Messamore Erik, Hoffman William F, Janowsky Aaron
Behavioral Health and Clinical Neurosciences Division, 3710 SW US Veterans Hospital Road, Portland, OR 97201, USA.
Schizophr Res. 2003 Aug 1;62(3):251-8. doi: 10.1016/s0920-9964(02)00311-0.
Niacin dilates cutaneous blood vessels, resulting in a pronounced skin flush in most people. The flush response to niacin is attenuated in schizophrenia, but the quantification and physiological mechanism of this abnormality have not been described in detail. It is not clear whether the mechanism involves changes in the pharmacological sensitivity to niacin, or whether there is a reduced ability of the vasculature to dilate adequately in subjects with schizophrenia. We address this question in the present study by characterizing the dose-response relationship between topically applied alpha-methylnicotinate (AMN) and cutaneous blood flow changes, which were quantified by laser Doppler flowmetry. The dose-response curve was shifted to the right in subjects with schizophrenia. The EC(50) value of AMN was significantly increased in the schizophrenia group (mean: 1.66 mM; 95% confidence interval: 1.04-2.65 mM) as compared to the control group (mean: 0.38 mM; 95% confidence interval: 0.263-0.547 mM). The blood flow responses to higher AMN doses were lower in the schizophrenics; however, there was no statistically significant difference in the extrapolated maximal blood flow response value (F(max)) between the two groups. The results suggest that the skin flush abnormality in schizophrenia primarily reflects reduced pharmacological sensitivity to niacin rather than an inadequate cutaneous vasodilatory response to the stimulus. Since vasodilatation in response to niacin requires the release of prostaglandins, the data from this study suggest that schizophrenia is associated with abnormalities in enzymes, receptors, or signal transduction mechanisms that affect the synthesis, release, or response to vasodilatory prostaglandins.
烟酸可扩张皮肤血管，导致大多数人出现明显的皮肤潮红。精神分裂症患者对烟酸的潮红反应减弱，但这种异常的量化及生理机制尚未得到详细描述。目前尚不清楚该机制是涉及对烟酸药理敏感性的变化，还是精神分裂症患者的血管充分扩张能力降低。在本研究中，我们通过描述局部应用α-甲基烟酸酯（AMN）与皮肤血流变化之间的剂量反应关系来解决这个问题，皮肤血流变化通过激光多普勒血流仪进行量化。精神分裂症患者的剂量反应曲线向右移动。与对照组（平均值：0.38 mM；95%置信区间：0.263 - 0.547 mM）相比，精神分裂症组中AMN的半数有效浓度（EC50）值显著升高（平均值：1.66 mM；95%置信区间：1.04 - 2.65 mM）。精神分裂症患者对较高AMN剂量的血流反应较低；然而，两组之间外推的最大血流反应值（Fmax）没有统计学上的显著差异。结果表明，精神分裂症患者的皮肤潮红异常主要反映了对烟酸药理敏感性的降低，而非对刺激的皮肤血管舒张反应不足。由于对烟酸的血管舒张反应需要前列腺素的释放，本研究数据表明，精神分裂症与影响血管舒张前列腺素合成、释放或反应的酶、受体或信号转导机制异常有关。
