Co-Morbidity Of Bipolar Disorder İn Children And Adolescents With Attention Deficit/Hyperactivity Disorder (Adhd) İn An Outpatient Turkish Sample
Abstract
This study aimed to assess the prevalence of bipolar disorder (BPD) in children and adolescents with attention deficit
hyperactivity disorder (ADHD), and to compare the clinical characteristics of a group with ADHD with a group with
co-morbidity of ADHD and BPD. The study includes 121 individuals, aged 616 years, with a diagnosis of ADHD. Comorbidity
of BPD was evaluated using the Schedule for Affective Disorders and Schizophrenia for School-age Children-
Present and Lifetime version (K-SADS-PL) and the Parent-Young Mania Rating Scale (P-YMRS). The Child Behavior
Checklist (CBCL) was used to assess psychopathology in two groups. Ten children (8.3%) in the ADHD sample received
the additional diagnosis of BPD. The ADHDBPD group had significantly higher scores than the ADHD group on
withdrawn, anxiety/depression, social problems, thought problems, attention problems, aggression, externalization, total
score items of CBCL, and on the P-YMRS. It could be concluded that BPD is not a rare co-morbid condition in children
with diagnosis of ADHD and subjects with this co-morbidity show more severe psychopathology than subjects with pure
ADHD. Differential diagnosis of BPD disorder in subjects with ADHD seems crucial in establishing an effective treatment
program, and therefore improving mental health outcomes.
Key words: Attention deficit/hyperactivity disorder, bipolar disorder, comorbidity
Introduction
Attention deficit/hyperactivity disorder (ADHD)
consists of a persistent pattern of inattention, hyperactivity
and impulsivity (APA 2000). It is well
established that ADHD is frequently comorbid with
other psychiatric disorders such as oppositional
defiant disorder, conduct disorder, anxiety disorders,
depression, tic disorders, substance abuse and bipolar
disorders (AACAP 2007). Perhaps the most diagnostically
challenging and controversial of co-occurring
disorders in ADHD is bipolar disorder (BPD). When
they occur in combination, these conditions often
complicate the assessment process, clinical diagnosis
and treatment. Literature reviews indicate that this
topic has received increased clinical and scientific
attention in recent years. Many studies have been
conducted to assess the rate of this co-morbidity,
phenomenology, clinical characteristics and differential
diagnosis with BPD.
Despite the increasing amount of research in
paediatric bipolar disorder, there is still confusion
and controversy surrounding clinical diagnosis of
this condition. This confusion is partly due to the
lack of awareness and clinical bias, in certain setting,
against the diagnosis of mania in children (Geller
et al. 1998; Biederman 2003). Symptom overlap
between BPD and other childhood-onset psychiatric
disorders is another important factor contributing to
diagnostic difficulties (Diler et al. 2007). Differential
diagnosis with ADHD is an especially crucial issue.
Since several symptoms are shared by ADHD and
BPD, the debate regarding the validity of paediatric
bipolar disorder has shifted from whether paediatric
bipolar disorder exists to which symptoms should be
considered cardinal symptoms of bipolar disorder in
children (Mick et al. 2005). Irritability, impulsivity,
hyperactivity, and distractibility are very frequent in
both disorders, therefore not specific for mania
(Mick et al. 2005). Elation, grandiosity, racing
Correspondence: Prof. Dr. Nahit Motavalli Mukaddes, Sezai Selek Sok-Sevim Ap No: 7/4 Nisantasi, Istanbul 80200, Turkey.
Tel: 90 212 2349207. Fax: 90 212 2349208. E-mail: nmotavalli@yahoo.com
The World Journal of Biological Psychiatry, 2009; 10(4): 488494
(Received 17 September 2008; accepted 20 February 2009)
ISSN 1562-2975 print/ISSN 1814-1412 online # 2009 Informa UK Ltd. (Informa Healthcare, Taylor & Francis AS)
DOI: 10.3109/15622970902929876thoughts, decreased need for sleep and hypersexuality
are common in bipolar disorder and can
discriminate BPD from ADHD (Geller et al. 2002;
Pavuluri et al. 2005).
Additionally, several instruments such as the
Child Behavior Checklist (CBCL) (Achenbach
1991), Young Mania Rating Scale (Young et al.
1978), and the Child Mania Rating Scale (Pavuluri
et al. 2006) are considered effective instruments for
helping clinicians differentiate mania in an ADHD
population.
Results of studies evaluating the effectiveness of the
CBCL in differential diagnosis of paediatric bipolar
disorder are controversial. A few studies proposed a
CBCL paediatric bipolar profile (BPD) based on the
significant elevation in the anxiety/depression, attention
problems and aggression subscales (Mick et al.
2003; Farone et al. 2005). However, the predictive
validity of CBCL-BPD in identifying BPD has been
recently questioned (Volk and Todd 2007; Meyer
et al. 2008). Some authors have attempted to
differentiate ADHD from mania using the Young
Mania Rating Scale and the Parent-Young Mania
Rating Scale (Fristad et al. 1995; Diler et al. 2007).
However, other investigators stated that this instrument
is designed to quantify rather than diagnose an
episode of mania (Carlson and Kelly 1998).
Regarding the rate of this co morbidity, several
studies have investigated the rate of BPD in ADHD
and vice versa. Six population-based studies evaluated
the co-occurrence of ADHD and BPD in
youths, three of which showed elevated rates of
BPD in participants who have ADHD; however,
three failed to show an association between the two
disorders (Galanter and Leibenluft 2008). Clinical
studies have found rates of BPD ranging from 8.2 to
23% in youths who have ADHD (Wozniak et al.
1995; Butler et al. 1995; Biederman et al. 1996;
Diler et al. 2007). Regarding the rate of ADHD in
clinic referred subjects with BPD, rates vary widely
across samples, from 4 to 98% (Kowatch et al. 2005;
Birmaher et al. 2006; Jaideep et al. 2006). Setting,
participants age, age of onset of BPD, referral source
and ascertainment bias affect these rates.
The relatively high degree of co-occurrence
between these disorders raises the question of probable
common aetiological factors. Several studies
proposed the role of dopamine transporter genes in
ADHD (Cook et al. 1995; Faraone et al. 2005) and
BPD (Greenwood et al. 2006). Further, the involvement
of the brain-derived neutrophic factor (BDNF)
gene in the pathogenesis of ADHD (Kent et al. 2005)
and BPD (Geller et al. 2004) was reported. Family
studies strongly suggest that paediatric onset bipolar
disorder has a strong familial component. Some
investigators documented that bipolar disorder and
ADHD co segregated in relatives support the
hypothesis that ADHD and co morbid bipolar disorder
may represent a unique developmental subtype
of bipolar disorder (Faraone et al. 1997; Biederman
et al. 2004).
