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Child Adolesc Ment Health. Author manuscript; available in PMC 2014 September 01.
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Child Adolesc Ment Health. 2013 September 1; 18(3): . doi:10.1111/camh.12021.
Bipolar disorder in children and adolescents

Boris Birmaher1
1Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh
School of Medicine, 3811 O’Hara Street, Bellefield Towers Room 612, Pittsburgh, PA 15213,
USA. [email protected]
Abstract
Background—The existence of bipolar disorder (BP) in youth is controversial.
Methods—The current evidence regarding the diagnosis of BP in youth was reviewed.
Results—BP is a recurrent familial disorder that occurs in 1–3% of youth, particularly in
adolescents. Except for subsyndromal BP, the prevalence of BP-I is similar across most countries.
Due to the child’s immaturity, the presence of comorbid disorders, and divergent interpretations of
manic symptomatology it is difficult to diagnose BP in youth. Youth with subsyndromal mania
and family history of BP, are at high risk to develop BP-I and BP-II. Both the full and
subsyndromal syndromal BP are associated with significant psychosocial difficulties and
increased risk for use of substances, suicidality, legal problems, and services utilization.
Conclusion—BP disorder exists in youth, but it is difficult to diagnose. The recurrent nature and
psychosocial morbidity associated with this illness during critical developmental stages calls for
comprehensive longitudinal evaluation and accurate recognition and treatment because delays in
treatment are associated with poor outcome.
Keywords
children; adolescents; bipolar disorder; diagnostic controversies; family history
Introduction
Tom is a 12-year-old boy whose parents sought psychiatric consultation because he
experienced a one-month episode of depression which improved without intervention.

Thereafter, he became very happy and silly, talkative, energetic, and hypersexual. At the
same time, he slept only for few hours at night, was unable to sit still in class, his self-
esteem was elevated, or irritable. Due to recurrent disruptive behaviors, Tom was suspended
from school. He responded readily to treatment with a second-generation antipsychotic and
returned to his regular academic and social activities. Discontinuation of the medication
resulted in a recurrence of the depressive and later on, manic symptoms. Tom resumed the
same medication and began psychotherapy and he has been asymptomatic for one year.
Amy is a 9-year-old girl who for the last 2 years has been experiencing intermittent 2–3 day
episodes of increased activity, silliness, poor concentration, increased creativeness and self-
esteem, and lack of need for sleep without noticeable tiredness the next day. In addition, she
has had periods lasting 3–5 weeks where she is more sullen, angry, sad, tired, tearful,
distractible, and with less motivation and more defiant behaviors at home and at school.
Amy was diagnosed with attention deficit hyperactive disorder (ADHD) and oppositional
No other competing or potential conflicts of interest arise from the publication of this work.
Birmaher Page 2
defiant disorder (ODD) and treated with individual and family psychotherapy and thereafter
with stimulants, without response. After presenting to our clinic, it was decided to start
psychotherapy and observe her mood using mood diaries and frequent communication with
our clinic through visits, phone calls and emails. Six months later, it became clear that Amy
was experiencing recurrent episodes of major depression that lasted between 3–8 weeks,
interspersed with periods of normal mood or 3–4 days of hypomanic-like episodes. During
the hypomanic episodes she was very fidgety, very happy and silly above what is expected
for her age, disinhibited (talking to strangers, doing push-ups in the clinic’s waiting room),
very talkative, disorganized, and with less need for sleep. While in this mood, Amy
described herself as being “on fast-forward”. Treatment with mood stabilizers and
psychotherapy resulted in normalization of her mood and behavior at school and at home.
As reviewed in this article, there is growing literature showing that similar to the examples
of Tom and Amy, there are children and adolescents with symptoms that suggest bipolar
disorder (BP). In fact, several studies across the world have consistently reported that up to
60% of adult patients with BP report the onset of their mood symptoms before age 21 years
old (e.g., Baldessarini, Bolzani, Cruz, Jones, Lai, Lepri, Perez, Salvatore, Tohen, Tondo, &
Vieta, 2010; Chengappa, Kupfer, Frank, Houck, Grochocinski, Cluss, & Stapf, 2003;
Goodwin & Jamison, 2007). Despite the above information and multiple studies that have
shown that BP disorder can be reliably diagnosed in children and adolescents, the presence
of BP in youth continues to be controversial and often discounted. Moreover, there are
disagreements among clinicians within and among countries how to ascertain and interpret
the symptoms of mania or hypomania in youth (Dubidka et al., 2008; Diler 2007; Diler &
Birmaher 2012). The main goal of this article is to summarize the current literature and
complexities in diagnosing BP in youth with special emphasis on the areas of controversy.
Throughout this article, unless specified, the word youth denotes both, children and
adolescents.
Clinical presentation
BP is defined by the presence of recurrent episodes of mania or hypomania with and without
episodes of depression. First, the symptoms and problems encountered in ascertaining
symptoms of mania or hypomania will be discussed. Thereafter, the symptoms of major
depression will be addressed.
Mania/Hypomania
Youth can be diagnosed with mania or hypomania using the existing DSM criteria for adults
(APA, 2000; Axelson, Birmaher, Strober, Gill, Valeri, Chiappetta, Ryan, Leonard, Hunt,
Iyengar, Bridge, & Keller, 2006; Birmaher, Axelson, Pavaluri, 2007; Carlson, 2011;
Findling, Youngstrom, Fristad, Birmaher, Kowatch, Arnold, Frazier, Axelson, Ryan,

