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DOI:
10.1016/S2215-0366(16)30032-3

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Citation for published version (APA):

Asherson, P., Buitelaar, J., Faraone, S. V., & Rohde, L. A. (2016). Adult attention-deficit hyperactivity disorder:
key conceptual issues. The Lancet Psychiatry, 3(6), 568-578. https://doi.org/10.1016/S2215-0366(16)30032-3

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Download date: 17. Oct. 2019

 Series

Attention-deficit hyperactivity disorder 2

Adult attention-deficit hyperactivity disorder:
key conceptual issues
Philip Asherson, Jan Buitelaar, Stephen V Faraone, Luis A Rohde

Lancet Psychiatry 2016; For many years, attention-deficit hyperactivity disorder (ADHD) was thought to be a childhood-onset disorder that
3: 568–78 has a limited effect on adult psychopathology. However, the symptoms and impairments that define ADHD often
Published Online affect the adult population, with similar responses to drugs such as methylphenidate, dexamphetamine, and
May 13, 2016
atomoxetine, and psychosocial interventions, to those seen in children and adolescents. As a result, awareness of
http://dx.doi.org/10.1016/
S2215-0366(16)30032-3 ADHD in adults has rapidly increased and new clinical practice has emerged across the world. Despite this progress,
See Series page 555 treatment of adult ADHD in Europe and many other regions of the world is not yet common practice, and diagnostic
This is the second in a Series of
services are often unavailable or restricted to a few specialist centres. This situation is remarkable given the strong
two papers about attention- evidence base for safe and effective treatments. Here we address some of the key conceptual issues surrounding the
deficit hyperactivity disorder diagnosis of ADHD relevant to practising health-care professionals working with adult populations. We conclude
MRC Social Genetic and that ADHD should be recognised in the same way as other common adult mental health disorders, and that failure
Developmental Psychiatry, to recognise and treat ADHD is detrimental to the wellbeing of many patients seeking help for common mental
Institute of Psychiatry
Psychology and Neuroscience,
health problems.
King’s College London, London,
UK (Prof P Asherson PhD); Attention-deficit hyperactivity disorder (ADHD) childhood. The present DSM-5 criteria allow for this
Radboud University Medical as a lifespan disorder possibility by stating that the criterion for age of onset is
Center, Donders Institute for
Brain, Cognition and
ADHD is classified in the American Psychiatric that “several inattentive or hyperactive-impulsive
Behaviour, Department of Association’s Diagnostic and Statistical Manual of Mental symptoms were present prior to age 12 years”.1 This
Cognitive Neuroscience and Disorders (5th edition; DSM-5) as a childhood-onset criterion allows children with subthreshold levels of
Karakter Child and Adolescent neurodevelopmental disorder, defined by the presence of ADHD symptoms and no impairment to meet diagnostic
Psychiatry University Centre,
Nijmegen, Netherlands
developmentally inappropriate and impairing levels of criteria for ADHD later in life and raises the possibility
(J Buitelaar PhD); Department inattention, hyperactivity, and impulsivity.1 Epidemio- that the full diagnosis of ADHD might emerge at
of Psychiatry and Department logical surveys find that 5–6% of children meet DSM-IV different developmental stages. The traditional
of Neuroscience and
criteria for ADHD,2,3 with a slightly higher prevalence explanation for this is that children with high intelligence
Physiology, State University
of New York (SUNY) Upstate expected when DSM-5 criteria are applied.4 Meta-analysis quotients (IQs) or well developed executive function
Medical University, Syracuse, of follow-up studies of children with ADHD found that skills, who are well supported by structured home and
NY, USA (S V Faraone PhD); 15% of children retained the full diagnostic criteria by the school settings, might make use of so-called external
K G Jebsen Centre for
age of 25 years, with a further 50% of those meeting scaffolding that facilitates compensatory behavioural
Neuropsychiatric Disorders,
Department of Biomedicine, subthreshold criteria with persistence of ADHD mechanisms. Once such external scaffolding is removed,
University of Bergen, Bergen, symptoms causing continued impairments.5 Another when leaving home and school for example, the full
Norway (S V Faraone); Hospital study using a survey approach of 629 adults in ten syndrome could emerge. Interestingly, this account of
de Clinicas de Porto Alegre,
countries found that 50% of children with ADHD later-onset ADHD shows the interdependence of the
Federal University of Rio
Grande do Sul, Porto Alegre, continued to meet diagnostic criteria for ADHD as association between symptoms and impairments of the
Brazil (Prof L A Rohde); and adults.6 More recently, two follow-up studies of children disorder. An alternative hypothesis suggests that ADHD
National Institute for from child mental health clinics in southeast England symptom expression depends on the efficiency of
Developmental Psychiatry,
and the Netherlands, meeting DSM-IV combined-type executive control processes.13 Poor maturation of cortical
Brazil (Prof L A Rohde)
(inattention and hyperactivity-impulsivity) criteria for control during the adolescent years might lead to later-
Correspondence to:
Prof Philip Asherson, MRC Social ADHD, found far higher persistence rates of ADHD in emerging ADHD in some cases. Findings suggest that a
Genetic and Developmental young adulthood, in the region of 80%.7,8 The increased late-onset ADHD-like syndrome might emerge, even in
Psychiatry, Institute of Psychiatry prevalence of persistence in these studies might be the absence of substantial childhood symptoms, perhaps
Psychology and Neuroscience,
related to the focus on combined-type cases, greater reflecting an acquired syndrome with a different set of
King’s College London, SE5 8AF
London, UK severity of ADHD in patients treated in European child causal risk factors.10,14
[email protected] mental health services, and the use of informant data Nevertheless, for the vast majority of patients diagnosed
when establishing the diagnosis at follow-up.7,9,10 with ADHD in clinical settings during adulthood, there is
These findings are largely consistent with the estimated a clear account of ADHD from childhood. Therefore, to
prevalence of ADHD in adults, which ranges from 2·5% provide an understanding of the developmental trajectory
to 3·4% in meta-analytic studies of population surveys.11,12 of the disorder, the way it presents in adults, and its effect
However, all adults meeting diagnostic criteria for ADHD on adult mental health is of considerable interest. Across
did not necessarily meet full ADHD criteria during their many regions of the world, ADHD is only just emerging as

