Belmonte M K, Cook E H, Anderson G M, Rubenstein J L R, Greenough W T, Beckel-Mitchener A, Courchesne E, Boulanger L M, Powell S B, Levitt P R, Perry E K, Jiang Y H, DeLorey T M, Tierney E
Autism Research Centre, Departments of Psychiatry and Experimental Psychology, University of Cambridge, Douglas House, 18b Trumpington Road, Cambridge CB2 2AH, UK.
Mol Psychiatry. 2004 Jul;9(7):646-63. doi: 10.1038/sj.mp.4001499.
The broad variation in phenotypes and severities within autism spectrum disorders suggests the involvement of multiple predisposing factors, interacting in complex ways with normal developmental courses and gradients. Identification of these factors, and the common developmental path into which they feed, is hampered by the large degrees of convergence from causal factors to altered brain development, and divergence from abnormal brain development into altered cognition and behaviour. Genetic, neurochemical, neuroimaging, and behavioural findings on autism, as well as studies of normal development and of genetic syndromes that share symptoms with autism, offer hypotheses as to the nature of causal factors and their possible effects on the structure and dynamics of neural systems. Such alterations in neural properties may in turn perturb activity-dependent development, giving rise to a complex behavioural syndrome many steps removed from the root causes. Animal models based on genetic, neurochemical, neurophysiological, and behavioural manipulations offer the possibility of exploring these developmental processes in detail, as do human studies addressing endophenotypes beyond the diagnosis itself.
自闭症谱系障碍在表型和严重程度上存在广泛差异，这表明多种易感因素参与其中，它们以复杂的方式与正常发育过程和梯度相互作用。从因果因素到大脑发育改变存在很大程度的汇聚，从异常大脑发育到认知和行为改变又存在差异，这阻碍了对这些因素及其共同影响的发育路径的识别。关于自闭症的遗传学、神经化学、神经影像学和行为学研究结果，以及对正常发育和与自闭症有共同症状的遗传综合征的研究，都对因果因素的性质及其对神经系统结构和动态的可能影响提出了假设。神经特性的这种改变反过来可能会干扰依赖活动的发育，从而产生一种与根本原因相距甚远的复杂行为综合征。基于遗传学、神经化学、神经生理学和行为操纵的动物模型提供了详细探索这些发育过程的可能性，针对超出诊断本身的内表型的人体研究也是如此。
