A prospective follow-up study of pediatric bipolar disorder in boys with attention-deficit/hyperactivity disorder

Abstract

Objective

To examine patterns of persistence and remission in pediatric bipolar disorder attending to syndromatic, symptomatic, functional and affective definitions of remission of bipolar symptomatology in a longitudinal sample of ADHD children with comorbid bipolar disorder.

Methods

ADHD boys (128) were followed over 1- and 4-year follow-up assessments with structured diagnostic interviews to assess the persistence of psychiatric comorbidity. The course and duration of bipolar disorder was estimated by calculating the time from age at onset and the age at remission reported at either the 1- or 4-year follow-up assessments.

Results

Twenty-two (17%, Prevalent Cases) subjects met criteria for bipolar disorder at the baseline assessment. The average age of these subjects was 10.5±3.0 (range: 6 to 17 years) at baseline and 14.4±3.1 years of age at follow-up. The rate of remission was heavily dependent on the definition used. The rate of functional remission was the lowest and the rate of syndromatic remission was the highest. Regardless of the definition used, however, the disorder was chronic and lasted many years.

Limitations

These data should be considered preliminary due to the sample size and the absence of mood symptom rating scales.

Conclusions

That less than 20% of subjects attained functional remission or euthymia over the entire time period evaluated provides further evidence that pediatric bipolar disorder is a chronic mood disorder with a poor prognosis.

Introduction

Despite continued debate and controversy over the diagnosis of mania in children (Biederman, 1998, Klein et al., 1998), exhaustive reviews support the existence of the disorder in youth (Weller et al., 1995, Faedda et al., 1995, Geller and Luby, 1997). Yet, lingering concerns remain as to its validity.

As recommended by Robins and Guze (1970), for a psychiatric disorder to be considered valid it requires a unique set of differentiating features, evidence of familiality, specific treatment responsivity and a unique course. The literature consistently shows that mania in children is frequently chronic and characterized by predominantly irritable mood and mixed presentation (symptoms of major depression and mania co-occurring; Carlson, 1983, Carlson, 1984, Wozniak et al., 1995a). The irritability observed in bipolar children is very severe, with “affective storms”, or prolonged and aggressive temper outbursts (Davis, 1979). In between outbursts, these children are described as persistently irritable or angry in mood (Carlson, 1983, Carlson, 1984, Geller and Luby, 1997).

Although there are no twin or adoption studies of pediatric bipolar disorder, family studies strongly suggest that the pediatric onset form of the disorder has a strong familial component (Faraone et al., 1997, Wozniak et al., 1995b, Todd et al., 1996, Strober et al., 1988, Strober, 1992). Strober et al. (1988), Strober (1992) and Todd et al. (1993) proposed that pediatric mania might be a distinct subtype of bipolar disorder with a high familial loading. Consistent with their idea, Wozniak et al. (1995b) and Faraone et al., 1997, Faraone et al., 2001 documented that children with bipolar disorder of both genders have a significant familial risk for bipolar disorder in first degree relatives within and without the context of ADHD. These investigators also documented that bipolar disorder and ADHD cosegregated in relatives providing compelling support for the hypothesis that pediatric bipolar disorder may represent a unique developmental subtype of bipolar disorder.

Treatment studies have also begun to document that antimanic agents are selectively efficacious in the treatment of pediatric bipolar disorder. Biederman et al. (1998a) systematically reviewed the clinical records of all pediatrically referred patients who, at initial intake satisfied diagnostic criteria for bipolar disorder based on a structured diagnostic interview. Mood stabilizers were associated with selective and significant improvement of manic symptoms as documented by the medical record. Consistent with these results, a prospective open study (Kowatch et al., 2000) documented that mood stabilizers (lithium, valproic acid and carbamezapine) are efficacious in the treatment of pediatric bipolar disorder. Likewise, both retrospective (Frazier et al., 1999) and prospective (Frazier et al., 2001) studies document that risperidone and olanzapine are also efficacious in the management of bipolar youth.

In contrast to phenomenological, family aggregation, and treatment response data supporting the validity of pediatric bipolar disorder much less is known about its course. Recently, Geller et al. (2002) reported on the 2-year outcome of a longitudinal sample of children with pediatric bipolar disorder. This study found that by the last follow-up period 65% of subjects recovered from mania but that 55% relapsed after recovery. However, since this study focused exclusively on full syndromatic persistence of manic symptomatology, it did not address the possibility of continued affective instability in the form of sub-syndromal symptoms of the disorder and its associated impairments. This issue is not trivial since sub-syndromal forms of bipolar disorder have been shown to be associated with significant functional impairment (Lewinsohn et al., 1995).

As recently proposed by Keck et al. (1998), the distinction between different types of remission may clarify components of complex recovery processes. These investigators suggested three levels of remission for psychiatric disorders: syndromatic, symptomatic and functional. Syndromatic remission refers to the loss of full diagnostic status, symptomatic remission refers to the loss of partial diagnostic status; functional remission refers to the loss of partial diagnostic status plus functional recovery (full recovery).

For bipolar disorder, another critical dimension in assessing patterns of remission is the persistence of depressive symptomatology since some subjects may remit from mania but may continue to manifest depression. In fact, a recent study documented that the overall symptomatic structure of bipolar disorder may be primarily depressive, rather than manic (Judd et al., 2002). Thus, a better understanding of remission patterns of pediatric bipolar disorder can benefit from a better understanding of the type of remission and associated functional outcome in bipolar youth grown ups.

The purpose of this report was to examine patterns of persistence and remission in pediatric bipolar disorder attending to syndromatic, symptomatic, functional and affective definitions of remission of bipolar symptomatology in a longitudinal sample of ADHD children with comorbid bipolar disorder. Based on the extant literature, we hypothesized that bipolar disorder will follow a chronic and dysfunctional course associated with the absence of euthymia.