across multiple aspects of life and across the life span. The professional-parent

relationship included two-way trainer/trainee interaction, mutual emotional

support, shared community advocacy, collaborative staff selection, and working
together in classrooms and other settings.
The TEACCH approach today is characterized by understanding and
managing autism in the context of a “culture of autism,” developing appropriate
structures, promoting independent work skills, emphasizing strengths and
interests, and fostering communication, social, and leisure outlets. Of continued
importance in the TEACCH model is that these aspects of management are
implemented on a systems level (i.e., applied across age groups and agencies) (7).
Since its inception, TEACCH has also been regarded as a more discrete
intervention—a structured teaching program (1) with special emphasis on
training social skills and communication, (2) through a visual, nonverbal
restructuring of the teaching environment, (3) individualized to each child’s
developmental levels, (4) in which parents are regarded as critical agents of
change and are trained to be active collaborators and teachers. This specific
method of instruction is known as structured teaching. The method involves
teaching children with autism to use visual schedules and visual work systems
that are individualized to the developmental level of the child. These can be
extended and graduated as development occurs.
2. How Is Structured Teaching Purported to Work?

Visually clear organizational components are expected to help people with
autism cognitively organize and manage themselves for learning. A fundamental
assumption is that a child who understands what is expected will be able to work
independently on satisfying tasks that are within her/his capabilities. This child
will be less likely to engage in aggressive or self-injurious behavior than a
disorganized, anxious, agitated child who lacks a meaningful organizational
framework in which to understand productive activity.
Management of behavior problems within structured teaching is based on
the assumption that all inappropriate behaviors result from the cognitive and
sensory-processing problems that typify autism. For example, agitation (i.e.,
screaming without apparent cause) and aggression (i.e., pushing someone,
running away) may result from noxious hypersensitivity to sounds that the child
may attribute to people in the surroundings. It may be due to excessive frustration
experienced when the child needs to negotiate himself or herself out of an
upsetting situation—but has severe communication limitations. TEACCH
intervention responds to aggressive behaviors or behaviors that interfere with
learning by examining deficit areas associated with autism, then developing skill
training (i.e., training to become more functionally communicative or develop
frustration management skills), and environmental manipulation to reduce or
remove obstacles that are too great for the person with autism (8). If the behavior,

286 Butler
e.g., finger tapping, does not interfere with the child’s learning, this behavior is
accepted in the belief that this will advance the accomplishment of educational
objectives.
Most people will need special classrooms (or social or job settings) for part
or all of the time where their physical environment, curriculum, and personnel
can be structured to support individual needs. Some higher-functioning children
need less structure and can work effectively and benefit from regular educational
or other programs.
3. What Studies Have Been Done?

Electronic search for outcome studies using TEACCH with individuals
diagnosed with autism yielded only four citations: three studies and one report
listing publications by TEACCH through 1991. References in these publications
led to an additional eight citations. Three provided only background information,
one was a review of earlier work, and four were studies. Of the seven studies
located, one was excluded because only 51% of the participants had autism with
no data given for the autism subgroup. Six studies met the inclusion criteria and
are summarized in Tables 1 and 2. Table 3 is the evidence table.
4. How Much and What Kind of Evidence Is There?

Impairment of Body Function. Social-emotional development and
language development are the primary developmental domains that are
impaired in autism. Therefore, it is surprising that developmental status in only
the cognitive, motor, and perceptual domains has been measured. However,
developmental domains do influence one another. In 12 of 13 measures, exposure
to TEACCH resulted in improved developmental scores. The thirteenth measure
showed the TEACCH group to have slightly worse eye-hand coordination than
the control group.
What about the impact on autistic behaviors that are expected to improve
with the behavioral supports provided by TEACCH intervention? Unexpectedly,
this has been measured or reported anecdotally only five times. The impact of
structured teaching was positive with reductions in problem behaviors in all five
results; however, only one measure was statistically significant, three were not
statistically evaluated, and two were not statistically significant.
Activity Limitations and Participation Restrictions. Is more meaningful
activity and participation in family, school, and community life displayed as the
result of TEACCH? Out of three results about whether children were more
engaged with their environment (all positive), only one result was statistically
significant, one was not, and one was not statistically evaluated.

Table 1 Summary of Studies About TEACCH (Structured Teaching): Interventions and Participants
Study Intervention Duration Sample population Age N

1971 Structured vs. 8 wk Autistic children within 4 – 8 yr 5 (acted as own
Schopler (9) unstructured treatment psychotic range by Creak controls)
sessions criteria; social maturity
quotient 29– 86; 4 boys, 1 girl;
all social classes
1978 Parent training for and 2 mo Mothers of autistic children 33– 69 mo 10
Marcus (10) delivery of structured (psychosis rating range 4– 6 on
teaching/behavior Psychotic Rating Scale; IQ
management range 12– 89; all social
classes; 9 boys, 1 girl)
1980 Parent training for and 3 mo Psychotic (autistic) children Not known
Short (11) delivery of structured
teaching/behavior
management
1982 TEACCH system of Not reported Moderate to severely autistic 17 yr 115 in TEACCH
Schopler (12) programs vs. no older adolescents series
community support
1993 Cox (8) Structured teaching 2 wk Males with moderate to severe 16 and 19 yr 2
autism, moderate mental
retardation, severe temper
tantrums and dangerous
aggressive attacks
(continued )

Table 1 Continued

1997 Structured teaching 12 mo Autistic children and adolescents 7 – 18 yr 18
Panerai (13) with severe and profound
mental retardation,
stereotyped movement and
behaviors, aggressiveness and
self-injury; not able to work
independent of adult
supervision; inadequate
communication (gestures,
crying, vocalizations)
1998 Parent training for and 8 – 12 wk 9 Boys, 2 girls with autism, most 2 – 6 yr 11 treated plus 11
Ozonoff (14) delivery of structured with mental retardation; 2- control
teaching in home parent family; 21 Caucasian
program vs. no American, 1 Hispanic
treatment American; in day preschools
(15 in special autism
programs; 7 in noncategorical
public preschools)

Table 2 Summary of Studies About TEACCH (Structured Teaching): Methods, Outcomes, Measures, and Results
Study and Dim. of Clin.

research design Outcome of interest disability Measure Result imp. Statistics LOE
1971 Schopler: Attending in meaningful A&P Observation/time sample þ Yes p ¼ , .10 ns II-S
crossover activity — — — — — —
trial (ABAB Affective behavior A&P Observation/time sample þ Yes p ¼ , .10 ns II-S
design) Bizarre behavior IBF Observation/time sample þ Yes p ¼ , .10 ns II-S
Relating to people A&P Observation/time sample þ Yes p ¼ , .10 ns II-S
Using meaningful language A&P Observation/time sample þ Yes p ¼ . .10 ns II-S
1978 Marcus Child compliance behavior A&P Video observation þ Yes p ¼ , .005 IV-S
(10): before (staying on task) — — — — — —
and after case Maternal teaching EF Structure Rating Scale þ Yes p , .005 IV-S
series effectiveness
1980 Short (11): Autistic behavior IBF Video: direct behavior þ IV-W
before and Parent involvement EF Video: direct behavior þ IV-W
after case
series
1982 Schopler Family and community A&P Rates of institutionalization þ Yes III-W
(12): cohort participation (residence)
study with
retrospective
control group
1993 Cox (8): Aggressive behavior IBF Observation þ Yes V
case reports
(continued )

Table 2 Continued
Study and Dim. of Clin.

research design Outcome of interest disability Measure Result imp. Statistics LOE
1997 Panerai Adaptive development IBF Vineland þ Yes p , .01 IV-S
(13): before Perceptual development IBF PEP-R subscale score þ p , .05 IV-S
and after case Gross motor development IBF PEP-R subscale score þ p , .05 IV-S
series Fine motor development IBF PEP-R subscale score þ p , .05 IV-S
Cognitive development IBF PEP-R subscale score þ Yes p , .05 IV-S
Stereotypical behaviors IBF Structured observations þ Yes p , .01 IV-S
Aggressive behavior IBF Structured observations þ Yes ns IV-S
Behavior problems IBF Anecdote þ Yes V
Attending and working A&P Anecdote þ Yes V
Cooperating and working A&P Anecdote þ Yes V
Communication: frequency A&P Anecdote þ Yes V
and variety
1998 Ozonoff Overall development IBF PEP-R total score þ p , .05 II-S
(14): cohort Eye-hand coordination dev. IBF PEP-R subscale score — — II-S
study with Cognitive verbal dev. IBF PEP-R subscale score þ p , .15 II-S
prospective Perceptual development IBF PEP-R subscale score þ p , .15 II-S
control group Imitation development IBF PEP-R subscale score þ p , .05 II-S
Gross motor development IBF PEP-R subscale score þ p , .05 II-S
Fine motor development IBF PEP-R subscale score þ p , .01 IL-S
Cognitive development IBF PEP-R subscale score þ p , .01 II-S
These 30 results reflect comparisons of two groups, the same group under two conditions, status of a group before and after TEACCH structured teaching, or
simply describe a group without any comparison.
LOE, level of evidence; IBF, impairment of body function; A&P, activity and participation; EF, environmental factors; þ , improved; —, worse; ns, not
statistically significant; Vineland, Vineland Adaptive Behavior Scales-Survey Form (communication, socialization and self-help care); PEP-R,
PsychoEducational Profile, Revised.

