Xing Guoqiang, Chavko Mikulas, Zhang Li-Xin, Yang Shutong, Post Robert M
Department of Psychiatry, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4799, USA.
Schizophr Res. 2002 Nov 1;58(1):21-30. doi: 10.1016/s0920-9964(01)00388-7.
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.
为了进一步了解一氧化氮合酶（NOS）在精神分裂症和情感障碍中的潜在作用，我们测定了单相、双相和精神分裂症患者以及非精神疾病对照者（每组n = 15）死后大脑前额叶皮质中钙依赖性组成型NOS（cNOS）的酶活性和蛋白质水平。在任何患者组中，两种NOS亚型nNOS和eNOS的蛋白质水平与非精神疾病对照者相比均无显著差异。然而，精神分裂症患者的cNOS活性（平均值±标准误= 19.1±3.2 cpm/μg/45分钟）显著低于对照组（28.5±3.4，P < 0.05）。在单相（20.3±2.6，P = 0.062）和双相患者（20.8±3.0，P = 0.079）中发现了cNOS活性降低的趋势。男性的NOS活性（25.4±2，n = 36，P = 0.01）显著高于女性（17.3±1.9，n = 24），但未发现显著的诊断与性别交互作用。为了尽量减少死后间隔时间（PMI）对NOS活性和蛋白质的潜在影响，将PMI限制在30小时，并对数据（n = 38）进行了重新分析。精神分裂症患者（15.8±5.6，P = 0.026）和单相抑郁症患者（18.8±3.2，P = 0.042）的cNOS活性显著低于对照组（29.5±3.7），但双相情感障碍患者（22.9±3.4，P = 0.21）并非如此。在总样本（r = 0.28，P < 0.05，n = 60）和PMI控制的亚组（r = 0.43，P < 0.01，n = 38）中，cNOS活性与脑pH值显著相关。我们的数据提供了精神分裂症和抑郁症患者死后大脑中cNOS活性降低的证据。
