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

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/microg/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.