Table 3 Evidence Table: Outcomes of TEACCH (Structured Teaching)
Improved Worse
Improved result result Unchanged or result
(statistically (not statistically ns ( p ¼ . .05) (statistically
Outcomes by dimensions of disability significant) evaluated) result significant)
Impairment of body structures
Impairment of body functions †† †† †† †† † †† †
†† †† ††
†
Developmental status (cognitive, motor, II-S (14,14,14,14,14,14,14) II-S (14)
perceptual domains)
IV-S (13,13,13,13,13)
Behavior (autistic, bizarre, aggressive, IV-S (13) IV-W (11) II-S (9)
problem) V (8,13) V (13)
Activity and participation † †† †† †† ††
Engaging in work and play activities IV-S (10) V (13) II-S (9)
(on-task, attending)
Engaging with people (affective, relating, V (13) II-S (9,9)
complying, cooperating)
Using language/communicating V (13) II-S (9)
Family and community participation (living III-W (12)
at home)
Environmental factors † †
Parent influence on child (effective IV-S (10) IV-W (11)
teaching/involvement)
The dots reflect 30 results from Table 4. Each dot is elucidated by its level of evidence (coded I –V for type of research design þ S, M, or W for strong,
moderate, or weak control to threats of validity in conducting the study) followed by the citation number for the study that produced this result.

292 Butler
There were also three results, positive, about engaging with other people,
but two were not statistically significant and the other was only an anecdotal
report.
Did TEACCH intervention produce more meaningful use of language?
There were three, positive, results about increased communication, but, again,
two were not statistically significant and the other was anecdotal.
Finally, one measure of participation limitation showed that even older
adolescents who were moderately to severely autistic were able to remain living
at home when supported by the TEACCH support system of structured teaching
at home and school plus training of and collaboration with parents. This result
was not statistically evaluated.
Environmental Factors. Parent influence on the child improved (with
statistical significance) in two measures that explored effect of structured
teaching training for parents. Parents became more effective in teaching their
own children and being involved with them.
5. How Good Is This Evidence?

This is an astonishingly weak body of evidence considering that Division
TEACCH has been the leader in autism theory and practice for over 30 years and
contains a university research unit that has published and taught professionals and
parents so extensively.
Levels of Evidence. The level of evidence derived from these studies is
Level II and III (one study each), Level IV (three studies), and Level V. In
addition, 6 of the 30 results are anecdotal and, consequently, reflect Level V
evidence.
Consistency of Results. While all the raw scores and anecdotal reports,
except one, were consistently positive in support of TEACCH, there were only 30
results of which only 15 demonstrated statistical significance.
Extent to Which Population Has Been Sampled. Only 41 children (and 11
control children) have ever been studied in five studies between 1971 and 1998.
Rates of institutionalization reported in the sixth study reflect residential data for
an additional 115 children.
6. Are There Subgroups for Whom TEACCH May Be More

Effective?
None of these studies reported uniformity of effect, that is, how many children
were better, worse, or unchanged after exposure. Factors that may account for
differing response to structured teaching were minimally explored in three

studies with no identification of subgroups on the basis of chronological age,

social age, socioeconomic status, severity of autism, and length of time in
treatment. Correlation with chronological age was inconsistent. One study (10)
found that younger children improved more than older children with mothers
trained to use TEACCH, but two others (9,14) found no correlation between age
and improvement. There was a tendency for children of lower socioeconomic
status to improve more when maternal teaching effectiveness and child
compliance were measured (10). Severity of autism correlated with improvement
in one of the studies (14) in that mildly autistic children who had higher initial
cognitive and language abilities benefited most, but in another study (9) more
severely involved adolescents were able to be managed at home (versus being
institutionalized) as often as were less severely involved adolescents. Social age
and length of time in treatment did not correlate with improvement (9).
B. Evidence for the Effects of Sensory Integration Therapy

for Individuals Diagnosed with Autism
1. What Is Sensory Integration Therapy?
A 1999 survey of occupational therapists showed that 99% of the 72 respondents
relied on sensory integration (SI) theory to inform their practice and provide the
therapy techniques they used with 2- to 12-year-old-children with autism (15).
The theoretical framework for SI therapy (16), based on the work of Jean Ayres
beginning in the early 1970s, holds that there is a natural human drive toward
purposeful somatosensory activity with its concomitant sensory input. The
neurophysiology of autism greatly reduces the capacity for this normal
engagement with the environment. Lacking the capacity for more complex
interaction as well as lacking normal somatosensory processing, the autistic
person’s drive toward action and sensory input is expressed, instead, in
nonproductive, stereotyped actions. Improving the person’s somatosensory
processing and capacity to register, orient to, and interact purposefully with the
environment will theoretically result in improved interactions and reduce the
need for autistic patterns of self-stimulation. The need for constant external
reinforcement will fade accordingly. Permanent changes in central nervous
system functioning are theorized to occur if the therapeutic process occurs early
in life while the system is still plastic.
SI therapy has been used in a number of pediatric populations. Meta-
analyses (17) of studies have shown effect sizes to vary from low to moderately
high depending on the populations studied, recency of the studies, and specific
parameters measured. Outcomes in psychoeducational and motor categories were
stronger than in other areas, at least for SI studies compared to no treatment
conditions; however, effects appeared to be equivocal when compared with

294 Butler
alternative treatments. However, autism is not a population that was represented

in these meta-analyses.
Clinical observations of children with autism and reports from Temple
Grandin (18) and Tito Mukhopadhyay (19), two individuals with autism who
have been able to write about their sensory experiences, lend credence to the
theory that autism involves a dysfunctional nervous system that does not
adequately modulate incoming sensory stimulation. Tactile defensiveness,
“nerve attacks,” anxiety, screaming, and tantrums may be overreactive responses
to incoming sensory stimuli by an overaroused nervous system. Stereotyped and
self-stimulatory behaviors may be attempts to calm one’s overly aroused nervous
system. The child may withdraw from the environment and people in it to block
out an onslaught of incoming stimulation. Alternatively, a child’s nervous system
may be underreactive to the extent that normal levels of sensory input fail to
register. Hyperactivity, stereotyped behavior, self-stimulation, and even self-
mutilation may reflect attempts of an underaroused nervous system to
compensate for the experience of physiological sensory deprivation. In such
cases, spontaneous abnormal motility (stereotyped behaviors) may be a way of
intensifying kinesthetic feedback.
2. How Is SI Therapy Purported to Work?

Disruptions in SI functions are treated by providing controlled, therapeutically
designed, meaningful sensory experiences (vestibular, kinesthetic, deep pressure,
and tactile stimuli) to which a child responds with adaptive motor actions.
Through this meaningful sensory input and appropriate active response to it, the
abnormal neurochemistry is corrected, and new neural circuits form to repair the
damaged nervous system (20).

Searching electronic databases and examining references in reviews and general
background articles yielded 25 citations. Upon examination, 11 articles provided
general information or were review articles and two (21,22) were studies not
relevant to this report. Twelve citations proved to be research studies in which
SI therapies were used for individuals with autism. Two (23,24) were not
retrievable for direct examination but were thoroughly reported in review articles
and were, therefore, included.
Variation of treatment implementation in studies has made it difficult to
establish equivalence of SI therapy for determining efficacy. Baranek (25)
classified the SI therapy that has been used in published studies as follows.

