Research reportA prospective follow-up study of pediatric bipolar disorder in boys with attention-deficit/hyperactivity disorder
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.
Section snippets
Methods
Detailed study methodology has been previously reported (Biederman et al., 1996). We sampled families through Caucasian, non-Hispanic, male probands between the ages of 6 and 17. The original sample included 140 ADHD and 120 normal control probands ascertained from psychiatric and nonpsychiatric settings (Biederman et al., 1996) at baseline and reassessed at 1- and 4-year follow-ups with identical assessment methodology. Only those ADHD subjects that returned for the 4-year follow-up are
Results
Of the 140 boys with ADHD assessed at baseline, 128 were available at follow-up. Ninety-nine (77%, Non-bipolar) subjects did not meet criteria for bipolar disorder at baseline or either follow-up; twenty-two (17%, Prevalent Cases) subjects met criteria for bipolar disorder at baseline; and seven subjects (6%; Incident Cases) reported a new onset over the course of follow-up.
This study focuses on the course and outcome of the 22 cases of bipolar disorder present at baseline. The average age of
Discussion
A systematic evaluation of the course of bipolar disorder in a longitudinal sample of well-characterized youth with ADHD found that the course of bipolar disorder was chronic, protracted, and dysfunctional. Although 50% of bipolar youth remitted from the full syndrome of bipolar disorder at follow up (i.e., they no longer met full diagnostic criteria), 80% failed to attain functional remission or euthymia over a course of 10 years. These longitudinal findings confirm and extend previous
Acknowledgements
This work was supported by grants R01HD036317 (JB), K01MH065523 (EM), and K08MH001503 (JW) from the National Institutes of Health.
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