title: Polyunsaturated fatty acid associations with dopaminergic indices in major depressive disorder.
abstract: Dopaminergic function is thought to be altered in major depression and, in animal studies, is reduced in omega-3 polyunsaturated fatty acid (PUFA) deficiency states. Therefore we studied PUFAs and resting prolactin, a marker for dopaminergic tone, and cerebrospinal fluid homovanillic acid (HVA), the chief dopamine metabolite. In medication-free adults (n = 23) with DSM-IV major depressive disorder (MDD), we measured plasma phospholipid levels of omega-3 PUFAs docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), the omega-6 PUFA arachidonic acid (AA), and plasma prolactin levels before and after administration of dl-fenfluramine (FEN). In a subset of patients (n = 14), cerebrospinal fluid levels of HVA and the serotonin metabolite, 5-hydroxyindoleacetic acid (5-HIAA), were obtained through lumbar puncture. Baseline prolactin was negatively correlated with omega-3 PUFAs (logDHA, F(1,21) = 20.380, p < 0.001; logEPA, F(1,21) = 10.051, p = 0.005) and positively correlated with logAA:DHA (F(1,21) = 15.263, p = 0.001), a measure of omega-6/omega-3 balance. LogDHA was negatively correlated with CSF HVA (Spearman's ρ = -0.675, p = 0.008) but not 5-HIAA (Spearman's ρ = -0.143, p = 0.626) after controlling for sex and HVA - 5-HIAA correlation. PUFAs did not predict the magnitude of the FEN-stimulated change in prolactin, considered to be a serotonin effect. The robust relationship of omega-3 PUFAs with dopaminergic but not serotonergic indices suggests that omega-6:omega-3 balance may impact depression pathophysiology through effects on the dopaminergic system.
authors.affiliation: Department of Psychiatry, Columbia University, New York, NY, USA.
authors.forename: M Elizabeth
authors.initials: ME
authors.lastname: Sublette
authors.affiliation: Department of Psychiatry, Columbia University, New York, NY, USA.
authors.forename: Hanga C
authors.initials: HC
authors.lastname: Galfalvy
authors.affiliation: National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, MD, USA.
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Hibbeln
authors.affiliation: Department of Psychiatry, Columbia University, New York, NY, USA.
authors.forename: John G
authors.initials: JG
authors.lastname: Keilp
authors.affiliation: School of Medicine & Medical Science, University College Dublin, Ireland.
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Malone
authors.affiliation: Department of Psychiatry, Columbia University, New York, NY, USA.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Oquendo
authors.affiliation: Department of Psychiatry, Columbia University, New York, NY, USA.
authors.forename: J John
authors.initials: JJ
authors.lastname: Mann
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000928:Antidepressive Agents / Q000627:therapeutic use; D003865:Major Depressive Disorder / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000188:drug therapy; D005231:Fatty Acids, Unsaturated / Q000097:blood*; D005260:Female; D005277:Fenfluramine / Q000627:therapeutic use; D006719:Homovanillic Acid / Q000134:cerebrospinal fluid*; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000134:cerebrospinal fluid; D008297:Male; D008875:Middle Aged; D011388:Prolactin / Q000097:blood; D011569:Psychiatric Status Rating Scales; D012044:Regression Analysis; D055815:Young Adult
chemical_list: D000928:Antidepressive Agents; D005231:Fatty Acids, Unsaturated; D005277:Fenfluramine; D006897:Hydroxyindoleacetic Acid; D011388:Prolactin; D006719:Homovanillic Acid