Journal of Affective Disorders 98 (2007) 263–266www.elsevier.com/locate/jad

Brief report

Is bipolar II disorder misdiagnosed as majordepressive disorder in children?

R.P. Bhargava Raman, S.P. Sheshadri, Y.C. Janardhan Reddy ⁎, S.C. Girimaji,S. Srinath, V.N.G.P. Raghunandan

Department of Psychiatry, National Institute of Mental health and Neurosciences (NIMHANS), Bangalore 560029, India

Received 12 July 2006; received in revised form 31 July 2006; accepted 1 August 2006Available online 1 September 2006

Abstract

Objectives: To estimate the lifetime prevalence of bipolar II disorder in children and adolescents presenting with DSM-IV majordepressive disorder (MDD).Methods: Sixty-one consecutive subjects aged ≤18 years attending the outpatient services of the Child and Adolescent Psychiatric(CAP) services of the National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India with a diagnosis ofMDD were evaluated using the Missouri Assessment of Genetics Interview for children (MAGIC). Two psychiatrists, one of whomwas a child psychiatrist diagnosed hypomania by consensus.Results: Twelve children had a past episode of hypomania (20%), which was hitherto undiagnosed clinically.Limitations: We recruited subjects from a psychiatric hospital, thus limiting the generalizability of the finding. Sample size wasrelatively small and assessments were cross-sectional.Conclusions: Our study shows that bipolar II disorder is often misdiagnosed as MDD in children. The study also highlights that thechance of diagnosing bipolarity is enhanced by using semi-structured interview in routine clinical practice.© 2006 Elsevier B.V. All rights reserved.

Keywords: Bipolar II disorder; Major depressive disorder; Children; Adolescents

1. Introduction

General population prevalence of bipolar-II (BP-II)disorder is 0.5% and 1.3% respectively according to theNational Comorbidity Survey (NCS) and the Epidemi-ological Catchment Area (ECA) studies (Kessler et al.,1994; Regier et al., 1998). In the NCS Replicated, theprevalence of bipolar-I plus BP-II disorder was 3.9%(Kessler et al., 2005). Similarly, other community-basedstudies too have reported a higher prevalence of bipolar

⁎ Corresponding author. Fax: +91 80 26564822.E-mail address: ycjreddy@yahoo.com (Y.C. Janardhan Reddy).

0165-0327/$ - see front matter © 2006 Elsevier B.V. All rights reserved.doi:10.1016/j.jad.2006.08.006

disorders (5 to 8%) with the inclusion of BP-II spectrumin the diagnosis (Angst, 1998; Judd and Akiskal, 2003;Szadoczky et al., 1998; Kiejna et al., 2005). Studiesinvolving outpatients with MDD (Szadoczky et al.,1998; Akiskal and Mallya, 1987; Cassano et al., 1992;Benazzi, 1997; Hantouche et al., 1998; Benazzi andAkiskal, 2003; Akiskal et al., 2000) have also reportedhigher prevalence of BP-II disorder.

There are, however, limited data on the prevalence ofBP-II disorder in depressed children. Recent reviewssuggest that the BP-II disorder is common in childrentoo (Kowatch et al., 2005; Soutullo et al., 2005). It ispostulated that many children who present with MDD

Table 1Demographic and clinical characteristics of the sample

Variables

Age at onset of illness, mean (SD) 13.23 (2.42)Age at onset of bipolarity, mean (SD) 13.29 (1.68)Gender, n (%)Male 33 (54)Female 28 (46)

Education, n (%)Currently schooling 31 (51)Currently no schooling 29 (48)No schooling ever 1 (2)

Background, n (%)Urban 48 (79)Rural 13 (21)

Referral status, n (%)Self referred 58 (95)By a psychiatrist 3 (5)

Depression, n (%)RDD 2 (4)MDD 59a (96)

Severity of the depressive episodes, n (%)Mild 2 (4)Moderate 52 (84)Severe 7 (12)

History of hypomania, n (%) 12 (20)Other comorbid disorders, n (%)b

Dissociative motor disorderc 15 (25)Obsessive–compulsive disorder 3 (5)Specific learning disabilityc 11 (18)

Probandswith family history of psychiatric disorders,n (%)Bipolar I disorder 3 (5)MDD 22 (36)Dysthymia 7 (11)Alcohol dependence 8 (13)Suicide 7 (11)Paranoid personality 2 (3)Antisocial personality 3 (5)a Two subjects had double depression.b None had disruptive behavior disorders.c Diagnosed clinically.

264 R.P. Bhargava Raman et al. / Journal of Affective Disorders 98 (2007) 263–266

are already bipolar with probable subsyndromal manicepisodes (Lewinson et al., 1995; Akiskal, 1995). Ourstudy, therefore, examined the prevalence of BP-II dis-order in children and adolescents diagnosed as havingMDD using a semi-structured interview that has both thechild and parent versions. We hypothesized that bipolarII disorder is often misdiagnosed as MDD in children.

2. Method

2.1. Subjects

Sixty-one consecutive subjects aged ≤18 years andattending the outpatient services of the child and ad-olescent psychiatric (CAP) services of the NationalInstitute of Mental Health and Neurosciences (NIM-HANS) with DSM IV diagnosis of MDD were recruitedin to the study after obtaining written informed consentfrom parents and wherever possible assent from thesubjects. We recruited them over a period of 13 monthsfrom December 2003 to December 2004. None of thechildren had a diagnosis of bipolar disorder at intake. Aresident in psychiatry had evaluated the subjects in detailby using a clinical proforma and diagnosis further con-firmed by a child and adolescent psychiatrist. We ex-cluded subjects with history of substance use.

