How best to identify a bipolar-related subtype among major depressive patients without spontaneous hypomania: Superiority of age at onset criterion over recurrence and polarity?

Background: History of high depressive recurrence (without history of mania/hypomania) has been proposed as a mood subtype close to bipolar disorders. Herein we test whether this is the best approach to this question. Methods: We systematically evaluated consecutive 224 Major Depressive (MDD) and 336 Bipolar II Disorders (BP-II) outpatients in a private practice, by the SCID for DSM-IV (modified for better probing hypomania by Akiskal and Benazzi [Akiskal, H.S., Benazzi, F., 2005. Optimizing the detection of bipolar II disorder in outpatient private practice: toward a systematization of clinical diagnostic wisdom. J. Clin. Psychiatry 66, 914-921]). We conducted univariate and multivariate analyses on such putative bipolar validators as early age at onset of first major depressive episode (before 21 years), high recurrence, family history for bipolar disorders, and depressive mixed states (mixed depression, i.e. depression plus concurrent hypomanic symptoms), in order to identify an MDD subgroup close to BP-II. Results: All bipolar validators were independent predictors of BP-II. Early onset was the only variable which identified an MDD subgroup significantly associated with all bipolar validators. This MDD subgroup was similar to BP-II on age at onset and bipolar family history, and had a high frequency of mixed depression. A dose-response relationship was found between number of bipolar validators present in MDD, and bipolar family history loading among MDD relatives. Limitations: Study limited to outpatients. Conclusions: From among the bipolar validators, early age at onset of first major depression (< 21 years) was superior to high recurrence (> 4 depressive episodes) in identifying an MDD subgroup close to BP-II, which might be subsumed under the broad bipolar spectrum. Implications of unipolar-bipolar boundaries and genetic investigations are discussed. (C) 2007 Elsevier B.V. All rights reserved.