title: 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.
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001344:Autopsy; D015153:Blotting, Western; D002118:Calcium / Q000502:physiology; D003720:Densitometry; D003863:Depression / Q000201:enzymology*; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III; D017397:Prefrontal Cortex / Q000201:enzymology*; D012559:Schizophrenia / Q000201:enzymology*
chemical_list: D007527:Isoenzymes; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D002118:Calcium