Bipolar disorder in children and adolescents: international perspective on epidemiology and phenomenology.
ABSTRACT There is considerable skepticism outside the US over the prevalence of pediatric bipolar disorder (BD). We wished to evaluate the epidemiology of BD in children and adolescents in non-US samples.
We reviewed studies on the prevalence of BD in children and adolescents in international samples. We also describe our sample of 27 children with BD at the University of Navarra.
There are important and frequently overlooked differences in the definition of BD between the International Classification of Diseases 10th edition (ICD-10) and DSM-IV and methodological differences in epidemiological studies that may partially explain international differences in prevalence of pediatric BD. The prevalence of bipolar spectrum disorder in young adults in Switzerland is 11%. In Holland the 6-month prevalence of mania in adolescents was 1.9% and of hypomania 0.9%. Only 1.2% of hospitalized youth (<15 years) in Denmark and 1.7% of adolescents in Finland had BD. In our clinic, the prevalence of DSM-IV BD in children 5-18 years old is 4%, and of any mood disorders 27%. There are also data from Brazil, India and Turkey with varying results.
Relative lack of data, ICD-10 and DSM-IV differences in diagnostic criteria, different levels of recognition of Child and Adolescent Psychiatry as a true specialty in Europe, clinician bias against BD, an overdiagnosis of the disorder in USA and/or a true higher prevalence of pediatric BD in USA may explain these results. US-International differences may be a methodological artifact and research is needed in this field.
- [show abstract] [hide abstract]
ABSTRACT: To evaluate the discriminative ability of the Child Behavior Checklist (CBCL) to identify children with structured interview-derived diagnosis of bipolar disorder. We evaluated the convergence of CBCL scales with the diagnosis of mania in 31 children with mania, 120 children with attention-deficit hyperactivity disorder, and 77 prepubertal normal control children aged 12 years or younger. We evaluated the strength of association between each CBCL scale and structured interview-derived diagnoses with total predictive value and the odds ratio. Excellent convergence was found between the CBCL scales of Delinquent Behavior, Aggressive Behavior, Somatic Complaints, Anxious/Depressed, and Thought Problems and the diagnosis of mania. These findings indicate that the CBCL could serve as a rapid and useful screening instrument to identify manic children in clinical settings.Journal of the American Academy of Child & Adolescent Psychiatry 05/1995; 34(4):464-71. · 6.97 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: To provide a review of the epidemiology, phenomenology, natural course, comorbidity, neurobiology, and treatment of child and adolescent bipolar disorder (BP) for the past 10 years. This review is provided to prepare applicants for recertification by the American Board of Psychiatry and Neurology. Literature from Medline and other searches for the past 10 years, earlier relevant articles, and the authors' experience and ongoing National Institute of Mental Health-funded project "Phenomenology and Course of Pediatric Bipolarity" were used. Age-specific, developmental (child, adolescent, and adult) DSM-IV criteria manifestations; comorbidity and differential diagnoses; and episode and course features are provided. Included are age-specific examples of childhood grandiosity, hypersexuality, and delusions. Differential diagnoses (e.g., specific language disorders, sexual abuse, conduct disorder [CD], schizophrenia, substance abuse), suicidality, and BP-II are discussed. Available data strongly suggest that prepubertal-onset BP is a nonepisodic, chronic, rapid-cycling, mixed manic state that may be comorbid with attention-deficit hyperactivity disorder (ADHD) and CD or have features of ADHD and/or CD as initial manifestations. Systematic research on pediatric BP is in its infancy and will require ongoing and future studies to provide developmentally relevant diagnostic methods and treatment.Journal of the American Academy of Child & Adolescent Psychiatry 10/1997; 36(9):1168-76. · 6.97 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: The authors suggest criteria for a range of narrow to broad phenotypes of bipolar disorder in children, differentiated according to the characteristics of the manic or hypomanic episodes, and present methods for validation of the criteria. Relevant literature describing bipolar disorder in both children and adults was reviewed critically, and the input of experts was sought. Areas of controversy include whether the diagnosis of bipolar disorder should require clearly demarcated affective episodes and, if so, of what duration, and whether specific hallmark symptoms of mania should be required for the diagnosis. The authors suggest a phenotypic system of juvenile mania consisting of a narrow phenotype, two intermediate phenotypes, and a broad phenotype. The narrow phenotype is exhibited by patients who meet the full DSM-IV diagnostic criteria for hypomania or mania, including the duration criterion, and also have hallmark symptoms of elevated mood or grandiosity. The intermediate phenotypes include 1) hypomania or mania not otherwise specified, in which the patient has clear episodes and hallmark symptoms, but the episodes are between 1 and 3 days in duration, and 2) irritable hypomania or mania, in which the patient has demarcated episodes with irritable, but not elevated, mood. The broad phenotype is exhibited by patients who have a chronic, nonepisodic illness that does not include the hallmark symptoms of mania but shares with the narrower phenotypes the symptoms of severe irritability and hyperarousal. The presence of distinct episodes and hallmark symptoms can be used to differentiate clinical phenotypes of juvenile mania. The utility and validity of this system can be tested in subsequent research.American Journal of Psychiatry 04/2003; 160(3):430-7. · 14.72 Impact Factor
Bipolar disorder in children and adolescents:
international perspective on epidemiology
Soutullo CA, Chang KD, Dı´ez-Sua ´ rez A, Figueroa-Quintana A,
Escamilla-Canales I, Rapado-Castro M, Ortun ˜ o F. Bipolar disorder in
children and adolescents: international perspective on epidemiology and
Bipolar Disord 2005: 7: 497–506. ª Blackwell Munksgaard, 2005
Objective: There is considerable skepticism outside the US over the
prevalence of pediatric bipolar disorder (BD). We wished to evaluate the
epidemiology of BD in children and adolescents in non-US samples.
Method: We reviewed studies on the prevalence of BD in children and
adolescents in international samples. We also describe our sample of 27
children with BD at the University of Navarra.
