title: Habenula volume in bipolar disorder and major depressive disorder: a high-resolution magnetic resonance imaging study.
abstract: BACKGROUND
  Increased activity of the habenula has been implicated in the etiology of major depressive disorder (MDD), in which reductions in habenula volume are present after death. We conducted the first magnetic resonance imaging analysis of habenula volume in MDD and bipolar disorder (BD).
  
  
  METHODS
  High-resolution images (resolution approximately .4 mm(3)) were acquired with a 3T scanner, and a pulse sequence was optimized for tissue contrast resolution. The habenula was manually segmented by one rater blind to diagnosis. Seventy-four healthy control subjects (HC) were compared with both medicated (lithium/divalproex, n = 15) and unmedicated, depressed BD (n = 22) patients; unmedicated, depressed MDD patients (n = 28); and unmedicated MDD patients in remission (n = 32).
  
  
  RESULTS
  The unmedicated BD patients displayed significantly smaller absolute (p < .01) and normalized (p < .05) habenula volumes than the HC subjects. In post hoc assessments analyzing men and women separately, the currently-depressed women with MDD had smaller absolute (p < .05) habenula volumes than the HC women. None of the other psychiatric groups differed significantly from the HC group.
  
  
  CONCLUSIONS
  We provide further evidence for the involvement of the habenula in affective illness but suggest that a reduction in volume might be more pronounced in unmedicated, depressed BD subjects and female currently depressed MDD subjects. The habenula plays major roles in the long-term modification of monoamine transmission and behavioral responses to stress and in the suppression of dopamine cell activity after the absence of an expected reward. A reduction in habenula volume might thus have functional consequences that contribute to the risk for developing affective disease.
authors.affiliation: Mood and Anxiety Disorders Program, National Institutes of Health/National Institute of Mental Health, Bethesda, Maryland, USA. jonathansavitz@hotmail.com
authors.forename: Jonathan B
authors.initials: JB
authors.lastname: Savitz
authors.forename: Allison C
authors.initials: AC
authors.lastname: Nugent
authors.forename: Wendy
authors.initials: W
authors.lastname: Bogers
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Roiser
authors.forename: Earle E
authors.initials: EE
authors.lastname: Bain
authors.forename: Alexander
authors.initials: A
authors.lastname: Neumeister
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Zarate
authors.forename: Husseini K
authors.initials: HK
authors.lastname: Manji
authors.forename: Dara M
authors.initials: DM
authors.lastname: Cannon
authors.forename: Sean
authors.initials: S
authors.lastname: Marrett
authors.forename: Fritz
authors.initials: F
authors.lastname: Henn
authors.forename: Dennis S
authors.initials: DS
authors.lastname: Charney
authors.forename: Wayne C
authors.initials: WC
authors.lastname: Drevets
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D000928:Antidepressive Agents / Q000627:therapeutic use; D018692:Antimanic Agents / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000188:drug therapy / Q000473:pathology*; D001931:Brain Mapping; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000473:pathology*; D005260:Female; D005473:Fluoxetine / Q000627:therapeutic use; D019262:Habenula / Q000473:pathology*; D006801:Humans; D016651:Lithium Carbonate / Q000627:therapeutic use; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009929:Organ Size; D014635:Valproic Acid / Q000627:therapeutic use
chemical_list: D000928:Antidepressive Agents; D018692:Antimanic Agents; D005473:Fluoxetine; D016651:Lithium Carbonate; D014635:Valproic Acid