Demeter, Gill, Fields, Depew, Kennedy, Marsh, Rowles, & Horwitz, 2010; Kowatch,
Youngstrom, Danielyan, & Findling, 2005; Youngstrom, Birmaher, & Findling, 2008).
However, the existing criteria must be used cautiously considering that the manic or
hypomanic symptoms:
1. must exceed expectations for the normal developmental stage of the child or
adolescent, particularly symptoms such as elation and grandiosity.
2. must cluster in episodes so that they either onset or intensify with the abnormal
mood. However, as discussed in detail below, some investigators have questioned
the need for episodicity (Mick, Biederman, Faraone, Murray, & Wozniak, 2003).
3. cannot be mainly accounted for by other disorders such as ADHD or ODD
(especially increased activity, agitation, irritability, distractibility, and
Birmaher Page 3
talkativeness). If either of these other disorders exists, the mood symptoms must
clearly worsen during the episode of mania or hypomania.
4. cannot be mainly explained by child’s environmental or cultural context or the
presence of any medical illness, or use of drugs or medications (e.g.,

corticosteroids).
5. must affect the functioning of the youth is several areas of functioning such as
academic, family and friends. However, hypomania, particularly when is not
severe, may improve the child’s functioning (e.g., more outgoing, increased energy
to do homework, and more creativity).
With some exceptions, the existing literature reports significant variations in the prevalence
of each manic symptom, highlighting the problems identifying manic symptoms in youth
(Axelson, et al., 2006; Carlson, 2011; Dubicka et al., 2008; Kowatch, et al., 2005; Stringaris
and Santosh 2010; Youngstrom, et al., 2008). The discrepancies among investigators may be
explained by methodological differences, the pre-conceptions of investigators and clinicians
about the way that manic symptoms manifest in youth, difficulties differentiating some
manic symptoms from normative mood/behaviors, and the overlap of these symptoms with
other psychopathology. In addition, due to the children’s cognitive and emotional
immaturity, they might have difficulty expressing describing their mood symptoms and/or
these symptoms may be modified by the developmental stage of the child. For example, the
identification of elation, grandiosity, and or increased goal activity may be challenging from
age-appropriate behavior in children. Elation can be difficult to ascertain because it is
expected that youth will at times be overly happy, silly, and goofy spontaneously or
triggered by certain situations (e.g. parties, visiting an amusement park). However, if these
symptoms are recurrent, inappropriate for the context, beyond what is expected for the age
of the child, and accompanied by other manic or hypomanic symptoms, elation needs to
should be ruled considered as a potential symptom of a manic episode. Grandiosity is also a
tricky symptom to diagnose in children because it is normal for them to overestimate their
abilities and to believe that he/she is “the best” at a particular sport, smarter than others, or
that he/she is or will be very important. Some children, particularly those with oppositional
defiant or conduct disorders, will chronically believe that they are above needing to follow
adults’ rules and requests. Therefore, identifying a change from the child’s usual behavior
and self-image is key. Some examples that can raise the suspicion that the grandiosity is
pathological include the following: a child who believes he/she is by far the best sports
player, singer, student etc., despite clear evidence to the contrary; a child who repeatedly
commands teachers, parents and coaches to do what they want despite that they are getting
in trouble; a child thinking he/she has superpowers and acts upon these thoughts doing
things that most kids of their age would not dare to do even if they were also fantasizing
about similar issues (e.g., trying to fly from a tall tree or a third floor from a building,
crossing the street without regard for traffic, not because of lack of attention or impulsivity,
but because they believe nothing will happen to them). Finally, to be considered a manic
symptom, increased goal activity in children has to be exaggerated, represent a change in
functioning and be recognized by others as excessive for the developmental age of the child.
For adolescents, with some exceptions (e.g., making many business deals for a kid who is
still in school) the behaviors described for adults with mania are appropriate. For younger
children, increased goal-activity can be hard to ascertain, particularly if they have ADHD.
Some examples include a child with uncharacteristically periods of driven creative activity
such as drawing, painting, writing or building things; the child who takes on many tasks
simultaneously (e.g. flies through school work while playing video games, watching TV,
and communicating with friends), starts devising elaborate and unrealistic plans for projects,
trips or peer activities; and the child who exhibits driven activity to rearrange and redecorate
his/her room, or to spontaneously complete many household chores well beyond
Birmaher Page 4
expectations (clean most of the house, do lots of laundry, etc.) especially if the child
typically does not engage in these activities or is performing them at unusual times such as
late at night.
Another symptom that can be complicated to ascertain in youth, but when present, can help
with the diagnosis of BP, is increased sexual activity. To be counted as a manic symptom,
increased sexual activity must be inappropriate for the age of the child and not mainly
accounted for by a history of sexual abuse, exposure to videos, TV or actual sex. For
children, this can manifest as preoccupation with viewing or drawing naked people,
provocative touching of the breasts, genital area or buttocks of others, intense and
inappropriate kissing, or sexually explicit dancing (grabbing crotch, exposing genitals).
Frequency, intensity and temporal association with elevated and/or irritable mood are key
factors when assessing potential hypersexual behavior, as mild expressions of these
behaviors could be normal if they are transient and do not impair functioning.
There are other important developmental differences between children and adolescents that
impact symptom presentations. For example, children tend to have more rapid fluctuations
in their mood, mixed presentations and behavior problems and separation anxiety than the
adolescents. In contrast, adolescents have more distinct manic and depressive episodes,
suicidality, substance abuse and panic disorder. Overall, children and adolescents have more
mixed presentations and rapid changes in polarity of their mood episodes than the BP adults,
explaining, at least in part, the difficulties diagnosing and treating them.
Hypomania
The symptoms of hypomania are of lesser duration and intensity than the ones of mania.
According to the DSM-IV (APA, 2000), the symptoms of hypomania must last at least 4
days. However, studies in both youth and adults have shown that people with 2–3 days of
symptoms do as poorly as those with 4 or more days, raising the question of the validity of
the DSM duration criteria (Angst, Gamma, Benazzi, Ajdacic, Eich, & Rossler, 2003;
Axelson, Birmaher, Strober, Goldstein, Ha, Gill, Goldstein, Yen, Hower, Hunt, Liao,
Iyengar, Dickstein, Kim, Ryan, Frankel, & Keller, 2011; Vieta & Suppes, 2008). While
hypomanic, youth can sometimes function better and show increased creativity and
productivity than when euthymic. However, recurrent hypomania can induce significant
psychosocial impairment and be associated with increased risk for suicide, substance abuse,
academic problems, and legal problems. Thus, it is important to always assess for the
presence of hypomanic symptoms, particularly in youth with depression and to be careful
not to assume that hypomanic-like symptoms are “normal”.
Major depression
Similar to the symptoms of mania or hypomania, the symptoms of Major Depression (APA,
2000). in youth must exceed what it is considered normal for the child’s developmental age,
must cluster in episodes, and not be mainly accounted for by the presence of comorbid
disorders.
As is also the case for assessing manic symptoms in youth, the child’s cognitive and
emotional immaturity may make it difficult to identify some of the symptoms of Major
Depression. For example, younger children may not report feeling depressed, but bored or
may appear as only irritable. A real intent to commit suicide can be masked because children
may choose methods that in reality are not lethal, such as holding their breath or putting
their head under water in the bathtub. Also, problems in describing their mood, together with
the increased irritability and other symptoms of depression (e.g., fatigue, sleep problems),
may make the child more likely to display behavior problems, rebel against parents and
Birmaher Page 5
teachers (e.g., not doing homework), and exhibit low frustration tolerance and frequent
temper outbursts. Depressed adolescents can be irritable, oppositional, befriend other teens
who are also experiencing difficulties, get in trouble with the law, skip school and
sometimes use substances. All these symptoms may be misinterpreted as behavioral

