Familial variation in episode frequency in bipolar affective disorder

Objective: Bipolar affective disorder is a familial illness characterized by recurrent episodes of mania and depression, but little is known about the familial nature of episode recurrence or its associated clinical features. The authors analyzed the recurrence frequency of affective episodes (episode frequency), along with associated clinical and demographic variables, in families with at least three members with a major affective disorder. Method: Members of 86 families ascertained through probands with bipolar affective disorder who had two or more first-degree relatives with a major affective disorder were interviewed by psychiatrists and assigned an all-sources diagnosis. Data for 407 subjects with a major affective disorder were analyzed. Episode frequency was estimated as the number of episodes of major depression, mania, and hypomania per year of illness. Results: Episode frequency was smoothly distributed over the range of 0.02-20.2 episodes/year. Episode frequency was significantly correlated among relatives (r=0.56, p<0.004). Earlier age at onset, bipolar II disorder, hallucinations or delusions, alcoholism, and suicidal behavior were all more prevalent in the highest than in the lowest quartiles of episode frequency. Female gender and recurrent major depression were more prevalent in the lowest quartile. Panic disorder, substance abuse, and thyroid disease were all unrelated to episode frequency. Subjects with DSM-IV rapid cycling did not differ from other affected subjects for most of the variables tested. Conclusions: Episode frequency is a highly familial trait in bipolar affective disorder, associated with several indicators of severity, and may be useful in defining clinical subtypes of bipolar affective disorder with greater genetic liability. DSM-IV rapid cycling was not supported by these data as the best predictor of familiality or severity.