Pediatric bipolar disorderCan a subtype of conduct disorder linked to bipolar disorder be identified? Integration of findings from the Massachusetts General Hospital Pediatric Psychopharmacology Research Program
Introduction
An emerging literature documents an elevated risk for conduct disorder (CD) among children with bipolar disorder (BPD). Kovacs and Pollack (1995) reported a 69% rate of CD in a referred sample of youth with BPD. In that study, the presence of CD heralded a more complicated course of BPD. Similarly, Kutcher et al (1989) found that 42% of hospitalized youth with BPD had comorbid CD, and Wozniak et al (1995a) showed that preadolescent children satisfying structured interview criteria for BPD frequently had comorbid CD. Notably, an epidemiologic study of youth (Lewinsohn et al 1995) found high rates of comorbidity between bipolar and disruptive behavior disorders. These findings in children are consistent with those in adults reporting a nearly sevenfold increase in the risk for BPD among individuals with antisocial personality disorder (Boyd et al 1984).
Although the reasons for these intriguing associations between CD and BPD remain unknown, a close inspection of the characteristics of juvenile BPD offers some clues. The literature indicates that juvenile BPD is frequently mixed and that the most common mood disturbance in manic children may be better characterized as irritable, with “affective storms,” or prolonged and aggressive, often violent temper outbursts Carlson 1983, Carlson 1984, Davis 1979. The irritable outbursts often include threatening or attacking behavior toward others, including family members, children, adults, and teachers.
In conceptualizing the overlap between BPD and CD, Kovacs and Pollock (1995) suggested that the high prevalence of comorbid CD in BPD youth might confuse the clinical presentation of childhood BPD and possibly account for some of the documented failure to detect bipolarity in children. Thus, the heterogeneity of BPD and that of CD may have important implications in helping to identify a subtype of BPD with early onset characterized by high levels of comorbid CD (Kovacs and Pollock 1995) and a subtype of CD with high levels of dysphoria and explosiveness.
Although these aberrant behaviors are consistent with the diagnosis of CD, they may be due to the behavioral disinhibition of BPD or the irritability and low frustration tolerance that frequently accompanies pediatric BPD. Considering the extreme severity of juvenile BPD, its emergence in CD children seriously complicates their already compromised life and vice versa. In a series of studies, our group attempted to delineate the relationship between bipolar and conduct disorder. These studies relied on systematic evaluation of clinical correlates in affected youth and their relatives and will be synthesized here into an integrated discussion to describe the comorbidity of these two conditions.
Section snippets
Overview of methodology
The results reviewed here are derived from four published research reports Biederman et al 1997, Biederman et al 1999, Biederman et al 2000, Wozniak et al 2001. Each of our studies employed similar assessment methods, and the study groups were drawn from referrals to the Pediatric Psychopharmacology clinic at the Massachusetts General Hospital.
In these studies, psychiatric assessments of children relied on the K-SADS-E (Orvaschel and Puig-Antich 1987) completed with the mothers. For children ≥
Diagnostic overlap between conduct disorder and bipolar disorder
We first tested the hypothesis that subtypes of CD with and without BPD could be distinguished from one another in our family study of 140 ADHD probands and 120 control subjects without ADHD, ascertained from psychiatric and pediatric clinics (Biederman et al 1997). All probands were Caucasian, non-Hispanic boys between the ages of 6 and 17. Of 140 ADHD probands, 38 (27%) also met diagnostic criteria for CD and 30 (23%) for BPD at either baseline or follow-up assessments; of those, 21 (55% of
Clinical correlates of CD, BPD, and CD+BPD
To further characterize the diagnostic comorbidity between BPD and CD, we stratified the samples based on these disorders and compared rates of hospitalization and psychiatric comorbidity (Table 1). From the family study of boys with ADHD (Biederman et al 1997), comparisons were made of ADHD probands with both BPD and CD (BPD+CD); ADHD probands with BPD only (BPD); ADHD probands with CD only (CD); ADHD probands with neither BPD nor CD (ADHD), and control subjects without ADHD, BPD, or CD
Parsing the association between bipolar and conduct disorder using familial risk analysis
Because both CD and BPD are known to be familial disorders, one useful approach to disentangling these diagnoses and answering questions regarding the nature of their association is the use of family aggregation data Faraone et al 1999, Pauls et al 1986a, Pauls et al 1986b, Reich et al 1972, Reich et al 1979. Such an approach can provide evidence external to the complicated diagnostic questions posed by the complex comorbid phenotype of individual patients. That is, examining familial patterns
Synthesis of reviewed work
We evaluated whether a subtype of CD linked to BPD could be identified. This program of research showed that children with both CD and BDP shared striking similarity in the phenotypic features of both disorders in children with both diagnoses irrespective of the comorbidity with the other disorder. These results were true for those sampled according to a diagnosis of ADHD in addition to a sample that took all cases of BPD and CD from an outpatient psychiatric clinic, regardless of their ADHD
Treatment implications
The diagnosis of BPD in some CD children offers important therapeutic possibilities because sociopathy and BPD may require different treatment strategies. A series of controlled clinical trials Campbell et al 1984, Campbell et al 1995, Cueva et al 1996, Malone et al 2000, Rifkin et al 1997 documented the efficacy of mood stabilizers (lithium carbonate and carbamazepine) in the treatment of aggressive CD children; however, these psychiatrically hospitalized CD youth were treated for severe,
Conclusions
Although CD and BPD are clearly different clinical conditions, differential diagnosis can be complex when youth present with a complicated clinical picture of symptoms suggestive of both CD and BPD. When a disinhibited and aggressive youth with BPD steals, lies, assaults, or vandalizes, are these behaviors a complication of the BPD? Or are they symptoms of an antisocial tendency? When a juvenile is arrested for antisocial acts and presents with a high degree of irritability, does he or she
Acknowledgements
This work was supported in part by National Institute of Health Grant Nos. R01HD036317 and R01 MH050657 (Dr. Biederman, PI), R01HD37999 and R01HD37694 (Dr. Faraone, PI), and by grants from the Stanley Foundation (Dr. Biederman, PI) and Johnson and Johnson (Dr. Biederman, PI).
Aspects of this work were presented at the conference “Pediatric Bipolar Disorder,” held March 9, 2002, in Boston, Massachusetts. The conference was sponsored by the Massachusetts General Hospital through an unrestricted
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