Association of plasma ω-3 and ω-6 lipids with burden of disease measures in bipolar subjects

Abstract

Omega-3 (n-3) fatty acids have been implicated in mood disorders, yet clinical trials supplementing n-3 fats have shown mixed results. However, the predominant focus of this research has been on the n-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). We used an unbiased approach to assay plasma n-3 and omega-6 (n-6) species that interact at the level of biosynthesis and down-stream processing, to affect brain function and, potentially, mood. We used lipomic technology to assay plasma levels of n-3 and n-6 fatty acids from 40 bipolar and 18 control subjects to investigate differences in plasma levels and associations with the burden of disease markers, neuroticism and global assessment of function (GAF) and mood state (Hamilton Depression Scale (HAM-D)). Most significantly, we found the levels of dihomo-gamma-linolenic acid (DGLA) to positively correlate with neuroticism and HAM-D scores and negatively correlate with GAF scores; and HAM-D to negatively correlate with linoleic acid (LA) and positively correlate with fatty acid desaturase 2 (FADS2) activity, an enzyme responsible for converting LA to gamma-linolenic acid (GLA). These associations remained significant following Bonferroni multiple testing correction. These data suggest that specific n-6 fatty acids and the enzymes that control their biosynthesis may be useful biomarkers in measurements of depressive disorders and burden of disease, and that they should be considered when investigating the roles of n-3s.

Conflict of interest statement

DISCLOSURES

All authors report no financial conflicts of interest or potential conflicts of interest.

Copyright © 2012 Elsevier Ltd. All rights reserved.

Figures

Figure 1

Schematic of the desaturation and elongation biosynthetic pathway of essential dietary fatty acids to longer chain fats. Precursors of the eicosanoid class of signaling molecules are also highlighted. n-6 acronyms: LA, linoleic acid; GLA, gamma-linolenic acid; DGLA, dihomo-gamma-linolenic acid; AA, arachidonic acid. n-3 acronyms: ALA, alpha-linolenic acid, EPA, eicosapentaenoic acid; DHA, docosahexaenoic acid. Enzyme acronyms: FADS1, fatty acid desaturase 1; FADS2 fatty acid desaturase 2.

Figure 2

Regression scatter plots of significant associations from the all subject analyses. Data from bipolar subjects are given as an open circle and data from control subjects are given as a filled circle, each with a solid regression line shown. The dotted regression line represents a fit line through all subjects. P-values and correlation coefficients are given in Table 2.