Selective deficits in erythrocyte docosahexaenoic acid composition in adult patients with bipolar disorder and major depressive disorder

Abstract

Background: Epidemiological and controlled intervention trials suggest that omega-3 (n-3) fatty acid deficiency represents a reversible risk factor for recurrent affective disorders. However, there is limited comparative information available regarding the n-3 fatty acid status and associated mood symptoms in medication-free patients with major depressive disorder (MDD) and bipolar disorder (BD).

Methods: The fatty acid composition of erythrocyte membranes from adult male and female healthy controls (n=20) and medication-free patients with MDD (n=20) and BD (n=20) was determined by gas chromatography. Associations with depression and mania symptom severity scores were investigated.

Results: After correction for multiple comparisons, both MDD (-20%) and BD (-32%) patients exhibited significantly lower erythrocyte docosahexaenoic acid (DHA, 22:6n-3) composition relative to healthy controls, and there was a trend for lower DHA in BD patients relative to MDD patients (-15%, p=0.09). There were no gender differences for DHA in any group. Other n-3 fatty acids, including eicosapentaenoic acid (EPA, 20:5n-3) and docosapentanoic acid (22:5n-3), and n-6 fatty acids, including arachidonic acid (AA, 20:4n-6), were not different. Erythrocyte DHA composition was inversely correlated with indices of delta-9 desaturase activity (18:1/18:0), and associated elevations in oleic acid (18:1n-9) composition, and delta-6 desaturase activity (20:3/18:2). DHA composition was not significantly correlated with depression or mania symptom severity scores.

Limitations: Data regarding diet and life style factors (cigarette smoking) were not available to evaluate their contribution to the present findings.

Conclusions: Male and female patients with MDD and BD exhibit selective erythrocyte DHA deficits relative to healthy controls, and this deficit was numerically greater in BD patients. Selective DHA deficits are consistent with impaired peroxisome function, which has implications for n-3 fatty acid interventions aimed at preventing or reversing this deficit.

Conflict of interest statement

Conflict of interest: No conflict declared.

Conflict of Interest Statement. None of the authors have any actual or potential conflict of interest, including any financial, personal or other relationships with other people or organizations within three (3) years of beginning the work submitted that could inappropriately influence, or be perceived to influence, their work.

Copyright 2010 Elsevier B.V. All rights reserved.

Figures

Figure 1

Comparison of the 20:3/18:2 ratio (A), an index of delta-6 desaturase activity, and the 20:4/20:3 ratio (B), an index of delta-5 desaturase activity, and the 18:1/18:0 ratio, an index of delta-9 desaturase activity (C), in healthy controls (HC) and patients with MDD or BD. Correlations between erythrocyte DHA composition and the 20:3/18:2 ratio (D), the 20:4/20:3 ratio (E), and the 18:1/18:0 ratio (F) among all subjects (n=55). Percent difference from controls and associated p-values (two-tailed) are presented in A-C, and Pearson correlation coefficients and p-values (two-tailed) are presented in D-F. Values are group mean ± S.E.M.

Figure 2

(A) Comparison of erythrocyte DHA (22:6n-3) composition in male and female healthy controls (HC) and patients with MDD or BD. Note that there are no gender differences in erythrocyte DHA composition in any group. (B) Comparison of the 20:3/18:2 ratio in male and female healthy controls (HC) and patients with MDD or BD. Note that unlike female patients with BD, female patients with MDD do not exhibit a greater 20:3/18:2 ratio relative to female controls. Percent difference from controls and associated p-values (two-tailed) are presented. Values are group mean ± S.E.M.

Figure 3

Diagram illustrating the biosynthetic pathways of omega-6 and omega-3 PUFAs from dietary precursors linolenic acid (LA, 18:2n-6) and alpha-linolenic acid (ALA, 18:3n-3), respectively. The biosynthesis of long-chain fatty acid products of LA and ALA requires a series of common microsomal elongation and delta (Δ) 5- and 6-desaturase-mediated reactions, and the final synthesis of DHA and DPA (22:5n-6) requires additional enzymatic modifications within peroxisomes. It is proposed that a defect in peroxisomal function could account for the selective DHA deficits, normal levels of n-3 fatty acid precursors of DHA including EPA (20:5n-3) and DPA (22:5n-3), and lack of reciprocal elevations in 22:5n-6 in patients with MDD and BD.