Despite increasing research on BPD, paediatric
bipolar disorder is still unrecognized in most countries
other than the USA. BPD research from
outside of the USA is limited and according to
some studies, there is significant ethnic differences in
the prevalence of BPD (Youngstrom et al. 2005) and
clinical presentation of BPD (Kennedy et al. 2004).
These findings underlie the need for further assessment
of bipolar disorder in children with different
ethnic origin.
This study aimed to: (a) assess the prevalence of
BPD in children and adolescents with diagnosis of
ADHD using a semi-structured interview; (b) compare
the clinical characteristics of children with
ADHD with a group with ADHD and comorbid
BPD.
Materials and methods
Subjects
The sample consisted of 121 individuals aged 616
years (23 girls, 98 boys), with diagnosis of ADHD
who had been referred to the ADHD unit at the
Child Psychiatry Department of Istanbul School of
Medicine, Istanbul University (IUITF), Turkey,
between October 2006 and September 2007. All
were referred from general out-patient child psychiatry
clinic. All consecutive referrals who met the
criteria mentioned below were included in the study.
Inclusion criteria were: (1) consensus for the
diagnosis of ADHD by at least two child psychiatrists;
(2) parent’s informed consent and patient’s
assent to be included in the study.
Exclusion criteria were presence of chronic medical
illness, any sensory-motor disability, neurological
disorder, diagnosis of pervasive developmental
disorder and other developmental disorders.
Procedures
The study protocol was reviewed and approved by
the Institutional Review Board at Istanbul School of
Medicine and all parents gave written consent for
their child’s participation in the study. Diagnosis of
ADHD was made by the consensus of two child
psychiatrists (NMM and GL) according to DSMIV-
TR criteria.
All individuals were referred from the general
outpatient clinic to the ADHD unit. Diagnosis of
ADHD was reconfirmed using DSM-IV-TR criteria.
All parents completed the Child Behavior Checklist
(CBCL) 418 and the Parent-Young Mania Rating
Scale (P-YMRS) prior to the structured clinical
interview. Comorbidity of Bipolar disorder was
detected using the Turkish version of Schedule
for Affective Disorders and Schizophrenia for
School-age Children-Present and Lifetime version
(K-SADS-PL) (Go¨kler et al. 2004). The K-SADSPL
was administered to the mother and the child
separately. In addition to K-SADS, DSM-IV-TR
mania criteria was applied. Final diagnosis of
BPD was made based on Leibenluft’s ‘‘the narrow
phenotype’’ definition (Leibenluft et al. 2003).
Therefore, only subjects who met the full criteria
in DSM-IV-TR for hypomania or mania, including
the duration criterion and hallmark symptoms of
elevated mood or grandiosity were diagnosed with
BPD. The onset of the first episode, the number of
episodes, and the offset of the last episode associated
with the bipolar disorder were assessed.
Assessment
1. The Schedule for Affective Disorders and
Schizophrenia for School Age Children-Present
and Lifetime Version Present and Life Time
version: The K-SADS PL is a semi structured
diagnostic interview designed to assess current
and past episodes of psychopathology in children
and adolescents according to DSM-III-R
and DSM-IV criteria and is worded such that it
discerns BPD criteria over and above chronic
symptoms. Probes and objective criteria are
provided to rate individual symptoms. It can be
effectively administered by clinicians or trained
interviewers, and has established psychometric
properties. The Turkish version of K-SADS-PL
was used in this study. The translator demonstrated
the reliability and validity of this version
(Go¨ kler et al. 2004).
2. Child Behavior Check List: The CBCL is one
of the best-studied, empirically derived checklists
that measure psychopathology (Achenbach
1991). The CBCL includes 118 problem
behaviour items rated from zero (not at all
typical of the child) to two (often typical of the
child). It has 11 scales: delinquency, aggression,
withdrawal, somatic complaints, anxiety/
depression, and social problems, thought
problems, attention problems, internalization,
externalization, and total score. Scores on the
scales are reported as t scores with a mean of 50
and a standard deviation of 10. A cut-off point
of 70 has been traditionally recommended as a
clinically meaningful cut-off point (Achenbach
1991).
3. Parent-Young Mania Rating Scale: The PYMRS
is an 11-item rating form adapted
from the Young Mania Rating Scale (YMRS)
(Gracious et al. 2002). Parents rate their child’s
manic symptoms on five explicitly defined
grades of severity, with item scores ranging
from 0 to 4 (and three items ranging from 0 to
8). The P-YMRS yields a total score that can
range from zero to 56, with higher scores
representing greater psychopathology. Ratings
were based on the reported presence of symptoms
over the previous week (Gracious et al.
2002).
Statistics
Statistical analysis was done using SPSS version
11.0. Two groups (ADHD and ADHDBPD) were
compared in terms of sociodemographic data and
clinical characteristics based on CBCL sub scores
and P-YMRS. Sociodemographic data was compared
using the Pearson chi-square test. CBCL
subscores and P-YMRS scores were analyzed using
the MannWhitney U-test and the Pearson chisquare
test.
Results
A total of 121 children and adolescents, with the
diagnosis of ADHD were evaluated. The mean age
of the total group was 10.5992.19 years. It included
98 boys (81%) and 23 girls (19%).
Ten children (8.3%) received the additional diagnosis
of BPD (ADHDBPD). There was no
statistically significant difference between the two
groups in terms of mean age and gender (Table I).
The age of onset of bipolar disorder in ADHD
BPD group ranged between 7 and 12 years (mean
age: 8.992.2 years). Two patients (20%) in the
ADHDBPD group had BPD type II and eight
patients (80%) had BPD type I, of whom two were
rapid cycling and one of them was rapid cycling with
psychotic features (Table II).
The ADHDBPD group had significantly higher scores than the ADHD group in the CBCL subscales
including; withdrawn (P0.005), anxiety/
depression (P0.023), social problems (P
0.004), thought problems (P0.043), attention
problems (P0.011), aggression (P0.00), externalization
(P0.002) and total score (P0.006)
items (Figure 1).
Further assessment evaluating the rate of CBCLproxy
showed that 55 subjects had CBCL-PBD
profile. However, only 10 of this group were
diagnosed with bipolar disorders. Therefore, the
490 G. Lus & N.M. Mukaddes
positive predictive validity of CBCL proxy in this
study was 18%.
