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

Nutr Neurosci. 2016 May;19(4):145-55. doi: 10.1179/1476830514Y.0000000135. Epub 2016 Mar 2.


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.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adolescent Nutritional Physiological Phenomena*
  • Adult
  • Child
  • Child Nutritional Physiological Phenomena
  • Deficiency Diseases / diet therapy*
  • Deficiency Diseases / metabolism
  • Deficiency Diseases / physiopathology
  • Deficiency Diseases / psychology
  • Depressive Disorder, Major / diagnostic imaging
  • Depressive Disorder, Major / etiology
  • Depressive Disorder, Major / metabolism
  • Depressive Disorder, Major / prevention & control*
  • Diagnostic and Statistical Manual of Mental Disorders
  • Dietary Supplements*
  • Fatty Acids, Essential / deficiency
  • Fatty Acids, Essential / metabolism
  • Fatty Acids, Essential / therapeutic use*
  • Female
  • Fish Oils / administration & dosage
  • Fish Oils / therapeutic use*
  • Gyrus Cinguli / diagnostic imaging
  • Gyrus Cinguli / metabolism
  • Humans
  • Intention to Treat Analysis
  • Lost to Follow-Up
  • Magnetic Resonance Imaging
  • Male
  • Neuroimaging
  • Prefrontal Cortex / diagnostic imaging
  • Prefrontal Cortex / metabolism
  • Psychiatric Status Rating Scales
  • Young Adult


  • Fatty Acids, Essential
  • Fish Oils