disorders causing the symptoms of depression to be overlooked.
Children with MDD usually have less neurovegetative or melancholic symptoms than
depressed adolescents or adults (Birmaher, Williamson, Dahl, Axelson, Kaufman, Dorn, &
Ryan, 2004; Yorbik, Birmaher, Axelson, Williamson, & Ryan, 2004). Depressed
adolescents appear to have more atypical symptomatology such as hypersomnia and
increased appetite and weight gain than adults (Birmaher, et al., 2004). Symptoms like
anhedonia are usually not as common as in depressed adults and can be selective to activities
that require more mental effort. Youth with MDD may still be active in sports and music,
but they do not enjoy these activities as much as before they became depressed. In addition,
some youth, particularly those interested in doing well at school and those who are
intelligent may continue to do well academically, but they may require more time and effort
to maintain grades or finish homework when depressed.
The symptoms of depression may fluctuate more frequently and be more reactive in
depressed youth compared to adults. Often, depressed children do not appear or feel
depressed all the time. They can be depressed at school, but feel or look happy when they
are with their friends or playing games. Thus, to consider MDD in youth, it is practical to
evaluate what proportion of time (e.g., a week) they are depressed. In fact, some
investigators have suggested that to consider the depression as significant they should be
depressed at least 50% of the time (Birmaher, et al., 2004; Yorbik, et al., 2004).
Finally, it is important to emphasize that there is consistent growing evidence that a

