To evaluate the effects of fish oil (FO), a source of the omega-3 polyunsaturated fatty acids (n-3 PUFA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), on emotion-generated corticolimbic functional connectivity in depressed youth at high risk for developing bipolar I disorder.
Thirty-nine antidepressant-free youth with a current depressive disorder diagnosis and a biological parent with bipolar I disorder were randomized to 12-week double-blind treatment with FO or placebo. At baseline and endpoint, fMRI (4 Tesla) scans were obtained while performing a continuous performance task with emotional and neutral distractors (CPT-END). Seed-to-voxel functional connectivity analyses were performed using bilateral orbitofrontal cortex (OFC) and amygdala (AMY) seeds. Measures of depression, mania, global symptom severity, and erythrocyte fatty acids were obtained.
Erythrocyte EPA+DHA composition increased significantly in the FO group (+47%, p≤0.0001) but not in the placebo group (-10%, p=0.11). Significant group by time interactions were found for functional connectivity between the left OFC and the left superior temporal gyrus (STG), and between the right AMY and right inferior temporal gyrus (ITG). OFC-STG connectivity increased in the FO group (p=0.0001) and decreased in the placebo group (p=0.0019), and AMY-ITG connectivity decreased in the FO group (p=0.0014) and increased in the placebo group (p<0.0001). In the FO group, but not placebo group, the decrease in AMY-ITG functional connectivity correlated with decreases in Childhood Depression Rating Scale-Revised and Clinical Global Impression-Severity Scale scores.
In depressed high-risk youth FO supplementation alters emotion-generated corticolimbic functional connectivity which correlates with changes in symptom severity ratings.

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