No evidence of exogenous origin for the abnormal glutathione redox state in schizophrenia

被引:29
作者
Ballesteros, Alejandro [1 ,2 ]
Jiang, Pan [1 ]
Summerfelt, Ann [1 ]
Du, Xiaoming [1 ]
Chiappelli, Joshua [1 ]
O'Donnell, Patricio [1 ,3 ]
Kochunov, Peter [1 ]
Hong, L. Elliot [1 ]
机构
[1] Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Dept Psychiat, Catonsville, MD 21228 USA
[2] Hosp Clin Salamanca, Dept Psychiat, Salamanca 37007, Spain
[3] Univ Maryland, Sch Med, Dept Anat & Neurobiol, Baltimore, MD 21201 USA
基金
美国国家卫生研究院;
关键词
Antioxidant; Food; Smoking; Antipsychotic; Glutathione; GSH; GSSG; ANTIOXIDANT ENZYME-ACTIVITIES; POLYUNSATURATED FATTY-ACIDS; OXIDATIVE STRESS; LIPID-PEROXIDATION; RAT-BRAIN; OXIDIZED GLUTATHIONE; BIPOLAR DISORDER; PSYCHOSIS; ANTIPSYCHOTICS; RISPERIDONE;
D O I
10.1016/j.schres.2013.02.001
中图分类号
R749 [精神病学];
学科分类号
100205 ;
摘要
Schizophrenia has been associated with low glutathione (GSH), one of the most important substrates for natural defense against oxidative stress. This abnormality is often attributed to genetic or other pathological causes. However, low GSH in schizophrenia could also be due to insufficient antioxidant consumption or other exogenous factors. We evaluated GSH in relation to diet, smoking, and medication status in schizophrenia patients. We recruited 54 participants (29 schizophrenia patients and 25 normal controls). The Antioxidant Dietary Source Questions was used to estimate the total antioxidant capacity (TAC) from participants' diet. GSH and the oxidized form of glutathione (GSSG) were assayed. We found that GSH was significantly lower (pb<0.001) while % GSSG was 2 to 5 fold higher (p = 0.023) in patients compared with controls. No evidence for lower TAC dietary intake was found in schizophrenia patients compared with controls; rather nominally higher TAC level was found in the patients diet (p = 0.02). Analysis of consumption of individual food categories also failed to find evidence of reduced dietary antioxidant intake in schizophrenia patients. Smoking and medications did not significantly predict the GSH deficit either. However, there was a significant smoking by diagnosis interaction on GSH (p = 0.026) such that smoking was associated with higher GSH level in controls while smoking in patients was not associated with this effect. Schizophrenia patients may have an impaired upregulation of GSH synthesis that normally occurs due to smoking-induced antioxidative response. Lower GSH was independently present in patients on clozapine (p = 0.005) and patients on other antipsychotics (pb<0.001) compared with controls. In conclusion, none of the exogenous sources played a major role in explaining abnormalities in the glutathione pathway in patients. The state of abnormal glutathione redox may therefore be a part of schizophrenia pathophysiology. (C) 2013 Elsevier B.V. All rights reserved.
引用
收藏
页码:184 / 189
页数:6
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