substantial proportion of adults and youth with major depression have unrecognized
subsyndromal manic symptoms (Angst, Azorin, Bowden, Perugi, Vieta, Gamma, Young, &
Group, 2011). These people usually have a poor prognosis and are resistant and/or adversely
respond to treatment with antidepressants (Angst, et al., 2011; Maalouf, Porta, Vitiello,
Emslie, Mayes, Clarke, Wagner, Asarnow, Spirito, Keller, Birmaher, Ryan, Shamseddeen,
Iyengar, & Brent, 2012).
Subtypes of BP
Similar to adults with BP, youth can be diagnosed with several subtypes of BP disorders
including BP-I (periods of mania and major depression), BP-II (episodes of hypomania and
major depression), Mixed episodes (symptoms of mania and depression occurring within the
same 2-week time frame), cyclothymia (periods of hypomania and mild depressions), and
BP-not otherwise specified (BP-NOS) (Axelson, et al., 2006; Birmaher, et al., 2007;
Birmaher, et al., 2004; DelBello, Hanseman, Adler, Fleck, & Strakowski, 2007; Findling, et
al., 2010; Youngstrom, et al., 2008). BP-NOS is vaguely defined in the DSM, but basically
children who do not have the required 4 days of hypomania or 7 days of mania or are short
of the symptoms required for mania or hypomania with functional impairment are given this
diagnosis. Nevertheless, to avoid overdiagnosing BP-NOS, some investigators have
suggested that a minimum number of days (e.g., 2), symptoms (elation plus 3 symptoms or
irritability plus 3 symptoms), number of episodes (e.g., at least 4 episodes), and clear change
in functioning need to be present to diagnose BP-NOS (Axelson, et al., 2006; Axelson, et al.,
2011). In fact, youth fulfilling these criteria have as much morbidity, comorbid disorders,
suicidality, substance abuse, and family history of mood disorders as youth with BP-I
(Axelson, et al., 2006; Axelson, et al., 2011). It is important to emphasize that this subtype
of BP is not related to the phenotype called Severe Mood Dysregulation (SMD) or the new
Birmaher Page 6
proposed Disruptive Mood Dysregulation Disorder (DMMD) (Axelson, Findling, Fristad,

Kowatch, Youngstrom, Horwitz, Arnold, Frazier, Ryan, Demeter, Gill, Hauser-Harrington,
Depew, Kennedy, Gron, Rowles, & Birmaher, in press; Axelson, et al., 2011; Leibenluft,
2011). These latter conditions are chronic and not episodic and appear to correspond to
youth with severe ODD (Axelson, et al., in press; Axelson, Birmaher, Findling, Fristad,
Kowatch, Youngstrom, Arnold, Goldstein, Goldstein, Chang, Delbello, Ryan, & Diler,
2011a; Leibenluft, 2011).
At the onset of the illness, BP can be manifested with any polarity (depressed, manic,
hypomanic), but it appears that more frequently it presents with depression (Birmaher,
2007). This may create a challenge for clinicians because treatment with antidepressants
may trigger an episode of mania in a child who is predisposed to develop BP. Currently
there are nonclinical or biological tests than can help to distinguish between unipolar and BP
depressions. However, some studies have suggested that depressed youth with a family
history of BP, pharmacologically induced mania/hypomania, and/or presence of depression
with psychosis are at high risk to develop BP (Akiskal, 1998; Geller, Fox, & Clark, 1994;
Strober & Carlson, 1982). Thus, these youth need to be monitored more carefully when
administered antidepressants. Moreover, several studies have consistently shown that 30%–
40% of adults and youth with unipolar MDD may have subtle symptoms of mania or
hypomania that often go under diagnosed (Angst, et al., 2011; Maalouf, et al., 2012;
Zimmermann, Bruckl, Nocon, Pfister, Lieb, Wittchen, Holsboer, & Angst, 2009). Compared
with unipolar MDD without BP symptoms, e patients with “hidden’ bipolarity have younger
onset age, more depressive episodes less response to antidepressants and higher risk to
develop BP. Also, they have more frequent suicide attempts, comorbidity anxiety, problems
controlling their impulses, substance abuse, family members with BP, and worse course.
Although not a specific subtype of BP, like adults, youth can experience symptoms of
psychosis (presence of hallucinations and/or delusions) while manic or depressed (Birmaher,
et al., 2007; Youngstrom, et al., 2008). These symptoms may also be present during the
depressive phase of the illness. Perhaps due to their cognitive immaturity, children tend to
have more hallucinations than delusions whereas adolescents tend to have more delusions
than hallucinations (Birmaher, 2007). Up to 40% of the youth with BP may have psychotic
symptoms (hallucinations or delusions) with rates depending on the source of the sample
and instruments used to ascertain these symptoms (Axelson, et al., 2006; Birmaher, Axelson,
Goldstein, Strober, Gill, Hunt, Houck, Ha, Iyengar, Kim, Yen, Hower, Esposito-Smythers,
Goldstein, Ryan, & Keller, 2009; Carlson, Kotov, Chang, Ruggero, & Bromet, 2012;
Kowatch, et al., 2005).
Comorbidity
Bipolar disorder is often accompanied by other psychiatric disorders (20%–80%),

particularly disruptive behavior disorders, ADHD, anxiety disorders, and in adolescents,
substance use disorders (Axelson, et al., 2006; Goldstein, Strober, Birmaher, Axelson,
Esposito-Smythers, Goldstein, Leonard, Hunt, Gill, Iyengar, Grimm, Yang, Ryan, & Keller,
2008; Kowatch, Fristad, Birmaher, Wagner, Findling, & Hellander, 2005a; Kowatch, et al.,
2005; Sala, Axelson, Castro-Fornieles, Goldstein, Ha, Liao, Gill, Iyengar, Strober,
Goldstein, Yen, Hower, Hunt, Ryan, Dickstein, Keller, & Birmaher, 2010). However, the
rates of these disorders in very heterogeneous, depending on the methods utilized to
ascertain them and the sample studied, as well as the age of the sample. For example, the
prevalence of BP is higher in clinical versus community samples. ADHD and oppositional
defiant disorder are more common in children with BP, while rates of conduct and substance
use disorders are greater in adolescents. The presence of these disorders conveys a challenge
for the differential diagnoses because some of the symptoms, especially those of ADHD,
Birmaher Page 7
overlap with the symptoms of mania or hypomania. Furthermore, comorbid disorders

