Centre for Developmental Neurobiology, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE1 1UL, United Kingdom.
Centre for Developmental Neurobiology, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE1 1UL, United Kingdom; MRC Centre for Neurodevelopmental Disorders, King's College London, London SE1 1UL, United Kingdom.
Curr Opin Neurobiol. 2018 Feb;48:174-182. doi: 10.1016/j.conb.2017.12.013. Epub 2018 Jan 10.
Neuropsychiatric disorders arise from the alteration of normal brain developmental trajectories disrupting the function of specific neuronal circuits. Recent advances in human genetics have greatly accelerated the identification of genes whose variation increases the susceptibility for neurodevelopmental disorders, most notably for autism spectrum disorder (ASD) and schizophrenia. In parallel, experimental studies in animal models-most typically in mice-are beginning to shed light on the role of these genes in the development and function of specific brain circuits. In spite of their limitations, understanding the impact of pathological gene variation in animal models at the level of specific neuronal populations and circuits will likely contribute to orienting human clinical studies in the search for precise disease mechanisms and novel treatments.
神经精神疾病源于正常大脑发育轨迹的改变,破坏了特定神经元回路的功能。人类遗传学的最新进展极大地加速了对增加神经发育障碍易感性的基因的鉴定,尤其是自闭症谱系障碍(ASD)和精神分裂症。与此同时,动物模型(最典型的是小鼠)中的实验研究开始揭示这些基因在特定脑回路发育和功能中的作用。尽管存在局限性,但在特定神经元群体和回路水平上了解动物模型中病理性基因变异的影响可能有助于指导人类临床研究,以寻找精确的疾病机制和新的治疗方法。