Advanced Institute for Medical Sciences, Dalian Medical University, Dalian, 116044, China.
Department of Neurosurgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, 116027, China.
Metab Brain Dis. 2024 Jan;39(1):147-171. doi: 10.1007/s11011-023-01271-x. Epub 2023 Aug 5.
Schizophrenia is a devastating neuropsychiatric disorder affecting 1% of the world population and ranks as one of the disorders providing the most severe burden for society. Schizophrenia etiology remains obscure involving multi-risk factors, such as genetic, environmental, nutritional, and developmental factors. Complex interactions of genetic and environmental factors have been implicated in the etiology of schizophrenia. This review provides an overview of the historical origins, pathophysiological mechanisms, diagnosis, clinical symptoms and corresponding treatment of schizophrenia. In addition, as schizophrenia is a polygenic, genetic disorder caused by the combined action of multiple micro-effective genes, we further detail several approaches, such as candidate gene association study (CGAS) and genome-wide association study (GWAS), which are commonly used in schizophrenia genomics studies. A number of GWASs about schizophrenia have been performed with the hope to identify novel, consistent and influential risk genetic factors. Finally, some schizophrenia susceptibility genes have been identified and reported in recent years and their biological functions are also listed. This review may serve as a summary of past research on schizophrenia genomics and susceptibility genes (NRG1, DISC1, RELN, BDNF, MSI2), which may point the way to future schizophrenia genetics research. In addition, depending on the above discovery of susceptibility genes and their exact function, the development and application of antipsychotic drugs will be promoted in the future.
精神分裂症是一种严重的神经精神疾病,影响着全球 1%的人口,是对社会造成最严重负担的疾病之一。精神分裂症的病因仍然不清楚,涉及多种风险因素,如遗传、环境、营养和发育因素。遗传和环境因素的复杂相互作用与精神分裂症的病因有关。
本综述概述了精神分裂症的历史起源、病理生理机制、诊断、临床症状和相应的治疗方法。此外,由于精神分裂症是一种由多个微效基因共同作用引起的多基因遗传疾病,我们进一步详细介绍了几种常用于精神分裂症基因组学研究的方法,如候选基因关联研究 (CGAS) 和全基因组关联研究 (GWAS)。已经进行了许多关于精神分裂症的 GWAS,希望能确定新的、一致的、有影响的风险遗传因素。
近年来,已经确定并报道了一些精神分裂症易感基因,并且列出了它们的生物学功能。本综述可以作为过去精神分裂症基因组学和易感基因 (NRG1、DISC1、 RELN、BDNF、MSI2) 研究的总结,这可能为未来的精神分裂症遗传学研究指明方向。此外,根据上述易感基因及其确切功能的发现,未来将促进抗精神病药物的开发和应用。