Escudero Irene, Johnstone Mandy
The Centre for Genomic and Experimental Medicine, The Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU, United Kingdom.
Curr Psychiatry Rep. 2014 Nov;16(11):502. doi: 10.1007/s11920-014-0502-8.
The genetic basis of schizophrenia has been a hotly debated research topic for decades, yet recent studies, especially in the past year, have confirmed genetics as the major cause of this complex condition. Psychiatry has come of age: it is perhaps more difficult for the current generation of psychiatrists, to comprehend how the biological root of the condition could have been denied for so long. Here we review how highly collaborative global efforts to pool samples, utilise the very latest advances in genotyping and high throughput sequencing technologies, and application of robust statistical analysis have reaped phenomenal rewards. The major findings are that schizophrenia is a highly polygenic disorder with a complex array of risk loci, many include genes implicated also in intellectual disability, autism spectrum disorders, bipolar disorder and major depressive disorder. These candidate genes converge on key neuronal signalling pathways identifying novel targets for potential future therapeutic intervention.
几十年来,精神分裂症的遗传基础一直是一个备受争议的研究课题,但最近的研究,尤其是在过去一年中,已证实遗传学是这种复杂病症的主要病因。精神病学已经成熟:对于当代精神病学家来说,或许更难理解的是,这种病症的生物学根源怎么会被否认这么久。在此,我们回顾一下全球高度协作的努力,包括样本汇集、利用基因分型和高通量测序技术的最新进展,以及应用强大的统计分析所取得的显著成果。主要发现是,精神分裂症是一种高度多基因的疾病,具有一系列复杂的风险基因座,其中许多基因也与智力残疾、自闭症谱系障碍、双相情感障碍和重度抑郁症有关。这些候选基因汇聚在关键的神经元信号通路,为未来潜在的治疗干预确定了新的靶点。