Fatty acids and recurrence of major depressive disorder: combined analysis of two Dutch clinical cohorts

Abstract

Fatty acids and recurrence of major depressive disorder: combined analysis of two Dutch clinical cohorts Thesing CS, Lok A, Milaneschi Y, Assies J, Bockting CLH, Figueroa CA, Giltay EJ, Penninx BWJH, Ruh e HG, Schene AH, Bot M, Mocking RJT. Fatty acids and recurrence of major depressive disorder: combined analysis of two Dutch clinical cohorts.Objective: Omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acid (PUFA) alterations in patients with major depressive disorder (MDD) have been shown to persist after remission. Whether these alterations are risk factors for MDD recurrence remains unknown. Here, we examined whether fatty acids predict time until MDD recurrence in remitted MDD patients. Methods: Data were used from remitted MDD patients of the Netherlands Study of Depression and Anxiety (n = 356) and the Depression Evaluation Longitudinal Therapy Assessment studies (n = 118). Associations of FAs with time until MDD recurrence up to 8-year follow-up were analyzed using Cox regression analyses. Studyspecific estimates were pooled using mega-and meta-analysis techniques. Results: 27.5% (NESDA) and 56.8% (DELTA) participants had an MDD recurrence. Pooled results showed that no FA was significantly associated with time until MDD recurrence (n-3 PUFAs: hazard ratio (HR) = 1.17, 95% confidence interval (CI) = 0.98-1.41, P = 0.082; n-6 PUFAs: HR = 1.08, 95% CI = 0.84-1.38, P = 0.55). Conclusion: In remitted MDD patients, circulating PUFAs were not associated with prospective risk of MDD recurrence. Consequently, circulating PUFAs are unlikely to reflect a vulnerability marker for recurrence, so correcting n-3 PUFA 'deficits' through supplementation does not seem a promising option to prevent MDD recurrence.This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.• Although PUFA alterations in depressed patients have been shown to persist after remission, these were not associated with prospective risk of MDD recurrence.• As circulating PUFAs are unlikely to reflect a vulnerability marker for disease recurrence, correcting n-3 PUFA 'deficits' through supplementation does not seem a promising option to prevent MDD recurrence.• Higher EPA and, although not statistically significant, other PUFAs were associated with a higher risk of recurrence, suggesting that alterations during remission may alternatively reflect an adaptive process. Limitations• Although MDD recurrence was assessed repeatedly during follow-up, recurrences were assessed retrospectively, and may therefore be influenced by memory bias.• Fatty acids in NESDA and DELTA were measured using two different assays in the two different study samples; however, by running meta-analyses with random effects, we acknowledged clustering of measures within cohorts.• EPA levels were missing in the NESDA study, and data on use of n-3 PUFA supplements were missing in the first DELTA cohort study. Fatty acids and depression rec...

Causal effects of fatty acids on depression: Mendelian randomization study

“…Our MR study found no association between total omega-6 PUFA and depression, showing consistent results compared with previous observational studies ( 61 , 62 ). In a previous cross-sectional observational study, no association was found between omega-6 PUFA levels and depression ( 61 ).…”

“…In a previous cross-sectional observational study, no association was found between omega-6 PUFA levels and depression ( 61 ). Meanwhile, observational research revealed that circulating omega-6 PUFA levels were not associated with depression relapse risk ( 62 ). As for the specific type of omega-6 PUFAs, the current investigation revealed that the higher level of adrenic acid was associated with a reduced risk of depression.…”

Metabolic features of recurrent major depressive disorder in remission, and the risk of future recurrence

“…More recently, increasing focus has been on metabolic alterations in MDD 8 . Metabolomic and lipidomic studies showed more widespread alterations in MDD [9][10][11] , that have been hypothesized to constitute a trait associated with recurrence 12 . Recently, a targeted metabolomic study focusing on neurotransmitters and their metabolites in plasma, found a biochemical signature that could diagnose MDD-patients with up to 95% accuracy 13,14 .…”

Effect of High Ratio of n-6/n-3 PUFAs on Depression: A Meta-Analysis of Prospective Studies

“…Publication date varied between 2006 and 2021. Four of the included studies were conducted in Europe ( 18 , 22 – 24 ), four in Asia ( 25 – 28 ), and four in America ( 19 , 20 , 29 , 30 ). Six studies were conducted on women, one study was conducted on men, while five studies included both genders.…”