Longitudinal trajectories of plasma polyunsaturated fatty acids and associations with psychosis-spectrum outcomes in early adulthood

Abstract

Evidence supports associations between polyunsaturated fatty acids such as docosahexaenoic acid (DHA) and psychosis. However, polyunsaturated fatty acid trajectories in the general population have not been characterized, and associations with psychosis spectrum outcomes in early adulthood are unknown. Plasma omega-6 to omega-3 ratio and DHA (expressed as percentage of total fatty acids) were measured by nuclear magnetic spectroscopy at 7, 15, 17, and 24 years of age in participants of ALSPAC (Avon Longitudinal Study of Parents and Children). Curvilinear growth mixture modeling evaluated body mass index-adjusted trajectories of both measures. Outcomes were assessed at 24 years. Psychotic experiences (PEs), at-risk mental state status, psychotic disorder, and number of PEs were assessed using the Psychosis-Like Symptoms interview (n= 3635; 2247 [61.8%] female). Negative symptoms score was measured using the Community Assessment of Psychic Experiences (n= 3484; 2161 [62.0%] female). Associations were adjusted for sex, ethnicity, parental social class, and cumulative smoking and alcohol use. Relative to stable average, the persistently high omega-6 to omega-3 ratio trajectory was associated with increased odds of PEs and psychotic disorder, but attenuated on adjustment for covariates (PEs adjusted odds ratio [aOR]= 1.63, 95% CI= 0.92-2.89; psychotic disorder aOR= 1.69, 95% CI= 0.71-4.07). This was also the case for persistently low DHA (PEs aOR= 1.42, 95% CI= 0.84-2.37; psychotic disorder aOR= 1.14, 95% CI= 0.49-2.67). Following adjustment, persistently high omega-6 to omega-3 ratio was associated with increased number of PEs (β= 0.41, 95% CI= 0.05-0.78) and negative symptoms score (β= 0.43, 95% CI= 0.14-0.72), as was persistently low DHA (number of PEs β= 0.45, 95% CI= 0.14-0.76; negative symptoms β= 0.35, 95% CI= 0.12-0.58). Optimization of polyunsaturated fatty acid status during development warrants further investigation in relation to psychotic symptoms in early adulthood.