Ross Christopher A, Margolis Russell L, Reading Sarah A J, Pletnikov Mikhail, Coyle Joseph T
Division of Neurobiology, School of Medicine, Johns Hopkins University, Baltimore, Maryland 21287, USA.
Neuron. 2006 Oct 5;52(1):139-53. doi: 10.1016/j.neuron.2006.09.015.
With its hallucinations, delusions, thought disorder, and cognitive deficits, schizophrenia affects the most basic human processes of perception, emotion, and judgment. Evidence increasingly suggests that schizophrenia is a subtle disorder of brain development and plasticity. Genetic studies are beginning to identify proteins of candidate genetic risk factors for schizophrenia, including dysbindin, neuregulin 1, DAOA, COMT, and DISC1, and neurobiological studies of the normal and variant forms of these genes are now well justified. We suggest that DISC1 may offer especially valuable insights. Mechanistic studies of the properties of these candidate genes and their protein products should clarify the molecular, cellular, and systems-level pathogenesis of schizophrenia. This can help redefine the schizophrenia phenotype and shed light on the relationship between schizophrenia and other major psychiatric disorders. Understanding these basic pathologic processes may yield novel targets for the development of more effective treatments.
精神分裂症伴有幻觉、妄想、思维紊乱和认知缺陷,会影响人类最基本的感知、情感和判断过程。越来越多的证据表明,精神分裂症是一种大脑发育和可塑性的细微病症。基因研究开始鉴定精神分裂症候选基因风险因素的蛋白质,包括失调素、神经调节蛋白1、DAOA、儿茶酚-O-甲基转移酶和DISC1,对这些基因的正常和变异形式进行神经生物学研究现在具有充分的依据。我们认为DISC1可能会提供特别有价值的见解。对这些候选基因及其蛋白质产物特性的机制研究应能阐明精神分裂症的分子、细胞和系统水平的发病机制。这有助于重新定义精神分裂症的表型,并揭示精神分裂症与其他主要精神疾病之间的关系。了解这些基本病理过程可能会为开发更有效的治疗方法带来新的靶点。