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.

Full text

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Review Article
Bipolar disorder in children and adolescents:
international perspective on epidemiology
and phenomenology
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
phenomenology.
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
varying results.
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
this field.
Ce ´sar A Soutulloa, Kiki D Changb,
Azucena Dı ´ez-Sua ´reza, Ana
Figueroa-Quintanaa, Inmaculada
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;
e-mail: csoutullo@unav.es
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 DISORDERS
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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
magnitudeofthiscomorbidity,theissueofADHD–
BDsymptomoverlapandthefactthatsomeauthors
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
underdiagnosisormisdiagnosisofpediatricBD.For
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
StanleyMedicalResearchInstitutefunds19Stanley
Research Centersineightcountries in the
Soutullo et al.
498

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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
Europe.
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
hospitalized adultpatients
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:
Methods
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
AdolescentPsychiatry
Psychiatry and Medical Psychology, University
Clinic, University of Navarra, Pamplona, Spain
recruited over a 4-year period.
Unit,Departmentof
Results
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
(Table 1).
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
499

Page 4

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
see (29).
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
16%.
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
years) (34).
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%
in Cavan-
Table 1. Epidemiological and clinical studies on pediatric bipolarity in non-US samples
Country
First author,
year (ref.)
Population: n (age
of subjects in years) Prevalence
Diagnostic
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
0% BD
38 cases in 22 years,
1.7 cases per year
2.2 cases/100,000
per year of BD
with psychosis (8 cases)
1.7 cases/100,000 per year
1.7% BD (8 cases)
4% BD
2.5% BD, 21 cases
4.2% BD
7.2% BD
7 cases BD
DSM-III-R Epidemiological
Denmark
UK
Thomsen, 1992 (30)
Ford, 2003 (33)
Sigurdsson, 1999 (34)
3250 (<15)
10,438 (5–15)
38 [11–18 (M ¼ 14.4)]
–
DSM-IV
ICD-9 and 10
Clinical, inpatients
Epidemiological
Clinical, inpatients
and outpatients
Epidemiological,
1st psychotic
episode
Clinical, inpatients
Clinical, inpatients
Clinical, outpatients
Clinical, inpatients
Clinical, inpatients
Clinical, outpatients
Clinical
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)
(10–19)
475 (2–18)
714 (<18)
840 (child and adol.)
119 (10–13)
35 (<15)
(7–15)
DSM-III-R
ICD-10
DSM-IV
DSM-III-R
DSM-IV
DSM-IV
DSM-IV
Spain
India
Brazil
Turkey
n ¼ number of subjects; M ¼ mean age.
Soutullo et al.
500

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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
symptomswere over-talkativeness
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)
(40).
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
(100%),
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
disorder nototherwise
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
501

Page 6

it does in adult patients with BD. A cross-
cultural US study diagnosed mania in prepuber-
talHispanic(Mexican)
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.
Therefore,itseemed
exposed to the same videotaped interviews of
childrenwithprior
and40.8 ±
thattrainedclinicians,
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).
Discussion
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
heritable,withthelikelihood
family history of BD leads to earlier, pediatric
that increased
96
80
72
64
12.5
48
36
5252
48
44
32
0
10
20
30
40
50
60
70
80
90
100
Irritable
Hyperactive
Rapid speech
Psychotic
Hallucinations
Grandiose
Paranoid
Euphoric
Hypersexual
Spending money
Decreased sleep
Inattentive
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.
502

Page 7

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
hospitalizedpatients.Possibly,
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,
children and
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.
(9).Furthermore,whetherirritability,noteuphoria,
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
(51).
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
mood disorders.
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
503

Page 8

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
research-basedsemistructured
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.
interviewsand
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