Omega-3 and Omega-6 fatty acids and risk of psychotic outcomes in the ALSPAC birth cohort

Background: Long chain polyunsaturated fatty acid (PUFA) levels have been implicated in the pathology of psychotic disorders. We investigated the relationship between childhood PUFA levels and later psychotic experiences (PE's) in a large birth cohort. Methods: Plasma levels of Omega-3 and Omega-6 fatty acids (FA's) were assayed at ages 7 and 16 years. PE's were assessed at ages 12 and 18 years using a semi-structured interview. Primary outcome was any PE's at 18 years; sensitivity analyses examined incident PE's between ages 12 and 18 years, persistent PE's (at 12 and 18) and psychotic disorder at 18 years. Genetic instruments for Omega-3 and Omega-6 were derived and used in a multivariable Mendelian Randomization analysis. Results: Higher levels of Omega-6 FA's AA, OA and AdA at age 7 years were weakly associated with a reduced risk for PE's at 18 years, however, effect sizes were small and attenuated after adjusting for confounders (strongest evidence for OA; adjusted OR, 0.842; 95% CI, 0.711, 0.998; p, 0.048). Total Omega-6 levels at age 16 years were associated with an increased odds of psychotic disorder at age 18 years. However, there was no association between Omega-6/Omega-3 ratio and psychosis outcomes, nor with genetic instruments of total Omega-3 or Omega-6 levels. Conclusions: There is no strong evidence that total plasma Omega-3 FA levels or Omega-6/Omega-3 ratios in childhood and mid adolescence are associated with increased risk for PE's or psychotic disorder, but very marginal evidence that alterations in the Omega-6 pathway at developmental time points might influence risk(2). Crown Copyright (C) 2020 Published by Elsevier B.V.