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a disorder that is diagnosed and treated by adult mental important for trait-like disorders such as ADHD and
health services, despite the high prevalence of adult ADHD personality disorders, where the symptoms do not reflect
and established links to psychosocial, functional, and a change from the premorbid state. Thus, the diagnosis
mental health problems. Even more striking are the very of ADHD is to some extent dependent on perceptions of
high rates of undiagnosed or untreated ADHD within what amounts to clinically significant impairment.
adult clinical and forensic services. Several studies point to However, the symptoms of inattention and hyperactivity-
high rates of undiagnosed ADHD in prisons impulsivity are known to reflect individual differences in
(roughly 26%),15 addiction units (roughly 12%),16,17 and brain structure and function that largely derive from
general adult mental health services (roughly 16%).18 Rates genetic influences,33 and the associated impairments are
of adult ADHD in primary care are less well established, often severe.34
but it is clear that a substantial group of patients presenting In clinical practice, the continuous nature of ADHD
with non-psychotic long-term mental health problems should not present diagnostic difficulties in moderate-to-
meet diagnostic criteria for ADHD.19 severe cases, but might cause difficulties in mild cases
with more subtle forms of impairment. Careful attention
The diagnostic construct of ADHD is needed to assess the effect of ADHD symptoms on
For many years, researchers have argued that most impairment and quality of life, including an
mental health disorders reflect the extreme and impairing understanding of the broader range of problems linked
tail of one or more continuously distributed traits. Present to ADHD (eg, executive function [self-regulation]
research strategies, such as the Research Domain Criteria impairments, sleep problems, irritability, and internal
(RDoC), increasingly focus on delineating the underlying restlessness), in addition to functional impairments such
neurobiological substrates that underpin dimensions of as traffic accidents and occupational underachievement.
psychopathology.20 Among these, ADHD is one of the Therefore, some individuals, who seem to function well,
best examples in which no point of rarity can be found in might nevertheless suffer from a substantial mental
the distribution of ADHD symptoms and impairments health problem related to ADHD. When assessing
seen throughout the population.21 Symptoms of ADHD impairments, it is important to take into account that
cluster together into two key dimensions of inattention even minor levels of symptoms can cause considerable
and hyperactivity-impulsivity, are reliably measured, and distress to individuals because of the chronic and
are strong predictors of functional impairments, but they persistent nature of ADHD symptoms, which are
reflect continuous traits rather than a categorical experienced by people with ADHD on a daily basis.
disorder.22,23 Of particular relevance to adult ADHD is the
relative persistence of inattention and improvements in Rater effects and measurement of ADHD
hyperactive-impulsive symptoms during development, so symptoms
that many patients who had the combined type One factor complicating the assessment of ADHD is the
presentation of ADHD as children present with change in informant during development. Throughout
predominantly inattentive symptoms as adults.7,23,24 most of childhood and early adolescence, the primary
Many studies support the continuous nature of ADHD informants for diagnostic information are parents and
symptoms, although most of this work has been done in teachers, who report mainly on the basis of observed
children rather than in adults.21,25–27 These studies report behaviours. For this reason, the ADHD symptoms listed
the following: estimates of heritability are similar for in DSM-IV/5 and International Classification of Diseases
continuous ratings of ADHD symptoms in the general (10th edition; ICD-10) are largely descriptions of observed
population and the categorical disorder (around behaviours rather than subjective reports of mental state
70–80%);28 group heritability estimates show that genetic changes. Rater effects turn out to be important in the
risk for the disorder is shared with genetic risk for the assessment of ADHD.9,35 Several pieces of evidence
continuous trait;26,29 polygenic risk scores for ADHD indicate that informant report (eg, parents) is more
predict ADHD trait scores in general population accurate than self-report, with adults tending to under-
samples;30 the association of ADHD with cognitive rate their symptoms. Quantitative genetic studies using
performance deficits is similar for the clinical disorder ADHD self-report scales in general population twin
and ADHD symptom scores in general population samples find far higher heritability for parent report
samples;25,31 and risk of impairment shows a linear (around 70–80%) than for self-report (around 35–50%).36
relationship with severity of ADHD symptoms in Although these figures might be related to rater bias in
population samples.27,32 As a result, the boundary parents inflating heritability estimates, this seems
between patients with and without a clinically significant unlikely when converging evidence is considered. For
disorder is defined by the presence of clinically example, high heritability estimates based on diagnosed
significant impairment. Although the presence of cases of adult ADHD (using multiple sources of
impairment is a defining characteristic of many adult information) are similar to those of childhood cases of
mental health disorders, such as anxiety and depression, ADHD.28 Rater effects were also seen in a 6-year
the inclusion of impairment criteria is particularly follow-up study of children with combined -type ADHD.

