title: A mixed state core for melancholia: an exploration in history, art and clinical science.
abstract: OBJECTIVE
  We argue for a mixed state core for melancholia comparing concepts of melancholia across centuries using examples from art, history and scientific literature.
  
  
  METHODS
  Literature reviews focusing on studies from Kraepelin onward, DSM-IV classification and view-points from clinical experience highlighting phenomenologic and biologic features as predictors of bipolar outcome in prospective studies of depression.
  
  
  RESULTS
  Despite the implied chemical pathology in the term endogenous/melancholic depression, frequently reported glucocortical and sleep neurophysiologic abnormalities, there is little evidence that melancholia is inherited independently from more broadly defined depressions. Prospective follow-up of 'neurotic' depressions have shown melancholic outcomes in as many as a third; hypomania has also been observed in such follow-up.
  
  
  CONCLUSIONS
  These findings and considerations overall do suggest that melancholia as defined today is more closely aligned with the depressive and/or mixed phase of bipolar disorder. Given the high suicidality from many of these patients the practice of treating them with antidepressant monotherapy needs re-evaluation.
authors.affiliation: University of California at San Diego, La Jolla, CA, USA. hakiskal@ucsd.edu
authors.forename: H S
authors.initials: HS
authors.lastname: Akiskal
authors.forename: K K
authors.initials: KK
authors.lastname: Akiskal
mesh_terms: D035843:Biomedical Research / Q000266:history*; D003866:Depressive Disorder / Q000175:diagnosis / Q000266:history* / Q000523:psychology*; D039721:Diagnostic and Statistical Manual of Mental Disorders; D049669:History, 16th Century; D049690:History, Ancient; D006801:Humans; D008512:Medicine in the Arts; D011570:Psychiatry / Q000266:history*