DEFICIENT CALCIUM-DEPENDENT NITRIC
OXIDE SYNTHASE ACTIVITY IN THE PREFRONTAL CORTEX OF SCHIZOPHRENIA AND DEPRESSION
Guoqiang Xing, Mikulas Chavko, and
Robert Post
USUHS, Bethesda, MD
Brain nitric oxide (NO), a molecule
synthesized by NO synthase (NOS) has multiple functions in neural development,
neuroprotection, brain plasticity, neurotoxicity, and behavior. The
calcium-dependent constitutive NOS activity consists of neuronal NOS (nNOS) and
endothelial NOS (eNOS) isoforms that are constitutively expressed in the
brain. To understand the potential role of nitric oxide synthase (NOS) in
schizophrenia and affective disorders, the calcium-dependent constitutive NOS
(cNOS) enzymatic activity and protein levels of nNOS and eNOS were determined in
the prefrontal cortex of postmortem brains of patients with unipolar, bipolar,
and schizophrenic disorders and non-psychiatric controls (n=60). nNOS
protein levels were lower in psychiatric patients compared to controls but not
significantly so. There were no differences in eNOS protein levels between
the psychiatric patients and the controls. cNOS activity, however, was
significantly lower in schizophrenic patients (P<0.05) than in the control. Similar trends of lower cNOS activity were found in unipolar (P=0.062) and bipolar patients (P=0.079). Covariance analysis showed that postmortem interval did not have a confounding effect on cNOS activity. These results, together with previous studies, suggest that deficient prefrontal cNOS activity may contribute to the pathophysiology and hypofrontality of schizophrenia and mood disorders.