Free radicals, antioxidant defense systems, and schizophrenia

Prog Neuropsychopharmacol Biol Psychiatry. 2013 Oct 1;46:200-6. doi: 10.1016/j.pnpbp.2013.02.015. Epub 2013 Mar 5.


The etiopathogenic mechanisms of schizophrenia are to date unknown, although several hypotheses have been suggested. Accumulating evidence suggests that excessive free radical production or oxidative stress may be involved in the pathophysiology of schizophrenia as evidenced by increased production of reactive oxygen or decreased antioxidant protection in schizophrenic patients. This review aims to summarize the basic molecular mechanisms of free radical metabolism, the impaired antioxidant defense system and membrane pathology in schizophrenia, their interrelationships with the characteristic clinical symptoms and the implications for antipsychotic treatments. In schizophrenia, there is accumulating evidence of altered antioxidant enzyme activities and increased levels of lipid peroxidation, as well as altered levels of plasma antioxidants. Moreover, free radical-mediated abnormalities may contribute to specific aspects of schizophrenic symptomatology and complications of its treatment with antipsychotic drugs, as well as the development of tardive dyskinesia (TD). Finally, the potential therapeutic strategies implicated by the accumulating data on oxidative stress mechanisms for the treatment of schizophrenia are discussed.

Keywords: 4-hydroxynonenal; 8-isoPGF2 alpha; Antioxidant defense systems; CAT; CT; EGb; Free radicals; GR; GSH; GSH-Px; GSSG; Ginkgo biloba extract; H(2)O(2); HNE; MDA; NADPH; NO; NOS; Neuroleptics; O(2)(−); OH; Oxidative stress; PUFA; ROS; SNP; SOD; Schizophrenia; TAS; TBARS; TD; TRX; TXB2; Tardive dyskinesia; alpha-tocopherol; catalase; computed tomography; glutathione peroxidase; glutathione reductase; hydrogen peroxide; hydroxyl radical; isoprostane--8-epi-prostaglandin F2 alpha; malonyldialdehyde; nicotinamide adenine dinucleotide-phosphate; nitric oxide; oxidized form glutathione disulfide; polyunsaturated fatty acids; reactive nitrogen species; reactive oxygen species; redox; reduced glutathione; reduction–oxidation; single nucleotide polymorphism; superoxidase dismutases; superoxide radical; tardive dyskinesia; thiobarbituric acid reactive substances; thioredoxin; thromboxane B2; total antioxidant status; vitamin E.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use*
  • Antipsychotic Agents / pharmacology
  • Antipsychotic Agents / therapeutic use*
  • Free Radicals / antagonists & inhibitors
  • Free Radicals / metabolism*
  • Humans
  • Lipid Peroxidation / drug effects
  • Lipid Peroxidation / physiology
  • Oxidative Stress / drug effects
  • Oxidative Stress / physiology*
  • Schizophrenia / drug therapy*
  • Schizophrenia / metabolism*


  • Antioxidants
  • Antipsychotic Agents
  • Free Radicals