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

A.D Thompson,H.J Jones,J Heron,J Hibbeln,S Sullivan,S Zammit

doi:10.1016/j.schres.2020.09.018

Abstract

BackgroundLong 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. MethodsPlasma levels of Ω-3 and Ω-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 Ω-3 and Ω-6 were derived and used in a multivariable Mendelian Randomization analysis. ResultsHigher levels of Ω-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 Ω-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 Ω-6/Ω-3 ratio and psychosis outcomes, nor with genetic instruments of total Ω-3 or Ω-6 levels. ConclusionsThere is no strong evidence that total plasma Ω-3 FA levels or Ω-6/Ω-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 Ω-6 pathway at developmental time points might influence risk22AA, arachidonic acid (20:4n-6); AdA, docosatetraenoic acid (trivial name adrenic acid; 22:4n-6); OA, omega-6 docosapentaenoic acid (trivial name osbond acid; 22:5n-6)..

Highlights

The role of nutritional factors in mental health has recently received greater research focus (Sarris et al, 2015)
The summary statistics for the fatty acid levels at 7 and 16 years are shown in Supplementary Table 3
Whilst higher levels of a number omega-6 PUFAs in childhood appeared to be protective against psychotic experiences, we found in our sensitivity analyses that higher levels of omega-6 PUFAs in adolescence appeared to increase the risk for developing a psychotic disorder

Summary

Introduction

The role of nutritional factors in mental health has recently received greater research focus (Sarris et al, 2015). Low levels of omega-3 (and omega-6) fatty acids have been found in the red cell membranes of patients with schizophrenia (Peet et al, 1995), this is not consistent across all studies (Medema et al, 2016). A causal role of PUFA's in development of schizophrenia is supported by a trial that demonstrated a beneficial effect of relatively high dose omega-3 supplementation (750 mg EPA/DHA) on risk of transition to psychosis in a clinical high risk for psychosis sample(Amminger et al, 2010). Conclusions: There is no strong evidence that total plasma Ω-3 FA levels or Ω-6/Ω-3 ratios in childhood and midadolescence are associated with increased risk for PE's or psychotic disorder, but very marginal evidence that alterations in the Ω-6 pathway at developmental time points might influence risk.

Objectives

Methods

Conclusion