SI-Classical Therapy. SI therapy is classically a one-on-one intervention

model in a clinic environment that uses specialized equipment, specifically
suspended swings. Treatment plans are designed individually to provide a just-
right challenge to the child and engage that child in developmentally appropriate
play interactions. Therapy is guided by the child’s meaningful play, not by adult-
determined cognitive-behavioral strategies or repetitive drills. Treatment goals
center on improving sensory processing to either (1) develop better sensory
modulation as related to attention and behavioral control, or (2) integrate sensory
information to form better perceptual schemas and practice abilities as a
precursor for academic skills, social interactions, or more independent
functioning. The therapy is carried out in 1-hour sessions by an SI-trained
occupational therapist, 1– 3 times per week, usually for several months. Home/
school programs are often provided concurrent with the direct intervention.
SI-Based Approaches. These are interventions that deviate from classic
SI techniques in one or more criteria. (1) Somatosensory (e.g., brushing) and
vestibular activities are provided, but suspended equipment is not used. (2)
Treatment is more adult-structured or passively applied rather than being child-
directed play. (3) Treatment is more cognitively focused. Structured perceptual-
motor training approaches, sensory summation approaches (i.e., Sensory Diet),
and cognitive-behavioral approaches (i.e., Alert program) are examples. In
Sensory Diet therapy, the child is provided with a home and/or school program
of sensory-based activities aimed at fulfilling the child’s sensory needs. In the
Alert program a child (usually with higher functioning level and verbal abilities)
is given additional cognitive strategies to assist with his/her arousal modulation.
These models often utilize a direct intervention (one-on-one or group) plus
consultation/collaboration with caregivers who carry out home and school
programs.
Sensory Stimulation Techniques. These interventions use techniques (i.e.,
touch pressure, vestibular stimulation) that vary but involve the passive provision
of some type of sensory stimulation in a prescribed regime. They may be used in
isolation or be incorporated in a broader SI-based program. The assumptions vary
but most are based on neurophysiological principles stipulating that a given
sensory experience provides facilitatory or inhibitory influences on the nervous
system that change arousal modulation and behavior. For example, the
commonly used technique of “touch pressure” to provide a calming effect may be
applied via therapeutic touch (e.g., massage, joint compression) or an apparatus
(e.g., Hug Machine, pressure garments, or weighted garments). Vestibular
stimulation, another technique, applied in different ways may be used to
modulate arousal, facilitate postural tone, and increase vocalizations.
Four of the 12 studies matched Baranek’s criteria (25) for classic SI therapy
(16,26 – 28). Three studies matched the criteria for SI-based approaches (23,24,

296 Butler
29). (Two used structured sensorimotor interventions based on SI principles and

one used Sensory Diet. No studies of specific perceptual-motor treatments or
Alert program in which the children had autism were found.) Five studies were
found in which sensory stimulation techniques were the intervention (30 –34).
One of these reviewed effects of vestibular stimulation (30) and the others
investigated effects of somatosensory stimulation (i.e., some type of touch or
deep pressure). These 12 studies are summarized in Tables 4 and 5, Parts A and
B. Table 6 is the evidence table in Parts A and B.

Impairment of Body Function. Given that impaired sensory processing
and modulation is the primary problem in autism according to SI theory and
practice, it was surprising that outcomes about processing and modulation have
been measured only four times in two studies. While all four of these showed
improvement, only two measures were statistically significant, one was not, and
one was not statistically evaluated.
Autistic behaviors that are presumed to arise from sensory dysfunction
have been measured 19 times in seven studies with 17 positive results and two
unchanged results. However, only four of the positive results were statistically
significant, and 10 were not statistically evaluated. Five of the six measures of
anxiety (physiological and behavioral) in one study (34) were not statistically
significant.
One measure (29), not statistically evaluated, documented notable
improvement in physical posture after SI therapy.
Activity Limitations and Participation Restrictions. Was there an

increase in meaningful activity and participation in family, school, and
community life? Twenty-three results suggest there was. Greater engagement in
productive activity was measured five times. However, only two of these results
were statistically significant; two were not; one was not statistically evaluated.
One measure of self-help activity (toileting) was positive but not evaluated
statistically.
There were six measures about engagement with other people, two of
which showed statistically significant improvement with SI therapy. Another
positive measure was not statistically significant, and three were not subjected to
statistical evaluation.
What about communicating? These results were much weaker, including
three that showed the control group demonstrating greater improvement. Only
two of nine measures were positive but without statistical significance.
Finally, two anecdotes reported improvements in family and community
participation. After SI therapy, the single participant in one study (29) was able to

accompany family in the car safely and take advantage of community dental care
rather than requiring expensive, specialty dental care necessary before.
Environmental Factors. An anecdotal report (29) for the same child
indicated that caregiving in general was made easier as a result of SI therapy.

Levels of Evidence. Three studies used relatively strong research designs,
which produced half of the outcomes shown in Part A of Table 6. Twenty results
represent Level I evidence; 6, Level II; 5, Level III; 6, Level IV; and 11, Level V.
Part B results that illuminate how many of group did better represent Level IV
(nine results) and Level V (one result) evidence. Although the conduct of the two
Level I studies was also strong and one Level IV study was moderate, there can
be little confidence in the validity of the evidence from the others because it
derived from poorly conducted studies that employed weak designs.
Consistency of Results. Forty-one of the 48 group-average results and all
10 of the uniformity-of-effect results were positive. All 24 results about impaired
function were consistently positive.
Extent to Which Population Has Been Sampled. The greatest weakness in
this body of evidence is that only 75 people have ever been studied. Evidence is
available from only 12 studies, 6 of which contained only a single individual.
Only four studies contained 10 or more participants.
6. Are There Subgroups for Whom SI Therapy May Be More

Effective?
The uniformity-of-effect data in Part B of Table 6 shows that all individuals did
not respond equally to SI therapy. Six of 10 studied by Ayres and Tickle (26), all
five studied by Case-Smith and Bryan (27), and both studied by Linderman and
Stewart (28) showed improvement on some, but not all, measures.
Three studies investigated factors that may be associated with better
outcomes. Ayres and Tickle (26) and Edelson et al. (34) analyzed variables that
correlated with better and poorer responses to therapy. Ayres and Tickle found
that their good responders were those who, though few, initially presented with
normal reactions to sensory input. Of those with abnormal reactions, the ones
who initially showed tactile defensiveness ( p , .05) had the best outcomes.
Good responders also were those who initially tended to react to touch pressure
(p , .10), vibration (p , .10), and movement ( p , .10). Reaction to air puff,
pain, joint traction, insecurity in gravitational forces, postrotary nystagmus,
watching spinning stripes, bell and white noise sound, odor, and taste (flavor) did

Table 4 Summary of Studies About Sensory Integration Therapy: Interventions and Participants

1980 Ayres (26) SI-Classic: 50 min, 2/wk 1 yr Autism: 2 mild, 5 moderate, 3 – 13 yr 10
3 severe; 2 deaf; 1 partially
sighted; 6 ethnic groups; in
special education programs
1983 Ayres (16) SI-Classic: 2/wk 2 yr Severe autism, partially-sighted, 11.5 yr 1
deaf, female
1999 Case-Smith (27) SI-Classic: 30 min/?þschool 10 wk Autism, mental retardation; 2 4 – 5 yr 5
consultation bilateral hearing impairment; 1
bipolar disorder; in half-day
special needs preschool;
detailed behavioral description
of each child
1999 Linderman (28) SI-Classic: 1 hr/wk in clinic 7, 11 wk Autism, tactile hypersensitivity 3 yr 2
2; vestibular hyposensitivity 1
1983 Reillya (23) SI-based therapy/vestibular 3 wk Autism 6 – 11 yr 18 (own
treatment vs. tabletop controls)
activities (2 30-min
sessions of each)
1999 Larrington (29) SI-based therapy/oral motor 2 yr Severe mental retardation/ 15 1
stim., sensory stim. þ school autism, male; increasingly
and home program destructive and self-abusive;
normal hearing and sight, no
speech, some sign language
and receptive language

1999 Stagnittib (24) SI-based therapy/sensory diet 2 wk, 2, Sensory defensiveness, possible 5 yr 1
(brushing, joint compression, 5 mo apart autism
etc.) 3 – 5/day þ home
program
1988 Ray (30) SS techniques/self-initiated 4 wk Autism, male, dyspraxia, 9 yr 1
vestibular activity (15 min dysarthric speech, low muscle
2/wk) þ daily SI therapy tone, sluggish activity level,
normal hearing, sleep
problems, delayed cognitive,
motor and social development,
better receptive language,
actively seeks vestibular
stimulation
1990 McClure (31) SS techniques. Part 1: daily Part 1: Autism; mental retardation; 13 yr 1
elastic pressure wraps (elbow 53 days male; severe aggression, self-
splints); baths: vestibular Part 2: injury, stimulatory behaviors;
inputs. Part 2: elastic wraps, 15 days in psychiatric unit
arms or legs vs. no wraps,
4 sessions
1991 Zissermann (32) SS techniques/pressure garments Part 1: 2 mo Autism; female; severe 8 yr 1
worn only during Part 2: developmental delay, possible
measurement. Part 1: Gloves 18 wk seizures; self-stimulation;
(5 –30-min/sessions). Part 2: non-ambulator; in special
Jobst vest (9– 30-min sessions) education class for students
with multiple disabilities
(continued )