Results: There are important and frequently overlooked differences in
the definition of BD between the International Classification of Diseases
10th edition (ICD-10) and DSM-IV and methodological differences in
epidemiological studies that may partially explain international
differences in prevalence of pediatric BD. The prevalence of bipolar
spectrum disorder in young adults in Switzerland is 11%. In Holland the
6-month prevalence of mania in adolescents was 1.9% and of hypomania
0.9%. Only 1.2% of hospitalized youth (<15 years) in Denmark and
1.7% of adolescents in Finland had BD. In our clinic, the prevalence of
DSM-IV BD in children 5–18 years old is 4%, and of any mood
disorders 27%. There are also data from Brazil, India and Turkey with
Conclusion: Relative lack of data, ICD-10 and DSM-IV differences in
diagnostic criteria, different levels of recognition of Child and Adolescent
Psychiatry as a true specialty in Europe, clinician bias against BD, an
overdiagnosis of the disorder in USA and/or a true higher prevalence of
pediatric BD in USA may explain these results. US–International
differences may be a methodological artifact and research is needed in
Ce ´sar A Soutulloa, Kiki D Changb,
Azucena Dı ´ez-Sua ´reza, Ana
Escamilla-Canalesa, Marta Rapado-
Castroaand Felipe Ortun ˜oa
aChild and Adolescent Psychiatry Unit, Department
of Psychiatry and Medical Psychology, Clı ´nica
Universitaria, University of Navarra, Pamplona,
Spain,bDivision of Child and Adolescent
Psychiatry, Department of Psychiatry and
Behavioral Sciences, Stanford University School of
Medicine, Stanford, CA, USA
Key words: adolescents – bipolar – children –
epidemiology – mania – phenomenology
Received 30 November 2004, revised and
accepted for publication 9 September 2005
Corresponding author: Cesar A Soutullo, MD, PhD,
Child and Adolescent Psychiatry Unit, Department
of Psychiatry and Medical Psychology, Clı ´nica
Universitaria, University of Navarra, Apartado 4209,
31008 Pamplona, Spain. Fax: +34 948 296 500;
An abstract of this paper was presented at the
American Academy of Child and Adolescent Psy-
chiatry Annual Meeting, In: Saxena K, Kowatch R,
Liebenluft E, Chang KD. AACAP Symposium 63,
Scientific Proceedings: 99-100, Miami, FL, USA,
October 18 2003.
CAS has received research funding from Abbott Laboratories, Eli Lilly & Co., Novartis, Solvay, The Alicia Koplowitz Foundation, The Spanish
Department of Health (Instituto de Salud Carlos III-FIS), Navarra Department of Health; consultant for EINAQ-Thomson ATC, Eli Lilly & Co.,
Janssen-Cilag, Shire; and serves on the speakers bureau for Admirall-Prodesfarma, AstraZeneca, Bristol-Myers Squibb, Eli Lilly & Co., Esteve,
GlaxoSmithKline, Janssen-Cilag, Novartis, Pharmacia Spain and Solvay. KDC has received research funding from Abbott Laboratories,
AstraZeneca, GlaxoSmithKline, NIH, The Heinz C. Prechter Foundation, The National Alliance for Research in Schizophrenia and Depression;
consultant for Abbott Laboratories, AstraZeneca, Eli Lilly & Co., GlaxoSmithKline, Janssen Pharmaceutica, Shire US, UCB Pharma; and serves on
the speakers bureau for Abbott Laboratories, AstraZeneca, Eli Lilly & Co. and GlaxoSmithKline. AD-S has received research funding from Eli Lilly
& Company and The Alicia Koplowitz Foundation. FO has received research funding from The Alicia Koplowitz Foundation, The Spanish
Department of Health (Instituto de Salud Carlos III-FIS), Navarra Department of Health, University of Navarra Research Funds (PIUNA); and
serves on the speakers bureau for Admirall-Prodesfarma, AstraZeneca, Bristol-Myers Squibb/Otsuka Pharmaceutical, Eli Lilly & Co., Esteve,
GlaxoSmithKline, Janssen-Cilag, Novartis and Solvay. AF-Q, IE-C and MR-C have no reported conflict of interest.
Bipolar Disorders 2005: 7: 497–506
Copyright ª Blackwell Munksgaard 2005
Bipolar disorder (BD) is a chronic, highly heritable
psychiatric disorder that has long been thought to
begin in adolescence or early adulthood and is
associated with significant morbidity and mortality
(1). The prevalence of BD in adults has been
reported to be similar across both genders and
cultures within the US (1). Bipolar I disorder in the
US has a lifetime prevalence of 1%, but if other
forms of the spectrum, such as bipolar II disorder
or cyclothymia are included, prevalence may
exceed 3–7% (2).
Outside the US, prevalence rates of BD have
varied somewhat. In a recent cross-national epide-
miological study in adults, the lifetime prevalence
of BD I or II in different countries was: Iceland
0.2%, Taiwan 0.4%, Korea 0.5%, Puerto Rico
0.9%, Canada 1.1%, New Zealand 2.4%, Israel
2.6%, USA 3.0%, Italy 3.4%, Switzerland 5.1%
and Hungary 5.5% (23). These studies show that
the epidemiology and phenomenology of adult BD
in international samples is not very different than
that of adult BD in the USA, and that there are
even higher prevalences in some countries.
The international prevalence of ?softer? bipolar
spectrum disorders in adults is less clear. A recent
20-year prospective epidemiological study screened
4547 young adults representative of Zu ¨ rich’s can-
ton in Switzerland, from 1978 to 1999. They
defined ?soft bipolar spectrum? as all forms of
BD, including BD-I, BD-II, minor BD [dysthymia,
minor depression or recurrent brief depression
associated with: (i) the hypomanic syndrome or (ii)
hypomanic symptoms only], and pure hypomania
[either (i) the hypomanic syndrome or (ii) hypo-
manic symptoms only]. The cumulative prevalence
of ?soft bipolar spectrum? was 23.7%, with rates of
10.9% for ?broad bipolar II disorder? (BD-II),
9.4% for ?minor BD? and 3.3% for pure hypoma-
nia. They estimate that the lifetime prevalence of
BD that strictly satisfies diagnostic criteria is closer
to 11%, and that another 13% represents the
softest forms of bipolarity (22).
There has been more recent interest in the onset
age of BD as well. A survey by the Depression and
Bipolar Support Alliance (DBSA; previously the
NDMDA) of members in the US found that up to
59% of members with BD had signs of the illness
prior to the age of 20, the first episode in
adolescence was generally depressive, and 13%
had been hospitalized by age 20 (3). In a survey
across 12 national patient organizations in 12
European countries (Finland, Spain, Portugal,
Austria, Italy, France, Sweden, UK, Hungary,
Russia and the Netherlands), 33.1% patients with
BD aged 18–83 reported an onset prior to age 20.
The mean ± SD diagnostic delay was 5.7 ±
8.1 years (4). These findings would support that
many to most patients with BD in and outside the
US had a childhood onset of the disorder.
