1. 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.
- Author
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McNamara RK, Jandacek R, Rider T, Tso P, Stanford KE, Hahn CG, and Richtand NM
- Subjects
- Adult, Alcoholism metabolism, Antipsychotic Agents therapeutic use, Autopsy, Bipolar Disorder blood, Bipolar Disorder drug therapy, Cerebral Cortex metabolism, Chromatography, Gas, Control Groups, Docosahexaenoic Acids analysis, Erythrocytes chemistry, Erythrocytes 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, Arachidonic Acid metabolism, Bipolar Disorder metabolism, Cerebral Cortex chemistry, Docosahexaenoic Acids metabolism, Fatty Acids metabolism
- Abstract
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.
- Published
- 2008
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