Plasma polyunsaturated fatty acids and mental disorders in adolescence and early adulthood: 2 cross-sectional and longitudinal associations in a general population cohort

Polyunsaturated fatty acids (PUFAs) may be pertinent to the development of mental disorders, for example 28 via modulation of inflammation and synaptogenesis. We wished to examine cross-sectional and longitudinal 29 associations between PUFAs and mental disorders in a large cohort of young people. Participants in the 30 Avon Longitudinal Study of Parents and Children were interviewed and provided blood samples at two 31 sampling periods when approximately 17 and 24 years old. Plasma PUFA measures (total omega-6 [n-6], 32 total omega-3 [n-3], n-6:n-3 ratio and docosahexaenoic acid [DHA] percentage of total fatty acids) were 33 assessed using nuclear magnetic resonance spectroscopy. Cross-sectional and longitudinal associations 34 between standardised PUFA measures and three mental disorders (psychotic disorder, moderate/severe 35 depressive disorder and generalised anxiety disorder [GAD]) were measured by logistic regression, adjusting 36 for age, sex, body mass index and cigarette smoking. There was little evidence of cross-sectional 37 associations between PUFA measures and mental disorders at age 17. At age 24, the n-6:n-3 ratio was 38 positively associated with psychotic disorder, depressive disorder and GAD, while DHA was inversely 39 associated with psychotic disorder. In longitudinal analyses, there was evidence of an inverse association 40 between DHA at age 17 and incident psychotic disorder at age 24 (adjusted odds ratio 0.44, 95% confidence 41 interval 0.22 - 0.87) with little such evidence for depressive disorder or GAD. There was little evidence for 42 associations between change in PUFA measures from 17 to 24 years and incident mental disorders at 24 43 years. These findings provide support for associations between PUFAs and mental disorders in early 44 adulthood, and in particular, for DHA in adolescence in relation to prevention of psychosis.