Brain Responses to Emotional Stimuli after Eicosapentaenoic Acid and Docosahexaenoic Acid Treatments in Major Depressive Disorder: Toward Personalized Medicine with Anti-Inflammatory Nutraceuticals

Abstract

N-3 polyunsaturated fatty acid supplements improve the symptoms of major depressive disorder (MDD) in randomized-controlled trials and meta-analyses, with the higher efficacy from anti-inflammatory eicosapentaenoic acid (EPA) than brain-dominant docosahexaenoic acid (DHA). To investigate the specific brain mechanisms of the anti-inflammatory anti-depressant nutraceutical compounds, we recruited 24 MDD subjects in this double-blind, head-to-head study with a 12-week EPA or DHA treatment (clinical trial registration number: NCT03871088). The depression severity was assessed by Hamilton depression rating scale (HAM-D). Brain responses to emotional stimuli were measured by a 3-Tesla MRI. The correlation between HAM-D scores and brain responses also were tested. Compared to 18 healthy controls, the brain responses of untreated 24 MDD patients mainly revealed hypoactivity in the regions associated with emotion perception and emotion control when processing positive emotion. After treatment, more remitted MDD patients have been observed in the EPA as compared to the DHA groups. In addition, the EPA, but not DHA, treatment revealed increased activity in the regions associated with emotion perception and cognitive control when processing positive emotion. The correlation analysis further revealed negative correlation between HAM-D scores and brain responses in cognitive control regions. The results of this study may imply the compensatory brain responses of cognitive and emotion controls by EPA but not DHA and underpin personalized medicine with anti-inflammatory nutraceuticals toward depression treatments.

Keywords: docosahexaenoic acid (DHA); eicosapentaenoic acid (EPA); functional magnetic resonance imaging (fMRI); major depressive disorder (MDD); omega-3 polyunsaturated fatty acids (n-3 PUFAs).

Figure 1

The changes in brain emotional processing in MDD patients. Compared to healthy controls, the untreated MDD patients revealed significant decreased brain responses when processing positive emotion (A) and negative emotion (B). After treatment, increased brain responses when processing positive emotion has been revealed in EPA group (C), while decreased brain responses when processing positive emotion has been revealed in DHA group (D). The changes in brain responses were correlated with the changes of HAM-D scores in the EPA (E) and DHA (F) group. The warm/cold color denotes increased/decreased activity (A–D) and positive/negative correlation (E,F), respectively. Abbreviation: dmPFC, dorsomedial prefrontal cortex; dlPFC, dorsolateral prefrontal cortex; vlPFC, ventrolateral prefrontal cortex.