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commission, and reaction time). The assumption made

Panel 1: Age-appropriate attention-deficit hyperactivity is that omission errors reflect behavioural inattention,
disorder symptoms (DSM-5) commission errors reflect behavioural impulsivity, and
• Mind seems elsewhere, even in the absence of any reaction time variability reflects fluctuations in
obvious distraction attention. An additional measure has been the use of
• Starts tasks, but quickly loses focus and is easily side-tracked actigraph data to capture overactivity during
• Fails to finish tasks in the workplace experimental tasks or in daily life. Of these measures,
• Reporting unrelated thoughts activity level rather than cognitive performance might
• Problems returning calls, paying bills, keeping appointments provide the best prediction of adult ADHD.7,37,38
• Difficulty in managing sequential tasks; difficulty in Preliminary studies show reasonable separation of cases
keeping materials and belongings in order; messy, from healthy controls when all parameters are combined
disorganised work (sensitivity and specificity around 85–90%), but poor
• Poor time management separation of cases from clinical controls,37,38 due to
• Tends to fail to meet deadlines heterogeneity and absence of specificity of the cognitive
• Feeling restless impairments to ADHD. Persistence of the disorder
• Unable or uncomfortable being still for an extended time, from childhood into adulthood might also be predicted
such as in restaurants or meetings by objectively measured activity level but not by
• Might be perceived by others as being restless and difficult cognitive performance measures.7
to keep up with Cognitive performance measures have also been
• Butts into conversations or activities, might start using investigated in children as predictors of the clinical
other people’s belongings without permission, might response to methylphenidate. Although drug effects on
intrude into or take over what others are doing cognitive performance measures are observed, these do
not seem to covary with the clinical response, suggesting
that the test variables cannot be considered proxies for
Higher prevalence of persistent ADHD was found when ADHD symptoms.39,40 Another approach has been the
the diagnosis was based on parent report than on self- use of electroencephalography as a cost-effective measure
report. Moreover, parent-reported ADHD, but not self- of neuronal activity, in particular the use of the theta-beta
reported ADHD was subsequently validated by the ratio (TBR) as an aid to diagnosis. Unfortunately,
association with cognitive performance measures on available publications and meta-analyses were unable to
sustained attention and inhibitory control tasks.35 find consistent case-control differences, indicating that
An attempt to improve the criteria by including more TBR has limited value as a diagnostic tool.41
age-appropriate descriptions has been included in DSM-5 Further research is clearly needed to identify clinically
(panel 1). These descriptions of ADHD symptoms are useful cognitive and neural biomarkers of ADHD,
nevertheless largely behavioural and might still be subject although these approaches are hampered by the marked
to rater effects. One alternative that could lead to more heterogeneity of the cognitive and neural deficits seen in
accurate self-ratings of ADHD is to focus on subjective adult ADHD. This obstacle complicates the identification
accounts of mental state phenomena, in the same way as of cognitive or neural measures, although it is feasible
individuals might report feeling depressed, experiencing a that such approaches will identify more homogeneous
panic attack, or hearing a voice. Surprisingly, there have subtypes of ADHD. Nevertheless, promising findings
been only limited attempts to pursue such a are beginning to emerge from neuroimaging studies,
phenomenological approach in ADHD. Another option is showing the increased sensitivity of measures of neural
to develop more objective cognitive or neuroimaging tests activity compared with cognitive performance measures.33
for ADHD. A further approach is to provide a more Examples include consistent evidence of reduced
detailed account of the types of behavioural problems activation of the ventral striatum when anticipating a
reported by adults with ADHD. As a result, providing reward42 and deficits in deactivation of the default mode
alternative accounts of adult ADHD that might provide network when engaging in cognitive tasks.43
more objective measures of ADHD symptoms, or a better One particularly interesting approach is to look for
understanding of the mental state changes and behavioural markers of clinical change which covary with the clinical
problems experienced by adults is of considerable interest. disorder, either during the treatment response to drugs
or during follow-up studies. An investigation of the
Cognitive and neuroimaging markers of ADHD covariation of ADHD symptoms with regional brain
Cognitive performance measures of attention and activation patterns during a functional MRI (fMRI)
impulsivity have been suggested in neurocognitive go/no-go paradigm (assessing inhibitory processes)
studies as markers of ADHD symptoms, with several during treatment with methylphenidate and atomoxetine
companies marketing different versions of continuous found that ADHD symptom improvement was associated
performance tasks (sustained attention and inhibitory with reductions in bilateral motor cortex activation for
control tasks that measure errors of omission, both treatments. Symptom improvements were also

