Deficits in docosahexaenoic acid and associated elevations in the metabolism of arachidonic acid and saturated fatty acids in the postmortem orbitofrontal cortex of patients with bipolar disorder

Psychiatry Res. 2008 Sep 30;160(3):285-99. doi: 10.1016/j.psychres.2007.08.021. Epub 2008 Aug 20.


Previous antemortem and postmortem tissue fatty acid composition studies have observed significant deficits in the omega-3 fatty acid docosahexaenoic acid (DHA, 22:6n-3) in red blood cell (RBC) and postmortem cortical membranes of patients with unipolar depression. In the present study, we determined the fatty acid composition of postmortem orbitofrontal cortex (OFC, Brodmann area 10) of patients with bipolar disorder (n=18) and age-matched normal controls (n=19) by gas chromatography. After correction for multiple comparisons, DHA (-24%), arachidonic acid (-14%), and stearic acid (C18:0) (-4.5%) compositions were significantly lower, and cis-vaccenic acid (18:1n-7) (+12.5%) composition significantly higher, in the OFC of bipolar patients relative to normal controls. Based on metabolite:precursor ratios, significant elevations in arachidonic acid, stearic acid, and palmitic acid conversion/metabolism were observed in the OFC of bipolar patients, and were inversely correlated with DHA composition. Deficits in OFC DHA and arachidonic acid composition, and elevations in arachidonic acid metabolism, were numerically (but not significantly) greater in drug-free bipolar patients relative to patients treated with mood-stabilizer or antipsychotic medications. OFC DHA and arachidonic acid deficits were greater in patients plus normal controls with high vs. low alcohol abuse severity. These results add to a growing body of evidence implicating omega-3 fatty acid deficiency as well as the OFC in the pathoaetiology of bipolar disorder.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Alcoholism / metabolism
  • Antipsychotic Agents / therapeutic use
  • Arachidonic Acid / metabolism*
  • Autopsy
  • Bipolar Disorder / blood
  • Bipolar Disorder / drug therapy
  • Bipolar Disorder / metabolism*
  • Cerebral Cortex / chemistry*
  • Cerebral Cortex / metabolism
  • Chromatography, Gas
  • Control Groups
  • Docosahexaenoic Acids / analysis
  • Docosahexaenoic Acids / metabolism*
  • Erythrocytes / chemistry
  • Erythrocytes / metabolism
  • Fatty Acids / metabolism*
  • Fatty Acids, Omega-6 / analysis
  • Fatty Acids, Omega-6 / metabolism
  • Female
  • Frontal Lobe / chemistry
  • Frontal Lobe / metabolism
  • Humans
  • Male
  • Palmitic Acid / analysis
  • Palmitic Acid / metabolism
  • Stearic Acids / analysis
  • Stearic Acids / metabolism
  • Suicide / statistics & numerical data


  • Antipsychotic Agents
  • Fatty Acids
  • Fatty Acids, Omega-6
  • Stearic Acids
  • Docosahexaenoic Acids
  • Arachidonic Acid
  • Palmitic Acid
  • stearic acid