Low serum omega-3 levels linked to psychiatric disorders in young adults, Study

Polyunsaturated fatty acids (PUFAs) may be pertinent to the development of mental disorders, for example via modulation of inflammation and synaptogenesis. Specifically, n-3 PUFAs have an anti-inflammatory role in body and their deficiency has been linked to mental disorders in early adulthood according to a study by Mongan et al, published in Translational Psychiatry Journal this week.

Omega-3 (n-3) PUFAs, including alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), produce n-3 eicosanoids which are generally anti-inflammatory. Dietary sources of ALA include flaxseed and soybean oils, while EPA and DHA are found in oily fish or supplements.

Observational studies provide evidence of decreased n-3 PUFA levels in patients with schizophrenia, depressive and anxiety disorders relative to controls.

Mongan et al sought to address three main questions regarding temporal associations between plasma PUFA measures and three mental disorders (psychotic disorder, depressive disorder and generalised anxiety disorder) in adolescence and early adulthood:

(1) Are PUFAs associated with these disorders cross-sectionally at age 17 years?

(2) Are PUFAs associated with these disorders cross-sectionally at age 24 years?

(3) Are PUFAs at age 17 years associated with these disorders longitudinally at age 24 years?

Authors aimed to examine the cross-sectional and longitudinal associations between PUFAs and mental disorders in a large cohort of young people. Participants in the Avon Longitudinal Study of Parents and Children were interviewed and provided blood samples at two sampling periods when approximately 17 and 24 years old.

Cross-sectional and longitudinal associations between standardised PUFA measures and three mental disorders (psychotic disorder, moderate/severe depressive disorder and generalised anxiety disorder [GAD]) were measured by logistic regression, adjusting for age, sex, body mass index and cigarette smoking.

1. There was little evidence of cross-sectional associations between PUFA measures and mental disorders at age 17.

2. At age 24, the n-6:n-3 ratio was positively associated with psychotic disorder, depressive disorder and GAD, while DHA was inversely associated with psychotic disorder.

3. In longitudinal analyses, there was evidence of an inverse association between DHA at age 17 and incident psychotic disorder at age 24 with little such evidence for depressive disorder or GAD. There was little evidence for associations between change in PUFA measures from 17 to 24 years and incident mental disorders at 24 years.

These findings provide support for associations between PUFAs and mental disorders in early adulthood, and in particular, for DHA in adolescence in relation to prevention of psychosis.

Total n-6 and total n-3 levels were not associated with mental disorders cross-sectionally or longitudinally. This contrasts with evidence for cross-sectional associations between the ratio of n-6:n-3 fatty acids and mental disorders at age 24. This might suggest that it is the balance of n-6 to n-3 fatty acids that is of greater importance in relation to these disorders in early adulthood rather than their absolute levels.

A higher n-6:n-3 ratio predisposes to increased inflammation. Increasing the proportion of n-3 PUFAs while decreasing n-6 PUFAs could potentially reduce risk of mental illness (at least in part) by reduction of neuroinflammation, for example via increased synthesis of specialised pro-resolving mediators by n-3 fatty acids.

The study observed cross-sectional associations between DHA and psychotic disorder at age 24, but not age 17. These findings could suggest that adult-onset psychotic disorder is more associated with PUFA abnormalities than early-onset psychosis.

Long-term trials specifically in adolescent and clinical high-risk for psychosis samples may further clarify the potential role of PUFAs in prevention of mental disorders.

Source: Translational Psychiatry: Mongan, D., Healy, C., Jones, H.J. et al. Plasma polyunsaturated fatty acids and mental disorders in adolescence and early adulthood: cross-sectional and longitudinal associations in a general population cohort. Transl Psychiatry 11, 321 (2021). https://doi.org/10.1038/s41398-021-01425-4