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differentially related to gains in task-related activations Excessive mind-wandering

for atomoxetine and reductions for methylphenidate in Another common feature of adult ADHD is excessive
the right inferior frontal gyrus, left anterior cingulate, mind-wandering, also referred to as mental
and bilateral posterior cingulate cortex.44 Although these restlessness.56–58 In DSM-5, mind-wandering is briefly
preliminary findings are proof-of-principle at this stage, mentioned as the occurrence of unrelated thoughts.
they do show the value of outcome studies in Mind-wandering occurs when a person’s mind drifts
identification of neural biomarkers for ADHD symptoms. away from a task and focuses on internal thoughts and
images that are unrelated to the task or situation at hand.
Characteristic features of ADHD that support Although mind-wandering is a universal experience,
the diagnosis some forms of mind-wandering are detrimental because
Focus on the mental state of adult patients with ADHD they arise spontaneously and interfere with task
has been of more immediate clinical value than the use of performance. Interestingly, mind-wandering is
cognitive or neuroimaging data. Symptoms such as associated with performance deficits overlapping with
feeling physically restless, emotional dysregulation, those seen in ADHD, including educational performance,
excessive mind wandering, and sleep-onset insomnia are driving accidents, and cognitive performance errors such
all clinically relevant symptoms that are commonly seen as commission errors and reaction time variability on
in adult ADHD. Surprisingly, these symptoms are not sustained attention and inhibition tasks.59 Mind-
well studied in ADHD despite their potential value in wandering is also strongly correlated with neural activity
clinical practice. within the brain’s default mode network, which has
consistently shown deficient deactivation during task
Sleep problems conditions in ADHD.59,60 For these reasons, spontaneous
Disturbed sleep is reported by 70% or more of adults mind-wandering, detrimental to performance, has been
with ADHD. In particular, diurnal rhythm abnormalities proposed as a mechanism explaining some of the
have been identified that are associated with sleep-onset symptoms and impairments of ADHD.56
insomnia.45 Although not formally a criterion for ADHD, Several studies have reported increased spontaneous
the presence of sleep-onset problems associated with mind-wandering in adult ADHD.57,58 Adults with ADHD
reports of ADHD symptoms can be used to support the frequently report a distractible mental state with
diagnosis of ADHD. For example, many adults with multiple unrelated thoughts that are constantly on the
ADHD complain that they are too physically and mentally go and jump from one topic to another.61 Mind-
restless to fall asleep. We should also be alert to the wandering is also a feature of other mental health
possibility that sleep apnoea might cause symptoms of disorders such as depressive ruminations or obsessional
ADHD.46 thoughts and might therefore lack specificity. However
in ADHD, mind-wandering is characterised by
Emotional dysregulation unfocused, short-lived distractible thoughts with no
Another associated feature of ADHD, recommended by pattern of repeated thoughts or abnormality of content.61
DSM-5 as supporting the diagnosis, is emotional Our research62 showed that excessive mind-wandering
dysregulation including low frustration tolerance, was strongly correlated with ADHD symptoms, was a
irritability, and mood lability.1 Several reports highlight strong predictor of the diagnosis (sensitivity and
the very high frequency of emotional dysregulation in specificity around 90% for case-control differences), co-
adult ADHD with either rating scale measures47–49 or varied with ADHD symptoms over a 6-month period,
experience sampling of mood states throughout the day.50 and was a better predictor of ADHD-related impairments
These studies show that emotional dysregulation is than the inattentive and hyperactive-impulsive
present in non-comorbid cases of adult ADHD and symptoms of ADHD. Excessive mind-wandering has
predicts impairment beyond that explained by inattention several potential advantages as a clinical measure
and hyperactivity-impulsivity.47,48,50 A common set of because it reflects a characteristic feature of the mental
genes influence emotional dysregulation and core state reported by adults with ADHD and can be
ADHD symptoms in children.51 Importantly, emotional measured with rating scales56,58 and experience sampling
dysregulation in adults with ADHD responds to in daily life63 or during sustained attention tasks.57
stimulants and atomoxetine with a similar effect size as
the core ADHD symptoms of inattention and Executive function
hyperactivity-impulsivity.52–55 Although these findings Another aspect of ADHD is behaviour reflecting
suggest that symptoms of emotional dysregulation difficulties with executive functions such as inhibition
should be viewed as a core component of ADHD, because and working memory. Whether dysfunctions of executive
they frequently occur in other disorders (eg, anxiety, control reflect primary causal processes in ADHD is
mood disorders, substance misuse, and personality hotly debated. For example, cognitive test measures of
disorders) they are not used as primary diagnostic criteria executive control do not seem to predict long-term
for the classification of ADHD. outcome in ADHD,35,64 are not strong predictors of

