Effects of fish oil supplementation on prefrontal metabolite concentrations in adolescents with major depressive disorder: a preliminary 1H MRS study

Abstract

Objective: To use proton magnetic resonance spectroscopy ((1)H MRS) to investigate the effects of fish oil (FO) supplementation on cortical metabolite concentrations in adolescents with major depressive disorder (MDD).

Methods: Metabolite concentrations were determined by (1)H MRS in the anterior cingulate cortex and bilateral dorsolateral prefrontal cortex (DLPFC) of adolescents with MDD before and following 10-week open-label supplementation with low (2.4 g/day, n = 7) or high (16.2 g/day, n = 7) dose FO. Depressive symptom severity scores and erythrocyte fatty acid levels were also determined.

Results: Baseline erythrocyte eicosapentaenoic acid (EPA) composition was positively correlated, and arachidonic acid (AA) and the AA/EPA ratio were inversely correlated, with choline (Cho) concentrations in the right DLPFC. Docosahexaenoic acid (DHA) composition was inversely correlated with myo-inositol (mI) concentrations in the left DLPFC. Erythrocyte EPA and DHA composition increased, and AA decreased, significantly following low-dose and high-dose FO supplementation. In the intent-to-treat sample, depressive symptom severity scores decreased significantly in the high-dose group (-40%, P < 0.0001) and there was a trend in the low-dose group (-20%, P = 0.06). There were no significant baseline-endpoint changes in metabolite levels in each voxel. In the low-dose group there were changes with large effect sizes, including a decrease in mI in the left DLPFC (-12%, P = 0.18, d = 0.8) and increases in glutamate + glutamine (Glx) (+12%, P = 0.19, d = 0.8) and Cho (+15%, P = 0.08, d = 1.2) in the right DLPFC. In the high-dose group, there was a trend for increases in Cho in the right DLPFC (+10%, P = 0.09, d = 1.2).

Discussion: These preliminary data suggest that increasing the LCn-3 fatty acid status of adolescent MDD patients is associated with subtle changes in Glx, mI, and Cho concentrations in the DLPFC that warrant further evaluation in a larger controlled trial.

Keywords: Adolescent; Anterior cingulated cortex; Docosahexaenoic acid; Dorsolateral prefrontal cortex; Major depressive disorder; Proton magnetic resonance spectroscopy.

Figure 1

Spectroscopic voxel placement in the left (A) and right (B) DLPFC (BA9), and ACC (BA32/33) (C).

Figure 2

CDRS-R total scores (A), erythrocyte EPA+DHA composition (weight percent total fatty acid composition, wt% TTL) (B), erythrocyte AA composition (C), and the AA/EPA+DHA ratio in MDD patients treated with low-dose or high-dose FO and had baseline (Base) and endpoint (End, week 10) ¹H MRS values (n = 7/dose group). Values are group means±SD. *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.0001 vs. baseline.