UC San Diego

Abstract Background: Omega-3 Fatty Acids (FAs), EPA (eicosapentaenoic acid) and DHA (Docosahexaenoic acid), are essential for normal brain development and may also have neuroprotective properties. Dietary supplementation of EPA and DHA has beneficial effects in medical illnesses as well as depression, bipolar disorder, and dementia. Abnormal FA metabolism may play a role in the etiology of psychiatric illness. Studies of erythrocytes and skin fibroblasts have shown reduced levels of FAs and phospholipids in schizophrenia. Studies of Omega-3FA supplementation in schizophrenia have been mixed. Amminger et al performed a randomized, double-blind, placebo-controlled trial in 81 subjects with prodromal symptoms of psychosis. The treatment consisted of 1.2g/day of Omega-3FAs (700 mg EPA, 480 mg DHA). After 12 weeks, 2 (4.9%) of 41 individuals in the Omega-3FA group and 11 of 40 (27.5%) in the placebo group converted to a psychotic disorder. Omega-3FAs also significantly reduced symptoms and improved functioning. The Aims of the current study were to replicate the Amminger study in Clinical High Risk (CHR) subjects from the NAPLS consortium. Methods: This was a 24-week, randomized, double-blind, placebo, fixed dose-controlled study of Omega-3FA versus placebo in 127 CHR subjects. The Omega-3FA compound contained a 2:1 proportion of EPA to DHA. The total dose was 740 mg of EPA and 400 mg of DHA. Baseline diet characterization was assessed using a systematic checklist that includes Omega-3FA foods. In addition, fasting erythrocyte FA composition was assessed. Results: Of the 127 CHR subjects recruited into the trial, 118 completed baseline assessment, and 70 (59%) completed the 6-month trial. Seven (10% Kaplan-Meier) subjects converted to psychosis during the 24 months. The rate of psychotic conversion did not differ in the Omega-3FA (13%) versus Placebo (8%) samples. Conversion to psychosis was predicted by low Omega-3FA rich foods in the diet (Wald Statistic = 4.96, P < .05). Although there were significant improvements in symptom and functioning over time in Mixed Model analyses, there were no significant group or Group × Time interaction effects. Conclusion: The rate of conversion to psychosis in the present sample was lower than is typically observed in an at-risk population. Given the study attrition and low rate of conversion to psychosis, the trial was underpowered to replicate the conversion effect in the Amminger et al.’s study. Despite the overall improvement in symptoms and functioning over time in all subjects, there was no clear evidence of a differential effect in the sample on Omega-3FA vs Placebo. Further work is needed to better tease out the role of diet and Omega-3FA in mental illness. The finding of a significant association between baseline diet low in Omega-3FA rich foods and later conversion to psychosis raises the question of whether it is possible to influence both physical and mental health with lifestyle choices including diet.