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ADHD symptoms and impairments,65 and are neither psychiatric comorbidity, exposure to adversity, and a family
necessary or sufficient to cause ADHD.66 Furthermore, history of the disorder.76,77
the results of neuropsychological tests of executive There is also considerable interest in understanding
functions do not correlate highly with behavioural rating the cognitive and neural deficits that mediate genetic
scale measures of executive dysfunction.67 Nevertheless, risks on ADHD and might also be involved in persistence
at a behavioural level, ecologically valid descriptions of and remission of the disorder throughout development.
executive functions seem to show core behavioural One prominent hypothesis is that at the cognitive and
problems that are strongly related to ADHD and respond neural level, measures of executive control and
well to drug treatments for ADHD.68–70 These clinically preparation-vigilance reflect interacting processes with
useful measures can be captured by the Brief Rating different developmental courses that contribute to risk
Inventory of Executive Function,71 which assesses for ADHD. In a 6-year follow-up study using cognitive
organising, prioritising, and initiating work; focusing, and electroencephalographic data of 110 young people
sustaining, and shifting attention to tasks; regulating with childhood DSM-IV combined type ADHD and
alertness, sustaining effort, and processing speed; 169 controls, ADHD persisters differed from remitters
managing frustration and regulating emotions; using on preparation-vigilance measures but not on executive
working memory and accessing recall; and monitoring control measures.35 This finding suggests that the
and self-regulation of behaviour. preparation-vigilance measures might be markers of
remission that improve alongside ADHD symptoms. As
Course and outcome such, they might reflect malleable processes that can be
Reasons for the persistence and desistence of ADHD into targeted for prevention of long-term persistence of the
adulthood are not well understood, but are of considerable disorder. High IQ also seemed to play a part in reducing
interest because they identify potential targets for early risk for persistence of ADHD into young adulthood.
prevention and treatment. Factors influencing course and
outcome include general cognitive ability, severity of Adult-onset ADHD: a potential new trajectory
ADHD, causal factors (genes and environment), brain for the disorder
maturation and development, and the presence of co- ADHD has been traditionally conceptualised as a
occurring mental health and neurodevelopmental neurodevelopmental disorder and is included under this
disorders.33 Protective factors, such as exercise,72 might umbrella term in DSM-5.1 Although some disorders
also have an important role. One study73 using an adoption known to have a neurodevelopmental trajectory, such as
at birth design to control for genetic influences showed schizophrenia, do not necessarily begin in childhood,
the possible role of hostile parenting using mothers’ ICD-10 clearly defines that a neurodevelopmental
reports of their own hostile behaviour towards their child. disorder should have an onset during infancy or
In this study, hostile parenting was both evoked in parents childhood. Thus, it is not surprising that age-of-onset
by having an infant with high levels of impulsive and during early childhood emerged as a key element in the
overactive behaviour, but also acted as a causal influence definition of ADHD. However, in the past four decades,
by increasing the later development of ADHD symptoms experts behind diagnostic manuals have struggled with
in children. Consistent with this finding, another study the lack of evidence to define an accurate age of onset
found that high levels of parental criticism were associated beyond which symptoms should no longer be considered
with persistence of hyperactive behaviour between the part of the ADHD syndrome. The age of onset definitions
ages of 7 and 13 years, even after controlling for applied were based solely on clinical wisdom; DSM-III
oppositional defiant behaviour.74 Whether such parental introduced ADHD criterion B, requiring symptoms to be
effects have any effect on longer term outcomes in adults present before the age of 7 years, and DSM-IV-TR added
is not known. that impairment must also be present by this same age.
The role of genetic influences on stability and change in Under DSM-5 this definition has been changed to several
ADHD during adolescence and young adulthood has been symptoms (with or without impairment) before the age
investigated in population twin studies.75 The findings of 12 years.
suggest a core set of genetic influences that explain stability A report by Moffitt and colleagues10 presented new data
of the syndrome. However, in addition, new genetic effects challenging the notion that ADHD always begins in
influence risk for the disorder at different developmental childhood. In a representative birth cohort including
stages, which suggests that maturational or developmental 1037 subjects born in Dunedin, New Zealand, that were
processes come into play, altering the interplay of followed up to age 38 years with a retention rate of
neurobiological processes that lead to ADHD symptoms 95%, prevalence rates of childhood and adulthood
and impairments at different ages. At the clinical level, disorder were in accordance with estimates from
persistence of ADHD is associated with the severity of previously published work (6% in childhood and 3·1% in
ADHD during childhood,76 and might be particularly high adulthood). However, one finding challenged the present
for people with high levels of both childhood inattentive conceptualisation of ADHD. The great majority of
and hyperactive-impulsive symptoms6 and for those with individuals qualifying for a diagnosis of adult ADHD