influence the response to treatment and the prognosis for BP, indicating the need to
accurately identify these youth and to effectively treat them.
Some clinical tips that may be helpful for the differential diagnoses between BP and ADHD
and ODD are presented in tables 1 and 2.
Controversies regarding the criteria for diagnosing BP in youth

There are four main controversies regarding the diagnosis of BP in youth. (1) Can mania
present with irritability without elation? (2) Can mania present without episodes?; (3) Does
BP in youth present with very rapid cycling?; and (4) Is BP over diagnosed in youth,
particularly in the USA?
Can mania present with irritability without elation?

It has been suggested that mania in youth is mainly manifested by irritability and rarely with
elation (Mick, et al., 2003). However, most of the studies have shown that elation is a
common symptom of mania in youth and that mania rarely manifests itself with only elation
or only irritability, but with both (Carlson, 2007; Hunt, Birmaher, Leonard, Strober,
Axelson, Ryan, Yang, Gill, Dyl, Esposito-Smythers, Swenson, Goldstein, Goldstein, Stout,
& Keller, 2009; Merikangas, Cui, Kattan, Carlson, Youngstrom, & Angst, 2012). In any
case, mania should not be diagnosed when irritability is not accompanied by the other
symptoms of mania, and when it is not episodic (Axelson, et al., 2011; Birmaher, et al.,
2007; Carlson, 2007; Carlson, Potegal, Margulies, Gutkovich, & Basile, 2009; Leibenluft,
2011; Stringaris 2011).
Nevertheless, it is important to emphasize that perhaps irritability in the context of family

history of BP may be an indicator that the youth is at risk to develop BP, but longitudinal
studies are needed to corroborate this.
Can mania present without episodes?

Although some have suggested that BP in youth is manifested by chronic symptoms without
episodes (Mick, et al., 2003) most investigators have shown that, similar to adults, mania is
manifested episodically (Birmaher, 2007; Birmaher, et al., 2009; Leibenluft, 2011).
Furthermore, cases of chronic irritability without clear episodicity seems to be more
associated with ADHD and disruptive disorders than BP or the SMD phenotype (Axelson, et
al., 2011; Carlson, 2007; Stringaris, 2011; Stringaris, Cohen, Pine, & Leibenluft, 2009).
Thus, it is important to follow these youth with probable symptoms of BP longitudinally in
order to clearly document the presence of episodes.
Does BP in youth present with very rapid cycling?

The DSM and the ICD criteria define rapid cycling as at least four mood episodes (major
depression, mania, mixed, or hypomanic) of a mood disturbance in a 12-month period
(APA, 2000). Some authors have suggested that BP youths have very rapid cycling (Geller
& Cook, 2000). Using these criteria, it appears that youth with BP are more prone to rapid
cycling than adults with BP. However, it seems that there is some confusion between having
recurrent full-syndromal mood episodes and experiencing mood variations within an episode
(Birmaher, et al., 2009). For example, during an episode of depression children may be
depressed, irritable, euthymic or sometimes even happy. These children have fluctuation in
their mood during the same episode, but they do not have separate mood episodes. This
misunderstanding has given origin to the concept of “ultradian cycling” (Geller & Cook,
Birmaher Page 8
2000) and sometimes contributes to the misdiagnosing youth with BP, when in fact they
may be experiencing mood lability in the context of other non-mood disorders.
Is BP over-diagnosed in youth, particularly in the US?

