Full Text:   <1343>

CLC number: R749

On-line Access: 

Received: 2006-05-26

Revision Accepted: 2006-09-18

Crosschecked: 0000-00-00

Cited: 30

Clicked: 3906

Citations:  Bibtex RefMan EndNote GB/T7714

-   Go to

Article info.
1. Reference List
Open peer comments

Journal of Zhejiang University SCIENCE B 2006 Vol.7 No.12 P.981~986


Imbalanced free radicals and antioxidant defense systems in schizophrenia: A comparative study

Author(s):  LI Hui-chun, CHEN Qiao-zhen, MA Ying, ZHOU Jun-fu

Affiliation(s):  Department of Psychiatry, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China

Corresponding email(s):   zrjsk@zju.edu.cn

Key Words:  Schizophrenia, Nitric oxide (NO), Lipid peroxide (LPO), Glutathione peroxidase (GSH-Px), Catalase (CAT), Superoxide dismutase (SOD), Symptom

LI Hui-chun, CHEN Qiao-zhen, MA Ying, ZHOU Jun-fu. Imbalanced free radicals and antioxidant defense systems in schizophrenia: A comparative study[J]. Journal of Zhejiang University Science B, 2006, 7(12): 981~986.

@article{title="Imbalanced free radicals and antioxidant defense systems in schizophrenia: A comparative study",
author="LI Hui-chun, CHEN Qiao-zhen, MA Ying, ZHOU Jun-fu",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T Imbalanced free radicals and antioxidant defense systems in schizophrenia: A comparative study
%A LI Hui-chun
%A CHEN Qiao-zhen
%A MA Ying
%A ZHOU Jun-fu
%J Journal of Zhejiang University SCIENCE B
%V 7
%N 12
%P 981~986
%@ 1673-1581
%D 2006
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.2006.B0981

T1 - Imbalanced free radicals and antioxidant defense systems in schizophrenia: A comparative study
A1 - LI Hui-chun
A1 - CHEN Qiao-zhen
A1 - MA Ying
A1 - ZHOU Jun-fu
J0 - Journal of Zhejiang University Science B
VL - 7
IS - 12
SP - 981
EP - 986
%@ 1673-1581
Y1 - 2006
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.2006.B0981

Objective: To examine changes of blood oxidative-antiovidative level in schizophrenic patients and its relationship with clinical symptoms. Methods: Forty-six Chinese patients met DSM-IV (Diagnostic and Statistical Manual of Mental Disorders-IV) criteria for schizophrenia and fifty age- and sex-matched healthy controls were enrolled in the present study. Baseline psychiatric symptom severity was assessed with brief psychiatric rating scale, positive and negative syndrome scale on the blood draw day. Fresh blood samples were collected to measure levels of nitric oxide and lipid peroxide in plasma as well as activities of superoxide dismutase, catalase and glutathione peroxidase in red blood cells by spectrophotometric assays simultaneously. Results: Comparison of the biochemical parameters indicated that the level of nitric oxide and lipid peroxide increased in patient group, which represented a positive correlation with positive scale scores; while the activities of three critical enzymes decreased and showed a negative linear correlation. Conclusion: This study showed that there are dysregulation of free radical metabolism and poor activities of the antioxidant defense systems in schizophrenic patients. Excess free radicals formation may play a critical role in the etiology of schizophrenia. Using antioxidants might be an effective therapeutic approach to partially alleviate or prevent the symptoms of schizophrenia.

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


[1] Akyol, O., Zoroğlu, S.S., Armutcu, F., Sahin, S., Gurel, A., 2004. Nitric oxide as a physiopathological factor in neuropsychiatric disorders. In Vivo, 18(3):377-390.

[2] American Psychiatric Association, 1994. Diagnostic and Statistical Manual of Mental Disorders, 4th Ed. American Psychiatric Association, Washington DC.

[3] Bujas-Bobanovic, M., Robertson, H.A., Dursun, S.M., 2000. Effects of nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester on phencyclidine-induced effects in rats. Eur. J. Pharmacol., 409(1):57-65.

[4] Dakhale, G.N., Khanzode, S.D., Khanzode, S.S., Saoji, A., 2005. Supplementation of vitamin C with atypical antipsychotics reduces oxidative stress and improves the outcome of schizophrenia. Psychopharmacology (Berl), 182(4):494-498.