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when the age-of-onset criterion was not applied (87%) did similar or different neural underpinnings, response to
not have prior childhood ADHD. Importantly, the ADHD treatments, and prognosis to the child-onset group.
features in these adults did not seem to be accounted by
their present comorbidities. Although both the child- ADHD, treatment, and comorbidity
onset and adult-onset groups showed similar levels of One reason for the under-diagnosis of ADHD by adult
impairments in adulthood, they seemed to differ with mental health services is the nature of the clinical
regard to symptoms of ADHD in adulthood, genetic syndrome, which shares characteristics with other
influences, and cognitive deficits. common adult mental health disorders. These include
Two other investigations in representative population clinical features associated with adult ADHD that do not
samples from other regions (Brazil and the UK) found form part of the present DSM-5 or ICD-10 diagnostic
similar results. In the 1993 Pelotas Birth Cohort, criteria. Examples include poor concentration,
5249 individuals were followed up to age 18–19 years, distractibility, restlessness, over-talkativeness, sleep
with 81·3% retention. Only 12·6% of young adults problems, irritability, impulsiveness, and low self-
meeting the symptom and impairment criteria for esteem. However, in this regard, adult ADHD is no
ADHD as adults had the disorder in childhood.78 In the different from other common mental health disorders,
E-Risk Longitudinal Twin Study, a UK nationally many of which also share a similar set of overlapping
representative birth cohort of 2232 twins born in England symptoms. One clear distinction from most adult-onset
and Wales with 93% retention at age 18 years, ADHD disorders is the typical early onset and trait-like
diagnoses were assessed in childhood at ages 5, 7, 10, and persistence of ADHD symptoms, which show what
12 years and in young adulthood at age 18 years. In someone is usually like, rather than a change in
individuals meeting ADHD criteria as adults, 67·5% did premorbid mental state and episodic course. Because
not meet the criteria for ADHD at any assessment at or diagnostic symptom overlap is common for adult mental
before age 12 years. Individuals with late-onset ADHD health disorders, this is unlikely to provide a full
showed similar ADHD symptoms and impairment explanation for under-diagnosis of ADHD. A far more
compared with the persistent group.79 likely explanation is the present absence of awareness
These findings suggest the existence of two and training in the diagnosis and clinical management of
phenotypically similar syndromes, with childhood onset ADHD in adults. Understanding of the similarities and
and adulthood onset of ADHD symptoms and impair- differences between adult ADHD and common mental
ments reflecting distinct developmental trajectories, health disorders such as anxiety, depression, bipolar
potentially linked to different causal influences and disorder, personality disorder, substance misuse, and
neural mechanisms. However, these are very recent antisocial behaviour is therefore of great importance to
findings and should be interpreted with caution. A third clinical practice. Such disorders occur at increased rates
of the sample in the Dunedin study14 had conduct in adult ADHD, when they could have a further effect on
disorder as children and others showed signs of ADHD, long-term negative outcomes. Comorbid medical
so the adulthood-onset individuals were not free from
earlier developmental problems during childhood.
Attention also needs to be paid to measurement issues Panel 2: Symptoms and impairments of ADHD that can
such as the use of self-ratings versus informant-ratings. mimic other mental health disorders
In the Dunedin sample, both the childhood-onset and Anxiety
adulthood-onset groups had similar levels of adult • Worrying about performance deficits, excessive
ADHD symptoms according to informant reports, but mind-wandering, feeling overwhelmed, feeling restless,
not according to self-ratings, and similar levels of adult avoidance of situations due to ADHD symptoms, such as
impairment. 14 This finding is in line with the ADHD difficulty waiting in queues or social situations requiring
clinical follow-up studies that show greater diagnostic focused attention, and sleep problems linked to mental
rates at follow-up when informant report, rather than restlessness
self-report, is used as the primary source of information.35
Further studies are therefore needed to clarify the Depression
proportion of adult cases that had subthreshold ADHD • Unstable moods, impatience, irritability, poor
symptoms as children, as well as to provide an improved concentration, sleep disturbance, low self-esteem
understanding of the clinical presentation of adults who • Personality disorder (eg, borderline and antisocial)
had ADHD as children. As discussed previously, • Chronic trait-like psychopathology linked to behavioural
alternative measures such as sleep problems, excessive problems, emotional instability, impulsive behaviour, and
mind-wandering, emotional dysregulation, and executive poor social relationships
function deficits could also be used to investigate the Bipolar disorder
onset and developmental trajectory of ADHD. Because at • Restlessness, sleep disturbance, mood instability,
present there are no clinical investigations of the ceaseless unfocused mental activity, and distractibility
adult-onset group, it is unknown whether they have

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and non-stimulant drugs show clinically significant