However, the prevalence in children and adoles-
cents presenting with BD has not been well studied,
either within or outside the US. Pediatric BD
frequently presents as non-episodic, chronic, rapid
cycling, with mixed manic states (5). Furthermore,
patients with pediatric BD often have comorbid
attention-deficit/hyperactivity disorder (ADHD),
anxiety disorders and/or oppositional defiant disor-
der (ODD) or conduct disorder (CD) (6–8). The
postulate ADHD as a possible precursor of bipo-
larity in some children are still controversial issues
undergoing further research (9). These specific
features of pediatric BD often contribute to the
example, many children with juvenile mania are
frequently misdiagnosed as having ADHD with
comorbid CD (7, 10). Despite considerable symp-
tom overlap, mania can be distinguished from
ADHD by the presence of core symptoms of mania
such as euphoria and grandiosity (11). Also, new
data available suggest that the structure of mania
may be multidimensional and more complex than
the classic euphoric–dysphoric dichotomy (12).
Available data regarding epidemiology of pedi-
atric BD in US samples found a weighted first
incidence of BD through age 18 of 1.4%, a
prevalence of sub-syndromal BD through age 18
of 4.5%, and a point prevalence of 0.6% at
baseline, 0.5% 1 year later, and 0.7% at age 24
(13). However, there is a considerable transatlantic
debate and European skepticism over the high
prevalence of pediatric BD in the US (14–16). A
large epidemiological study in the UK did not
detect any cases of pre-adolescent mania (17). Even
in clinical samples, the diagnosis of mania is
extremely unusual in England; for example, among
the 2500 children 10 years or younger referred to
the Royal Manchester Children’s Hospital Univer-
sity Department of Child and Adolescent Psychi-
atry over a period of 10 years, by anecdotal report
none had a diagnosis of mania or BD (18).
Nonetheless there are older descriptions of pediat-
ric mania by European authors such as Emil
Kraepelin (19), who found that 0.4% of his sample
of patients with BD were children under 10 years
of age. Yet this prevalence rate would still make
pediatric BD seem to be extremely rare.
There are several important European sites
interested in the study of BD. For example, the
Research Centersineightcountries in the
Soutullo et al.
European Union: UK, Denmark, Germany, Spain,
Sweden, Ireland, Italy and Holland. However,
these centers are mostly studying adult BD, and
epidemiological data on children are scarce. More-
over, in the few available studies about children
and adolescents with BD, there have been impor-
tant methodological differences between studies.
Thus, we wished to evaluate the data on the
phenomenology and epidemiology of pediatric BD
outside the US. Our hypothesis is that as pediatric
BD is a highly biological and genetic psychiatric
disorder, it likely has similar prevalence and
phenomenology cross-culturally that there is no
compelling reason for pediatric BD to have a
different prevalence in the US versus Europe. The
differences in epidemiological studies might be due
to factors such as clinician bias against a diagnosis
of BD in children or a different and more strict
definition of BD in International Classification of
Diseases 10th edition (ICD-10) (20) that requires
an episode of depression plus two or more episodes
of mania, versus DSM-IV (21) that requires only
one episode of mania or one of depression plus one
of hypomania. However, it may also be possible
that the prevalence of BP in children and adoles-
cents in the US is truly higher than in other
countries or that there is an overdiagnosis of
pediatric BD in the US.
We will review the available literature on inter-
national studies of child and adolescent BD, and
we will describe our sample of youth with BD at
the University of Navarra (Spain). Throughout
this paper we will use the terms ?BD in children and
adolescents? or ?pediatric BD? to refer to BD in
patients ages 17 and below. When we refer to a
specific phenotype of BD in prepubertal and early
adolescent children that requires the presence of
elation or grandiosity, we will use the term
prepubertal and early-adolescent BD (11).
For comparative purposes we will review first
two large epidemiological studies in adult BD in
A recent 20-year prospective epidemiological
study screened 4547 young adults representative
of Zu ¨ rich’s canton in Switzerland, from 1978 to
1999. They used personal interviews and analyzed
clinical validity by family history, course and
clinical characteristics. They defined ?soft bipolar
spectrum? as all forms of BD, including BD-I,
BD-II, minor BD and pure hypomania. The
cumulative prevalence of ?soft bipolar spectrum?
was 23.7%, with rates of 10.9% for BD-II, 9.4%
for ?minor BD? and 3.3% for pure hypomania.
Childhood conduct problems were more frequent
in the BD-II group (39.1%) than in controls
(20.2%). They propose a broader concept of
bipolarity that includes soft bipolarity and indicate
that just as euphoria and irritability are, hyperac-
tivity should be included in the stem criterion of
hypomania. They estimate that the lifetime prev-
alence of BD that strictly satisfies diagnostic
criteria is closer to 11%, and that another 13%
represents the softest forms of bipolarity (22). A
cross-sectional multicenter analysis of adults in
France showed evidence of a multidimensional
phenomenology of mania, in a group of 104
43 ± 13 years). They assessed mania intensity
with the Beigel-Murphy Manic State Rating Scale
(MSRS). They found seven independent factors of
mania: (i) disinhibition–instability, (ii) paranoia–
hostility, (iii) deficit (distractibility and poor judg-
ment), (iv) grandiosity–psychosis, (v) elation–eu-
phoria, (vi) depression and (vii) (hyper)sexuality. A
factor analysis found that disinhibition-instability
can be associated with different emotional presen-
tations (euphoric, depressive or irritable/hostile),
as well as psychotic symptoms (12). These studies
show that the epidemiology and phenomenology of
adult BD in international samples is not very
different from that in the USA.
(mean ± SDage:
We reviewed recent studies (1990 to the present)
regarding the prevalence of pediatric BD in inter-
national samples via MEDLINE and manual
search. Key words used in the search were: mania,
bipolar, children, adolescents, phenomenology and
epidemiology. We then reviewed the clinical char-
acteristics of a sample of 27 children meeting
DSM-IV BD criteria evaluated at the Child and
Psychiatry and Medical Psychology, University
Clinic, University of Navarra, Pamplona, Spain
recruited over a 4-year period.
We found 11 published studies regarding the
prevalence of pediatric BD outside the US. Only
three studies examined epidemiological samples,
and eight reports evaluated the prevalence of BD in
clinical samples: inpatients, outpatients or both
An epidemiological study of a national sample
of 780 Dutch adolescents (13–18 years old) used
structured interviews for parents (Diagnostic Inter-
view Schedule, DISC-P) and children (DISC-C) to
estimate the prevalence of DSM-III-R psychiatric
disorders in Dutch youth. They found a 6-month
prevalence of mania of 1.9%, hypomania 0.9%,
Bipolar disorder in children and adolescents: international perspective
any mood disorder 7.2% and conduct disorder 6%
(24). Another study assessed the prevalence of
psychopathology in a group of 140 offspring (12–
21 years old) of 86 BD parents in the Netherlands.
