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OBJECTIVE: Puerperal psychosis, an episode of mania or psychosis precipitated by childbirth, follows approximately one in 1,000 deliveries. The evidence of clinical, outcome, and genetic studies supports the hypothesis that the majority of puerperal psychotic episodes are manifestations of an affective disorder diathesis with a puerperal trigger. Family studies of puerperal psychosis consistently demonstrate familial aggregation of psychiatric (particularly affective) disorder and suggest a major overlap in the familial factors predisposing to puerperal psychosis and bipolar disorder. The single large study that used direct interview of relatives suggested that familial factors play a role in vulnerability to puerperal triggering itself. The authors’ goal was to test this hypothesis further. METHOD: They conducted a study of the occurrence of episodes of puerperal psychosis in families multiply affected with bipolar disorder participating in an ongoing molecular genetic study of bipolar disorder in sibling pairs. RESULTS: Episodes of puerperal psychosis followed 81 (26%) of 313 deliveries to 152 parous women with bipolar disorder, 58 (38%) of whom had at least one puerperal psychotic episode. Puerperal episodes clustered in families. Episodes of puerperal psychosis occurred in 74% (N=20) of the 27 parous women with bipolar disorder who had a family history of puerperal psychosis in a first-degree relative but in only 30% (N=38) of the 125 women with bipolar disorder with no such family history. CONCLUSIONS: These results conclusively demonstrate that familial (probably genetic) factors are implicated in susceptibility to triggering of puerperal episodes in women with bipolar disorder. These findings have implications for future research and will be of use clinically in the management of women with bipolar disorder who are considering pregnancy.