[5] Das, I., Khan, N.S., Puri, B.K., Sooranna, S.R., de Belleroche, J., Hirsch, S.R., 1995. Elevated platelet calcium mobilization and nitric oxide synthase activity may reflect abnormalities in schizophrenic brain. Biochem. Biophys. Res. Commun., 212(2):375-380.

[6] Elkashef, A.M., Al-Barazi, H., Venable, D., Baker, I., Hill, J., Apud, J., Wyatt, R.J., 2002. Dopamine effect on the mitochondria potential in B lymphocytes of schizophrenic patients and normal controls. Prog. Neuropsychopharmacol. Biol. Psychiatry, 26(1):145-148.

[7] Herken, H., Uz, E., Ozyurt, H., Sogut, S., Virit, O., Akyol, O., 2001a. Evidence that the activities of erythrocyte free radical scavenging enzymes and the products of lipid peroxidation are increased in different forms of schizophrenia. Mol. Psychiatry, 6(1):66-73.

[8] Herken, H., Uz, E., Ozyurt, H., Akyol, O., 2001b. Red blood cell nitric oxide levels in patients with schizophrenia. Schizophr. Res., 52(3):289-290.

[9] Kay, S.R., Fiszbein, A., Opler, L.A., 1987. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr. Bull., 13(2):261-276.

[10] Lohr, J.B., Browning, J.A., 1995. Free radical involvement in neuropsychiatric illnesses. Psychopharmacol. Bull., 31(1):159-165.

[11] Mahadik, S.P., Evans, D., Lal, H., 2001. Oxidative stress and role of antioxidant and omega-3 essential fatty acid supplementation in schizophrenia. Prog. Neuropsychopharmacol. Biol. Psychiatry, 25(3):463-493.

[12] Montague, P.R., Gancayco, C.D., Winn, M.J., Marchase, R.B., Friedlander, M.J., 1994. Role of NO production in NMDA receptor-mediated neurotransmitter release in cerebral cortex. Science, 263(5149):973-977.

[13] Overal, J.E., Gorhan, D.R., 1962. The brief psychiatric rating scale. Psychological. Rep., 10:799-812.

[14] Parikh, V., Khan, M.M., Mahadik, S.P., 2003. Differential effects of antipsychotics on expression of antioxidant enzymes and membrane lipid peroxidation in rat brain. J. Psychiatr. Res., 37(1):43-51.

[15] Pillai, A., Parikh, V., Terry, A.V.Jr, Mahadik, S.P., 2006. Long-term antipsychotic treatments and crossover studies in rats: differential effects of typical and atypical agents on the expression of antioxidant enzymes and membrane lipid peroxidation in rat brain. J. Psychiatr. Res., (in Press) Available Online 27 Mar. 2006, http://www.sciencedirect.com

[16] Reddy, R., Keshavan, M., Yao, J.K., 2003. Reduced plasma antioxidants in first-episode patients with schizophrenia. Schizophr. Res., 62(3):205-212.

[17] Ramirez, J., Garnica, R., Boll, M.C., Montes, S., Rios, C., 2004. Low concentration of nitrite and nitrate in the cerebrospinal fluid from schizophrenic patients: a pilot study. Schizophr. Res., 68(2-3):357-361.

[18] Seol, I.W., Kuo, N.Y., Kim, K.M., 2004. Effects of dopaminergic drugs on the mast cell degranulation and nitric oxide generation in RAW 264.7 cells. Arch. Pharm. Res., 27(1):94-98.

[19] Suzuki, E., Nakaki, T., Nakamura, M., Miyaoka, H., 2003. Plasma nitrate levels in deficit versus non-deficit forms of schizophrenia. J. Psychiatry Neurosci., 28(4):288-292.

[20] Taneli, F., Pirildar, S., Akdeniz, F., Uyanik, B.S., Ari, Z., 2004. Serum nitric oxide metabolite levels and the effect of antipsychotic therapy in schizophrenia. Arch. Med. Res., 35(5):401-405.

[21] Vaiva, G., Thomas, P., Leroux, J.M., Cottencin, O., Dutoit, D., Erb, F., Goudemand, M., 1994. Erythrocyte superoxide dismutase (eSOD) determination in positive moments of psychosis. Therapie, 49(4):343-348.

[22] Volterra, A., Trotti, D., Tromba, C., Floridi, S., Racagni, G., 1994. Glutamate uptake inhibition by oxygen free radicals in rat cortical astrocytes. J. Neurosci., 14(5 Pt 1):2924-2932.