Panel 3: Key points and conclusions evidence for efficacy, the stimulants are more effective
Main findings for the short durations of treatment which are
• Adult ADHD is a common mental health problem affecting 2·5–3·4% of the adult characteristic of placebo-controlled studies.88 Evidence
population from controlled trials for the longer term benefits of
• Undiagnosed ADHD is found in 10% or more of non-psychotic patients attending pharmacological treatments is largely absent, although a
general adult, addiction, and prison mental health services systematic review identified five randomised controlled
• Beyond the core symptoms of inattention and hyperactivity-impulsivity, ADHD is trials and ten open-label extension studies with total
characterised by a wide range of mental health symptoms and impairments including follow-up of at least 24 weeks. All of the randomised
initial sleep insomnia, excessive mind-wandering, restlessness, emotional instability, trials reported that drug treatment was significantly
and behaviour showing difficulty with executive functions better than placebo for treating ADHD in adults; the
• ADHD symptoms and impairments can mimic other common mental health extension studies all reported that the favourable effect of
disorders, leading to incorrect diagnoses and targeting of treatments drugs seen in short-term trials was maintained during
• The treatment response of adult ADHD symptoms and impairments to stimulants and open-label follow-up.89 Pharmacoepidemiological studies
atomoxetine shows these drugs to be among the most effective pharmacological using national registry data highlight the potential for
treatments for any mental health disorder very substantial long-term benefits of treatment, not only
• Pharmacoepidemiological studies show reductions in criminal convictions, accidental on core ADHD symptoms, but also on serious co-
injuries, substance misuse, and suicides after treatment of ADHD occurring problems. By comparison of periods of patients
on and off ADHD drug treatments, reductions in
Research recommendations criminal convictions,90 transport accidents,91 substance
• Investigate the prevalence of undiagnosed ADHD in patients receiving treatments for misuse,92 and suicidal behaviour have been shown during
mental health problems in primary care periods on ADHD drug treatments.93
• Investigate objective measures of ADHD symptoms, characterisation of the mental Psychosocial treatments including psychoeducation,
state and behavioural problems experienced by adults to improve recognition of cognitive behaviour therapy, and use of support groups,
ADHD in clinical practice skills training, and coaching are thought to provide
• Identify cognitive, neural, and genetic biomarkers to aid in diagnosis, clinical additional benefits in the clinical management of
subtyping, and targeting or selection of treatments ADHD,94,95 although studies are generally small and not
• Investigate the effectiveness of ADHD drug treatments on ADHD symptoms and well designed. Whether such approaches reduce the core
impairments in the context of co-occurring personality, anxiety, and mood disorders symptoms of ADHD or rather improve secondary
• Investigate the effects of ADHD drug treatments on a wider range of outcomes outcomes such as psychosocial and functional
including emotional instability, aggression, dysthymia, and sleep problems impairments is uncertain. A study of 419 adult patients
• Investigate the effectiveness of psychosocial treatments (including cognitive with ADHD randomised to drug or placebo, with
psychological education, cognitive behaviour therapy, and mindfulness-based and without group psychotherapy, provides some
interventions) on longer term outcomes in ADHD clarification.96 Short-term and 1-year effects of drug
• Investigate ADHD trajectories comparing clinical and population samples with special treatment, but not psychotherapy, were seen on ADHD
attention to potential adulthood-onset ADHD symptoms. Group psychotherapy was, however,
associated with better 1-year outcome on a measure of
overall clinical improvement (clinical global impression)
disorders are also a concern, with substantial evidence when combined with the trial drug than when combined
associating adult ADHD with obesity,80–82 and data linking with placebo. This finding is consistent with present
the disorder to increased mortality, with the strongest guidelines that recommend psychological therapies are
single predictor being accident rates.83 used as an adjunct to drug treatment in adult ADHD.97

Treatment Comorbidity
The high rate of undiagnosed ADHD in individuals with Despite the obvious contribution that ADHD makes to
mental health problems is also a concern, given the adult psychopathology and mental health problems, the
availability of effective drug and behavioural treatments similarities and differences from other common mental
for ADHD. Short-term, randomised, placebo-controlled health disorders and the effects on treatment in comorbid
trials of methylphenidate, d-amphetamine, and cases are poorly understood. Three main groups should
atomoxetine all show marked clinical effects on ADHD be considered. In the first group, ADHD might mimic
symptoms, with standardised mean differences between other disorders, either because of overlap with core
drug and placebo groups in the range of 0·4 to 0·7 in ADHD symptoms such as restlessness and poor
adult ADHD.84–87 These moderate-to-large clinical effects concentration, or because of characteristic associated
compare favourably with the effects of antidepressants features of ADHD such as emotional instability, low self-
on depression or antipsychotics on psychosis, for esteem, and sleep problems (panel 2). This group of
example, demonstrating the importance of appropriate individuals is important to identify because they are likely
targeting of ADHD treatments. Although both stimulant to respond to appropriate drug treatment for ADHD.