They used the Schedule for Affective Disorders and
Schizophrenia for School-Age Children (K-SADS-
PL) and also parent and teacher reports. In this
high-risk sample, they found a lifetime prevalence
of 27% for mood disorders, 3% for BD and 1%
for cyclothymic disorder (25). In these children of
BD parents, these rates were lower than the 14–
50% rates reported from other contemporary
studies performed in the US (26–28), for review
A nationwide psychiatric case registry study
covering a population of 5.1 million between 1970
and 1986 in Denmark found that only 39 (1.2%) of
hospitalized children (£15 years old) had a diag-
nosis of BD. The mean age of their first admission
was 12.7 years and 26 (67%) of the 39 children
received the diagnosis of BD on their first admis-
sion. The most common prior diagnoses were other
psychotic disorders in boys and oppositional and
emotional problems (borderline personality disor-
der 17%, anxiety disorders 17%, anorexia nervosa
8% and adjustment disorder 8%) in girls (30). For
comparison to a similar US sample, Biederman
(31) found a prevalence of BD in child and
adolescent patients in their outpatient clinic of
A study in England found that most children
(74%) with ?pervasive ADHD? had seen their
general practitioner (GP) the previous year, but
only 28% had been recognized by the GPs as
having a psychiatric disorder. Parental concern
about being blamed for the child’s problems
contributed to a reluctance to identify the behav-
iors as the presenting complaint (32). The 1999
British Child and Adolescent Mental Health Sur-
vey described the prevalence of DSM-IV disorders
in the UK. Using the Developmental and Well-
Being Assessment (DAWBA) that records infor-
mation from parents, teachers and children, 10,438
patients aged 5–15 years were evaluated. The
prevalence of any DSM-IV psychiatric disorder
was 9.48%, 0.92% of any depressive disorders,
0.68% of major depression and 5.9% of disruptive
disorders, including ADHD, ODD and conduct
disorders. In this study, BD was not mentioned in
the list of possible diagnoses. However, other
diagnoses with relatively low prevalences were
listed, such as post-traumatic stress disorder
(PTSD) (0.14%), panic disorder (0.14%), agora-
phobia (0.07%) or pervasive developmental disor-
ders (PDD; 0.29%) (33). A retrospective review of
patients evaluated at the Maudsley Hospital in
South London identified only 38 cases of ICD-10
pediatric BD over a period of 22 years (1974–
1996), which would be approximately 1.7 cases per
year. Their mean age was 14.2 years (range 11–18
A first-episode psychosis study
Monaghan (rural Ireland), in adolescents and
adults >15 years, from 1995 to 2000, found an
incidence of DSM-IV BD of 2.2 cases per 100,000
per year (35). The incidence was 6.6-fold lower in
women than in men.
Ra ¨ sa ¨ nen et al. (36) found that the annual rate
of DSM-III BD in all psychiatrically hospitalized
patients in Finland was only 0.03%, and only 2%
Table 1. Epidemiological and clinical studies on pediatric bipolarity in non-US samples
Population: n (age
of subjects in years) Prevalence
criteriaType of sample
HollandVerhulst 1997 (24)780 (13–18) 1.9% mania, 0.9% hypomania,
7.2% mood disorders,
6% conduct disorder
1.2% (39 cases) BD
38 cases in 22 years,
1.7 cases per year
per year of BD
with psychosis (8 cases)
1.7 cases/100,000 per year
1.7% BD (8 cases)
2.5% BD, 21 cases
7 cases BD
Thomsen, 1992 (30)
Ford, 2003 (33)
Sigurdsson, 1999 (34)
38 [11–18 (M ¼ 14.4)]
ICD-9 and 10
IrelandScully, 2002 (35)102,810 (‡15) DSM-IV
FinlandRa ¨sa ¨nen, 1998 (36)
Sourander, 2004 (37)
Soutullo, 2003 (58)
Reddy, 1997 (39)
Alexander, 1997 (38)
Tramontina, 2003 (42)
Emiroglu, 2004 (41)
840 (child and adol.)
n ¼ number of subjects; M ¼ mean age.
Soutullo et al.
of them (0.0006% or 1.7 cases per 100,000 per
year) were younger than 20 years. They concluded
that the onset of BD in Finland appears to be later
than in other countries. In a group of 475 Finnish
psychiatrically hospitalized pediatric patients aged
2–18 years, eight (1.7%) had an ICD-10 diagnosis
of BD (37). These are both very low prevalences,
considering they are clinical populations, but it
may be possible that Finnish pediatric patients
with BD may not be hospitalized and/or are
treated as outpatients only.
There are three available studies on the preva-
lence of pediatric BD in clinical samples in India.
The first one found that five (4.2%) of 119
hospitalized children over a period of 18 months
in the Child Psychiatry Unit in Manipal, India, had
a diagnosis of DSM-IV BD. The age of onset of
BD ranged from 10 to 13 years. The most frequent
decreased need for sleep, psychomotor agitation,
involvement in potentially risky activities and
oppositionality (80% each), irritability (60%),
euphoria (40%) and grandiose or persecutory
delusions (20% each) (38). The second study
reported that 21 (2.5%) of 840 children and
adolescents assessed in a clinic in Bangalore, south
India, met DSM-III criteria for mania, and that
none of them had comorbid ADHD. Thirteen
(61%) of the children with mania had delusions
and/or hallucinations. The most frequent symp-
toms were: pressured speech, irritability, elation,
distractibility, grandiosity and expansive mood
(39). The third study was a retrospective chart
review without epidemiological data of 139 chil-
dren and adolescents <16 years with DSM-IV
BD, also conducted in Bangalore over a period of
almost 5 years. The mean ± SD time to relapse
was 15 ± 14 months (89% within the first 2 years)
A recent case report in Turkey reported seven
cases of children between 7 and 15 years with BD,
assessed by Washington University in St. Louis
Kiddie Schedule for Affective Disorders and
Schizophrenia, Lifetime and Present Episode Ver-
sion, DSM-IV (WASH-U-KSADS). The research-
ers found that the most frequent symptoms were
grandiosity, distractibility and elevated energy.
Furthermore, four (57%) cases had mixed mania,
and five (71%) had ultradian cycling (41).