Recent studies have shown sharp increases in the rates in the diagnosis of BP in youth,
raising the possibility that BP is being over-diagnosed, especially in the US (Blader &
Carlson, 2007; Moreno, Laje, Blanco, Jiang, Schmidt, & Olfson, 2007). Before the diagnosis
of BP, most adolescents were already diagnosed with depressive disorders, and most
children with disruptive behavior disorders or ADHD, and they were already receiving
treatment with psychotropic medications (stimulants, antidepressants and/or antipsychotics)
(Olfson, Crystal, Gerhard, Huang, & Carlson, 2009). Moreover, many did not continued to
carry the diagnosis of BP suggesting that the diagnosis of BP was given tentatively to youth
with severe psychopathology.
A meta-analysis and other recent studies reported that the prevalence of BP spectrum
disorders in youth is on average 1.8% and for BP-I 1.2%, with rates of BP-I being consistent
among most countries (e.g., US and UK) (Kozloff, Cheung, Schaffer, Cairney, Dewa,
Veldhuizen, Kurdyak, & Levitt, 2010; Merikangas, et al., 2012; Stringaris and Santosh
2010; Van Meter, Moreira, & Youngstrom, 2011). In contrast, the prevalence of
subsyndromal cases, seems to be higher is the US (up to 6.7%) when compared with other
countries (2.4%). The results of all of these studies suggest that: 1) the prevalence of BP-I in
youth is similar to the current prevalence estimates of BP-I in adults (e.g., Kessler,
Avenevoli, Costello, Georgiades, Green, Gruber, He, Koretz, McLaughlin, Petukhova,
Sampson, Zaslavsky, & Merikangas, 2012); 2) the rates of BP increase after puberty; 3)
despite that BP is being diagnosed more commonly, the prevalence of BP in youth in the
community apparently is not increasing. Moreover, the increase in diagnosis of BP in youth
is not higher that that the increase in the diagnosis of depression; 4) the number of youth
treated for BP appears to lag far behind the population prevalence; and 5) the main
difference in the prevalence of BP between the US and other countries is the increased
prevalence of subsyndromal BP or BP-NOS, but not BP-I. The difference in subsyndromal
BP may be attributable to the imprecise DSM-IV definition of BP-NOS and the issues
regarding the inclusion of youth with only irritability, non-episodic BP or ‘ultradian’ cycles
discussed above. However, it is also possible that in some studies, the presence of
subsyndromal BP was overlooked. Thus, as described below, more studies evaluating the
diagnostic criteria and the significance of episodic subsyndromal manic symptomatology are
warranted (Axelson, et al., 2011).
If pediatric BP is a valid disorder, it should specifically run in families

Most studies have demonstrated that, even after controlling for confounding factors (e.g.,
non-BP parental psychopathology), offspring of parents with BP are at higher risk to
develop BP than offspring of control parents (Chang, Steiner, & Ketter, 2003; DelBello &
Geller, 2001; Henin, Biederman, Mick, Sachs, Hirshfeld-Becker, Siegel, McMurrich,
Grandin, & Nierenberg, 2005; Hillegers, Reichart, Wals, Verhulst, Ormel, & Nolen, 2005).
In general, when one parent has BP the risk of the child having BP is between 10 and 25%
with higher rates when both parents have BP (Goldstein, Shamseddeen, Axelson, Kalas,
Monk, Brent, Kupfer, & Birmaher, 2010; Goodwin & Jamison, 2007). The risk of
developing BP increases after puberty (Birmaher, Axelson, Monk, Kalas, Goldstein, Hickey,
Obreja, Ehmann, Iyengar, Shamseddeen, Kupfer, & Brent, 2009a; Duffy, 2010; Hillegers, et
al., 2005). In the same way, other studies have shown that the first-degree relatives of youth
with BP are at higher risk to have BP when compared with families of healthy children or
children with MDD or ADHD (Geller, Tillman, Bolhofner, Zimerman, Strauss, &
Kaufmann, 2006; Wozniak, Faraone, Mick, Monuteaux, Coville, & Biederman, 2010). The
Birmaher Page 9
above research as well as studies of twins (Taylor, Faraone, & Tsuang, 2002) have
demonstrated that BP specifically runs in families and it is one of the most hereditable
psychiatric disorders.
It is important to mention that offspring of parents with BP are also at high risk to develop
other disorders, especially unipolar major depression, and disruptive and anxiety disorders.
Thus, a child of a parent with BP who has behavior problems, increased irritability, or
sadness does not necessarily have BP.
Course and outcome

Although the rates of recovery from index episodes are high (70%– 100%), of those who
recover, up to 80% will experience one or more syndromal recurrences over a period of 2 to
5 years, particularly depressive episodes, and multiple subsyndromal recurrences (Birmaher,
2007; Birmaher, et al., 2009; Carlson, et al., 2012; DelBello, et al., 2007; Diler 2007; Geller,
Tillman, Bolhofner, & Zimerman, 2008).
An analysis of the percentage of the follow-up time spent asymptomatic or with clinically
significant mood symptomatology showed that youth with BP spent approximately 20% of
the time with full syndromal symptoms, 40% of the time with subsyndromal symptoms, and
40% of the time euthymic (Birmaher, et al., 2009). Most of the symptoms were of
depressive or mixed type. Similar findings have been reported in other longitudinal studies
(Birmaher, 2007; Carlson, et al., 2012; DelBello, et al., 2007; Geller, et al., 2008).
Compared with adult BP studies, youth with BP spend more time symptomatic and with
mixed/rapid cycling, subsyndromal symptoms, and with more mood changes (Birmaher, et
al., 2009). These findings explain, at least in part, the difficulties diagnosing and treating
youth with BD.
Several factors have been associated with worse course and outcome. These include early
age of onset, long duration of illness, low socioeconomic status, mixed or rapid cycling
episodes, psychosis, subsyndromal mood symptoms, comorbid disorders, exposure to
negative life events, high expressed-emotion, and family psychopathology (Birmaher, 2007;
Birmaher, et al., 2009; Carlson, et al., 2012; DelBello, et al., 2007).
Due to the recurrent nature of this illness and its effects on the youth’s mood and behaviors,
BP is associated with significant negative psychosocial consequences, family, interpersonal,
academic, and legal problems, and increased risk for suicidality and substance abuse (Bella,
Goldstein, Axelson, Obreja, Monk, Hickey, Goldstein, Brent, Diler, Kupfer, Sakolsky, &
Birmaher, 2011; Birmaher, et al., 2009; Birmaher, et al., 2007; DelBello, et al., 2007;
Goldstein, et al., 2008; Goldstein, Birmaher, Axelson, Goldstein, Gill, Esposito-Smythers,

