Omega-6 to omega-3 polyunsaturated fatty acid ratio and subsequent mood disorders in young people with at-risk mental states: a 7-year longitudinal study

Berger, M.E., Smesny, S., Kim, S-W., Davey, C.G., Rice, S., Sarnyai, Z., Schlöegelhofer, M., Schafer, M.R., Berk, M., McGorry, P.D., and Amminger, G.P. (2017) Omega-6 to omega-3 polyunsaturated fatty acid ratio and subsequent mood disorders in young people with at-risk mental states: a 7-year longitudinal study. Translational Psychiatry, 7.

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While cross-sectional studies suggest that patients with mood disorders have a higher ratio of omega-6 to omega-3 polyunsaturated fatty acids (PUFAs) and lower levels of omega-3 PUFAs, it is unknown if a high n-6/3 ratio indicates vulnerability for depression. We tested this hypothesis in a 7-year follow-up study of young individuals with an ultra-high risk (UHR) phenotype. We conducted a secondary analysis of the Vienna omega-3 study, a longitudinal study of omega-3 PUFAs in individuals at UHR for psychosis (n = 69). Levels of n-6 and n-3 PUFAs were measured in the phosphatidylethanolamine fraction of erythrocyte membranes at intake into the study. Mood disorder diagnosis was ascertained with the Structured Clinical Interview for DSM-IV-TR and confirmed by review of medical records and interviews of caregivers. A higher n-6/3 PUFA ratio at baseline predicted mood disorders in UHR individuals over a 7-year (median) follow-up (odds ratio = 1.89, 95% CI = 1.075-3.338, P = 0.03). This association remained significant after adjustment for age, gender, smoking, severity of depressive symptoms at baseline and n-3 supplementation. Consistent results were obtained for individual PUFAs, including lower levels of eicosapentaenoic acid and docosahexaenoic acid. The predictive capacity of these findings was specific to mood disorders as no associations were found for any other psychiatric disorder. To our knowledge, our data provide the first prospective evidence that the n-6/3 PUFA ratio is associated with an increased risk for mood disorders in young people exhibiting an UHR phenotype. These findings may have important implications for treatment and risk stratification beyond clinical characteristics.

Item ID: 50516
Item Type: Article (Research - C1)
ISSN: 2158-3188
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Copyright Information: This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit
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A version of this publication was included as Chapter 5 of the following PhD thesis: Berger, Maximus (2018) Biological endophenotypes of prodromal psychosis and depression. PhD thesis, James Cook University, which is available Open Access in ResearchOnline@JCU. Please see the Related URLs for access.

Funders: Stanley Medical Research Institute (SMRI), James Cook University (JCU), Ministry of Health and Wellfare (MHW), Korea, National Health and Medical Research Council (NHMRC), Society for Mental Health Research (SMHR)
Projects and Grants: SMRI Grant 03T-315, JCU Postgraduate Research Scholarship, MHW Mental Health Technology R&D Project HM15C114, NHMRC Career Development Fellowship 1061757, NHMRC Senior Research Fellowship 1080963, NHMRC Senior Principal Research Fellowship 1060996, NHMRC Senior Principal Research Fellowship 1059660, SMHR Early Career Fellowship
Date Deposited: 20 Sep 2017 09:48
FoR Codes: 32 BIOMEDICAL AND CLINICAL SCIENCES > 3209 Neurosciences > 320903 Central nervous system @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920111 Nervous System and Disorders @ 100%
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