A study from Brazil reported a prevalence of
7.2% of DSM-IV BD in a retrospective review of
all outpatients under age 15 evaluated in an clinic
in Porto Alegre. In this study the mean age of the
children with BD was 9.6 ± 3.5 years, with a high
rate (42%) of family history of BD. Most patients
(78%) required two or more medications to control
their symptoms. Irritable mood was present in
91.7% of patients. They found that 42% of
children with BD presented with only irritability
(without elation), 8% presented only elevated
mood (without irritability) and 50% presented
both symptoms (42).
We evaluated a total of 714 children and
adolescents at the Child and Adolescent Psychiatry
Unit, Department of Psychiatry and Medical
Psychology at the University of Navarra, in
Pamplona, Spain, from 2000 to 2004. The preva-
lence of any DSM-IV mood disorder was 27% and
of BD 4% (about seven new cases per year). We
naturalistically recruited patients as they came to
the clinic. They received clinical evaluations using
DSM-IV criteria and a semistructured DSM-IV-
based clinical interview to screen for ADHD,
mood and anxiety disorders. We then performed
a chart review searching for patients with a
diagnosis of BD. BD represented 15% of all mood
disorders. The mean age ± SD (range) of the
children with BD was 13.2 ± 3.5 (5–19) years,
78% were boys and 22% girls. The mean ± SD
(range) age of onset was 8.8 ± 4.4 (3–17) years.
The mean time from onset of symptoms to
diagnosis was 4.4 years. Most patients had prior
diagnoses of depression (55%), ADHD (44%),
ODD (40%), conduct disorder (12%), anxiety
disorders (32%), psychotic disorder (20%) or
substance abuse (20%). The mean number of prior
diagnoses per patient was 2.2. Forty-eight percent
had DSM-IV bipolar I disorder, 16% had bipolar
II disorder and 36% had BD-NOS (bipolar
frequent symptoms in children and adolescents
with mania were irritability (96%), hyperactivity
(80%), rapid speech (72%), psychotic features
(64%) (hallucinations: 12.5%, grandiose delusions:
48%, paranoid delusions: 36%), euphoric mood
(52%), hypersexuality (52%), excessive money
spending (48%), decreased need for sleep (44%)
and inattention (32%) (Fig. 1). We found an onset
of BD before 6 years in 28% of patients, an onset
between ages 6 and 12 in 44% of patients and an
onset between ages 13 and 17 in 28% of patients.
Comorbidity with ADHD was present in 18.5%,
ODD in 20%, anxiety disorders in 32% and
substance abuse in 20% of the cases. Despite a
relatively low comorbidity with ADHD, the most
frequent presentation was a non-episodic, chronic,
mixed-manic state. We recruited these patients over
a period of 4 years, so we still do not know if they
will continue to meet BD criteria into adulthood.
However, so far, their diagnosis has not changed.
Cross-cultural and ethnic factors can also
influence the diagnosis of children with BD, as
specified). The most
Bipolar disorder in children and adolescents: international perspective
it does in adult patients with BD. A cross-
cultural US study diagnosed mania in prepuber-
diagnoses of depression and conduct disorder
(43). DelBello et al. (44) reported that African
American adolescents were more likely to be
diagnosed with psychotic-spectrum disorders and
conduct disorders than Caucasian adolescents,
who were more commonly diagnosed with mood
disorders. In a recent study, videotaped inter-
views of two American adults with DSM-IV
mania were shown to trained clinicians with
experience with patients with BD and with the
Young Mania Rating Scale (YMRS). The raters
were from three English-speaking countries: the
UK (n ¼ 20), India (n ¼ 24) and the USA (n ¼
82). Total YMRS scores differed significantly
between the US and UK (p < 0.001), India and
UK (p < 0.001), and US and India (p ¼ 0.004).
The mean ± SD YMRS scores for subject A
and subject B were: USA: 31.6 ± 0.33 and
38.6 ± 0.32; India: 30.5 ± 0.78
0.68; and UK: 20.6 ± 0.58 and 27.1 ± 0.97.
The authors found significant differences between
raters on 10 of 11 YMRS items. The most
profound differences were found in mood eleva-
tion, irritability, thought content and disruptive-
aggressive behavior. In most cases, the UK
scores were lower than the US and Indian scores.
exposed to the same videotaped interviews of
patients, were more likely to rate higher YMRS
if the clinician was from the USA and lower
YMRS if they were from the UK. Therefore,
trained psychiatrists in the US may recognize and
report more severity of manic symptoms than
psychiatrists from the UK (45).
Research on child and adolescent BD in Europe
and countries, other than the USA is scarce.
Despite extensive research on adult BD in Europe,
there is lack of information about the international
prevalence and phenomenology of pediatric BD.
Nevertheless, current data suggest that pediatric
BD is fairly rare outside the US, perhaps 0% in the
UK (33) to 1.9% in Holland (24) in epidemiolog-
ical samples. Samples in outpatient clinics found
prevalences ranging from 0% in the UK (18) to 4%
in our clinic in Spain. Finally, studies in psychiatric
hospitals found BD in 0.0006% of hospitalized
patients in Finland (37), 1.2% in Denmark (30),
and 2.5–4.2% (38, 39) in India.
The suggestion that pediatric BD is rare
outside the US is a surprising one, given that
recent studies have reported a high percentage of
adults with BD having their first mood episode
before age 18, both in the US (59%) (3) and in
Europe (33.1%) (4). Furthermore, BD is highly
family history of BD leads to earlier, pediatric
Fig. 1. Frequency (%) of symptoms in 27 children or adolescents with bipolar disorder recruited at the Child and Adolescent
Psychiatry Unit, Department of Psychiatry and Medical Psychology, University of Navarra, Pamplona, Spain.
Soutullo et al.
onset (46). Prevalence rates of adults with BD
are variable internationally, but rates in the US
(3.0%) are not even as high as in Italy (3.4%),
Switzerland (5.1%) and Hungary (5.5%) (23).
Offspring studies in the US have reported high
rates of BD in children of parents with BD (29).
Therefore, one would expect that the prevalence
of pediatric-onset BD might be at least compar-
able in countries outside the US.
There may be several reasons for this discrep-
ancy. First, there are important differences in
methodology in the available pediatric BD studies,
such as range of age considered, rating scales used,
person interviewed and duration of assessment
(6-month versus lifetime prevalence) reported. The
person who is interviewed, whether the parent, the
child or both, is relevant to the epidemiology of
BD, and many of the studies did not consider
information gathered from the children themselves.