2.2. Assessments

The Missouri Assessment of Genetics Interview forchildren (MAGIC), the revised version of the DiagnosticInterview for Children and Adolescents (DICA) (Reich,2000) was used to confirm the diagnosis of MDD and toassess hypomania and other comorbid conditions (Reichand Todd, 1999). It is a clinician-administered poly-diagnostic, semi-structured clinical interview, whichgenerates DSM IV diagnoses. The instrument coversindividual symptoms of hypomania in detail by askingquestions about their frequency of occurrence and thedegree of impairment caused in academics and in rela-tionship with peers, teachers and family members. TheMAGIC has three versions: the child version (7–12 years), the adolescent version (13–17 years) andthe parent version. Subjects were assessed using thechild/adolescent version and the parent version. Basedon the ratings of child/adolescent and parent versions theclinician arrived at the final rating. Wherever, majordiscrepancies arose, a final rating was made after obtain-ing clarifications from both the parent and the subject.

For eliciting a diagnosis of hypomania, we asked allthe questions in the section without skipping the screen-ing question (Benazzi and Akiskal, 2003). We adopted

this strategy to enhance the recall rates of past moodsymptoms (Benazzi and Akiskal, 2003). Behavioralsymptoms of hypomania once remembered help patientand family to recall the mood state and other symptomsthat help in the diagnosis of hypomania (Benazzi andAkiskal, 2003). For a diagnosis of hypomania,we reducedthe duration from 4 days to ≥2 days because there isevidence that≥2 days of symptoms is sufficient for BP-IIdiagnosis (Akiskal, 1996; Akiskal et al., 2000; Angst,1998; Angst et al., 2003; Benazzi, 2001; Benazzi andAkiskal, 2003; Judd et al., 2003; Spitzer et al., 1978). Theprincipal author (BR) performed all the assessments andthen made a final diagnosis of hypomania with the con-sensus of a child and adolescent psychiatrist. Family in-terview of genetic studies (FIGS) was used for assessing

265R.P. Bhargava Raman et al. / Journal of Affective Disorders 98 (2007) 263–266

the family history of probands (Maxwell, 1992). Parentswere the informants for family evaluation.

3. Results

Table 1 shows the sociodemographic details of thesubjects. A majority of the subjects were self-referredand all were drug-naive. Of the 61 subjects, 12 had apast episode of hypomania, which gave a lifetime prev-alence of 20%. However, none had been diagnosedpreviously as suffering from bipolar disorder. With theexception of one subject, hypomania was the first ever-affective episode in all the subjects. In other words, for11 children, hypomania was their first episode and theydeveloped depression subsequently. Of the 12 childrendiagnosed as bipolar II disorder, nine had only one pastepisode of hypomania whereas three other children hadtwo episodes during their lifetime. Mean (SD) durationof hypomania was 12 (7.98) days with a median of17.5 days (range 4–30). Minimum duration of hypo-mania in these children was 4 days. Comorbidity pat-terns and family history of the sample is shown in theTable 1. The sample did not have any subjects withcomorbid disruptive behavior disorders but had unusu-ally high rates of dissociative motor disorders.

4. Discussion

The main finding of this study is a high prevalence ofBP-II disorder in children with either MDD or recurrentdepressive disorder (RDD). To our knowledge, this isthe first study to examine the prevalence of BP-II dis-order in an outpatient population of children and ado-lescents with depression. Further, this is the only studyto examine this issue in an Indian population.

The 20% prevalence of BP-II disorder is lowercompared to the 27–62% rate of BP-II disorder in adultoutpatients with MDD (Szadoczky et al., 1998; Akiskaland Mallya, 1987; Cassano et al., 1992; Benazzi, 1997;Hantouche et al., 1998; Benazzi and Akiskal, 2003;Akiskal et al., 2000). The reasons for the comparativelylow rate of BP-II could be due to the sample char-acteristics. The sample was mostly self-referred, drug-naive and from an outpatient clinic. It also consisted ofmostly mild to moderately ill children with very rates ofcomorbidity. Moreover, a lower rate in children is ex-pected since the risk period is not over and many of themmay switch in the due course of illness. Nonetheless, ourfinding has clearly supported the basic hypothesis ofexistence of undiagnosed BP-II disorder in children withMDD. The reasons for detecting bipolarity in hithertoundiagnosed sample are possibly because of the use of a

semistructured interview schedule by a clinician. Semi-structured interview schedules help clinicians elicit historysystematically and thereby aid in diagnosingmilder formsof illness. In addition, we did not skip any questions inhypomania section and this may have further helped indiagnosis. Previous studies demonstrated that reduction ofhypomania duration requirement from 4 to ≥2 daysincreased the diagnostic yield of BP-II disorder (Akiskalet al., 2000). This prompted us to reduce the durationrequirement to ≥2 days, at the start of this study.However, this change in the requirement did notcontribute to enhanced detection of BP-II disorder. Noneof the subjects had an episode of hypomania of less than4 days. Our study has demonstrated that even with the useof usual DSM-IV diagnostic criterion of 4 days BP-IIdisorder is diagnosable if assessed systematically.

Our study highlights the need for systematic eval-uation of children presenting with MDD for milderbipolar phenotypes. Undetected bipolarity may result inaggressive use of antidepressants, which may acceleratecycling and induce mania/hypomania (Ghaemi et al.,1999). Moreover, it is vital to detect and treat bipolardisorder in children aggressively since it runs an ag-gressive course with multiple relapses (Srinath et al.,1998; Rajeev et al., 2004; Geller et al., 2002).

Our study has certain limitations. The sample wassmall and recruited from a major psychiatric hospital.Our findings, therefore, may not be generalize to de-pressed patients in other settings. The assessments werecross-sectional and performed by a single interviewer.The familial rate of bipolarity in our sample was lowpossibly due to the family history method employed.

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