title: Oxidative stress predicts depressive symptom changes with omega-3 fatty acid treatment in coronary artery disease patients.
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.
authors.affiliation: Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Graham
authors.initials: G
authors.lastname: Mazereeuw
authors.affiliation: Hurvitz Brain Sciences Program, Sunnybrook Research Institute and Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Nathan
authors.initials: N
authors.lastname: Herrmann
authors.affiliation: Centre for Addiction and Mental Health, and Departments of Pharmacology/Toxicology and Psychiatry, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Ana C
authors.initials: AC
authors.lastname: Andreazza
authors.affiliation: Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Scola
authors.affiliation: Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada.
authors.forename: David W L
authors.initials: DWL
authors.lastname: Ma
authors.affiliation: University Health Network at Toronto Rehabilitation Institute, Toronto, Ontario, Canada.
authors.forename: Paul I
authors.initials: PI
authors.lastname: Oh
authors.affiliation: 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.
authors.forename: Krista L
authors.initials: KL
authors.lastname: Lanctôt
mesh_terms: D000928:Antidepressive Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D003324:Coronary Artery Disease / Q000097:blood* / Q000188:drug therapy; D003863:Depression / Q000097:blood*; D015525:Fatty Acids, Omega-3 / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D018384:Oxidative Stress / Q000502:physiology*
chemical_list: D000928:Antidepressive Agents; D015415:Biomarkers; D015525:Fatty Acids, Omega-3
keywords: Cardiovascular; Coronary artery disease; DHA; Depression; Docosahexaenoic acid; EPA; Eicosapentaenoic acid; Fish oil; Heart disease; Hydroperoxide; Hydroxynonenal; Isoprostane; Lipid peroxidation; Malondialdehyde; Mood; Omega-3 fatty acid; Oxidative stress