Differences in prevalence of mania symptoms may
be due, in part, to whether the child is assessed or
not, especially if only the parents are evaluated
since they may under-report certain symptoms
such as elation, grandiosity, flight of ideas, racing
thoughts or decreased need for sleep (47). The
origin of the sample, inpatients or outpatients, may
be another methodological difficulty, as most of
the studies reported here were conducted in
adolescents with milder symptoms of BD might
be treated without hospitalization and therefore
missed in these studies.
Second, the lack of relevant studies outside the
US may reflect an overall bias among international
researchers that BD is very rare in children and
adolescents. A similar phenomenon happened in
the US in the 1970s and 1980s with pediatric
depression (48) and in the UK with ADHD (49). In
fact, acceptance of the common existence of
pediatric BD has been growing in the US only
over the past 10 years or so (5). This acceptance
might still occur outside the US.
Third, actual criteria used to diagnose BD may
differ somewhat among countries. Differences in
ICD-10 and DSM-IV diagnostic criteria for BD
may be relevant (20, 21). For example, the ICD-10
requires more than one manic episode for a
diagnosis of BD. One US study found the mean
episode duration of mania in children with BD to
be 79.2 weeks (50). Therefore, identification of
multiple manic episodes in children may be difficult
and lead to a lower rate of diagnosis by ICD-10
criteria. These differences are also important in the
criteria for ADHD and hyperkinetic disorder
(HKD), which would have a significant impact
on the rates of comorbidity BD–ADHD. However,
it should be noted that only two of the studies
actually used ICD, the rest using various forms of
DSM, suggesting that ICD/DSM differences can at
best only account for a small part of the variance.
Also, the use of ?softer? forms of the BD spectrum,
such as BD-II or BD-NOS, is more widespread in
the US compared with European and other coun-
tries. It may be important for non-US countries to
study the validity in their pediatric populations of
different clinical phenotypes that differ by the
presence of clinically defined episodes, the duration
of episodes and the presence of specific ?hallmark?
symptoms such as the narrow, intermediate and
broad phenotypes suggested by Leibenluft et al.
should be the main hallmark of pediatric mania
has been debated somewhat in the US (9, 11).
However, some data indicate that the characteris-
tics of children with mania presenting with irrita-
bility versus those with euphoria or episodic versus
continuous cycling, may be very similar anyway
Fourth, a different level of recognition of child
and adolescent psychiatry as a specialty between
countries in Scandinavia or Central-Western Eur-
ope (high recognition) and Mediterranean Europe
(low recognition) also may have a big impact on
the resources available to study children with
Fifth, despite the lack of data it is possible that
pediatric BD is not diagnosed as frequently in
Europe as in the US, partly due to clinician bias
towards the diagnosis of severe HKD, conduct,
major depressive and personality disorders instead
of BD. There is also evidence that even in the US,
BD is underdiagnosed in minorities (43, 44). Thus,
due in part to clinician bias, the same may be
happening in non-US samples.
Sixth, it is possible that BD is indeed overdiag-
nosed in children in the US. Few studies have
prospectively followed US children diagnosed with
BD into adulthood to establish that they continue
to meet DSM or ICD criteria for BD. Some
children may have what in Europe is called severe
forms of ADHD with pronounced emotional
dysregulation or ADHD with comorbid language
disorders, perceptual difficulties or developmental
coordination disorder that can be confused with
mania because they are associated with irritability
and severe impairment (18). This issue is important
particularly in pre-adolescent mania, where the
discrepancy in prevalence is even larger.
Seventh, the phenomenology of child and ado-
lescent BD is somewhat different than that of adult
BD, including prepubertal non-episodic, chronic,
rapid-cycling, mixed manic states that could easily
Bipolar disorder in children and adolescents: international perspective
be misdiagnosed as ODD, conduct disorder or
severe ADHD (5, 11, 43, 47, 52, 53).
Finally, it is also possible that pediatric BD is
indeed rarer outside the US. This might be
predominantly due to environmental/cultural dif-
ferences. One difference may be the frequency of
stimulant or antidepressant use in children and
adolescents. Greater use of these medications in the
US might be leading to an earlier onset of BD, as
they could trigger hypomanic or manic episodes in
children with a genetic predisposition for BD (54).
A recent retrospective chart review of 82 children
with BD (mean age 10.6 ± 3.6 years, range 3–17
years) found treatment-emergent mania associated
with use of an antidepressant in 75.7% and with
use of a stimulant in 24.2% (55). Prior studies have
shown that children with ADHD and BD had a
mean onset of ADHD at age 5.5 years, the onset of
treatment with stimulants at age 6.9 years and the
onset of BD at age 7.1 years (56), raising the
question of whether stimulant treatment acceler-
ated or caused the first manic episode. Also,
another retrospective study reported that patients
exposed to stimulants compared with those not
exposed to stimulants had earlier age of onset of
BD and a more severe course (10.7 versus
13.9 years, respectively) (52, 53). This was not true
for patients with prior exposure to antidepressants
(52). However, in these studies it was difficult to
separate whether the exposure to stimulants or the
severity of comorbid ADHD was the factor that
explained the earlier onset or the worse course of
hospitalization. Until we have more data we
should be cautious about linking the onset of
manic symptoms to treatment with stimulants or
antidepressants. Other environmental and cultural
differences might include nuclear versus extended
families, different parenting and educational styles
and environmental toxins. Indeed, long (20 years)
follow-up studies indicate that at least 50% of all
mood disorders turned out to be bipolar, and that
most of the literature on major depression may be
dealing with heterogeneous samples that include
large numbers of undiagnosed bipolar II patients
(57). Undoubtedly, time will help clarify the
discrepancies in prevalence of pediatric BD within
and outside the US. Longitudinal studies of US
children with BD will reveal whether they continue
to meet BD criteria as adults. Further studies on
children and adolescents with BD could determine
if children with ?non-classic BD? have similar
family history, patterns of comorbidity, genetic
characteristics and response to treatment (improve-
ment with mood-stabilizer agents, worsening due
to mania or increased cycling with antidepressants)
to those with ?classic? BD. On the contrary, if these
children have just ?severe ADHD? comorbid with
ODD/conduct disorder/substance abuse or they
have a type of developmental low frustration
tolerance and explosiveness, they should have
characteristics similar to children with severe and
complicated ADHD or developmental explosive-
ness and will not continue having BD symptoms in
later adolescence and adulthood. Time may also
lead to more international children being treated
with stimulants and antidepressants, which might
unfortunately lead to an increased incidence of
pediatric-onset BD. Additional research outside
the US of pediatric BD, with standardized
including direct interviews of the children them-
selves, might lead to growing acceptance of both
the possibility of such a diagnosis in children as
well as of the field of child and adolescent
psychiatry as a whole. Until then these questions
regarding the differences in the epidemiology and
phenomenology of pediatric BD in non-US sam-
ples will remain unanswered.
