Department of Psychiatry and Behavioral Sciences, Neuroscience Graduate Program, and Weill Institute for Neurosciences, University of California, San Francisco.
Am J Psychiatry. 2021 Jan 1;178(1):30-38. doi: 10.1176/appi.ajp.2020.20111608.
Recent progress in the identification of genes and genomic regions contributing to autism spectrum disorder (ASD) has had a broad impact on our understanding of the nature of genetic risk for a range of psychiatric disorders, on our understanding of ASD biology, and on defining the key challenges now facing the field in efforts to translate gene discovery into an actionable understanding of pathology. While these advances have not yet had a transformative impact on clinical practice, there is nonetheless cause for real optimism: reliable lists of risk genes are large and growing rapidly; the identified encoded proteins have already begun to point to a relatively small number of areas of biology, where parallel advances in neuroscience and functional genomics are yielding profound insights; there is strong evidence pointing to mid-fetal prefrontal cortical development as one nexus of vulnerability for some of the largest-effect ASD risk genes; and there are multiple plausible paths forward toward rational therapeutics development that, while admittedly challenging, constitute fundamental departures from what was possible prior to the era of successful gene discovery.
近年来，自闭症谱系障碍（ASD）相关基因和基因组区域的鉴定取得了重大进展，这极大地促进了我们对一系列精神疾病遗传风险本质的理解，促进了我们对 ASD 生物学的理解，并明确了该领域目前面临的主要挑战，即如何将基因发现转化为对病理学的可操作理解。尽管这些进展尚未对临床实践产生变革性影响，但仍有理由感到乐观：可靠的风险基因列表庞大且正在迅速增加；已鉴定出的编码蛋白已经开始指向相对较少的生物学领域，神经科学和功能基因组学的平行进展正在产生深远的见解；有强有力的证据表明，胎儿中期前额皮质发育是一些影响最大的 ASD 风险基因的一个脆弱性枢纽；并且有多种合理的治疗药物开发途径，尽管具有挑战性，但与成功基因发现之前的时代相比，这是根本性的突破。