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In the second group, neurodevelopmental traits and management of ADHD should be an essential component
disorders are often seen to develop alongside ADHD. of adult mental health care. A list of key points and
These include features of autism spectrum disorder, research recommendations is provided in panel 3.
specific reading difficulties (dyslexia), and developmental Contributors
coordination disorder (dyspraxia). Such neuro- The first draft of the report was written by PA and LAR. All authors
developmental comorbidities have a marked effect on contributed to the Review and writing of the report.
functional impairment but, unlike ADHD symptoms, do Declaration of interests
not respond to drug treatments for ADHD. In the past 3 years, JB has been a consultant or member of advisory
board or speaker for Janssen-Cilag BV, Eli Lilly, Lundbeck, Roche,
In the third group, co-occurring disorders might Shire, and Servier. He has received no other financial or material
develop as a complication of ADHD. For example, support, including expert testimony, patents, and royalties, or been an
children with ADHD are at greater risk for the employee of any of these companies, and is not a stock shareholder of
development of substance misuse disorders, anxiety, any of these companies. In the past year, SVF received income,
potential income, travel expenses, or research support from Arbor,
depression, personality disorders (including antisocial Pfizer, Ironshore, Shire, Akili Interactive Labs, CogCubed, Alcobra,
and borderline), and criminal behaviour. The effects of VAYA Pharma, Neurovance, Impax, and NeuroLifeSciences. With his
treating ADHD in this third group are not yet well institution, SVF has aUSA patent (US20130217707 A1) for the use of
researched and the present advice is based mainly on the sodium-hydrogen exchange inhibitors in the treatment of ADHD. In
previous years, SVF received income or research support from Shire,
experience of individual expert clinicians. For example, Alcobra, Otsuka, McNeil, Janssen, Novartis, Pfizer, and Eli Lilly.
although we know that emotional dysregulation often SVFaraone receives royalties from books. LAR reports grants and
improves when treating adult ADHD, there is little personal fees from Eli Lilly, grants and personal fees from Novartis
information on the effect of treating ADHD in comorbid Biociencias, grants and personal published by Guilford Press (Straight
talk about your child’s mental health), Oxford University Press
ADHD patients with borderline or antisocial personality (Schizophrenia: the facts), and Elsevier (ADHD: non-pharmacologic
disorders. Nevertheless, pharmacoepidemiological interventions), fees from Janssen-Cilag, grants and personal fees from
studies90–93 suggest that treating ADHD can reduce Shire, other from Oxford Press, and other from Artmed, outside the
submitted work. PA reports grants from Vifor Pharma and GW
associated criminal behavior, substance misuse, and
Pharma, other (non-personal pecuniary) from Shire, grants and other
suicide. (non- personal pecuniary) from Jannssen, other (non-personal
Another question is the part that ADHD plays in the pecuniary) from Eli Lilly, other (non-personal pecuniary) from Novartis,
maintenance of anxiety and depression and the effects of grants from QbTech, and other (non-personal pecuniary) from Alcobra
outside the submitted work.
treating ADHD in comorbid cases. The ubiquitous
nature of emotional symptoms in adult mental health Acknowledgments
PA is supported by NIHR Biomedical Research Centre for mental health,
means that all individuals with a non-episodic form of
NIHR/MRC (14/23/17), Action Medical Research (GN 2315), and
emotional instability should be screened for ADHD, European Union (643051, 602805, 667303). SVF is supported by the
including those with chronic dysthymia, cyclothymia, K G Jebsen Centre for Research on Neuropsychiatric Disorders,
and personality disorders. At present, such patients are University of Bergen, Bergen, Norway, and the European Union’s
Seventh Framework Programme for research, technological
often mistakenly diagnosed as having bipolar disorder, development, and demonstration under grant agreement no 602805 and
cyclothymia, or borderline personality disorder, even in NIMH grant R01MH094469. LAR is supported by a grant from National
cases where there are moderate-to-severe levels of ADHD Counsel of Technological and Scientific Development (CNPq; grant
symptoms and impairments.98 number 304678/2010-4). JB is supported by grants from the Netherlands
Organization for Health Research and Development
(ZonMw 60-60600-97-193), the Netherlands Organization for Scientific
Conclusions Research (NWO; grants 1750102007010, 433-09-242, and 056-13-015), and
We conclude that ADHD should be recognised in the by the European Commission’s Seventh Framework programme
same way as other common adult mental health conditions, (FP7/2007-2013) under grant agreement 278948 (TACTICS), 602450
(IMAGEMEND), 602805 (AGGRESSOTYPE), and 603016 (MATRICS),
and that failure to recognise and treat ADHD is detrimental and Horizon 2020 research programme (grant agreement 643051 [MiND]
to the wellbeing of many patients seeking help for and 642996 [BRAINVIEW]). His research also receives funding from the
mental health problems. Although further research is US NIH Consortium grant U54 EB020403, supported by a cross-NIH
needed to assess the effects of ADHD drug treatments in alliance that funds Big Data to Knowledge Centers of Excellence.
ADHD complicated by comorbidities, effective clinical References
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