Abstract

Background There are no data on the bipolar family history (BPFH) of the hypomanic symptoms and dimensions of mixed depression (defined as a depression plus concurrent hypomanic symptoms). These data may be important for the genetics of mixed depression. The study aim was to investigate the BPFH of the hypomanic symptoms of mixed depression. Methods Consecutive 243 bipolar II disorder (BP II) and 189 major depressive disorder (MDD) outpatients, presenting for treatment of a major depressive episode (MDE), were interviewed using the Structured Clinical Interview for DSM-IV, the Hypomania Interview Guide, and the Family History Screen. Mixed depression was defined as an MDE plus 3 or more intra-MDE hypomanic symptoms (following a definition validated by Akiskal and Benazzi [J Affect Disord 2003;73:113-22]). Results Major depressive episode with BPFH vs MDE without BPFH had significantly more BP II, lower age of onset, more MDE recurrences, more atypical depressions, more mixed depressions, and more intra-MDE hypomanic symptoms (irritability, racing/crowded thoughts, psychomotor agitation, more talkativeness, distractibility). Factor analysis of intra-MDE hypomanic symptoms found 2 factors (dimensions): one factor including psychomotor agitation and more talkativeness, and one factor including racing/crowded thoughts, irritability, and distractibility. Logistic regression showed that mixed depression was more strongly associated with BPFH than hypomanic symptoms and dimensions. There was a dose-response relationship between number of intra-MDE hypomanic symptoms and BPFH loading (marked increase at n = 3) in the entire BP II and MDD sample. Conclusions Findings showed that hypomanic symptoms were more common in the MDE with BPFH of BP II and of MDD, suggesting that a bipolar vulnerability may be required for mixed depression. Mixed depression was more strongly associated with BPFH than hypomanic symptoms and dimensions, suggesting that it could be the focus of future FH studies.

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