Clinical and factor-analytic validation of depressive mixed states: a report from the Ravenna-San Diego collaboration

The syndrome of depression intermixed with isolated hypomanic signs and symptoms termed 'depressive mixed state' here, and defined as a major depressive episode plus at least three concurrent intra-episode hypomanic symptoms short of the full criteria for hypomania, is common in clinical practice, but it is not formally included in the official nosology of International Classification of Diseases, 10th edition (ICD-10) or Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision (DSM-IV-TR). The purpose of this report is to document the rigor of the clinical methodology required in the diagnosis of a depressive mixed state, and, more specifically, that required to assess intra-episode hypomanic signs and symptoms in patients with a major depressive episode. Among 405 consecutive private out-patients with a major depressive episode, past hypomanic episodes as well as hypomanic symptoms during the index major depressive episode were systematically recorded. The evaluation of intra-episode hypomanic features represents an innovative procedure superimposed on the Structured Clinical Interview for DSM-IV. The ensemble of depressive and hypomanic signs and symptoms was studied by using principal component factor analysis with varimax rotation. Then multivariate regression was used to test the associations between the symptoms of the depressive mixed state factor and bipolar validator variables. Diagnostically, 241 of the major depressive episodes met the criteria for bipolar II disorder, and 164 met the criteria for major depressive disorder (unipolar disorder). Factor analysis revealed four major depressive episode factors, one of which comprised the intra-episode hypomanic symptoms of irritability, racing (crowded) thoughts, distractibility, and psychomotor agitation in up to 31% of patients with a major depressive episode. Furthermore, comparison of bipolar II and unipolar patients revealed that depressive mixed state occurred in 59% of the former and 27% of the latter. It is proposed that the foregoing hypomanic features delineate the depressive mixed state factor, which is highly and significantly associated with such bipolar II validators as young age at onset, atypical features of depression, and family history of bipolar disorder. The methodological innovation described in this report permitted the delineation of the depressive mixed state as a distinct form of major depressive episode, which belongs to the bipolar realm.