A prospective study of the offspring of bipolar parents responsive and nonresponsive to lithium treatment

Background: The descriptions of clinical course among bipolar youths vary significantly and differ markedly from the findings described in classical studies of bipolar adults'. This difference may in part reflect genetic heterogeneity. Response to lithium monotherapy identifies a homogeneous subgroup of bipolar adults. The aim of this study was to prospectively characterize the clinical course, including antecedent and comorbid conditions, among the offspring of 2 groups of bipolar parents divided on the basis of response to lithium. Method: Parents were identified from families participating in ongoing molecular genetic studies and selected from specialty affective disorder clinics. For each child, 1 parent met Research Diagnostic Criteria/DSM-IV criteria for bipolar I disorder and either response or nonresponse to lithium prophylaxis. The other parent had no lifetime history of a major psychiatric illness. Blind to family affiliation and lithium response, all eligible offspring aged 10 to 25 years were interviewed using the Schedule for Affective Disorders and Schizophrenia for School-Aged Children-Present and Lifetime Version (K-SADS-PL), and best-estimate diagnoses were made by a panel of experts. Offspring were then reassessed over a 5-year period. Results: Offspring of lithium responders (N = 34) had good premorbid functioning and manifested classical mood disorders with an episodic course. Comorbid conditions in this group-remitted prior to the mood disorder: In contrast, offspring of lithium nonresponders (N = 21) had poorer premorbid functioning and manifested mood disorders with a chronic course. Comorbid conditions continued alongside the mood disorder. Clinical course among affected offspring was predicted by the disease course of the parent. Conclusion: The pattern of clinical course, remitting or nonremitting, appears to be inherited. Among the offspring of lithium-responsive bipolar parents, an early-onset subgroup with a classical episodic clinical course can be identified.