Decreased calcium-dependent constitutive nitric oxide synthase (cNOS) activity in prefrontal cortex in schizophrenia and depression

Xing, Guoqiang; Chavko, Mikulas; Zhang, Li-Xin; Yang, Shutong; Post, Robert M

« Previous Next »Schizophrenia Research
Volume 58, Issue 1 , Pages 21-30, 1 November 2002

Decreased calcium-dependent constitutive nitric oxide synthase (cNOS) activity in prefrontal cortex in schizophrenia and depression

Guoqiang Xing
- Corresponding author. Department of Psychiatry, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814-4799, USA. Tel.: +1-301-295-2291; fax: +1-301-295-3213
- Department of Psychiatry, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4799, USA
- Biological Psychiatry Branch, National Institute of Mental Health, NIH, MD 20892, USA
Mikulas Chavko
- Naval Medical Research Center, Silver Spring, MD 20910, USA
Li-Xin Zhang
- Department of Psychiatry, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4799, USA
Shutong Yang
- Molecular Hematology Branch, National Heart, Lung, and Blood Institute, NIH, USA
Robert M Post
- Biological Psychiatry Branch, National Institute of Mental Health, NIH, MD 20892, USA

Received 10 July 2001; received in revised form 29 October 2001; accepted 31 October 2001.

Abstract

To further understand the potential role of nitric oxide synthase (NOS) in schizophrenia and affective disorders, we determined the calcium-dependent constitutive NOS (cNOS) enzymatic activity and protein levels in the prefrontal cortex of postmortem brains of patients with unipolar, bipolar, and schizophrenic disorders and non-psychiatric controls (n=15 for each group). Protein levels of two NOS isoforms, nNOS and eNOS, were not significantly different from the non-psychiatric controls in any of the patient groups. However, cNOS activity was significantly lower in schizophrenic patients (mean±S.E.=19.1±3.2 cpm/μg/45 min) than in the control group (28.5±3.4, P<0.05). Trends of lower cNOS activity were found in unipolar (20.3±2.6, P=0.062) and bipolar patients (20.8±3.0, P=0.079). Males had significantly higher NOS activity (25.4±2, n=36, P=0.01) than females (17.3±1.9, n=24), but no significant diagnosis and gender interactions were found. To minimize potential effects of extended postmortem interval (PMI) on NOS activity and proteins, the PMI was limited to 30 h and the data (n=38) were re-analyzed. cNOS activity was significantly (P<0.05) lower in patients with schizophrenia (15.8±5.6, P=0.026) and unipolar depression (18.8±3.2, P=0.042) but not in patients with bipolar illness (22.9±3.4, P=0.21) than in the control group (29.5±3.7). cNOS activity was significantly correlated with brain pH in the total sample (r=0.28, P<0.05, n=60) and in the PMI controlled subgroup (r=0.43, P<0.01, n=38). Our data provide evidence of reduced cNOS activity in the postmortem brains of patients with schizophrenia and depression.