Table 4 Continued

1997 Field (33) SS techniques/touch therapy vs. 4 wk Autism diagnosed DSM-IIIR, in 4.5 yr mean 11/11
placebo/1 : 1 quiet play held in half-day special preschool, 12
lap (each 15 min 2/wk) boys, middle socioeconomic
status
1999 Edelson (34) SS techniques/touch pressure 6 wk Autism; 9 boys; meaningful 4 – 13 yr 5/7
(Hug Machine) vs. placebo (no communication 6, nonverbal
pressure) 220 min/wk or echolalic 6
a
Data extracted from review papers (25,35,36).
b
Data extracted from review (25).

Table 5 Summary of Studies About Sensory Integration Therapy: Methods, Outcomes, Measures, and Results
Part A. Average-of-Group Results: Experimental versus control groups, same group under experimental versus control conditions, before
versus after status of treated group, or description of posttreatment only
Study and Dim. of
research design Outcome of interest disability Measure Result Clin. imp. Statistics LOE
1983 Ayres Self-stimulatory behaviors IBF Time samples þa Yes V
(16):
prospective
case study
1983 Reilly Variety of speech A&P SVB of ASIEPb — Sign. IIc
(23):
single subject Mean length of utterance A&P SBV of ASIEPb — Sign. IIc
alternating Autistic speech A&P SVB of ASIEPb — Sign. IIc
treatments Speech function A&P SVB of ASIEPb ns IIc
ABAB design Articulation A&P SVB of ASIEPb ns IIc
Rate of vocalizations A&P SVB of ASIEPb ns IIc
1999 Larrington Physical posture IBF Photographs þ Yes IV-W
(29): single- Destructive behavior IBF Home/school charts/notes þ Yes IV-W
subject AB Engaging/playing A&P Home/school charts/notes þ Yes IV-W
design Toileting A&P Home/school charts/notes þ Yes IV-W
Family activity participant A&P Parent report/anecdote þ Yes V
Going to dentist A&P Parent report/anecdote þ Yes V
Easier caregiving EF Group home/family anecdote þ Yes V
1999 Stagnitti Tactile tolerance IBF Anecdote þd Yes V
(24): Affect A&P Anecdote þd Yes V
(continued )

Table 5 Continued
Study and Dim. of

research design Outcome of interest disability Measure Result Clin. imp. Statistics LOE
descriptive Activity level IBF Anecdote þd Yes V
case report Temper tantrums IBF Anecdote þd Yes V
1988 Ray (30) Vocalizing A&P Avg. % of time (audiotapes) þ Yes III-W
single- Spontaneous vocabulary A&P New word count (audiotapes) þ Yes III-W
subject ABA
design
1990 McClure Part 1: Long term — Part 1. — — —
(31): Part 1: Self-stimulation IBF Clinical notes þ Yes V
descriptive Self-injury IBF Clinical notes þ Yes V
case report; Interaction A&P Clinical notes þ Yes V
Part 2: Part 2: Short term — Part 2. — — —
single- Self-stimulation IBF Observation: % of time þe Yes III-W
subject ABA Self-injury IBF Observation: % of time þe Yes III-W
design Interaction A&P Observation: % of time þe Yes III-W
1991 Part 1: — Part 1. — — —
Zissermann Self-stimulation IBF Observation/frequency count þ Yes IV-M
(32): single- Part 2: — Part 2. — — —
subject ABA Self-stimulation IBF Observation/frequency count þ Yes IV-M
design
1997 Field (33): Orienting to sounds IBF Classroom observation þ p , .05 I-S
randomized Stereotypic behaviors IBF Classroom observation þ p , .01 I-S
controlled Touch aversion IBF Classroom observation þ ns I-S
trial Off-task behavior A&P Classroom observation þ ns I-S
Sensory responses IBF ABC (sensory score) þ p , .05 I-S

Relating A&P ABC (relating score) þ p , .05 I-S
Object use A&P ABC (object use score) þ ns I-S
Language A&P ABC (language score) þ ns I-S
Social skills A&P ABC (social skills score) þ ns I-S
Autistic behavior IBF ABC (total score) þ p , .05 I-S
Attention A&P ESCS ( joint attention score) þ p , .05 I-S
Behavior regulation IBF ESCS (regulation score) þ p , .01 I-S
Social behavior A&P ESCS (social beh. score) þ p , .05 I-S
Initiating behavior A&P ESCS (init. beh. score) þ p , .01 I-S
1999 Edelson Anxiety: behavioral IBF Tension Scalef þ Yes p , .01 I-S
(34): Anxiety: behavioral IBF Anxiety Scalef þ Yes p , .10 I-S
randomized Anxiety: behavioral IBF Restlessness/Hyperactivity Scf þ Yes p , .10 I-S
controlled Anxiety: physiological IBF Galvanic skin response-min U — ns I-S
trial Anxiety: physiological IBF Galvanic skin response-max U — ns I-S
Anxiety: physiological IBF Galvanic skin response-range þ — p , 10 ns I-S
LOE, level of evidence; IBF, impairment of body function; A&P, activity and participation; EF, environmental factors; þ , improved; —, worse; U,
unchanged; ns, not statistically significant.
a
Effective at 20 weeks, then deteriorated during subsequent 26 weeks while in body case following scoliosis surgery and after subsequent menarch.
b
Sample of Vocal Behavior of the Autism Screening Instrument for Educational Planning.
c
Inadequate information to rate conduct of study.
d
Improvement faded by 5 months posttreatment but 6- and 9-month assessments showed “sensory defensiveness cured.”
e
Carryover also present; ABC, Autism Behavior Checklist; ESCS, Early Social Communication Scales.
f
Based on items from Conners Patent Rating Scale.

Table 5 Continued
Part B. Uniformity-of-Effect-Within-a-Treated-Group Results
Study and research Improved Worse Unchanged
design Dim. Outcome of interest Measure result result result LOE
1980 Ayres (26): IBF Behavior (language, awareness Observations (qualitative and 6/10a IV-W
single-subject of environment, purposeful different for each participant)
ABA design; pre activities, self-stimulation,
and post social and emotional behavior)
measures

1999 Case-Smith A&P Mastery play Engagement check/videotapes 3/5 IVb

(27): single- A&P Nonengagement Engagement check/videotapes 4/5 IVb

subject ABA A&P Interactions Engagement check/videotapes 1/5 IVb
design: 3 wk
baseline, 10
week treatment

1999 Linderman A&P Social interaction FBA for CSIDc 2/2 d — IV-W

(28): single- A&P Response to affection FBA for CSIDc 1/1 d — IV-W

subject ABA A&P Response to movement FBA for CSIDc 1/1 d — IV-W

design: 2 wk A&P Approach new activities FBA for CSIDc 1/1 d 0/1 IV-W
baseline, 7 or A&P Functional communication FBA for CSIDc — V
11 wk treatment IBF Disruptive behaviors Anecdote 2/2

Indicates a statistically significant (p , .05) result.
a
All improved but 6 were rated as good responders and 4 as poor responders.
b
c
Modified Functional Behavior Assessment for Children with Sensory Integrative Dysfunction.
d
Visual analysis of trend, slope, level, and serial dependency calculations.

not predict the good responders. Edelson et al. found that their best responders
were those who presented with higher anxiety levels compared with those with
lower levels.
Ayres and Mailloux (16) reported a tendency for regression in adolescent
years associated with the onset of puberty. The authors offered this as possible
support for the success of SI therapy being based, at least in part, “on the capacity
to enter into the neurobiological development of the child during the early critical
period for maturation of sensory integrative mechanisms.”
7. Have Any Medical Complications Been Documented?