The ADHDBPD group had a significantly
higher P-YMRS mean score than the ADHD group
(31.6094.42 versus 11.2595.97 and P0.00)
(Table III).
Discussion
The goal of this study was to assess the prevalence of
BPD in children and adolescents with the diagnosis
of ADHD and to compare the clinical characteristics
of children with ADHD with a group with co morbid
ADHD and BPD. The prevalence of BPD was 8.3%
in this population and the ADHDBPD group had
significantly higher scores on the CBCL items
(withdrawn, anxiety/depression, social problems,
thought problems, attention problems, aggression,
externalization and total score), and P-YMRS than
the ADHD group.
The first point that needs to be discussed is the
prevalence of BPD in our ADHD group. The
majority of studies report a higher prevalence than
our findings. Biederman et al. (1996) assessed 140
children with ADHD at baseline and then again 4
years later, and they found that BPD was diagnosed
in 11% of ADHD children at baseline and in an
additional 12% at 4-year follow-up (Biederman et al.
1996), and they reported that their findings are
consistent with a 22% rate among hospitalized
ADHD children reported by Butler et al. (1995).
In these studies, diagnosis of mania was made
according to DSM-III-R criteria and K-SADS-E
(epidemiological version) was used. A recent study
from Turkey with similar assessment methods reported
the similar rate (8.2%) in prepubertal,
clinical referred children with ADHD. The low
rate, in our study and Diler’s study seems to be
related with applying Leibenlufts’ ‘‘the narrow
phenotype’’ criteria.
Comparing the clinical features of the two groups
using CBCL and P-YMRS showed that the groups
can be distinguished by using both tools. Most of the
previous studies comparing CBCL scores between
individuals with ADHD and BPD accompanying
ADHD showed that the later group displays higher
scores in several subscales of CBCL (Geller et al.
1998; Hazell et al. 1999; Diler et al. 2007).
Compatible with some of these studies, we found
that the ADHDBPD group had significantly
higher rates than the group with ADHD on the
withdrawn, anxiety/depression, social problems,
thought problems, attention problems, aggression,
and externalization subscales of CBCL. Mick et al.
(2003) and Faraone et al. (2005) studies reported a
relatively homogenous profile of CBCL associated
Table II. Characteristics of ADHDBPD group.
Age Gender
Age of first episode
of BPD Number of episodes Type of BPD
Case 1 7 Male 7 1 manic episode BPD 1
Case 2 7 Male 7 1 manic episode1 depressive episode BPD 1
Case 3 14 Male 12 2 manic1 depressive episodes BPD 1
Case 4 10 Female 7 5 manic episodes BPD 1 rapid cycling
Case 5 9 Male 7 5 manic episodes BPD 1 rapid cycling
Case 6 12 Male 12 2 depressive 1 hypomanic episodes BPD II
Case 7 9 Male 7 3 manic episodes BPD 1
Case 8 9 Female 9 4 manic episodes BPD 1 rapid cycling with
psychotic features
Case 9 11 Female 9 2 manic episodes BPD 1
Case 10 14 Male 12 2 depressive 1 hypomanic episodes BPD II
ADHD, attention-deficit hyperactivity disorder; BPD, bipolar disorder; BPD 1, bipolar disorder 1; BPD II, bipolar disorder II.
with paediatric bipolar disorder with clinically
significant elevations in the anxiety/depression,
attention problems and aggression subscales. However,
evaluating the predictive validity of CBCL
profile of BP in our study revealed a poor positive
predictive validity (18%) for CBCL- BPD profile. In
addition to this a recent longitudinal study examined
diagnostic and functional trajectories of individuals
with the CBCL-BPD profile from early childhood
through young adulthood. The results of this study
showed that children with the CBCL-BPD profile
are at risk for ongoing, severe psychiatric symptomatology,
including behaviour and emotional
comorbidities in general, and bipolar disorder,
anxiety, ADHD and cluster B personality disorders
in particular. The authors concluded that the value
of this profile might be in predicting ongoing
comorbidity and impairment, rather than any one
specific DSM-IV diagnosis (Meyer et al. 2008).
Although the present study showed the poor predictive
validity of CBCL-BPD profile in identifying
youths with BPD, it seemed that subjects with
co-morbidity of ADHD and BPD had more clinical
impairment and more behavioural problems as
indicated by higher scores in the CBCL subscales.
Consistent with previous studies, our study
reconfirms that P-YMRS is a powerful instrument
in differentiating ADHD and BPD (Youngstrom
et al. 2004; Diler et al. 2007). While the mean total
scores of the ADHD group was 11.2595.975, the
mean total scores of ADHDBPD were 31.609
4.427 (P 0.00). Therefore, it could be concluded
that along with findings based on detailed clinical
examination, P-YMRS could help clinicians to
assess BPD symptoms and differentiate this group
from ADHD.
Regarding the age of onset of BPD, in the present
group it was 8.992.2 years old. The previous
studies reported a different range of onset for BPD.
Biederman et al. (2004) reported that the average
age at onset of BPD in ADHD children was 6.394.7
years, and stated that in 55%, onset was before the
age of 6 years in another study. The reported average
age of onset of manic episodes in another study from
Turkey was 9.2490.68 years. The age of onset of
BPD in Spain was reported as 13.293.5 (Soutollo
et al. 2005) and in Brazil 9.693.5 (Tramontina et al.
2003). It is not clear if the difference in the age of
onset is related with ethnic difference, or it could be
related to sample characteristics. Further studies
need to assess this point.
In conclusion, the present study revealed a
significant rate of comorbidity of BPD in children
with ADHD and it has been detected that children
with comorbidity of BPD can be distinguished
from children with ADHD alone based on clinical
examination and supporting tools such as P-YMRS.
Further, we found that CBCL-BP profile does not
have a high positive predictive value in identification
of this group.
Table III.
The present study suffers from some limitations
such as small sample size and including only clinicreferred
children. However, since there is a shortage
of studies on this topic from non-western countries,
it may contribute to the knowledge of BPD presentation
in different cultures. In addition, it may
help raise clinician awareness about the presence of
BPD in subjects with ADHD.
Acknowledgements
None.
Statement of Interest
None.
References
American Psychiatric Association. 2000. Diagnostic and statistical
manual of mental disorders. 4th ed. Text Revision.Washington,
DC: American Psychiatric Association Press.
American Academy of Child and Adolescent Psychiatry. 2007.
Practice parameter for the assessment and treatment of
children and adolescent with attention-deficit/hyperactivity
disorder. J Am Acad Child Adolesc Psychiatry 46(7):894921.
