Graham Mazereeuw1, Nathan Herrmann2, Ana C Andreazza3, Gustavo Scola4, David W L Ma5, Paul I Oh6, Krista L Lanctôt7. 1. Department of Medicine, University of Toronto, Toronto, Ontario, Canada. 2. Hurvitz Brain Sciences Program, Sunnybrook Research Institute and Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada. 3. Centre for Addiction and Mental Health, and Departments of Pharmacology/Toxicology and Psychiatry, University of Toronto, Toronto, Ontario, Canada. 4. Centre for Addiction and Mental Health, Toronto, Ontario, Canada. 5. Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada. 6. University Health Network at Toronto Rehabilitation Institute, Toronto, Ontario, Canada. 7. Hurvitz Brain Sciences Program, Sunnybrook Research Institute and Departments of Psychiatry and Pharmacology/Toxicology, University of Toronto, Toronto, Ontario, Canada. Electronic address: Krista.Lanctot@sunnybrook.ca.
Abstract
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 1.9g/day n-3 PUFA or placebo for 12weeks, after which HAM-D scores were reassessed. Baseline LPH, 4-HNE, 8-ISO, MDA and n-3 PUFA 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: F1,33=6.20, beta=-0.35, p=0.018), 4-HNE/LPH (exploratory analysis: F1,33=5.35, beta=-0.32, p=0.027), and 8-ISO/LPH (exploratory analysis: F1,33=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: F1,33=11.05, p=0.002; 4-HNE/LPH: F1,33=11.36, p=0.002; 8-ISO/LPH: F1,33=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.
RCT Entities:
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 1.9g/day n-3 PUFA or placebo for 12weeks, after which HAM-D scores were reassessed. Baseline LPH, 4-HNE, 8-ISO, MDA and n-3 PUFA 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: F1,33=6.20, beta=-0.35, p=0.018), 4-HNE/LPH (exploratory analysis: F1,33=5.35, beta=-0.32, p=0.027), and 8-ISO/LPH (exploratory analysis: F1,33=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: F1,33=11.05, p=0.002; 4-HNE/LPH: F1,33=11.36, p=0.002; 8-ISO/LPH: F1,33=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.
Authors: Kiki P van der Burg; Lachlan Cribb; Chee H Ng; Joseph Firth; Diana Karmacoska; David Mischoulon; Gerard J Byrne; Chad Bousman; Con Stough; Jenifer Murphy; Georgina Oliver; Michael Berk; Jerome Sarris Journal: Eur J Nutr Date: 2019-09-25 Impact factor: 5.614
Authors: W Swardfager; M Hennebelle; D Yu; B D Hammock; A J Levitt; K Hashimoto; A Y Taha Journal: Neurosci Biobehav Rev Date: 2018-02-02 Impact factor: 8.989
Authors: Robert M Carney; Kenneth E Freedland; Eugene H Rubin; Michael W Rich; Brian C Steinmeyer; William S Harris Journal: J Clin Psychiatry Date: 2019-06-04 Impact factor: 4.384
Authors: Katherine M Appleton; Philip D Voyias; Hannah M Sallis; Sarah Dawson; Andrew R Ness; Rachel Churchill; Rachel Perry Journal: Cochrane Database Syst Rev Date: 2021-11-24
Authors: Jay P McLaughlin; Jason J Paris; Dionyssios Mintzopoulos; Kristen A Hymel; Jae K Kim; Thomas J Cirino; Timothy E Gillis; Shainnel O Eans; Gordana D Vitaliano; Jessica M Medina; Richard C Krapf; Heather M Stacy; Marc J Kaufman Journal: Biol Psychiatry Cogn Neurosci Neuroimaging Date: 2017-04-20
Authors: Kuldeep Dhama; Shyma K Latheef; Maryam Dadar; Hari Abdul Samad; Ashok Munjal; Rekha Khandia; Kumaragurubaran Karthik; Ruchi Tiwari; Mohd Iqbal Yatoo; Prakash Bhatt; Sandip Chakraborty; Karam Pal Singh; Hafiz M N Iqbal; Wanpen Chaicumpa; Sunil Kumar Joshi Journal: Front Mol Biosci Date: 2019-10-18
Authors: Graham Mazereeuw; Nathan Herrmann; Ana C Andreazza; Gustavo Scola; David W L Ma; Paul I Oh; Krista L Lanctôt Journal: Cardiovasc Psychiatry Neurol Date: 2017-11-02