None were reported in the only study that tracked unintentional side effects (34).
C. Evidence of the Effects of Megavitamin B6 in Children

Diagnosed with Autism
Linus Pauling’s orthomolecular hypothesis appeared in 1968, proposing that
some forms of mental illness and disease are related to biochemical errors in the
body. In the early 1970s, Rimland (37), an advocate of megavitamin therapy,
reported that some autistic children responded favorably to high doses of vitamin
B6. In a subsequent trial of megavitamin B6, Rimland (38) observed that some
children experienced increased irritability, sound sensitivity, and enuresis when
vitamin B6 was given in large amounts, but these problems disappeared when
increased amounts of magnesium were added to dietary intake. Otherwise, there
was no evidence that massive doses of vitamin B6 had been harmful. Studies that
followed, therefore, used pyridoxine or vitamin B6 supplemented with
magnesium.
1. How Does Megavitamin B6 Therapy Purport to Work?

The proposed mechanism of action for megavitamin B6 is that a disturbance in
dopaminergic systems causes faulty central nervous system functioning that is
responsible for autistic behaviors. Vitamin B6 is involved in the formation of
dopamine and other neurotransmitters (i.e., serotonin, aminobutyric acid,
norepinehrine, and epinephrine) (39). Although vitamin B6 deficiency has not
been documented in individuals with autism (40), subclinical deficiencies might
be present, and vitamin therapy is believed to be a means of compensating for
such errors.

Table 6 Evidence Table: Outcomes of Sensory Integration Therapy
Part A. Average-of-Group Results. Experimental vs. control groups, same group under experimental vs. control conditions, before vs. after
status of treated group, or posttreatment-only description
Improved result Improved Worse result
Outcomes by dimensions of (statistically (but not statistically Unchanged or ns (statistically
disability significant) evaluated) (p ¼ , .05) results significant)
Impairment of body functions †† †† †† †† †† †† †† †† †† †† †† ††
Sensory response (tactile I-S (33,33) V (24) I-S (33)
tolerance, aversion,
defensiveness, orienting to
sound)
Behavior (self-stimulation, I-S (33,33,33,34) III-W (31,31) I-S (34,34,34,34,34)
destructive, tantrums, IV-W (29)
restlessness, activity level, IV-M (32,32)
self-injury, anxiety, V (16,24,24,31,31)
stereotypie, behavior
regulation)
Physical posture IV-W (29)
Activity and participation †† †† †† †† †† †† † †† †† †† † †† †
Engaging in work/play I-S (33,33) IV-W (29) I-S (33,33)
activities (off-task, using
objects, attending,
initiating)
Self-care (toileting) IV-W (29)
Engaging with people I-S (33,33) III-W (31) I-S (33)
(relating, socialization, V (24,31)
affect)

Using language/ III-W (30,30) I-S (33) IIa (23,23,23) IIa (23,23,23)
communicating (various
aspects of speech)
Family/community V (29,29)
participation (going to
dentist; riding family car)
Environmental factors †
Caregiving V (29)
a

Outcomes by dimensions of Unchanged
disability Improved result Worse result result
Impairment of body function ††
Behavior (general, disruptive) 6/10 IV-W (26)
2/2 V (28)
Activity and participation †† †† †† ††
Engaging in activities 3/5 IV (27)
4/5 IV (27)
1/1 IV-W (28)
Engaging and communicating 2/2 IV-W (28)
with people 1/1 IV-W (28,28,28)
1/5 IV (27)

Indicates a statistically significant (p , .05) result.

308 Butler

Electronic searching was completed on January 3, 2003 and yielded 15 citations
of interest. One citation was a letter to an editor about a 1995 review (39) of
megavitamin B6. Bernard Rimland, of the Autism Research Institute, in his letter
criticized the authors for failing to include some of the published reports. Despite
his assertation that there were 18 studies and despite attempting to secure those
citations directly from the Autism Research Institute, only nine discrete studies of
megavitamin B6 in which the participants had autism could be determined.
On examination of the initial 15 citations, two publications (39,41) were
excluded because each was a review article rather than a study, and another (40)
was an article containing only general information. Of the research studies, one
trial was excluded because it used a low dose of vitamin B6 that documented no
treatment effect at low dosage (42). Four were found to be multiple publications
of a study and were, therefore, excluded (43 – 46).
Two additional trials (39,41) were identified through the review articles.
Although these trials were published only in French (47,48), there was
sufficiently thorough description of the trials between the two English reviews to
include them in this evidence report. Nine studies met the inclusion criteria: (1)
large doses of vitamin B6 in (2) individuals with autism only or a subgroup with
autism for which separate data are given, and (3) only one publication of a study
included. Tables 7 and 8 summarize the studies. Table 9 summarizes medical
complications that have been reported, and Table 10 is the evidence table. Some
studies reported results that compared the average of the group’s results whereas
one reported results according to the uniformity of the effect within the treated
group (i.e., how many were better, worse, unchanged after treatment). This
requires that the summary-of-results table and the evidence table be presented in
two parts; Part A contains comparisons of the average of a group’s results and
Part B contains uniformity of effect results.

Impairment of Body Function. Table 7 (Part A) shows 15 results that
provide evidence about whether dopamine metabolism, hypothesized to regulate
central nervous system functioning, responded to megavitamin B6 therapy. Nine
studies used urinary homovanillic acid (uHVA), a metabolite of dopamine (39),
as a biochemical measure of dopamine neurotransmission, evoked potentials
(EP) as an electrophysiological measure of dopamine neurotransmission, or both.
Children with autism did appear to have higher levels of uHVA than did
healthy children based on evidence from an index group of 11 healthy children in
one study (50). What happened to those high uHVA levels in individuals with
autism? That was measured nine times (Table 10). Eight measures found more

normal uHVA levels with megavitamin B6 – magesium; two were statistically

significant, two not statistically evaluated, and four were not statistically
significant. One result showed no effect on uHVA levels (52).
Evoked potentials provide an electrophysiological measure of the brain’s
ability to process external sensory stimuli (39). Auditory and visual-evoked
potentials involve catecholamine metabolism, a system that includes the
neurotransmitter dopamine. Only two of four results confirmed more normal
evoked potentials when scores were averaged across occipital (O) and central (C)
sites. There were lower amplitudes, shorter latency periods, and greater
variability in individuals with autism compared to an index group of healthy
children. Given that averaging scores may obscure a treatment effect, the most
recent study calculated results for the occipital (O) and central (C) sites
separately. They found a statistically significant positive effect at the O site but
no treatment effect at the C site.
Did autistic behaviors diminish? Autistic behaviors were measured 13
times in seven studies (42,48 – 51,53,54). Although improvement was noted in
each result with 5 of the 13 measures reporting moderate to marked clinical
improvement (see Table 8), Table 10 shows that 8 of these 13 measures did not
attain statistical significance and two were not evaluated statistically.

Levels of Evidence. The majority of the studies produced Level I or Level
II evidence for 20 outcomes. There is Level III and IV evidence for the other 11
outcomes. In addition to using relatively strong research designs, the conduct of
most studies was moderate to strong in controlling threats to validity of the
results.
Consistency of Results. The 31 group-average results were not consistent.
Half showed improvement in dopamine metabolism and fewer than half
confirmed improvement in autistic behaviors. This may be explained in part by
the uniformity of results, which showed that although behavior improved in some
participants, it did not in the majority, and this positive effect for the responders
would be obscured when the results for a group were averaged.
Extent to Which Population Has Been Sampled. The greatest weakness in
this body of evidence is the extremely limited number of people who have ever
been studied. Evidence is available from only nine studies in which the exact
number of individuals who have been studied is clouded. There are 26
participants from two studies (49,54) who are clearly drawn from separate pools
of participants. The rest, drawn from a pool studied in France, almost certainly
reflect the repeat use of the same participants in more than one study. These seven
studies were done by a French group that included Martineau (first author for four

310 Butler
studies in this evidence report), Barthelemy, Jonas, and Lelord (each first author
for one study). One study (50) is known to have used participants in another study
(45). Given the time frame and place in which these studies were conducted and
the participant number in some of the publications, it is highly likely that there
were overlaps of participants between some or all of the studies published by the
French group. Thus, the total number of individuals from whom evidence is
available is almost certainly much fewer than the apparent 182 and may be as few
as 86 people shown in six of the studies (45,49,14).
5. Are There Subgroups for Whom Megadoses of B6 May Be

More Effective?
In a 1989 publication (53), Martineau et al. stated that, based on their experience,
approximately 15% of participants respond to B6-magnesium treatment and 30%
have mild positive effects. The only data that can be gleaned from this body of
evidence, however, is from one open trial (45) (Table 10, Part B) that reported 15
of 44 participants, or 34%, to be responders. When a group of responders and
nonresponders from this open trial were subsequently studied in a double-blind,
placebo-controlled trial, positive effects for B6-magnesium were documented in
12, or 57%, of the 21 participants.
Only one study (50) has attempted to identify the relationships between
various factors that may illuminate who the responders are. Potential variables
were examined but no relationships were discovered between uHVA and degree
of autism, Rimland scale, service scale, associated deficit, language development,
motor deficits, length of hospitalization, agitation, age of onset, and drug
treatment.
6. Have Any Medical Complications Been Documented?