Achenbach TM. 1991. Manual for the child behaviour checklist
418 and profile. Burlington, VT: University of Vermont
Department of Pschiatry.
Biederman J. 2003. Pediatric bipolar disorder coming of Age. Biol
Psychiatry 53:931934.
Biederman J, Faraone S, Mick E,Wozniak J, Chen L, Ouellette C,
et al. 1996. Attention-deficit hyperactivity disorder and juvenile
mania: an overlooked comorbidity? J Am Acad Child Adolesc
Psychiatry 35(8):9971008.
Biederman J, Mick E, Faraone SV, Van Patent S, Burback M,
Wozniak J. 2004. A prospective follow-up study of pediatric
bipolar disorder in boys with attention-deficit hyperactivity
disorders. J Affect Disord (82):1723.
Birmaher B, Axelson D, Strober M, Gill MK, Valeri S, Chiappetta
L, et al. 2006. Clinical course of children and adolescents with
bipolar spectrum disorders. Arch Gen Psychiatry 63(2):
175183.
Butler FS, Arredondo DE, McClosky V. 1995. Affective comorbidity
in children and adolescents with attention deficit
hyperactivity disorder. Ann Clin Psychiatry 7:5155.
Carlson GA, Kelly KL. 1998. Manic symptoms in psychiatrically
hospitalized childrenwhat do they mean? J Affect Disord
51:123135.
Cook EH Jr, Stein MA, Krasowski MD, Cox NJ, Olkon DM,
Kieffer JE, et al. 1995. Association of attention-deficit disorder
and the dopamine transporter gene. Am J Hum Genet
56(4):993998.
Diler RS. 2007. Pediatric bipolar disorder: A global perspective.
New York: Nova Science Publishers, Inc.
Diler RS, Emiroglu NI. 2007. Attention deficit/hyperactivity
disorder with bipolar disorder: A Familial subtype? J Am
Acad Child Adolesc Psychiatry 36(10):13781387.
Diler RS, Uguz S, Seydaoglu G, Erol N, Avci A. 2007.
Differentiating bipolar disorder in Turkish prepubertal children
with attention-deficit hyperactivity disorder. Bipolar Disord
9:243251.
Faraone SV, Perlis RH, Doyle AH, Smaller JW, Goralnick JJ,
Holmgre MA, et al. 2005. Molecular genetics of attention
deficits/hyperactivity disorder. Biol Psychiatry 57:13131323.
Fristad MA,Weller RA,Weller EB. 1995. The Mania Rating Scale
(MRS): further reliability and validity studies with children.
Ann Clin Psychiatry 7(3):127132.
Galanter CA, Leibenluft E. 2008. Frontiers between attention
deficit hyperactivity disorder and bipolar disorder. Child
Adolesc Psychiatr Clin N Am 17(2):325346.
Geller B, Williams M, Zimerman B, Frazier J, Beringer L, Warner
KL. 1998. Prepubertal and early adolescent bipolarity differentiate
from ADHD by manic symptoms, grandiose delusions,
ultra-rapid or ultradian cycling. J Affect Dis 51(2):8191.
Geller B, Zimerman B, Williams M, Delbello MP, Frazier J,
Beringer L. 2002. Phenomenology of prepubertal and early
adolescent bipolar disorder: examples of elated mood, grandiose
behaviors, decreased need for sleep, racing thoughts and
hypersexuality. J Child Adolesc Psychopharmacol 12(1):39.
Geller B, Badner JA, Tillman R, Christian SL, Bolhofner K, Cook
EH Jr. 2004. Linkage disequilibrium of the brain-derived
neurotrophic factor Val66Met polymorphism in children with
a prepubertal and early adolescent bipolar disorder phenotype.
Am J Psychiatry 161(9):16981700.
Gokler B, Unal F, Pehlivanturk B, Cengel Kultur E, Akdemir D,
Taner Y. 2004. Okul C¸ ag˘ı C¸ ocukları ic¸in dugulanim bozuklukları
ve s¸izofreni go¨ru¨ s¸me c¸izelgesi-s¸imdi ve Yas¸am boyu s¸ekli Tu¨ rkc¸e uyarlanmasinin gec¸erlilik ve gu¨ venirlig˘ i. C¸ ocuk ve
genc¸lik Ruh sag˘ lıg˘ı dergisi 11:109116 (in turkish).
Gracious BL, Youngstrom EA, Findling RL, Calabrese JR. 2002.
Discriminative Validity of a Parent Version of the Young Mania
Rating Scale. J Am Acad Child Adolesc Psychiatry
41(11):13501359.
Greenwood TA, Schork NJ, Eskin E, Kelsoe JR. 2006. Identification
of additional variants within the human dopamine
transporter gene provides further evidence for an association
with bipolar disorder in two independent samples. Mol
Psychiatry 11(2):125133.
Hazell PL, Lewin TJ, Carr VJ. 1999. Confirmation that Child
Behavior Checklist clinical scales discriminate juvenile mania
from attention deficit hyperactivity disorder J Paediatr Child
Health 35(2):199203.
Jaideep T, Reddy YC, Srinath S. 2006. Comorbidity of attention
deficit hyperactivity disorder in juvenile bipolar disorder.
Bipolar Disord 8(2):182187.
Kaufman J, Birmaher B, Brent D, Rao U, Flynn C, Moreci P,
et al. 1997. Schedule for affective disorders and schizophrenia
for school age children-present and lifetime version (K-SADSPL):
initial reliability and validity data. J Am Acad Child
Adolesc Psychiatry 36(7):980988.
Kennedy N, Boydell J, Van Os J, Murray RM. 2004. Ethnic
differences in first clinical presentation of bipolar disorder:
results from an epidemiological study. J Affect Disord 83
(23):161168.
Kent L, Green E, Hawi Z, Kirley A, Dudbridge F, Lowe N, et al.
2005. Association of the paternally transmitted copy of
common Valine allele of the Val66Met polymorphism of the
brain-derived neurotrophic factor (BDNF) gene with susceptibility
to ADHD. Mol Psychiatry 10(10):939943.
Kowatch RA, Youngstrom EA, Danielyan A, Findling RL. 2005.
Review and meta-analysis of the phenomenology and clinical
characteristics of mania in children and adolescents. Bipolar
Disorder 7(6):483496.
Leibenluft E, Charney DS, Towbin KE, Bhangoo RK, Pine DS.
2003. Defining clinical phenotypes of juvenile mania. Am J
Psychiatry 160(3):430437.
