Oxidative stress predicts depressive symptom changes with omega-3 fatty acid treatment in coronary artery disease patients

Background: Antidepressant efficacy of omega-3 polyunsaturated fatty acid (n-3 PUFA) treatment in coronary artery disease (CAD) patients remains unpredictable. N-3 PUFA can mitigate oxidative stress, which is common in CAD and may contribute to depressive symptoms. This study investigated whether greater pre-treatment oxidative stress, measured by the ratios of late-stage lipid peroxidation markers (malondialdehyde [MDA], 4-hydroxy-2-nonenal [4-HNE], and 8-isoprostane [8-ISO]) to an early-stage marker (lipid hydroperoxides [LPH]), predicted n-3 PUFA antidepressant benefits in CAD. Methods: This was a secondary analysis of CAROTID (CAD Randomized Omega-3 Trial in Depression, NCT00981383). Patient demographics and medical characteristics were collected. Depressive symptoms were measured using the 17-item Hamilton Depression Rating Scale (HAM-D). Patients were then randomized to receive either 1.9 g/day n-3 PUFA or placebo for 12 weeks, after which HAM-D scores were reassessed. Baseline LPH, 4-HNE, 8-ISO, MDA and n-3 PUPA concentrations were analysed from fasting blood. Results: Seventy-nine patients (age = 61.1 +/- 8.5, 76% male, HAM-D = 7.5 +/- 6.1) were included (n = 45 placebo, n = 34 n-3 PUFA). In the n-3 PUFA group, higher baseline ratios of MDA/LPH (primary analysis: F-1,F-33 = 6.20, beta = 0.35, p = 0.018), 4-HNE/LPH (exploratory analysis: F-1,F-33 = 5.35, beta = -0.32, p = 0.027), and 8-ISO/LPH (exploratory analysis: F-1,F-33 = 6.10, beta = -0.33, p = 0.019), indicating higher oxidative stress, were associated with greater depressive symptom improvement. In each model, higher baseline EPA + DHA concentrations independently predicted depressive symptom improvement with n-3 PUFA (MDA/LPH: F-1,F-33 = 11.05, p = 0.002; 4-HNE/LPH: F-1,F-33 = 11.36, p = 0.002; 8-ISO/LPH: F-1,F-33 = 13.15, p = 0.001). No associations were observed in the placebo group. Conclusions: n-3 PUFA may be more likely to improve depressive symptoms in CAD patients with pre-treatment evidence of oxidative stress. (C) 2016 The Authors. Published by Elsevier Inc.