Oxidative stress in schizophrenia: an integrated approach

Neurosci Biobehav Rev. 2011 Jan;35(3):878-93. doi: 10.1016/j.neubiorev.2010.10.008. Epub 2010 Oct 23.


Oxidative stress has been suggested to contribute to the pathophysiology of schizophrenia. In particular, oxidative damage to lipids, proteins, and DNA as observed in schizophrenia is known to impair cell viability and function, which may subsequently account for the deteriorating course of the illness. Currently available evidence points towards an alteration in the activities of enzymatic and nonenzymatic antioxidant systems in schizophrenia. In fact, experimental models have demonstrated that oxidative stress induces behavioral and molecular anomalies strikingly similar to those observed in schizophrenia. These findings suggest that oxidative stress is intimately linked to a variety of pathophysiological processes, such as inflammation, oligodendrocyte abnormalities, mitochondrial dysfunction, hypoactive N-methyl-d-aspartate receptors and the impairment of fast-spiking gamma-aminobutyric acid interneurons. Such self-sustaining mechanisms may progressively worsen producing the functional and structural consequences associated with schizophrenia. Recent clinical studies have shown antioxidant treatment to be effective in ameliorating schizophrenic symptoms. Hence, identifying viable therapeutic strategies to tackle oxidative stress and the resulting physiological disturbances provide an exciting opportunity for the treatment and ultimately prevention of schizophrenia.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use
  • Genetic Predisposition to Disease
  • Homocystine / metabolism
  • Humans
  • Neurotransmitter Agents / metabolism
  • Nitric Oxide / metabolism
  • Oxidative Stress / drug effects
  • Oxidative Stress / physiology*
  • Schizophrenia / drug therapy
  • Schizophrenia / genetics
  • Schizophrenia / physiopathology*


  • Antioxidants
  • Neurotransmitter Agents
  • Nitric Oxide
  • Homocystine