Meyer SE, Carlson GA, Youngstrom E, Ronsaville DS, Martinez
PE, Gold PW, et al. 2009. Long-term outcomes of youth
This study aimed to assess the prevalence of bipolar disorder (BPD) in children and adolescents with attention deficit
hyperactivity disorder (ADHD), and to compare the clinical characteristics of a group with ADHD with a group with
co-morbidity of ADHD and BPD. The study includes 121 individuals, aged 616 years, with a diagnosis of ADHD. Comorbidity
of BPD was evaluated using the Schedule for Affective Disorders and Schizophrenia for School-age Children-
Present and Lifetime version (K-SADS-PL) and the Parent-Young Mania Rating Scale (P-YMRS). The Child Behavior
Checklist (CBCL) was used to assess psychopathology in two groups. Ten children (8.3%) in the ADHD sample received
the additional diagnosis of BPD. The ADHDBPD group had significantly higher scores than the ADHD group on
withdrawn, anxiety/depression, social problems, thought problems, attention problems, aggression, externalization, total
score items of CBCL, and on the P-YMRS. It could be concluded that BPD is not a rare co-morbid condition in children
with diagnosis of ADHD and subjects with this co-morbidity show more severe psychopathology than subjects with pure
ADHD. Differential diagnosis of BPD disorder in subjects with ADHD seems crucial in establishing an effective treatment
program, and therefore improving mental health outcomes.
Key words: Attention deficit/hyperactivity disorder, bipolar disorder, comorbidity
Introduction
Attention deficit/hyperactivity disorder (ADHD)
consists of a persistent pattern of inattention, hyperactivity
and impulsivity (APA 2000). It is well
established that ADHD is frequently comorbid with
other psychiatric disorders such as oppositional
defiant disorder, conduct disorder, anxiety disorders,
depression, tic disorders, substance abuse and bipolar
disorders (AACAP 2007). Perhaps the most diagnostically
challenging and controversial of co-occurring
disorders in ADHD is bipolar disorder (BPD). When
they occur in combination, these conditions often
complicate the assessment process, clinical diagnosis
and treatment. Literature reviews indicate that this
topic has received increased clinical and scientific
attention in recent years. Many studies have been
conducted to assess the rate of this co-morbidity,
phenomenology, clinical characteristics and differential
diagnosis with BPD.
Despite the increasing amount of research in
paediatric bipolar disorder, there is still confusion
and controversy surrounding clinical diagnosis of
this condition. This confusion is partly due to the
lack of awareness and clinical bias, in certain setting,
against the diagnosis of mania in children (Geller
et al. 1998; Biederman 2003). Symptom overlap
between BPD and other childhood-onset psychiatric
disorders is another important factor contributing to
diagnostic difficulties (Diler et al. 2007). Differential
diagnosis with ADHD is an especially crucial issue.
Since several symptoms are shared by ADHD and
BPD, the debate regarding the validity of paediatric
bipolar disorder has shifted from whether paediatric
bipolar disorder exists to which symptoms should be
considered cardinal symptoms of bipolar disorder in
children (Mick et al. 2005). Irritability, impulsivity,
hyperactivity, and distractibility are very frequent in
both disorders, therefore not specific for mania
(Mick et al. 2005). Elation, grandiosity, racing
Correspondence: Prof. Dr. Nahit Motavalli Mukaddes, Sezai Selek Sok-Sevim Ap No: 7/4 Nisantasi, Istanbul 80200, Turkey.
Tel: 90 212 2349207. Fax: 90 212 2349208. E-mail: nmotavalli@yahoo.com
The World Journal of Biological Psychiatry, 2009; 10(4): 488494
(Received 17 September 2008; accepted 20 February 2009)
ISSN 1562-2975 print/ISSN 1814-1412 online # 2009 Informa UK Ltd. (Informa Healthcare, Taylor & Francis AS)
DOI: 10.3109/15622970902929876thoughts, decreased need for sleep and hypersexuality
are common in bipolar disorder and can
discriminate BPD from ADHD (Geller et al. 2002;
Pavuluri et al. 2005).
Additionally, several instruments such as the
Child Behavior Checklist (CBCL) (Achenbach
1991), Young Mania Rating Scale (Young et al.
1978), and the Child Mania Rating Scale (Pavuluri
et al. 2006) are considered effective instruments for
helping clinicians differentiate mania in an ADHD
population.
Results of studies evaluating the effectiveness of the
CBCL in differential diagnosis of paediatric bipolar
disorder are controversial. A few studies proposed a
CBCL paediatric bipolar profile (BPD) based on the
significant elevation in the anxiety/depression, attention
problems and aggression subscales (Mick et al.
2003; Farone et al. 2005). However, the predictive
validity of CBCL-BPD in identifying BPD has been
recently questioned (Volk and Todd 2007; Meyer
et al. 2008). Some authors have attempted to
differentiate ADHD from mania using the Young
Mania Rating Scale and the Parent-Young Mania
Rating Scale (Fristad et al. 1995; Diler et al. 2007).
However, other investigators stated that this instrument
is designed to quantify rather than diagnose an
episode of mania (Carlson and Kelly 1998).
Regarding the rate of this co morbidity, several
studies have investigated the rate of BPD in ADHD
and vice versa. Six population-based studies evaluated
the co-occurrence of ADHD and BPD in
youths, three of which showed elevated rates of
BPD in participants who have ADHD; however,
three failed to show an association between the two
disorders (Galanter and Leibenluft 2008). Clinical
studies have found rates of BPD ranging from 8.2 to
23% in youths who have ADHD (Wozniak et al.
1995; Butler et al. 1995; Biederman et al. 1996;
Diler et al. 2007). Regarding the rate of ADHD in
clinic referred subjects with BPD, rates vary widely
across samples, from 4 to 98% (Kowatch et al. 2005;
Birmaher et al. 2006; Jaideep et al. 2006). Setting,
participants age, age of onset of BPD, referral source
and ascertainment bias affect these rates.
The relatively high degree of co-occurrence
between these disorders raises the question of probable
common aetiological factors. Several studies
proposed the role of dopamine transporter genes in
ADHD (Cook et al. 1995; Faraone et al. 2005) and
BPD (Greenwood et al. 2006). Further, the involvement
of the brain-derived neutrophic factor (BDNF)
gene in the pathogenesis of ADHD (Kent et al. 2005)
and BPD (Geller et al. 2004) was reported. Family
studies strongly suggest that paediatric onset bipolar
disorder has a strong familial component. Some
investigators documented that bipolar disorder and
ADHD co segregated in relatives support the
hypothesis that ADHD and co morbid bipolar disorder
may represent a unique developmental subtype
of bipolar disorder (Faraone et al. 1997; Biederman
et al. 2004).
