Freedman Robert, Olincy Ann, Ross Randall G, Waldo Merilyne C, Stevens Karen E, Adler Lawrence E, Leonard Sherry
Departments of Psychiatry and Pharmacology, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, C-268-71, Denver, CO 80262, USA.
Curr Psychiatry Rep. 2003 Jun;5(2):155-61. doi: 10.1007/s11920-003-0032-2.
Sensory gating abnormalities are an early clinical symptom of schizophrenia, and are characterized by a decrease in the brain's normal ability to inhibit the response to unimportant stimuli. Patients appear hypervigilant and have difficulty focusing their attention. A neurobiologic mechanism involved in these difficulties is nicotinic cholinergic modulation of inhibitory neuronal activity in the hippocampus. One measure of sensory gating abnormalities, diminished inhibition of the P50 evoked response to repeated auditory stimuli, has been linked to the chromosome 15q14 locus of the alpha-7-nicotinic receptor gene. This site is one of several that have shown evidence for linkage to schizophrenia, as well as to bipolar disorder, across several studies. Polymorphisms in the core promoter of the gene are associated with schizophrenia and also with diminished inhibition of the P50 response. These genetic data may identify a new pathophysiologic target for drug discovery.
感觉门控异常是精神分裂症的早期临床症状，其特征是大脑抑制对无关刺激反应的正常能力下降。患者表现出过度警觉，难以集中注意力。这些困难所涉及的一种神经生物学机制是海马体中抑制性神经元活动的烟碱胆碱能调节。感觉门控异常的一种测量方法，即对重复听觉刺激诱发的P50反应的抑制减弱，已与α-7-烟碱受体基因的15q14染色体位点相关联。在多项研究中，该位点是几个已显示出与精神分裂症以及双相情感障碍存在连锁证据的位点之一。该基因核心启动子中的多态性与精神分裂症相关，也与P50反应的抑制减弱相关。这些遗传数据可能为药物研发确定一个新的病理生理学靶点。