1. Goodwin FK, Jamison KR. Manic-depressive Illness. New
York, NY: Oxford University Press, 1990.
2. Angst J. The prevalence of depression. In: Briley M,
Montgomery SA eds. Antidepressant Therapy at the Dawn
of the Third Millennium. London: Martin Dunitz, 1998:
3. Lish JD, Dime-Meenan S, Whybrow PC, Price RA,
Hirschfeld RM. The National Depressive and Manic-
depressive Association (NDMDA) survey of bipolar
members. J Affect Disord 1994; 31: 281–294.
members of 12 European advocacy groups operating in the
field of mood disorders. Bipolar Disord 2003; 5: 265–278.
5. Geller B, Luby J. Child and adolescent bipolar disorder: a
review of the past 10 years. J Am Acad Child Adolesc
Psychiatry 1997; 36: 68–76.
6. Biederman J, Wozniak J, Kiely K et al. CBCL clinical
scales discriminate prepubertal children with structured
interview-derived diagnosis of mania from those with
ADHD. J Am Acad Child Adolesc Psychiatry 1995; 34:
7. Biederman J, Faraone S, Mick E et al. Attention-deficit
hyperactivity disorder and juvenile mania: an overlooked
comorbidity? J Am Acad Child Adolesc Psychiatry 1996;
8. Biederman J, Mick E, Bostic JQ et al. The naturalistic
course of pharmacological treatment of children with
manic-like symptoms: a systematic chart review. J Clin
Psychiatry 1998; 59: 628–637.
9. Leibenluft E, Charney DS, Towbin KE, Bhangoo RK,
Pine DS. Defining clinical phenotypes of juvenile mania.
Am J Psychiatry 2003; 160: 430–437.
10. Biederman J, Faraone SV, Chu MP, Wozniak J. Further
evidence of a bidirectional overlap between juvenile mania
and conduct disorder in children. J Am Acad Child
Adolesc Psychiatry 1999; 38: 468–476.
Soutullo et al.
11. Geller B, Zimerman MA, Williams M et al. DSM-IV
mania symptoms in a prepubertal and early adolescent
bipolar disorder phenotype compared to attention-deficit
hyperactive and normal controls. J Child Adolesc Psycho-
pharmacol 2002; 12: 11–25.
12. Akiskal HS, Azorin JM, Hantouche EG. Proposed mul-
tidimensional structure of mania: beyond the euphoric–
dysphoric dichotomy. J Affect Disord 2003; 73: 7–18.
13. Kraepelin E. Manic-depressive Insanity and Paranoia.
Translated by Barclay RM; edited by Robertson GM.
Edinburgh: E & S Livingstone, 1921 (reprinted 1976; New
York, NY: Arno Press).
14. Lewinsohn PM, Klein DN, Seeley JR. Bipolar disorder
during adolescence and young adulthood in a community
sample. Bipolar Disord 2000; 2: 281–293.
15. Clark AF. Particular aspects of diagnosis, management,
and treatment of bipolar disorders in children and
adolescents. Clin Approaches Bipolar Disord 2004; 3:
16. Gillberg C, Gillberg IC, Rasmussen P et al. Co-existing
disorders in ADHD – implications for diagnosis and
intervention. Eur Child Adolesc Psychiatry 2004; 13: I/80–
17. Taylor E, Do ¨ pfner M, Sergeant J et al. European clinical
guidelines for hyperkinetic disorder – first upgrade. Eur
Child Adolesc Psychiatry 2004; 13: I/7–I/30.
18. Meltzer H, Gatward R, Goodman R, Ford T. Mental
Health of Children and Adolescents in Great Britain.
London, UK: Stationery Office, 2000.
19. Harrington R, Myatt T. Is preadolescent mania the same
condition as adult mania? A British perspective. Biol
Psychiatry 2003; 53: 961–969.
20. World Health Organization. The ICD-10 Classification of
Mental and Behavioural Disorders: Diagnostic Criteria for
Research. Geneva: WHO, 1992.
21. American Psychiatric Association. Diagnostic and Statis-
tical Manual of Mental Disorders, 4th edn. Washington,
DC: American Psychiatric Association, 1994.
22. Angst J, Gamma A, Benazzi F, Ajdacic V, Eich D, Rossler
W. Toward a re-definition of subthreshold bipolarity:
epidemiology and proposed criteria for bipolar-II, minor
bipolar disorders and hypomania. J Affect Disord 2003;
23. Noaghiul S, Hibbeln JR. Cross-national comparisons of
seafood consumption and rates of bipolar disorders. Am J
Psychiatry 2003; 160: 2222–2227.
24. Verhulst FC, van der Ende J, Ferdinand RF, Kasius MC.
The prevalence of DSM-III-R diagnoses in a national
sample of Dutch adolescents. Arch Gen Psychiatry 1997;
25. Wals M, Hillegers MHJ, Reichart CG, Ormael J, Nolen
W, Verhulst FC. Prevalence of psychopathology in child-
ren of bipolar parents. J Am Acad Child Adolesc Psychi-
atry 2001; 40: 1049–1102.
26. Duffy A, Alda M, Kutcher S, Fusee C, Grof P. Psychiatric
symptoms and syndromes among adolescent children of
parents with lithium-responsive or lithium non-responsive
bipolar disorder. Am J Psychiatry 1998; 155: 431–433.
27. Soutullo CA, DelBello MP, McDonough-Ryan P, McEl-
roy SL, Strakowski SM, Keck PE Jr. Factor and receiving
operating characteristics (ROC) analyses of psychiatric
phenomenology in children of bipolar parents versus
controls. Am Acad Child and Adolescent Psychiatry
Annual Meeting, Miami, Florida, Oct 14–19 2003.
28. Chang KD, Steiner H, Ketter TA. Psychiatric phenome-
nology of child and adolescent bipolar offspring. J Am
Acad Child Adolesc Psychiatry 2000; 39: 453–460.
29. Chang K, Steiner H. Offspring studies in child and early
adolescent bipolar disorder. In: Geller B, DelBello MP,
eds. Bipolar Disorder in Childhood and Early Adoles-
cence. New York, NY: The Guilford Press, 2003.