Despite increasing research on BPD, paediatric
bipolar disorder is still unrecognized in most countries
other than the USA. BPD research from
outside of the USA is limited and according to
some studies, there is significant ethnic differences in
the prevalence of BPD (Youngstrom et al. 2005) and
clinical presentation of BPD (Kennedy et al. 2004).
These findings underlie the need for further assessment
of bipolar disorder in children with different
ethnic origin.
This study aimed to: (a) assess the prevalence of
BPD in children and adolescents with diagnosis of
ADHD using a semi-structured interview; (b) compare
the clinical characteristics of children with
ADHD with a group with ADHD and comorbid
BPD.
Materials and methods
Subjects
The sample consisted of 121 individuals aged 616
years (23 girls, 98 boys), with diagnosis of ADHD
who had been referred to the ADHD unit at the
Child Psychiatry Department of Istanbul School of
Medicine, Istanbul University (IUITF), Turkey,
between October 2006 and September 2007. All
were referred from general out-patient child psychiatry
clinic. All consecutive referrals who met the
criteria mentioned below were included in the study.
Inclusion criteria were: (1) consensus for the
diagnosis of ADHD by at least two child psychiatrists;
(2) parent’s informed consent and patient’s
assent to be included in the study.
Exclusion criteria were presence of chronic medical
illness, any sensory-motor disability, neurological
disorder, diagnosis of pervasive developmental
disorder and other developmental disorders.
Procedures
The study protocol was reviewed and approved by
the Institutional Review Board at Istanbul School of
Medicine and all parents gave written consent for
their child’s participation in the study. Diagnosis of
ADHD was made by the consensus of two child
psychiatrists (NMM and GL) according to DSMIV-
TR criteria.
All individuals were referred from the general
outpatient clinic to the ADHD unit. Diagnosis of
ADHD was reconfirmed using DSM-IV-TR criteria.
All parents completed the Child Behavior Checklist
(CBCL) 418 and the Parent-Young Mania Rating
Scale (P-YMRS) prior to the structured clinical
interview. Comorbidity of Bipolar disorder was
detected using the Turkish version of Schedule
for Affective Disorders and Schizophrenia for
School-age Children-Present and Lifetime version
(K-SADS-PL) (Go¨kler et al. 2004). The K-SADSPL
was administered to the mother and the child
separately. In addition to K-SADS, DSM-IV-TR
mania criteria was applied. Final diagnosis of
BPD was made based on Leibenluft’s ‘‘the narrow
phenotype’’ definition (Leibenluft et al. 2003).
Therefore, only subjects who met the full criteria
in DSM-IV-TR for hypomania or mania, including
the duration criterion and hallmark symptoms of
elevated mood or grandiosity were diagnosed with
BPD. The onset of the first episode, the number of
episodes, and the offset of the last episode associated
with the bipolar disorder were assessed.
Assessment
1. The Schedule for Affective Disorders and
Schizophrenia for School Age Children-Present
and Lifetime Version Present and Life Time
version: The K-SADS PL is a semi structured
diagnostic interview designed to assess current
and past episodes of psychopathology in children
and adolescents according to DSM-III-R
and DSM-IV criteria and is worded such that it
discerns BPD criteria over and above chronic
symptoms. Probes and objective criteria are
provided to rate individual symptoms. It can be
effectively administered by clinicians or trained
interviewers, and has established psychometric
properties. The Turkish version of K-SADS-PL
was used in this study. The translator demonstrated
the reliability and validity of this version
(Go¨ kler et al. 2004).
2. Child Behavior Check List: The CBCL is one
of the best-studied, empirically derived checklists
that measure psychopathology (Achenbach
1991). The CBCL includes 118 problem
behaviour items rated from zero (not at all
typical of the child) to two (often typical of the
child). It has 11 scales: delinquency, aggression,
withdrawal, somatic complaints, anxiety/
depression, and social problems, thought
problems, attention problems, internalization,
externalization, and total score. Scores on the
scales are reported as t scores with a mean of 50
and a standard deviation of 10. A cut-off point
of 70 has been traditionally recommended as a
clinically meaningful cut-off point (Achenbach
1991).
3. Parent-Young Mania Rating Scale: The PYMRS
is an 11-item rating form adapted
from the Young Mania Rating Scale (YMRS)
(Gracious et al. 2002). Parents rate their child’s
manic symptoms on five explicitly defined
grades of severity, with item scores ranging
from 0 to 4 (and three items ranging from 0 to
8). The P-YMRS yields a total score that can
range from zero to 56, with higher scores
representing greater psychopathology. Ratings
were based on the reported presence of symptoms
over the previous week (Gracious et al.
2002).
Statistics
Statistical analysis was done using SPSS version
11.0. Two groups (ADHD and ADHDBPD) were
compared in terms of sociodemographic data and
clinical characteristics based on CBCL sub scores
and P-YMRS. Sociodemographic data was compared
using the Pearson chi-square test. CBCL
subscores and P-YMRS scores were analyzed using
the MannWhitney U-test and the Pearson chisquare
test.
Results
A total of 121 children and adolescents, with the
diagnosis of ADHD were evaluated. The mean age
of the total group was 10.5992.19 years. It included
98 boys (81%) and 23 girls (19%).
Ten children (8.3%) received the additional diagnosis
of BPD (ADHDBPD). There was no
statistically significant difference between the two
groups in terms of mean age and gender (Table I).
The age of onset of bipolar disorder in ADHD
BPD group ranged between 7 and 12 years (mean
age: 8.992.2 years). Two patients (20%) in the
ADHDBPD group had BPD type II and eight
patients (80%) had BPD type I, of whom two were
rapid cycling and one of them was rapid cycling with
psychotic features (Table II).
The ADHDBPD group had significantly higher scores than the ADHD group in the CBCL subscales
including; withdrawn (P0.005), anxiety/
depression (P0.023), social problems (P
0.004), thought problems (P0.043), attention
problems (P0.011), aggression (P0.00), externalization
(P0.002) and total score (P0.006)
items (Figure 1).
Further assessment evaluating the rate of CBCLproxy
showed that 55 subjects had CBCL-PBD
profile. However, only 10 of this group were
diagnosed with bipolar disorders. Therefore, the
490 G. Lus & N.M. Mukaddes
positive predictive validity of CBCL proxy in this
study was 18%.
The ADHDBPD group had a significantly
higher P-YMRS mean score than the ADHD group
(31.6094.42 versus 11.2595.97 and P0.00)
(Table III).
