title: Oxidative stress in major depressive and anxiety disorders, and the association with antidepressant use; results from a large adult cohort.
abstract: BACKGROUND
  Oxidative stress has been implicated in the pathophysiology of major depressive disorder (MDD) and anxiety disorders and may be influenced by antidepressant use. This study investigated the association of oxidative stress, measured by plasma levels of F2-isoprostanes and 8-hydroxy-2'-deoxyguanosine (8-OHdG) reflecting oxidative lipid and DNA damage respectively, with MDD, anxiety disorders and antidepressant use in a large cohort.
  
  
  METHODS
  Data was derived from the Netherlands Study of Depression and Anxiety including patients with current (N = 1619) or remitted (N = 610) MDD and/or anxiety disorder(s) (of which N = 704 antidepressant users) and 612 controls. Diagnoses were established with the Composite International Diagnostic Interview. Plasma 8-OHdG and F2-isoprostanes were measured using LC-MS/MS. ANCOVA was performed adjusted for sampling, sociodemographic, health and lifestyle variables.
  
  
  RESULTS
  F2-isoprostanes did not differ between controls and patients, or by antidepressant use. Patients with current disorders had lower 8-OHdG (mean 42.1 pmol/l, 95% CI 40.4-43.8) compared to controls (45.0 pmol/l, 95% CI 42.9-47.2; p < 0.001) after adjustment for sampling, sociodemographics and lifestyle, but these differences disappeared after further adjustment for antidepressant use (p = 0.562). Antidepressant users had lower 8-OHdG levels (38.2 pmol/l, 95% CI 36.5-39.9) compared to controls (44.9 pmol/l, 95% CI 43.2-46.6; Cohen's d = 0.21, p < 0.001). Results for 8-OHdG were comparable across disorders (MDD and/or anxiety disorders), and all antidepressant types (SSRIs, TCAs, other antidepressants).
  
  
  CONCLUSIONS
  Contrary to previous findings this large-scale study found no increased oxidative stress in MDD and anxiety disorders. Antidepressant use was associated with lower oxidative DNA damage, suggesting antidepressants may have antioxidant effects.
authors.affiliation: Department of Psychiatry and EMGO+ Institute for Health and Care Research,VU University Medical Center, and GGZ inGeest,Amsterdam,The Netherlands.
authors.forename: C N
authors.initials: CN
authors.lastname: Black
authors.affiliation: Department of Psychiatry and EMGO+ Institute for Health and Care Research,VU University Medical Center, and GGZ inGeest,Amsterdam,The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Bot
authors.affiliation: Department of Clinical Chemistry,VU University Medical Center,Amsterdam,The Netherlands.
authors.forename: P G
authors.initials: PG
authors.lastname: Scheffer
authors.affiliation: Department of Psychiatry and EMGO+ Institute for Health and Care Research,VU University Medical Center, and GGZ inGeest,Amsterdam,The Netherlands.
authors.forename: B W J H
authors.initials: BW
authors.lastname: Penninx
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000494:pharmacology*; D001008:Anxiety Disorders / Q000188:drug therapy / Q000378:metabolism*; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D055815:Young Adult
chemical_list: D000928:Antidepressive Agents
keywords: Anxiety disorders; major depressive disorder; oxidative DNA damage; oxidative lipid damage; oxidative stress