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Oxidative Damage and Schizophrenia

An Overview of the Evidence and Its Therapeutic Implications

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Abstract

Free radicals are highly reactive chemical species generated during normal metabolic processes, which in excess can lead to membrane damage. Elaborate anti-oxidant defence systems exist to protect against oxidative stress.

There is accumulating evidence of altered antioxidant capacity in schizophrenia. Membrane dysfunction can be secondary to free radical-mediated pathology, and may contribute to specific aspects of schizophrenic symptomatology and complications of its treatment. Specifically, free radical-mediated abnormalities may contribute to the development of a number of clinically significant consequences, including prominent negative symptoms, tardive dyskinesia, neurological ‘soft’ signs and parkinsonian symptoms. Our previous results showing altered membrane dynamics and antioxidant enzyme activities in schizophrenia, and findings from other investigators, are consistent with the notion of free radical-mediated neurotoxicity in schizophrenia. These findings provide a theoretical basis from which the development of novel therapeutic strategies such as fatty acid and antioxidant supplementation can occur in the future.

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Notes

  1. 1In the studies referred to throughout the rest of this article, patients with chronic schizophrenia were being treated with antipsychotics, unless stated otherwise.

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Acknowledgements

This study was supported in part by the Office of Research and Development (Merit Review), Department of Veterans Affairs, the Highland Drive VA Pittsburgh Healthcare System, and research grants from the National Institute of Mental Health (MH43742, MH44841 and MH58141) and National Alliance for Research on Schizophrenia and Depression. The authors are grateful to L. McElhinny and C. Korbanic for their technical assistance. Appreciation is also owed to the patients and nursing staff of the Schizophrenia Research Unit for their participation and collaboration.

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Authors and Affiliations

  1. VA Pittsburgh Healthcare System, Neurochemistry and Psychopharmacology Laboratory (Building 13), 7180 Highland Drive, Pittsburgh, Pennsylvania, 15206-1297, USA

    Jeffrey K. Yao

  2. Department of Psychiatry, Western Psychiatric Institute & Clinic, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA

    Jeffrey K. Yao & Ravinder D. Reddy

  3. The Robert Wood Johnson Pharmaceutical Research Institute, Raritan, New Jersey, USA

    Daniel P. van Kammen

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Correspondence to Jeffrey K. Yao.

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Yao, J.K., Reddy, R.D. & van Kammen, D.P. Oxidative Damage and Schizophrenia. Mol Diag Ther 15, 287–310 (2001). https://doi.org/10.2165/00023210-200115040-00004

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