Discussion
The goal of this study was to assess the prevalence of
BPD in children and adolescents with the diagnosis
of ADHD and to compare the clinical characteristics
of children with ADHD with a group with co morbid
ADHD and BPD. The prevalence of BPD was 8.3%
in this population and the ADHDBPD group had
significantly higher scores on the CBCL items
(withdrawn, anxiety/depression, social problems,
thought problems, attention problems, aggression,
externalization and total score), and P-YMRS than
the ADHD group.
The first point that needs to be discussed is the
prevalence of BPD in our ADHD group. The
majority of studies report a higher prevalence than
our findings. Biederman et al. (1996) assessed 140
children with ADHD at baseline and then again 4
years later, and they found that BPD was diagnosed
in 11% of ADHD children at baseline and in an
additional 12% at 4-year follow-up (Biederman et al.
1996), and they reported that their findings are
consistent with a 22% rate among hospitalized
ADHD children reported by Butler et al. (1995).
In these studies, diagnosis of mania was made
according to DSM-III-R criteria and K-SADS-E
(epidemiological version) was used. A recent study
from Turkey with similar assessment methods reported
the similar rate (8.2%) in prepubertal,
clinical referred children with ADHD. The low
rate, in our study and Diler’s study seems to be
related with applying Leibenlufts’ ‘‘the narrow
phenotype’’ criteria.
Comparing the clinical features of the two groups
using CBCL and P-YMRS showed that the groups
can be distinguished by using both tools. Most of the
previous studies comparing CBCL scores between
individuals with ADHD and BPD accompanying
ADHD showed that the later group displays higher
scores in several subscales of CBCL (Geller et al.
1998; Hazell et al. 1999; Diler et al. 2007).
Compatible with some of these studies, we found
that the ADHDBPD group had significantly
higher rates than the group with ADHD on the
withdrawn, anxiety/depression, social problems,
thought problems, attention problems, aggression,
and externalization subscales of CBCL. Mick et al.
(2003) and Faraone et al. (2005) studies reported a
relatively homogenous profile of CBCL associated
Table II. Characteristics of ADHDBPD group.
Age Gender
Age of first episode
of BPD Number of episodes Type of BPD
Case 1 7 Male 7 1 manic episode BPD 1
Case 2 7 Male 7 1 manic episode1 depressive episode BPD 1
Case 3 14 Male 12 2 manic1 depressive episodes BPD 1
Case 4 10 Female 7 5 manic episodes BPD 1 rapid cycling
Case 5 9 Male 7 5 manic episodes BPD 1 rapid cycling
Case 6 12 Male 12 2 depressive 1 hypomanic episodes BPD II
Case 7 9 Male 7 3 manic episodes BPD 1
Case 8 9 Female 9 4 manic episodes BPD 1 rapid cycling with
psychotic features
Case 9 11 Female 9 2 manic episodes BPD 1
Case 10 14 Male 12 2 depressive 1 hypomanic episodes BPD II
ADHD, attention-deficit hyperactivity disorder; BPD, bipolar disorder; BPD 1, bipolar disorder 1; BPD II, bipolar disorder II.
with paediatric bipolar disorder with clinically
significant elevations in the anxiety/depression,
attention problems and aggression subscales. However,
evaluating the predictive validity of CBCL
profile of BP in our study revealed a poor positive
predictive validity (18%) for CBCL- BPD profile. In
addition to this a recent longitudinal study examined
diagnostic and functional trajectories of individuals
with the CBCL-BPD profile from early childhood
through young adulthood. The results of this study
showed that children with the CBCL-BPD profile
are at risk for ongoing, severe psychiatric symptomatology,
including behaviour and emotional
comorbidities in general, and bipolar disorder,
anxiety, ADHD and cluster B personality disorders
in particular. The authors concluded that the value
of this profile might be in predicting ongoing
comorbidity and impairment, rather than any one
specific DSM-IV diagnosis (Meyer et al. 2008).
Although the present study showed the poor predictive
validity of CBCL-BPD profile in identifying
youths with BPD, it seemed that subjects with
co-morbidity of ADHD and BPD had more clinical
impairment and more behavioural problems as
indicated by higher scores in the CBCL subscales.
Consistent with previous studies, our study
reconfirms that P-YMRS is a powerful instrument
in differentiating ADHD and BPD (Youngstrom
et al. 2004; Diler et al. 2007). While the mean total
scores of the ADHD group was 11.2595.975, the
mean total scores of ADHDBPD were 31.609
4.427 (P 0.00). Therefore, it could be concluded
that along with findings based on detailed clinical
examination, P-YMRS could help clinicians to
assess BPD symptoms and differentiate this group
from ADHD.
Regarding the age of onset of BPD, in the present
group it was 8.992.2 years old. The previous
studies reported a different range of onset for BPD.
Biederman et al. (2004) reported that the average
age at onset of BPD in ADHD children was 6.394.7
years, and stated that in 55%, onset was before the
age of 6 years in another study. The reported average
age of onset of manic episodes in another study from
Turkey was 9.2490.68 years. The age of onset of
BPD in Spain was reported as 13.293.5 (Soutollo
et al. 2005) and in Brazil 9.693.5 (Tramontina et al.
2003). It is not clear if the difference in the age of
onset is related with ethnic difference, or it could be
related to sample characteristics. Further studies
need to assess this point.
In conclusion, the present study revealed a
significant rate of comorbidity of BPD in children
with ADHD and it has been detected that children
with comorbidity of BPD can be distinguished
from children with ADHD alone based on clinical
examination and supporting tools such as P-YMRS.
Further, we found that CBCL-BP profile does not
have a high positive predictive value in identification
of this group.
Table III.
The present study suffers from some limitations
such as small sample size and including only clinicreferred
children. However, since there is a shortage
of studies on this topic from non-western countries,
it may contribute to the knowledge of BPD presentation
in different cultures. In addition, it may
help raise clinician awareness about the presence of
BPD in subjects with ADHD.
Acknowledgements
None.
Statement of Interest
None.
References
American Psychiatric Association. 2000. Diagnostic and statistical
manual of mental disorders. 4th ed. Text Revision.Washington,
DC: American Psychiatric Association Press.
American Academy of Child and Adolescent Psychiatry. 2007.
Practice parameter for the assessment and treatment of
children and adolescent with attention-deficit/hyperactivity
disorder. J Am Acad Child Adolesc Psychiatry 46(7):894921.
Achenbach TM. 1991. Manual for the child behaviour checklist
418 and profile. Burlington, VT: University of Vermont
Department of Pschiatry.