A serious side effect of very high doses of pyridoxine (i.e., sensory neuropathy)
has been reported in the literature at large (41). In these studies of individuals
with autism who took 1 g/kg/day of vitamin B6, however, only three studies
(Table 9) reported adverse side effects and these were said to be manageable or
relatively minor. Once magnesium was added to the megavitamin therapy,
adverse effects were fewer still.
IV. CRITICALLY APPRAISED TOPIC
In the absence of any scientific publications, a topic can be critically appraised.

The best evidence for the rapid-prompt method, for example, describes the nature
and extent of the media, popular press, or Internet reports about an intervention
and what it is purported to accomplish in which dimensions of disability.

Table 7 Summary of Studies About Megavitamin B6: Interventions and Participants
Daily
megavitamin Comparison
Study treatment treatment Duration Population Na Age
1978 Rimland 2.4 mg/kg to 3 Phases of no Variable 12 Boys, 4 girls with autistic symptoms 16 4 – 19 yr
(49) 94.3 mg/kg treatment and from earlier megavitamin/cluster
B6 (mode 1 phase of analysis study who were B6-
6 mg/kg) placebo responsive and relapsed on
withdrawal; 6 had score indicating
definite presence of autism; living at
home
1980 30 mg/kg Placebo phase 14 da Autism diagnosed with DSM criteria 37
Barthelemy B6 þ 10 mg/
(47)a kg Mg
(continued )

Table 7 Continued
Daily
1981 Lelord 30 mg/kg Part 1: 2 phases Variable 4 wk Part 1: 26 boys, 18 girls with autistic 44 3.5– 16 yr
(45) B6 þ 10– of no symptoms: social withdrawal, (mean age
15 mg/kg Mg treatment stereotypies, tantrums, 9.3 yr)
hypersensitivity to stimuli,
aggressive toward self and others,
disordered eating and sleeping
behavior; 28 in long-term
institutional care; 7 severe MR; 33 no
speech. Heterogenous group: 16 most
clearly resembled Kanner’s original
description of autism, 28 had other
development/neurological disorders
with autistic signs (11 mild signs,
9 moderate, 8 severe)
Part 2: placebo Part 2: 13 responders (hospitalized in 21
phase child psychiatric service) and 8
nonresponders from Part 1

1981 Martineau 30 mg/kg 31 da 6 Boys; 6 girls from the Lelord study 12 Mean age
(50) B6 þ 10– 15 da above; severely disordered with 7 yr
15 mg/kg Mg autism: bizarre responses to
environment, stereotypies, aggressive
and self-destructive behavior, temper
tantrums, hyperesthesias, eating
problems, disordered sleep;
hospitalized in child psychiatric
service; associated disorders of
epilepsy 3/12, stunting 2/12,
hydrocephalus sequelae 1/12; 50%
on psychotrophic medications
1984 Jonas (48)b 1000 mg Placebo phase 42 da Autism diagnosed with DSM criteria 8
B6 þ 380 mg
Mg
1985 Martineau Up to 1 g/kg B6 2 Phases of no 8 wk each type 37 Boys, 23 girls with autism diagnosed 60 Mean
(51) or B6 þ 10– treatment; of phase with DSM-III criteria; hospitalized in age 8 yr
15 mg/kg Mg alternating day-care psychiatric unit; excluded
treatment patients with gross neurological
phases of Mg deficits, severe seizures, endocrine or
and placebo systematic disease
1986 Martineau 30 mg/kg 2 Phases of 8 mo Autism diagnosed with DSM-III 1 4 yr
(52) pyridoxine þ no treatment criteria: language retardation, social
15 mg/kg Mg detachment, seclusiveness: near-
normal nonverbal language age,
below-average social age, excellent
physical health, no developmental or
neurological abnormalities, normal
blood chemistry, urinalysis, and EEG
(continued )

Table 7 Continued
Daily
1989 Martineau 30 mg/kg 2 Phases of no 14 wk Boys with autism diagnosed with DSM- 6 4 y 7 mo –
(53) pyridoxine þ treatment III criteria: most disturbed in 8 yr
10 mg/kg Mg impaired communication, lack of
socially appropriate facial
expressions/gestures, resistance to
change, frustration, abnormal
aggression; global DQ 30– 70
1997 Findling 1 g/kg No treatment 10 wk 11 Boys, 1 girl diagnosed with autism 10 3– 17 yr
(54) B6 þ 10 mg/ and placebo using DSM-IIIR criteria; no medical
kg Mg phases or neurological disorders; no
psychotropic agents within 3 mo; all
lived at home
CPRS, Children’s Psychiatric Rating Scale; B6, vitamin B6 or pyridoxine; Mg, magnesium.
a
All participants crossed between treatment and control conditions.
b
Data taken from reviews (39, 41).

Table 8 Summary of Studies About Megavitamin B6: Methods, Outcomes, Measures, and Results
Part A. Average-of-Group Results. Average status of group during megavitamin B6 therapy compared with average status before andor after
therapy
Study and research Dim. of Clin.

design Outcome of interest disability Measure Result imp. Statistics LOE
1978 Rimland (49): Autistic behaviors IBF Individualized behavior þ Yes p , .05 II-S
placebo- checklists þ teacher/
controlled trial parent narratives
1980 Barthelemy Autistic behaviors IBF Bretonneau II (18 items) þ Moderate ns I-W
(47): Biochemistry: dopamine IBF uHVA þ I-W
randomized, metabolism
placebo-
controlled,
crossover trial
1981 Lelord (45): Biochemistry: dopamine IBF uHVA (gas þ Signif. III-M
Part 1: open metabolism chromatography)
ABA trial
1981 Martineau Part 1: Autistic behaviors IBF Bretonneau II (18 items) þ Marked — III-M
(50): Part 1: open Part 2: Biochemistry: IBF uHVA (gas þ p , .01 IV-W
ABA triala dopamine metabolism chromatography)
Part 2: open Electrophysiology: IBF AER middle latency þ IV-W
ABA triala dopamine metabolism amplitude
1984 Jonas (48): Autistic behaviors IBF Bretonneau III (22 items) þ Signif. II-S
placebo- Biochemistry: dopamine IBF uHVA þ ns II-S
controlled trial metabolism
(continued )

Table 8 Continued
Study and research Dim. of Clin.

design Outcome of interest disability Measure Result imp. Statistics LOE
1985 Martineau Part 1: Autistic behaviors IBF Behavior Summarized þ — ns II-M
(51): sequential Evaluation
controlled trialsb
Part 1: B6 Mg/ Part 2: Biochemistry: IBF uHVA þ ns II-M
Mg dopamine
Electrophys: dopamine IBF EP amplitude/ þ ns II-M
morphology
Part 2: B6 Mg/ Part 2: Autistic behaviors IBF Behavior Summarized þ Marked p , .05 II-M
placebo Evaluation
Biochemistry: dopamine IBF uHVA þ ns II-M
Electrophys.: dopamine IBF EP amplitude/ þ ns II-M
morphology
Part 3: B6/ Part 3: Autistic behaviors IBF Behavior Summarized þ ns II-M
placebo Evaluation
Biochemistry: dopamine IBF uHVA U II-M
1986 Martineau Autistic behaviors IBF Behavior Summarized þ Yes d
III-M
(52): open ABA Evaluation
trial Biochemistry: dopamine IBF uHVA (gas þ d
III-M
metabolism chromatography)
Electrophysiology: IBF EP amplitude/ þc d
III-M
dopamine metabolism morphology
1989 Martineau Electrophysiology: IBF AER frequency/ þ p , .05 III-W
(53): open ABA dopamine metabolism amplitude at O site
trial IBF AER frequency/ U III-W
amplitude at C site