Ryan, Strober, Hunt, Keller, & Goldstein, 2009; Goldstein, Ha, Axelson, Goldstein, Liao,
Gill, Ryan, Yen, Hunt, Hower, Keller, Strober, & Birmaher, 2012). Therefore, the need for
early identification, accurate diagnosis, and ongoing psychosocial and pharmacological
treatments is crucial.
Youth with subsyndromal mania (BP-NOS), particularly those with family history of BP are
at risk to convert in to BP-I or II with rates of conversion of 45% (BP-I: 23% and BP-II:
22%) (Axelson, et al., 2011). Youth with BP-NOS have as much psychosocial impairment
and risk for suicidality and substance abuse as the children with full syndromal BP-I,
indicating the need to develop treatments for this population and hopefully protocols to
prevent the development of full syndromal BP-I/II.
Birmaher Page 10
Conclusions
BP spectrum disorder is a familial disorder that occurs in 1–3% of children and adolescents,
with increased rates of onset during the adolescent years. The symptoms of BP, especially
those for BP-I, can be reliably diagnosed in youth. However, making a diagnosis of BP
presents several challenges because the disagreement regarding the definition of episodes,
the ascertaining and interpretation of symptoms like elation and grandiosity, and the
difficulties to distinguish certain manic symptoms from developmentally appropriate
behavior in children. In addition, there are developmental differences in the clinical
presentation of BP, with older adolescents having more classic manic and depressive
symptoms and distinct episodes, whereas children with BP tend to have more mixed and
rapid cycling presentations. Finally, the high rates of comorbid disorders with overlapping
symptoms with mania make the diagnosis more difficult. Thus, the need for more studies
across countries to carefully and taking into account the development of the child, define the
key symptoms of mania in youth and how to differentiate them from other disorders.
Moreover, given the controversies and the consequences associated with the diagnosis of BP
in youth, it is crucial to perform comprehensive longitudinal evaluation of youth for whom
BP is suspected before making the final diagnosis of BP.
BP is manifested by recurrent syndromal, and more frequently subsyndromal episodes,

especially depressions. Youth with subsyndromal mania, particularly if there is family
history of BP, are at high risk to develop full syndromal episodes. Both the full syndromal
and the subclinical BP are associated with significant psychosocial difficulties and increased
risk for academic problems, family conflicts, use of substances, suicidality, legal problems,
increased utilization health care services, and economic problems. In fact, the World Health
Organization reported that BP is the 4th leading cause of disability among adolescents
worldwide.
The recurrent nature and psychosocial morbidity associated with this illness during critical
developmental stages calls for its prompt recognition and treatment, particularly since delays
in appropriate diagnosis and treatment are associated with less likelihood of full recovery
and poor outcome.
Although it is accurate that some youth are being misdiagnosed with BP, it is also true that
there are children and adolescents whose BP is unnoticed or misdiagnosed. Thus, until the
criteria for diagnosing BP in youth is better clarified and until more objective ways to
diagnose BP are identified (e.g., biomarkers), clinicians will continue to be confronted with
the dilemma of using more over-inclusive or excessively conservative criteria to diagnose
BP in youth. Each approach has its advantages and disadvantages. Using broader criteria has
the potential to misdiagnose children with BP, a diagnosis with long-term prognostic and
social implications, and expose them to medications with little benefit and unnecessary side
effects. In contrast, using a very strict diagnostic criteria or in extreme cases, denying the
existence of BP in youth, may exclude children and adolescents with real BP from the
proper treatment and as a consequence obstruct their normal development, increase the risk
for the serious consequences of BP (e.g., suicidal behavior, increase risk for substance
abuse, and legal problems), and expose them to medications and other non-efficacious
treatments that can worsen the course of BP.
Acknowledgments
B.B. has received research support from the National Institutes of Mental Health. He receives book royalties from
Random House, Inc., and Lippincott Williams & Wilkins. This review article was invited by the journal following
the presentation of some of the material as the 2011 Emmanuel Miller Lecture (ACAMH, June 2011, London), for
which B.B. received travelling expenses; the final manuscript was subject to full peer review.
Birmaher Page 11
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Birmaher Page 15
Key Practitioner Messages