Biederman J. 2003. Pediatric bipolar disorder coming of Age. Biol
Psychiatry 53:931934.
Biederman J, Faraone S, Mick E,Wozniak J, Chen L, Ouellette C,
et al. 1996. Attention-deficit hyperactivity disorder and juvenile
mania: an overlooked comorbidity? J Am Acad Child Adolesc
Psychiatry 35(8):9971008.
Biederman J, Mick E, Faraone SV, Van Patent S, Burback M,
Wozniak J. 2004. A prospective follow-up study of pediatric
bipolar disorder in boys with attention-deficit hyperactivity
disorders. J Affect Disord (82):1723.
Birmaher B, Axelson D, Strober M, Gill MK, Valeri S, Chiappetta
L, et al. 2006. Clinical course of children and adolescents with
bipolar spectrum disorders. Arch Gen Psychiatry 63(2):
175183.
Butler FS, Arredondo DE, McClosky V. 1995. Affective comorbidity
in children and adolescents with attention deficit
hyperactivity disorder. Ann Clin Psychiatry 7:5155.
Carlson GA, Kelly KL. 1998. Manic symptoms in psychiatrically
hospitalized childrenwhat do they mean? J Affect Disord
51:123135.
Cook EH Jr, Stein MA, Krasowski MD, Cox NJ, Olkon DM,
Kieffer JE, et al. 1995. Association of attention-deficit disorder
and the dopamine transporter gene. Am J Hum Genet
56(4):993998.
Diler RS. 2007. Pediatric bipolar disorder: A global perspective.
New York: Nova Science Publishers, Inc.
Diler RS, Emiroglu NI. 2007. Attention deficit/hyperactivity
disorder with bipolar disorder: A Familial subtype? J Am
Acad Child Adolesc Psychiatry 36(10):13781387.
Diler RS, Uguz S, Seydaoglu G, Erol N, Avci A. 2007.
Differentiating bipolar disorder in Turkish prepubertal children
with attention-deficit hyperactivity disorder. Bipolar Disord
9:243251.
Faraone SV, Perlis RH, Doyle AH, Smaller JW, Goralnick JJ,
Holmgre MA, et al. 2005. Molecular genetics of attention
deficits/hyperactivity disorder. Biol Psychiatry 57:13131323.
Fristad MA,Weller RA,Weller EB. 1995. The Mania Rating Scale
(MRS): further reliability and validity studies with children.
Ann Clin Psychiatry 7(3):127132.
Galanter CA, Leibenluft E. 2008. Frontiers between attention
deficit hyperactivity disorder and bipolar disorder. Child
Adolesc Psychiatr Clin N Am 17(2):325346.
Geller B, Williams M, Zimerman B, Frazier J, Beringer L, Warner
KL. 1998. Prepubertal and early adolescent bipolarity differentiate
from ADHD by manic symptoms, grandiose delusions,
ultra-rapid or ultradian cycling. J Affect Dis 51(2):8191.
Geller B, Zimerman B, Williams M, Delbello MP, Frazier J,
Beringer L. 2002. Phenomenology of prepubertal and early
adolescent bipolar disorder: examples of elated mood, grandiose
behaviors, decreased need for sleep, racing thoughts and
hypersexuality. J Child Adolesc Psychopharmacol 12(1):39.
Geller B, Badner JA, Tillman R, Christian SL, Bolhofner K, Cook
EH Jr. 2004. Linkage disequilibrium of the brain-derived
neurotrophic factor Val66Met polymorphism in children with
a prepubertal and early adolescent bipolar disorder phenotype.
Am J Psychiatry 161(9):16981700.
Gokler B, Unal F, Pehlivanturk B, Cengel Kultur E, Akdemir D,
Taner Y. 2004. Okul C¸ ag˘ı C¸ ocukları ic¸in dugulanim bozuklukları
ve s¸izofreni go¨ru¨ s¸me c¸izelgesi-s¸imdi ve Yas¸am boyu s¸ekli Tu¨ rkc¸e uyarlanmasinin gec¸erlilik ve gu¨ venirlig˘ i. C¸ ocuk ve
genc¸lik Ruh sag˘ lıg˘ı dergisi 11:109116 (in turkish).
Gracious BL, Youngstrom EA, Findling RL, Calabrese JR. 2002.
Discriminative Validity of a Parent Version of the Young Mania
Rating Scale. J Am Acad Child Adolesc Psychiatry
41(11):13501359.
Greenwood TA, Schork NJ, Eskin E, Kelsoe JR. 2006. Identification
of additional variants within the human dopamine
transporter gene provides further evidence for an association
with bipolar disorder in two independent samples. Mol
Psychiatry 11(2):125133.
Hazell PL, Lewin TJ, Carr VJ. 1999. Confirmation that Child
Behavior Checklist clinical scales discriminate juvenile mania
from attention deficit hyperactivity disorder J Paediatr Child
Health 35(2):199203.
Jaideep T, Reddy YC, Srinath S. 2006. Comorbidity of attention
deficit hyperactivity disorder in juvenile bipolar disorder.
Bipolar Disord 8(2):182187.
Kaufman J, Birmaher B, Brent D, Rao U, Flynn C, Moreci P,
et al. 1997. Schedule for affective disorders and schizophrenia
for school age children-present and lifetime version (K-SADSPL):
initial reliability and validity data. J Am Acad Child
Adolesc Psychiatry 36(7):980988.
Kennedy N, Boydell J, Van Os J, Murray RM. 2004. Ethnic
differences in first clinical presentation of bipolar disorder:
results from an epidemiological study. J Affect Disord 83
(23):161168.
Kent L, Green E, Hawi Z, Kirley A, Dudbridge F, Lowe N, et al.
2005. Association of the paternally transmitted copy of
common Valine allele of the Val66Met polymorphism of the
brain-derived neurotrophic factor (BDNF) gene with susceptibility
to ADHD. Mol Psychiatry 10(10):939943.
Kowatch RA, Youngstrom EA, Danielyan A, Findling RL. 2005.
Review and meta-analysis of the phenomenology and clinical
characteristics of mania in children and adolescents. Bipolar
Disorder 7(6):483496.
Leibenluft E, Charney DS, Towbin KE, Bhangoo RK, Pine DS.
2003. Defining clinical phenotypes of juvenile mania. Am J
Psychiatry 160(3):430437.
Meyer SE, Carlson GA, Youngstrom E, Ronsaville DS, Martinez
PE, Gold PW, et al. 2009. Long-term outcomes of youth
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