title: Is depression associated with increased oxidative stress? A systematic review and meta-analysis.
abstract: BACKGROUND
  It has been suggested that depressed persons have increased oxidative stress and decreased anti-oxidant defences. 8-Hydroxy-2'-deoxyguanosine (8-OHdG) and F2-isoprostanes, measures of oxidative DNA and lipid damage respectively, are among the most reliable oxidative stress markers, but studies on their association with depression show conflicting results. This meta-analysis quantifies the association between depression and these markers and explores factors that may explain inconsistencies in the results.
  
  
  METHODS
  A systematic literature search was conducted in PubMed, EMBASE and PsycINFO. Studies assessing the association of 8-OHdG or F2-isoprostanes with elevated depressive symptoms, major depressive disorder (MDD) or bipolar disorder (BD) were pooled in two random-effect models.
  
  
  RESULTS
  The pooled effect size (Hedges' g) for the association of depression with oxidative stress was 0.31 (p=0.01, I(2)=75%) for 8-OHdG (10 studies, 1308 subjects) and 0.48 (p=0.001, I(2)=73%) for F2-isoprostanes (8 studies, 2471 subjects), indicating that both markers are increased in depression. There was no indication of publication bias for either marker. The F2-isoprostane results did not differ by type of depression, biological specimen, laboratory method or quality, however subgroup analyses in the 8-OHdG studies showed significantly stronger associations in plasma/serum vs. urine samples (p<0.01), in measurements performed with immuno-assay vs. chromatography-mass spectrometry (p<0.01) and weaker associations in high quality studies vs. low (p=0.02).
  
  
  CONCLUSIONS
  This meta-analysis finds that oxidative stress, as measured by 8-OHdG and F2-isoprostanes, is increased in depression. Larger-scale studies are needed to extend the evidence on oxidative stress in depression, and examine the potential impact of treatment.
authors.affiliation: Department of Psychiatry, VU University Medical Center, Amsterdam, The Netherlands; EMGO Institute for Health and Care Research, Amsterdam, The Netherlands. Electronic address: c.black@ggzingeest.nl.
authors.forename: Catherine N
authors.initials: CN
authors.lastname: Black
authors.affiliation: Department of Psychiatry, VU University Medical Center, Amsterdam, The Netherlands; EMGO Institute for Health and Care Research, Amsterdam, The Netherlands.
authors.forename: Mariska
authors.initials: M
authors.lastname: Bot
authors.affiliation: Department of Clinical Chemistry, Metabolic Laboratory, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Peter G
authors.initials: PG
authors.lastname: Scheffer
authors.affiliation: Department of Clinical Psychology, VU University Amsterdam, The Netherlands; EMGO Institute for Health and Care Research, Amsterdam, The Netherlands.
authors.forename: Pim
authors.initials: P
authors.lastname: Cuijpers
authors.affiliation: Department of Psychiatry, VU University Medical Center, Amsterdam, The Netherlands; EMGO Institute for Health and Care Research, Amsterdam, The Netherlands.
authors.forename: Brenda W J H
authors.initials: BW
authors.lastname: Penninx
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D015415:Biomarkers / Q000378:metabolism; D001714:Bipolar Disorder / Q000378:metabolism*; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D003863:Depression / Q000378:metabolism*; D003865:Major Depressive Disorder / Q000378:metabolism*; D028441:F2-Isoprostanes / Q000378:metabolism*; D006801:Humans; D018384:Oxidative Stress / Q000502:physiology*
chemical_list: D015415:Biomarkers; D028441:F2-Isoprostanes; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine
keywords: 8-Hydroxy-2′-deoxyguanosine (8-OHdG); Bipolar disorder; Depression; F2-isoprostanes; Major depressive disorder; Oxidative stress