• Bipolar disorder (BP) is a familial illness that usually onsets during adolescence.
However, its diagnosis is difficult, especially the identification of episodes and

symptoms like grandiosity and elation in young children.
• Most of the discrepancies in the diagnosis of BP in youth are for the subclinical
subtypes
• BP is a recurrent illness with frequent syndromal and especially subsyndromal
depressive and mixed episodes that significantly affects the psychosocial
functioning of the youth.
• Youth with BP-NOS and family history of BP are at high risk to develop BP-I
and II.
• Given the existing problems interpreting the symptoms of mania in youth and
the overlap with symptoms of comorbid disorders (e.g., ADHD), the prevalence
is not well known, but current studies across the globe suggest a prevalence of
BP-I of about 1%
• Unrecognized and undertreated carries severe consequences for the normal
development of the child. However, a misdiagnosis also carries negative
consequences.
Birmaher Page 16
Table 1
Bipolar disorder versus attention deficit hyperactive disorder (ADHD)
(Reproduced from Birmaher, B. New Hope for Children and Adolescents with BP Disorders, New York:
Three Rivers Press, a division of Random House, Inc., 2004, with permission)
Suspect the presence of Bipolar Disorder in a child with ADHD if:

• The “ADHD” symptoms appeared later in life (e.g., at age 10 years old or older)
• The symptoms of “ADHD” appeared abruptly in an otherwise healthy child
• The ADHD symptoms were responding to stimulants and now are not
• The “ADHD” symptoms come and go and tend to occur with mood changes
• A child with ADHD begins to have periods of exaggerated elation, grandiosity, depression, no need for sleep, inappropriate sexual
behaviors
• A child with ADHD has recurrent severe mood swings, temper outbursts, or rages
• A child with ADHD has hallucinations and/or delusions
• A child with ADHD has a strong family history of bipolar disorder in his or her family, particularly if the child is not responding to
appropriate ADHD treatments
Note: A child may have both ADHD and BP. Moreover, above noted clinical situations may also be due to other psychiatric disorders (e.g.,
unipolar depression, substance abuse), medical problems (e.g., thyroid problems, seizures, tumors), use of medications (e.g., prednisone), and
environmental stressors (e.g., family conflict, chaotic environment, sexual or physical abuse) that may coexist with ADHD.
Birmaher Page 17
Table 2
Bipolar disorder versus behavior disruptive disorder
(Reproduced from Birmaher, B. New Hope for Children and Adolescents with BP Disorders, New York:
Three Rivers Press, a division of Random House, Inc., 2004, with permission.)
• If the behavior problems only occur while the child is in the midst of an episode of mania or depression, and the behavior problems
disappear when the mood symptoms improve, the diagnoses of oppositional or conduct disorder should not be made.
• If a child has “of and on” oppositional or conduct symptoms or these symptoms only appear when the child has mood problems, the
diagnosis of BP (or other disorders such as recurrent unipolar depression or substance abuse) should be considered.
• If the child had oppositional behaviors before the onset of the mood disorders, both diagnoses may be given.
• If a child has severe behavior problems that are not responding to treatment, consider the possibility of a mood disorder (bipolar and
non-bipolar depressions), other psychiatric disorder (e.g., ADHD, substance abuse), and/or exposure to stressors.
• If a child has behavior problems and a family history of bipolar, consider the possibility that the child has a mood disorder (unipolar
major depression or BP disorder).
• If a child has behavior problems and is having hallucinations and delusions consider the possibility of BP disorder. Also consider
the possibility of schizophrenia, use of illicit drugs/alcohol, or medical/neurological conditions.

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Child Adolesc Ment Health. 2013 September 1; 18(3): . doi:10.1111/camh.12021.

Bipolar disorder in children and adolescents

experienced a one-month episode of depression which improved without intervention.

Findling, Youngstrom, Fristad, Birmaher, Kowatch, Arnold, Frazier, Axelson, Ryan,

presence of any medical illness, or use of drugs or medications (e.g.,

explaining, at least in part, the difficulties diagnosing and treating them.

sometimes use substances. All these symptoms may be misinterpreted as behavioral

Finally, it is important to emphasize that there is consistent growing evidence that a

proposed Disruptive Mood Dysregulation Disorder (DMMD) (Axelson, Findling, Fristad,

Bipolar disorder is often accompanied by other psychiatric disorders (20%–80%),

overlap with the symptoms of mania or hypomania. Furthermore, comorbid disorders

Controversies regarding the criteria for diagnosing BP in youth

Can mania present with irritability without elation?

Nevertheless, it is important to emphasize that perhaps irritability in the context of family

Can mania present without episodes?

Does BP in youth present with very rapid cycling?

Is BP over-diagnosed in youth, particularly in the US?

If pediatric BP is a valid disorder, it should specifically run in families

Course and outcome

Goldstein, et al., 2008; Goldstein, Birmaher, Axelson, Goldstein, Gill, Esposito-Smythers,

BP is manifested by recurrent syndromal, and more frequently subsyndromal episodes,

76. [PubMed: 10743839]

Yen S, Hower H, Esposito-Smythers C, Goldstein T, Ryan N, Keller M. Four-year longitudinal

and adult inpatients, 1996–2004. Biological Psychiatry. 2007; 62(2):107–114. [PubMed:

Disorders. 2001; 3(6):325–334. [PubMed: 11843782]

Mick E, Biederman J, Faraone SV, Murray K, Wozniak J. Defining a developmental subtype of

Heterogeneity of DSM-IV major depressive disorder as a consequence of subthreshold bipolarity.

Key Practitioner Messages

However, its diagnosis is difficult, especially the identification of episodes and

Suspect the presence of Bipolar Disorder in a child with ADHD if:

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