title: Family history validation of the bipolar nature of depressive mixed states.
abstract: BACKGROUND
  Recent data indicate that depressive mixed states (DMX), major depressive episode (MDE) plus few concurrent hypomanic symptoms are common in clinical practice but omitted in DSM-IV. Our aims were to find the sensitivity and specificity of DMX for the diagnosis of bipolar II disorder, and validate it against familial bipolarity.
  
  
  METHODS
  377 consecutive private outpatients presenting with psychoactive drug-free MDE were interviewed with the Structured Clinical Interview for DSM-IV (Clinician Version). History of past hypomanic episodes and presence of hypomanic symptoms during the index MDE were systematically recorded. Of these, 226 were bipolar II and 151 unipolar. DMX3 was defined as an MDE plus three or more intra-episodic hypomanic symptoms.
  
  
  RESULTS
  DMX3 was present in 58.4% of bipolar II, and 23.1% of unipolar patients. It was significantly associated with variables distinguishing bipolar from strictly defined unipolar disorders (younger age at onset, more MDE recurrence, more atypical features, more bipolar II family history). Unipolar DMX3 (MDE with documented hypomania solely intra-episodically) was not significantly different from bipolar II MDE on age at onset, atypical features, and bipolar II family history.
  
  
  CONCLUSIONS
  Results support the inclusion of DMX3 (bipolar II and 'unipolar') into the bipolar spectrum. Adding the 23% of the UP-DMX3 to the roster of less-than-manic outpatient depressives will boost the rate of bipolarity in this outpatient depressive population to a respectable 70%, the highest rate yet reported for the bipolar spectrum below the threshold of mania.
authors.affiliation: VA Medical Center, University of California at San Diego, VA Psychiatry Service (116-A), 3350 La Jolla Village Drive, San Diego, CA 92161, USA. hakiskal@ucsd.edu
authors.forename: Hagop S
authors.initials: HS
authors.lastname: Akiskal
authors.forename: Franco
authors.initials: F
authors.lastname: Benazzi
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000145:classification / Q000235:genetics* / Q000523:psychology*; D003866:Depressive Disorder / Q000145:classification / Q000235:genetics* / Q000523:psychology*; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D008297:Male; D008487:Medical History Taking; D008875:Middle Aged; D010045:Outpatients; D011569:Psychiatric Status Rating Scales; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index