Emotion-Related Network Reorganization Following Fish Oil Supplementation in Depressed Bipolar Offspring: An fMRI Graph-Based Connectome Analysis

•Mood disorders are associated with structural and functional connectivity abnormalities.•Omega-3 polyunsaturated fatty acids (n-3 PUFA) promote cortical plasticity and connectivity.•A graph-based connectome analysis revealed that emotion-related network organization is altered in depressed bipolar offspring.•Supplementation with n-3 PUFA changes emotion-related network organization and connectivity in depressed bipolar offspring. Mood disorders are associated with fronto-limbic structural and functional abnormalities and deficits in omega-3 polyunsaturated fatty acids including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Emerging evidence also suggests that n-3 PUFA, which are enriched in fish oil, promote cortical plasticity and connectivity. The present study performed a graph-based connectome analysis to investigate the role of n-3 PUFA in emotion-related network organization in medication-free depressed adolescent bipolar offspring. At baseline patients (n = 53) were compared with healthy controls (n = 53), and patients were then randomized to 12-week double-blind treatment with placebo or fish oil. At baseline and endpoint, erythrocyte EPA+DHA levels were measured and fMRI scans (4 Tesla) were obtained while performing a continuous performance task with emotional and neutral distractors (CPT-END). Graph-based analysis was used to characterize topological properties of large-scale brain network organization. Compared with healthy controls, patients exhibited lower erythrocyte EPA+DHA levels (p = 0.0001), lower network clustering coefficients (p = 0.029), global efficiency (p = 0.042), and lower node centrality and connectivity strengths in frontal-limbic regions (p