1997 Findling (54) Autistic behaviors IBF CPRS ns II-M
placebo- Autistic behaviors IBF CGIS ns II-M
controlled, Autistic behaviors IBF OCS ns II-M
crossover Autistic behaviors IBF Teacher Rating Scale ns II-M
trial Autistic behaviors IBF Parent Rating Scale ns II-M
LOE, level of evidence; IBF, impairment of body function; A&P, activity and participation; þ , improved result with therapy; U, unchanged result; uHVA,
urinary homovanillic acid; AER, conditioned auditory evoked responses at occipital (O) and central (C) sites; EP, evoked potentials; ns, not statistically
significant; Signif., significant; CPRS, Children’s Psychiatric Rating Scale; CGIS, Clinical Global Impression Scale; OCS, NIMH Global Obsessive
Compulsive Scale.
a
Also contained an index healthy group.
b
Also contained an index group comparing magnesium and placebo.
c
Improvement after 1 mo followed by a shading off.
d
Data plots.
Part B. Uniformity-of-Effect-Within-a-Treated Group Results
Improved Worse Unchanged

Study Dim. Outcome Measure result result result LOE
1981 Lelord (45): IBF Part 1: Autistic behaviors Bretonneau II (18 items) 15/44 29/44 III-M
Part 1: open ABA
trial
Part 2: placebo- IBF Part 2: Autistic behaviors Bretonneau II (18 items) 12/21 II-S
controlled, crossover
trial in open-trial
responders

318 Butler
Table 9 Summary of Megavitamin B6 Studies: Medical Complications
Study Type of effect No. of cases

1978 Rimland (49) Increased irritability, sound sensitivity, and Not given
N ¼ 16 enuresis (resolved with addition of
magnesium to B6 administration)
1981 Lelord (45) Nausea 3
N ¼ 44 Increased excitability 3
Increased autistic symptoms 4
1997 Findling (54) Loose stools 5
N ¼ 10 Upper respiratory infection 5
A. Rapid-Prompt Method in Children Diagnosed

with Autism
1. What Is the Rapid-Prompt Method?
In January 2003, two national television stations [CBS’s 60 Minutes (55) and
ABC’s Good Morning America (56)] broadcast a story that challenges current
understanding about the limitations of communication in children with autism
and suggests a new educational strategy for teaching communication through
writing to severely autistic, nonverbal children.
In 1999, Tito Mukhopadhyay came to the attention of the National Autistic
Society in London, which brought him and his mother to a conference in the
United Kingdom. Tito is reported to be a boy with severe autism who is nearly
nonverbal but who writes poetry and essays in fluent English and whose written
communications have provided valuable insight about his experience of autism
through written answers to such questions as “Why do you flap? Why do you
rock? Why can’t you look me in the eyes?” In 2001, the Cure Autism Now
Foundation sponsored Tito and his mother to move to the United States to involve
them in the Carousel School for children with autism in Los Angeles. The Cure
Autism Now Foundation and its Carousel School have been interested not only in
the insights that Tito offers about autism, but also in the teaching technique his
mother, Soma Mukhopadhyay, used to get him to stay on task and eventually
write. They hope that other children with autism can be similarly “reached.”
Since coming to the United States, Tito, who is now age 14, has reportedly been
examined by several university researchers in autism and is said to be severely
autistic despite his unusual ability for written expression (57).
An American teacher who observed Soma Mukhopadhyay using rapid-
prompt method at the Carousel School with other students was said to have
described it as being “everything teachers of children with autism are trained not

Table 10 Evidence Table: Outcomes of Megavitamin B6
Part A. Average-of-Group Results
Improved result Improved result

Outcomes by dimensions of (statistically (but not statistically Worse Unchanged and ns
disability significant) evaluated) result results (p , .05)
Impairment of body functions †† †† †a †† †† †† †† †† ††
†† †† ††
†† †a
Dopamine metabolism III-M (45) IV-W (50) I-W (47) III-M (52) II-S (48,48)
(biochemistry) II-M (51,51,51)
Dopamine metabolism: III-W (53) III-M (52) II-M (51,51) III-W (53)
(electrophysiology) IV-W (50)
Autistic behaviors II-M (51) II-S (48,49) III-M (50,52) I-W (47) II-M (51,51,54,
54,54,54,54)
a
No effect at C site but positive effect at O site.
Outcomes by dimensions Improved Worse Unchanged

of disability result result result
Impairment of body function †† †
Behavior 15/44 III-M (45) 29/44 III-M (45)
12/21 II-S (45)

320 Butler
to do” (57). That is, teachers are currently trained to give basic directions and
wait for a response because too much verbalizing has been understood to be too
distracting. In contrast, Soma Mukhopadhyay talks constantly—repetitively
urging, prodding, and directing. Thus, her technique is being called “rapid-
prompt method.” Instead of being distracting, this rapid-prompt method seems to
keep the children’s attention focused long enough for them to communicate. She
also does not try to redirect students when they engage in stereotypic movements
and fail to make eye contact. Instead, she ignores their erratic movements and
wandering eyes because, according to insights gleaned from her son’s writings,
these behaviors appear to serve other important functions that do not interfere
with learning. Tito has written that he can either see or hear, but not both
simultaneously, so that he must choose one. He says that he rocks and spins
because he cannot feel his body unless it is in motion.
2. How Is It Purported to Work?

No mechanism of action has been proposed for the rapid-prompt method, but
Tito’s writings lend credence to a theory that autism involves scrambled brain
connections and faulty sensory processing. Such theory holds that during the first
years of life, children develop internal maps that involve brain regions
specializing in the sense of touch and movement. By imaging the brains of
higher-functioning autistic people who can stay still in scanners, researchers in
the laboratory of Dr. Eric Courchesne at the University of California at San Diego
were said to have found that autistic people had mixed-up brain maps (57). In
normal people, for example, face recognition occurs in a well-defined brain
region. In people with autism, face recognition occurs in other parts of the brain
such as the frontal lobes. The same is true of maps that help plan movements.
This means body maps are formed in autistic children, but they may be scrambled
differently in each person.
People who lack normal body maps may not build mental models of
the world that integrate sights, sounds, smells, touches, and tastes. Most people
can sense sound and light even when they are separated by only a fraction of a
second, but Tito cannot see light at all unless it is separated from sound by a full
3 seconds. Tito says he must choose one sensory channel at a time and prefers that
to be hearing. Vision is actually painful to him. To change channels, he needs
“time to prepare my eyes” or ears. “Otherwise the world is chaos” (57).

No citations for any professional reports were found in the medical or educational
literature with the search terms “rapid-prompt method,” “Tito or Soma
Mukhopadhyay.” To seek information in the lay media, a search on the Internet

via msn.com on February 2, 2003 yielded 114 results for websites that contained
the words “Tito Mukhopadhyay”; these included a link to the Cure Autism Now
website (58).
Examination of these Internet results showed, however, that all reflect the
same information that originated in a New York Times News Service story (57)
that subsequently appeared in multiple versions and venues: other newspapers,
People magazine, and three television broadcasts. In addition, one website shows
a book entitled Beyond the Silence, written by Tito Mukhopadhyay and published
by the National Autistic Society in London (19).

The New York Times article stated that Soma Mukhopadhyay is testing her
teaching method on a small group of children at the Carousel School in Los
Angeles, but no reports or research projects (proposed or funded) were listed on
the Cure Autism Now website. Cure Autism Now is a research foundation that
promotes and funds research, that is associated with the Carousel School, and that
sponsored the Mukhopadhyays to come to the United States. The sum total of
information about this intervention is that the rapid-prompt method has been tried
with a small group of students with autism, aged 9– 10, at the Carousel School in
Los Angeles with two outcomes that can be discerned from the stories. One
anecdotally reported outcome is marked improvement in communication (i.e.,
written language using full sentences, complex thoughts, correctly spelled words)
after 6 weeks in one boy with severe autism who is nonverbal, has unintelligible
sounds, engages in self-stimulation and/or uncontrollable movements (flapping,
rocking, lack of eye contact), and is diagnosed with probable mental retardation.
The other anecdotally reported outcome is improvement in a small group of
children with severe autism, a few of whom speak. After a year, their
instructional level improved from grade 1 to grade 4 and the variety of curriculum
used was expanded.

