Tamminga C A, Holcomb H H
Department of Psychiatry, UT Southwestern Medical School, Dallas, TX 75390, USA.
Mol Psychiatry. 2005 Jan;10(1):27-39. doi: 10.1038/sj.mp.4001563.
The discovery of the pathophysiology(ies) for schizophrenia is necessary to direct rational treatment directions for this brain disorder. Firm knowledge about this illness is limited to areas of phenomenology, clinical electrophysiology, and genetic risk; some aspects of dopamine pharmacology, cognitive symptoms, and risk genes are known. Basic questions remain about diagnostic heterogeneity, tissue neurochemistry, and in vivo brain function. It is an illness ripe for molecular characterization using a rational approach with a confirmatory strategy; drug discovery based on knowledge is the only way to advance fully effective treatments. This paper reviews the status of general knowledge in this area and proposes an approach to discovery, including identifying brain regions of dysfunction and subsequent localized, hypothesis-driven molecular screening.
发现精神分裂症的病理生理学对于为这种脑部疾病指明合理的治疗方向是必要的。关于这种疾病的确切知识仅限于现象学、临床电生理学和遗传风险领域；多巴胺药理学、认知症状和风险基因的某些方面是已知的。关于诊断异质性、组织神经化学和体内脑功能仍存在一些基本问题。这是一种适合采用合理方法和验证策略进行分子表征的疾病；基于知识的药物发现是推进全面有效治疗的唯一途径。本文综述了该领域的一般知识现状，并提出了一种发现方法，包括识别功能障碍的脑区以及随后进行局部的、基于假设的分子筛选。
