title: 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?
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Hecker Psychiatry Research Center, Department of Psychiatry, National Health Service, Forli, Italy. FrancoBenazzi@FBenazzi.it
authors.forename: Franco
authors.initials: F
authors.lastname: Benazzi
authors.forename: Hagop S
authors.initials: HS
authors.lastname: Akiskal
mesh_terms: D000328:Adult; D017677:Age Distribution; D017668:Age of Onset; D000553:Ambulatory Care; D001714:Bipolar Disorder / Q000145:classification* / Q000175:diagnosis* / Q000523:psychology; D003430:Cross-Sectional Studies; D003866:Depressive Disorder / Q000175:diagnosis / Q000523:psychology; D003865:Major Depressive Disorder / Q000175:diagnosis* / Q000523:psychology; D039721:Diagnostic and Statistical Manual of Mental Disorders; D005190:Family; D005260:Female; D006801:Humans; D007558:Italy; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011331:Private Practice; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data; D011570:Psychiatry; D012008:Recurrence; D009626:Terminology as Topic