Though interesting, these reports are exceedingly preliminary, do not even place
on the AACPDM levels of evidence classification, and do not constitute scientific
evidence at any level.
V. IN THE ABSENCE OF SCIENTIFIC EVIDENCE

OF EFFECTIVENESS, WHAT THEN?
Absence of evidence in support of an intervention should never be construed as

proof that a treatment is not effective; rather, it may reflect areas in which

322 Butler
research—or more meaningful research—is needed. Frequently, absence of

evidence of effectiveness in existing studies is related to lack of power in a study
or the lack of statistical calculations that examine whether there was adequate
power to detect an effect. Moreover, even in a robust trial, the group results may
obscure benefits to some individuals. Nevertheless, absence of evidence in
support of an intervention does demonstrate that clinicians should be circumspect
about the voracity of their treatment recommendations in the face of scarce or
inconclusive evidence.
Use the evidence reports to frame clinical questions about any intervention
you entertain. “What do the proponents of this intervention purport that it will do
and in what time frame?” “What is the theory of the mechanism of action of this
intervention?” “Is this purported outcome of greatest importance to the individual
under consideration?” “What duration of treatment is reasonable to determine
whether the intervention is effective?” “What valid and reliable measure(s) can
be used to evaluate the outcomes in which we are interested?” “How can we
control threats to the validity of the outcomes we may observe?”
Next, conduct the time-honored, but improved, “trial of therapy” to
determine whether an intervention is positive or negative—for this person. David
Sackett and other leading figures in evidence-based medicine have incorporated
randomized controlled trial methods to create a more robust N-of-1 trial that has
wide application. Guidelines for conducting such a trial are summarized in their
handbook on how to teach and practice evidence-based medicine (59, p. 174).
If the N-of-1 trial does not demonstrate the intervention as effective for this
individual within a reasonable period of time, or show a definite trend toward
improvement, move on promptly to systematically explore other interventions
that may be more beneficial.
Finally, to build more robust and extensive bodies of evidence, even these
clinically based N-of-1 trials need to be replicated, outcomes aggregated and
analyzed as group data, and submitted for publication to build the bodies of
evidence needed for evidence-based practice.
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Appendix: Prognosis in Autistic
Spectrum Disorders
Chris Plauché Johnson and Vidya Bhushan Gupta
The prognosis for ASD should be considered in terms of change for the better,
rather than cure. Cure is rare in ASD. Although some children, particularly those
with normal intelligence, functional language, and absence of stereotypies, may
not be readily recognized as autistic later in life, most continue to have at least
subtle deficits in social skills. Prognosis has been shown to depend on two
variables: the degree of abnormal autistic behaviors and the level of adaptive
functioning in the community. Adaptive functioning is dependent on intelligence
as well as on daily living abilities. Throughout the life span these two variables
interact. The prognosis for any given child depends upon his/her place in the
spectrum for each of these interacting trajectories. It appears that prognosis for
independence as an adult may correlate better with level of adaptive functioning
than with the severity of autistic behaviors (1,2,3).
. Cognitive skills (intelligence): Although prognosis is thought to be

correlated with general intelligence, an isolated performance IQ score
does not accurately predict outcome. Good visual memory and pattern
recognition may skew results and fail to accurately reflect the child’s
problem solving abilities in real life. Moreover, it is difficult to measure
verbal IQ accurately in younger children, especially in those without
functional language. Children with mental retardation (IQ , 50) and
no functional language have the poorest outcomes, despite interven-
tions. On the other hand, one third of children with normal general
intelligence and functional language tend to improve with time, such
that they are able to participate fully in the community. The autistic

328 Johnson and Gupta
features may become barely perceptible except to the trained

professional. Twenty to fifty percent may attend college as well (3,4).
Early diagnosis and intensive intervention especially improves out-
come in this group of children.
. Language: Children who do not develop joint attention skills by the age
of 4 years or meaningful speech by 5 years have a poor prognosis (3).
. Comorbid medical and psychiatric conditions: Prognosis is worse in
those with comorbid medical (tuberous sclerosis, PKU) and/or
psychiatric disorders (i.e., obsessive compulsive behavior, hyperactiv-
ity, aggression, self-injurious behavior, and schizophrenia). Twenty-
five to thirty-five percent of persons with autism will develop a seizure
disorder. There are two peaks of onset of seizures in early childhood
and ado-lescence. A seizure disorder, especially one with onset during
adolesc-ence, is a poor prognostic sign.
. Gender: Generally, females with autism have a worse prognosis, but
this may be due to the fact that as a group, they have lower intelligence.
Additionally, fewer girls demonstrate savant skills.
In summary, prognosis should be guarded in children with subnormal intelligence
and little or no functional language and cautiously optimistic in children with
normal or above average intelligence and functional language. Prediction of
prognosis during the preschool years is difficult since IQ test scores and the
impact of intervention during this period can vary widely.
REFERENCES
1. Szatmari P. The classification of autism, Asperger’s syndrome, and pervasive

developmental disorder. Can J Psych 2000; 45:731–738.
2. Szatmari J, Merette C, Bryson SE, Thivierge J, Roy MA, Cayer M, Maziade M.
Quantifying dimensions in autism: a factor-analytic study. Am Acad Child Adolesc
Psych 2002; 41:467–474.
3. Coplan J. Counseling Parents Regarding Prognosis in Autistic Spectrum Disorder.
Pediatrics 2000; 105:e65.
4. Stone WL, Ousley OY. Pervasive developmental disorders: autism. In: Wolraich ML,
ed. Disorders of Development and Learning. 2nd ed, Philadelphia: Mosby-Year Book
1996, p. 379–405.
5. Committee on Educational Interventions for Children with Autism. Educating
Children with Autism. National Research Council. Washington DC: National
Academy of Sciences, 2001.

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Autistic Spectrum

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1. Prevention of Mental Retardation and Other Developmental Disabilities,

ADDITIONAL VOLUMES IN PREPARA TION

Copyright © 2004 Marcel Dekker, Inc.

VIDYA BHUSHAN GUPTA, M.D., M.P.H. is Associate Professor of Clinical Pediatrics

Copyright © 2004 Marcel Dekker, Inc.

Copyright © 2004 Marcel Dekker, Inc.

Copyright © 2004 Marcel Dekker, Inc.

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Copyright © 2004 Marcel Dekker, Inc.

Vidya Bhushan Gupta

Copyright © 2004 Marcel Dekker, Inc.

Foreword Alfred L. Scherzer

1. History, Deﬁnition, and Classiﬁcation of Autistic Spectrum

2. The Epidemiology of Autism and Autism Spectrum Disorders

4. Neurological Basis of Autism

5. Early Clinical Characteristics of Children with Autism

6. Screening and Diagnosis for Autistic Spectrum Disorders

Copyright © 2004 Marcel Dekker, Inc.

Copyright © 2004 Marcel Dekker, Inc.

Pasquale J. Accardo, M.D. James H. Franklin Professor of Developmental

Charlene Butler, Ed.D. Special Education Consultant, Seattle School District,

Kari A. Glasgow, O.T.R./L. Occupational Therapist, Department of Rehabi-

Vidya Bhushan Gupta, M.D., M.P.H. Associate Professor of Clinical Pedia-

Chris Plauché Johnson, M.Ed., M.D. Professor, Department of Pediatrics,

Copyright © 2004 Marcel Dekker, Inc.

Craig J. Newschaffer, Ph.D. Associate Professor, Department of Epidemiol-

Alfred L. Scherzer, Ed.D., M.D., F.A.A.P. Clinical Professor Emeritus of

Elaine Dolgin Schneider, M.A., C.C.C. Speech Language Pathologist, Pedia-

Patricia M. Stevens, B.S./O.T.L. Occupational Therapist, Department of

John M. Suozzi, Ph.D. Clinical Psychologist, Department of Psychology,

Sallie Tidman, B.S., O.T./L. Community Rehabilitation Manager, Depart-

Catherine Trapani, Ph.D. Director of Education, Marcus Institute, and

Marshalyn Yeargin-Allsopp, M.D. Medical Epidemiologist, National Center

Copyright © 2004 Marcel Dekker, Inc.

Vidya Bhushan Gupta

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(5), because of “severe and characteristic difﬁculties of social integration.” Like

II. AUTISM AS A TYPE OF CHILDHOOD PSYCHOSIS

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incorporated in DSM-III under the category of infantile autism (20). These

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Table 1 DSM-IV and ICD-10 Classiﬁcation of Autism and Pervasive

Pervasive developmental disorders, Pervasive developmental disorders,

Autistic disorder Childhood autism

III. AUTISM: FROM A PSYCHOGENIC

Families of the 11 children described by Kanner were “highly intelligent families,

Copyright © 2004 Marcel Dekker, Inc.

IV. AUTISM: A NEW DISORDER OR RECENTLY

Although autism was described as a distinct syndrome in 1943, it most certainly

Copyright © 2004 Marcel Dekker, Inc.

Although popular myth gives the impression that psychosocial deprivation