Circulating Polyunsaturated Fatty Acids Not Associated With MDD Recurrence

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Investigators found data that show fatty acid markers during remission of major depressive disorder remission are not a marker for vulnerability.

Circulating polyunsaturated fatty acids (PUFAs) have shown no association with the risk for recurrence of major depressive disorder (MDD) among those in remission, thereby undermining the practice of correcting n-3 PUFA deficits with supplementation as a means of preventing relapse of MDD, according to a study recently published in Acta Psychiatrica Scandinavica.

This study included 356 participants from the Netherlands Study of Depression and Anxiety (NESDA) and 118 participants from the Depression Evaluation Longitudinal Therapy Assessment (DELTA) study, all of whom had remitted MDD at baseline. The study researchers measured baseline n-3 PUFA, n-6 PUFA, docosahexaenoic acid, the ratio of n-3:n-6 PUFA, degree of unsaturation index, and fatty acid carbon chain length index. Time to MDD recurrence was measured during follow-up periods of 6 and 8 years (NESDA and DELTA, respectively). Cox regression analyses were used to analyze associations between fatty acids with time to MDD relapse, while random-effects meta-analysis was used to check consistency among the pooled results.

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MDD recurrence was observed in 27.5% (n=98) of NESDA participants and 56.8% (n=67) of DELTA participants. No fatty acid was found to be significantly associated with time to MDD recurrence in the pooled results, and adjustments for baseline depression and use n-3 PUFA supplements, statin, or antidepressants did not alter results. In secondary analysis of results from the merged DELTA study, a significant association was identified between high eicosapentaenoic acid levels and a greater risk for MDD recurrence (fully adjusted hazard ratio 1.37; 95% CI, 1.04-1.78; P =.023), though pooled results showed no significant associations.  

Limitations to this study include potential memory bias due to the retrospective assessment of MDD recurrences, the use of 2 different assays to measure fatty acids, and missing data on EPA levels (NESDA study) and use of n-3 PUFA supplements (DELTA study). 

The study researchers “[refute] the idea that FA alterations during remission of MDD pose a vulnerability marker for recurrence.” They observed “no protective/preventive effect of high n-3 PUFA levels, high EPA levels, high DHA levels, low n-6 PUFA levels, high n-3:n-6 PUFA ratios, long FA carbon chain length, and a high degree of unsaturation for MDD recurrence in remitted MDD patients.”


Thesing CS, Lok A, Milaneschi Y, et al. Fatty acids and recurrence of major depressive disorder: combined analysis of two Dutch clinical cohorts [published online November 30, 2019]. Acta Psychiatr Scand. doi: 10.1111/acps.13136