Reduced plasma antioxidants in first-episode patients with schizophrenia

Recent findings suggest that free radical-mediated pathological processes may underlie membrane deficits that have been observed in schizophrenia. We have previously demonstrated that both total antioxidant status (TAS) and individual antioxidants were significantly reduced in plasma of chronic schizophrenic patients, on and off haloperidol. To test whether reductions in plasma antioxidants are independent of treatment or illness progression, levels of plasma antioxidants were evaluated in 43 patients at first-episode of psychosis, 31 patients meeting DSM-IV criteria for schizophrenia or schizoaffective disorder (reconfirmed after 6 months) and 12 patients with primary mood (bipolar or depressive (BP/D)) disorder, at neuroleptic-naive baseline as well as 40 age- and sex-matched normal controls (NC). The major plasma antioxidants albumin, uric acid and bilirubin were all significantly lower in the first-episode schizophrenic, but not in the BP/D patients, than in normal controls. Factors that can affect these antioxidants-age, gender, diet and smoking-were examined. Body mass index (BMI) was significantly lower in patients, but was not correlated with plasma albumin and bilirubin; there was a trend for a correlation with uric acid in schizophrenic patients. Lower antioxidant levels were independent of smoking status of patients. The present data suggest that a defect in the antioxidant defense system (AODS), which may lead to oxidative damage, occurs early in the course of illness and is independent of treatment effects.

[1]  Jeffrey K. Yao,et al.  Abnormal age-related changes of plasma antioxidant proteins in schizophrenia , 2000, Psychiatry Research.

[2]  W. Tsoi,et al.  Acute phase proteins in male Chinese schizophrenic patients in Singapore , 1996, Schizophrenia Research.

[3]  K. Ingold,et al.  The relative contributions of vitamin E, urate, ascorbate and proteins to the total peroxyl radical-trapping antioxidant activity of human blood plasma. , 1987, Biochimica et biophysica acta.

[4]  Jeffrey K. Yao,et al.  Reduced status of plasma total antioxidant capacity in schizophrenia , 1998, Schizophrenia Research.

[5]  T. Hanihara,et al.  Hypouricemia in chronic schizophrenic patients with polydipsia and hyponatremia. , 1997, The Journal of clinical psychiatry.

[6]  B. Ames,et al.  Oxidative damage and mitochondrial decay in aging. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[7]  H. Meltzer,et al.  Acute phase proteins in schizophrenia, mania and major depression: modulation by psychotropic drugs , 1997, Psychiatry Research.

[8]  D. J. Millward.  Protein Deficiency, Starvation and Protein Metabolism , 1979, The Proceedings of the Nutrition Society.

[9]  J. Lohr,et al.  Smoking and schizophrenia , 1992, Schizophrenia Research.

[10]  N. Fukagawa.  Aging: is oxidative stress a marker or is it causal? , 1999, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[11]  F. Pearlman,et al.  Detection and measurement of total bilirubin in serum, with use of surfactants as solubilizing agents. , 1974, Clinical chemistry.

[12]  C. Rice-Evans,et al.  A novel method for measuring antioxidant capacity and its application to monitoring the antioxidant status in premature neonates. , 1993, Clinical science.

[13]  R. Pioli,et al.  Effects of atypical antipsychotics on the inflammatory response system in schizophrenic patients resistant to treatment with typical neuroleptics , 2000, European Neuropsychopharmacology.

[14]  J. Fleiss,et al.  The global assessment scale. A procedure for measuring overall severity of psychiatric disturbance. , 1976, Archives of general psychiatry.

[15]  M. Soriani,et al.  Antioxidant potential of anaerobic human plasma: role of serum albumin and thiols as scavengers of carbon radicals. , 1994, Archives of biochemistry and biophysics.

[16]  D. Harman,et al.  Aging and Disease: Extending Functional Life Span , 1996, Annals of the New York Academy of Sciences.

[17]  L. Packer,et al.  Vitamin E in Health and Disease , 1997 .

[18]  Marshall Barnett Dunning,et al.  A Manual of Laboratory and Diagnostic Tests , 1980 .

[19]  Jeffrey K. Yao,et al.  Human plasma glutathione peroxidase and symptom severity in schizophrenia , 1999, Biological Psychiatry.

[20]  Jeffrey K. Yao,et al.  Oxidative Damage and Schizophrenia , 2001, CNS drugs.

[21]  I. Johansson,et al.  Use of smokeless tobacco and cigarettes--effects on plasma levels of antioxidant vitamins. , 1993, International journal for vitamin and nutrition research. Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung. Journal international de vitaminologie et de nutrition.

[22]  J. Johnson,et al.  Mitochondrial role in cell aging , 1980, Experimental Gerontology.

[23]  B. F. Becker.  Towards the physiological function of uric acid. , 1993, Free radical biology & medicine.

[24]  W. Pryor,et al.  Oxidants in Cigarette Smoke Radicals, Hydrogen Peroxide, Peroxynitrate, and Peroxynitrite a , 1993, Annals of the New York Academy of Sciences.

[25]  J. Overall,et al.  The Brief Psychiatric Rating Scale , 1962 .

[26]  W. Watson,et al.  Albumin standards and the measurement of serum albumin with bromcresol green. , 1997, Clinica chimica acta; international journal of clinical chemistry.

[27]  D. Kammen,et al.  Effects of haloperidol on antioxidant defense system enzymes in schizophrenia. , 1998, Journal of psychiatric research.

[28]  Jeffrey K. Yao,et al.  Reduced level of plasma antioxidant uric acid in schizophrenia , 1998, Psychiatry Research.

[29]  E. Niki,et al.  Membrane Damage from Lipid Oxidation Induced by Free Radicals and Cigarette Smoke a , 1993, Annals of the New York Academy of Sciences.