[23] Wiley, J.L., 1998. Nitric oxide synthase inhibitors attenuate phencyclidine-induced disruption of prepulse inhibition. Neuropsychopharmacology, 19(1):86-94.

[24] Yao, J.K., Reddy, R., McElhinny, L.G., van Kammen, D.P., 1998a. Reduced status of plasma total antioxidant capacity in schizophrenia. Schizophr. Res., 32(1):1-8.

[25] Yao, J.K., Reddy, R., McElhinny, L.G., van Kammen, D.P., 1998b. Effects of haloperidol on antioxidant defense system enzymes in schizophrenia. J. Psychiatr. Res., 32(6):385-391.

[26] Yao, J.K., Reddy, R.D., van Kammen, D.P., 1999. Human plasma glutathione peroxidase and symptom severity in schizophrenia. Biol. Psychiatry, 45(11):1512-1515.

[27] Yao, J.K., Leonard, S., Reddy, R.D., 2000a. Membrane phospholipid abnormalities in postmortem brains from schizophrenic patients. Schizophr. Res., 42(1):7-17.

[28] Yao, J.K., Reddy, R., van Kammen, D.P., 2000b. Abnormal age-related changes of plasma antioxidant proteins in schizophrenia. Psychiatry Res., 97(2-3):137-151.

[29] Yao, J.K., Reddy, R.D., van Kammen, D.P., 2001. Oxidative damage and schizophrenia: an overview of the evidence and its therapeutic implications. CNS Drugs, 15(4):287-310.

[30] Yao, J.K., Leonard, S., Reddy, R.D., 2004. Increased nitric oxide radicals in postmortem brain from patients with schizophrenia. Schizophr. Bull., 30(4):923-934.

[31] Zhang, X.Y., Zhou, D.F., Su, J.M., Zhang, P.Y., 2001a. The effect of extract of ginkgo biloba added to haloperidol on superoxide dismutase in inpatients with chronic schizophrenia. J. Clin. Psychopharmacol., 21(1):85-88.

[32] Zhang, X.Y., Zhou, D.F., Zhang, P.Y., Wu, G.Y., Su, J.M., Cao, L.Y., 2001b. A double-blind, placebo-controlled trial of extract of Ginkgo biloba added to haloperidol in treatment-resistant patients with schizophrenia. J. Clin. Psychiatry, 62(11):878-883.

[33] Zhang, X.Y., Zhou, D.F., Cao, L.Y., Chen, D.C., Zhu, F.Y., Wu, G.Y., 2003a. Blood superoxide dismutase level in schizophrenic patients with tardive dyskinesia: association with dyskinetic movements. Schizophr. Res., 62(3):245-250.

[34] Zhang, X.Y., Zhou, D.F., Cao, L.Y., Zhang, P.Y., Wu, G.Y., Shen, Y.C., 2003b. The effect of risperidone treatment on superoxide dismutase in schizophrenia. J. Clin. Psychopharmacol., 23(2):128-131.

[35] Zhang, X.Y., Tan, Y.L., Cao, L.Y., Wu, G.Y., Xu, Q., Shen, Y., Zhou, D.F., 2006. Antioxidant enzymes and lipid peroxidation in different forms of schizophrenia treated with typical and atypical antipsychotics. Schizophr. Res., 81(2-3):291-300.

[36] Zhou, J.F., Cai, D., Zhu, Y.G., Yang, J.L., Peng, C.H., Yu, Y.H., 2000. A study on relationship of nitric oxide, oxidation, peroxidation, lipoperoxidation with chronic chole-cystitis. World J. Gastroenterol., 6(4):501-507.

[37] Zoroğlu, S.S., Herken, H., Yürekli, M., Uz, E., Tutkun, H., Savaş, H.A., Bağci, C., Ozen, M.E., Cengiz, B., Cakmak, E.A., et al., 2002. The possible pathophysiological role of plasma nitric oxide and adrenomedullin in schizophrenia. J. Psychiatr. Res., 36(5):309-315.

Open peer comments: Debate/Discuss/Question/Opinion


Please provide your name, email address and a comment

Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou 310027, China
Tel: +86-571-87952783; E-mail: cjzhang@zju.edu.cn
Copyright © 2000 - Journal of Zhejiang University-SCIENCE