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Section 26
Comorbidity in Pediatric Bipolar Disorder

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Recently, there has been a suggestion that hyperactivity is the first developmentally age-specific manifestation of prepubertal-onset bipolar disorder, and that ADHD may be a developmental marker of a very early onset form of bipolar disorder. This hypothesis is consistent with the high prevalence of ADHD (57-98%) reported in some studies of juvenile bipolar disorder. Similarly, high rates of conduct disorder have been reported in juvenile bipolars. Kovacs and Pollock, in their recent study, reported a 69% rate of lifetime comorbidity and 54% rate of episode comorbidity with CD in bipolar youths. They also suggested that comorbid CD may identify a subtype of very early-onset bipolar disorder. The findings from an Indian study, however, do not support a strong association between ADHD/CD and juvenile bipolar disorder. Of the 30 subjects with bipolar disorder, only two had comorbid CD and none had comorbid ADHD. In another study of 30 juvenile bipolar subjects from the same centre (Shashikiran, personal communication), very few had received a comorbid diagnosis of ADHD or CD. This wide-ranging disparity in the rates of ADHD/CD in young bipolar subjects could be due simply to different ascertainment methods and differing clinical characteristics of the samples. The majority of previous studies included clinically referred subjects, and some of them were based on children referred to a pediatric psychopharmacology clinic well known for the treatment of ADHD children, resulting in a possible bias. The Indian sample, however, was recruited from a hospital setting and was largely self-referred. Similarly, very high rates of CD in the study by Kovacs and Pollock could possibly be due to high rates (90%) of psychiatric disorders before the onset of bipolar illness, and high rates of paternal substance abuse (64%) and antisocial personality disorder (38%). One method of addressing nosological validity is to examine the transmission of comorbid disorders in families. If ADHD and bipolar disorder are associated because of shared familial etiological factors, then family studies should find elevated rates of bipolar disorder in relatives of ADHD patients, and ADHD in relatives of bipolar patients. That ADHD and bipolar disorder in some children are familially related receives support from the findings of two studies reported from the same group, which suggest that ADHD with bipolar disorder could be a familial subtype. However, with the exception of one, none of the previous studies which examined rates of ADHD among the children of bipolar patients found statistically significant differences in the rates of ADHD among these children compared with controls. Similarly, none of the studies of relatives of children with ADHD found a statistically significant elevation of bipolar disorder compared to those of relatives of control children. The findings of Wozniac et al. and Faraone et al. have to be interpreted with caution, as the samples were ascertained from a pediatric psychopharmacology clinic well known for the treatment of children with ADHD or the management of difficult, comorbid cases. Moreover, the study by Faraone et al. had several other limitations. The subjects were all ascertained from cases with primary ADHD, and hence may not be representative of children with a primary diagnosis of bipolar disorder. In addition, of a sample of 140 probands with ADHD, only 15 probands met criteria for both ADHD and bipolar disorder, and only five of them could be interviewed directly. Questions have also been raised about sketchy methodological details about the sample, small numbers often expressed as inflated percentages, two rather unconvincing case histories given as representative cases, and the numbers and brief durations of the manic episodes (some lasting for as little as 15 minutes) inconsistent with what is known of bipolar disorder. Most of the data on comorbidity in subjects with ADHD over the past 5 years has come from the Harvard group, and hence replication outside Harvard and, indeed, the USA is needed to clarify the controversy associated with ADHD comorbidity in juvenile bipolar disorder.

Clearly, the issue of comorbidity with disruptive disorders, particularly ADHD, needs to be examined in larger representative samples of general psychiatric settings as well as epidemiological samples, because subjects recruited from special clinical settings could be suffering from very severe forms of illness, and from multiple comorbid conditions resulting in obvious ascertainment bias. Longitudinal follow-up studies of ADHD children have not shown an increased incidence of bipolar disorder, raising further doubts about the relationship between ADHD and juvenile bipolar disorder. Finally, elevated risk for bipolar disorder has been observed only when the probands had both ADHD and bipolar disorder, but not when the probands had ADHD alone. High rates of substance abuse are also noted in some samples with negative influence on prognosis and treatment response, but in the Indian follow-up study none had comorbid substance or alcohol abuse. The co-occurrence of mania and pervasive developmental disorders (PDD) has also been reported recently. Wozniac et al., in a study of consecutive clinic referrals, found that 21% of PDD patients also fulfilled the DSM criteria for mania, and these constituted 11% of all manic patients. The findings of this study need replication to confirm association between PDD and juvenile bipolar disorder.

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Personal Reflection Exercise #12
The preceding section contained information about comorbidity in pediatric bipolar disorder.  Write three case study examples regarding how you might use the content of this section in your practice.

QUESTION 26
According to Janardhan, symptoms of what two disorders may be the first manifestation of pediatric bipolar disorder? Record the letter of the correct answer the Answer Booklet.