title: Oxidative stress and antioxidant parameters in patients with major depressive disorder compared to healthy controls before and after antidepressant treatment: results from a meta-analysis.
abstract: OBJECTIVE
  To investigate the role of oxidative stress and antioxidants in depression.
  
  
  METHODS
  We searched the literature without language restrictions through MEDLINE/PubMed, Cochrane Library, Fisterra, and Galenicom from database inception until December 31, 2013, supplemented by a hand search of relevant articles. Search terms included (1) oxidative stress, antioxidant*, nitrosative stress, nitrative stress, nitro-oxidative stress, free radical*, and names of individual oxidative stress markers/antioxidants and (2) depression and related disorders and antidepressant.
  
  
  METHODS
  Included were studies in patients with depression comparing antioxidant or oxidative stress markers with those in healthy controls before and after antidepressant treatment.
  
  
  METHODS
  Two authors independently extracted the data for antioxidant or oxidative stress markers. Standardized mean differences (SMDs) ± 95% confidence intervals (CIs) for results from ≥ 3 studies were calculated.
  
  
  RESULTS
  Altogether, 29 studies (N = 3,961; patients with depression = 2,477, healthy controls = 1,484) reported on the oxidative stress marker malondialdehyde (MDA) and total nitrites, the antioxidants uric acid and zinc, or the antioxidant-enhancing enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX). When patients with depression were compared with healthy controls, depression was associated with higher oxidative stress MDA levels (8 studies; n = 916; SMD = 1.34; 95% CI, 0.57 to 2.11; P < .001), lower antioxidant uric acid (4 studies; n = 512; SMD = -0.64; 95% CI, -1.22 to -0.06; P = .030) and zinc levels (13 studies; n = 2,002; SMD = -0.66; 95% CI, -0.98 to -0.34; P < .0001), and higher antioxidant-enhancing enzyme SOD levels (11 studies; n = 902; SMD = 0.62; 95% CI, 0.07 to 1.17; P = .028), while differences in total nitrites and CAT and GPX were nonsignificant. Antidepressant treatment, which significantly reduced Hamilton Depression Rating Scale scores (24.6 ± 0.7 to 16.2 ± 1.6; SMD = 2.65; 95% CI, 1.13 to 4.15; P = .00065), reduced MDA (4 studies; n = 194; SMD = -1.45; 95% CI, -2.43 to -0.47; P = .004) and increased uric acid (3 studies; n = 212; SMD = 0.76; 95% CI, 0.03 to 1.49; P = .040) and zinc levels (3 studies; n = 65; SMD = 1.22; 95% CI, 0.40 to 2.04, P = .004), without differences in MDA (P = .60), uric acid (P = .10), and zinc (P = .163) levels compared to healthy controls.
  
  
  CONCLUSIONS
  Results suggest that oxidative stress plays a role in depression and that antidepressant activity may be mediated via improving oxidative stress/antioxidant function.
authors.affiliation: Department of Psychiatry and CTS-549 Research Group, Institute of Neurosciences, Center for Biomedical Research (CIBM), University of Granada, Granada, Spain.|Child and Adolescent Mental Health Unit, Jaén Medical Center, Jaén, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Jiménez-Fernández
authors.forename: Manuel
authors.initials: M
authors.lastname: Gurpegui
authors.forename: Francisco
authors.initials: F
authors.lastname: Díaz-Atienza
authors.forename: Lucía
authors.initials: L
authors.lastname: Pérez-Costillas
authors.forename: Miriam
authors.initials: M
authors.lastname: Gerstenberg
authors.forename: Christoph U
authors.initials: CU
authors.lastname: Correll
mesh_terms: D000928:Antidepressive Agents / Q000494:pharmacology*; D003865:Major Depressive Disorder / Q000097:blood / Q000188:drug therapy / Q000201:enzymology; D006801:Humans; D009573:Nitrites / Q000097:blood*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D010544:Peroxidases / Q000097:blood*; D013482:Superoxide Dismutase / Q000097:blood*; D014527:Uric Acid / Q000097:blood*; D015032:Zinc / Q000097:blood*
chemical_list: D000928:Antidepressive Agents; D009573:Nitrites; D014527:Uric Acid; D010544:Peroxidases; D013482:Superoxide Dismutase; D015032:Zinc