30. Thomsen PH, Moller LL, Dehlholm B, Brask BH. Manic-
depressive psychosis in children younger than 15 years: a
register-based investigation of 39 cases in Denmark. Acta
Psychiatr Scand 1992; 85: 401–406.
31. Biederman J, Faraone SV, Wozniak J et al. Clinical
correlates of bipolar disorder in a large, referred sample of
children and adolescents. J Psychiatric Res 2005; 39: 611–
32. Sayal K, Taylor E, Beecham J, Byrne P. Pathways to care
in children at risk for ADHD. Br J Psychiatry 2002; 181:
33. Ford T, Goodman R, Meltzer H. The British Child and
Adolescent Mental Health Survey 1999: the prevalence of
DSM-IV disorders. J Am Acad Child Adolesc Psychiatry
2003; 42: 1203–1211.
34. Sigurdsson E, Fombonne E, Sayal K, Checkley S. Neuro-
developmental antecedents of early-onset bipolar affective
disorder. Br J Psychiatry 1999; 174: 121–127.
35. Scully PJ, Quinn JF, Morgan MG et al. First-episode
schizophrenia, bipolar disorder and other psychoses in a
rural Irish catchment area: incidence and gender in the
Cavan–Monaghan study at 5 years. Br J Psychiatry 2002;
181(Suppl 43): 53–59.
36. Ra ¨ sa ¨ nen P, Tiihonen J, Hakko H. The incidence and
onset-age of hospitalized bipolar affective disorder in
Finland. J Affect Disord 1998; 48: 63–68.
37. Sourander A. Combined psychopharmacological treat-
ment among child and adolescent inpatients in Finland.
Eur Child Adolesc Psychiatry 2004; 13: 179–184.
38. Alexander PJ, Raghavan R. Childhood mania in India.
J Am Acad Child Adolesc Psychiatry 1997; 36: 1650–1651.
39. Reddy YC, Girimaji S, Srinath S. Clinical profile of mania
in children and adolescents from the Indian subcontinent.
Can J Psychiatry 1997; 42: 841–846.
40. Rajeev J, Srinath S, Girimaji S, Seshadri SP, Songh P. A
systematic review of the naturalistic course and treatment
of early-onset bipolar disorder in a child and adolescent
psychiatry center. Compr Psychiatry 2004; 45: 148–154.
41. Emiroglu FN. Case series with childhood bipolar disorder
phenotype features. Turk Psikiyatri Derg 2004; 15: 148–
42. Tramontina S, Schmitz M, Polanczyk G, Rohde L.
Juvenile bipolar disorder in Brazil: clinical and treatment
findings. Biol Psychiatry 2003; 53: 1043–1049.
43. Dilsaver SC. Unsuspected depressive mania in pre-pubertal
hispanic children referred for the treatment of ?depression?
with history of social ?deviance?. J Affect Disord 2001; 67:
44. DelBello MP, Lopez-Larson MP, Soutullo CA, Strakowski
SM. Effects of race on psychiatric diagnosis of hospitalised
adolescents: a retrospective review. J Child Adolesc Psy-
chopharmacol 2002; 11: 95–103.
45. Targum SD, Young AH, Kalali A, Rom D. Comparison of
mania ratings across three cultures. 17th Congress of the
European College of Neuropsychopharmacology (ECNP),
Stockholm, Sweden, 9–13 October 2004. Poster P.1.017.
Eur Neuropsychopharmacol 2004; 14: S181.
46. Faraone SV, Glatt SJ, Tsuang MT. The genetics of
pediatric-onset bipolar disorder. Biol Psychiatry 2003; 53:
47. Tillman R, Geller B, Craney JL, Bolhofner K, Williams M,
Zimerman B. Relationship of parent and child informants
to prevalence of mania symptoms in children with a
Bipolar disorder in children and adolescents: international perspective
prepubertal and early adolescent bipolar disorder pheno-
type. Am J Psychiatry 2004; 161: 1278–1284.
48. Weller EB, Weller RA, Rowan AB, Svadjian H. Depressive
disorders in children and adolescents. In: Lewis M ed.
Child and Adolescent Psychiatry. A Comprehensive Text-
book, 3rd edn. Philadelphia, PA: Lippincott Williams &
49. Prendergast M, Taylor E, Rapoport JL et al. The diagnosis
of childhood hyperactivity: a US-UK cross-national study
of DSM-III and ICD-9. J Child Psychol Psychiatry 1988;
50. Geller B, Tillman R, Craney JL, Kristine Bolhofner K.
Four-year prospective outcome and natural history of
mania in children with a prepubertal and early adolescent
bipolar disorder phenotype. Arch Gen Psychiatry 2004; 61:
Biederman J. Convergence between structured diagnostic
interviews and clinical assessment on the diagnosis of
pediatric-onset mania. Biol Psychiatry 2003; 53: 938–944.
52. Soutullo CA, DelBello MP, Ochsner JE et al. Severity of
bipolarity in hospitalized manic adolescents with and
without a history of stimulant or antidepressant treatment.
J Affect Disord 2002; 70: 323–327.
53. DelBello MP, Soutullo CA, Hendricks W, Niemeier RT,
McElroy SL, Strakowski SM. Prior stimulant treatment in
adolescents with bipolar disorder: association with age of
onset. Bipolar Disord 2001; 3: 53–57.
54. Reichart CG, Nolen WA. Earlier onset of bipolar disorder
in children by antidepressants or stimulants? An hypothe-
sis. J Affect Disord 2004; 78: 81–84.
55. Faedda GL, Baldessarini RJ, Glovinsky IP, Austin NB.
Treatment-emergent mania in pediatric bipolar disorder: a
56. Kowatch RA, Suppes T, Carmody TJ et al. Effect size of
lithium, divalproex sodium, and carbamazepine in children
and adolescents with bipolar disorder. J Am Acad Child
Adolesc Psychiatry 2000; 39: 713–720.
57. Angst J. Bipolar disorder. A seriously underestimated
health burden. Eur Arch Psychiatry Clin Neurosci 2004;
58. Soutullo CA. Pediatric bipolarity: international perspective
on epidemiology and phenomenology. In: Saxena K,
Kowatch R, Liebenluft E, Chang KD, eds. AACAP
Symposium 63. Scientific Proceedings: 99–100. Am Acad
Child & Adolesc Psychiatry Annual Meeting, Miami, FL,
USA. October 14–19, 2003.
Soutullo et al.