Autism as a disorder of neural information processing: directions for research and targets for therapy

被引:289
作者
Belmonte, MK
Cook, EH
Anderson, GM
Rubenstein, JLR
Greenough, WT
Beckel-Mitchener, A
Courchesne, E
Boulanger, LM
Powell, SB
Levitt, PR
Perry, EK
Jiang, YH
DeLorey, TM
Tierney, E
机构
[1] Univ Cambridge, Dept Psychiat, Autism Res Ctr, Cambridge CB2 2AH, England
[2] Univ Cambridge, Dept Expt Psychol, Autism Res Ctr, Cambridge CB2 2AH, England
[3] Univ Chicago, Dept Psychiat, Chicago, IL 60637 USA
[4] Univ Chicago, Dept Pediat, Chicago, IL 60637 USA
[5] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA
[6] Yale Univ, Child Study Ctr, New Haven, CT USA
[7] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA
[8] Univ Illinois, Beckman Inst, Urbana, IL 61801 USA
[9] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA
[10] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA
[11] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA
[12] Vanderbilt Univ, Kennedy Ctr Res Human Dev, Nashville, TN USA
[13] Newcastle Univ, Ctr Dev Clin Brain Ageing, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England
[14] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA
[15] Mol Res Inst, Mountain View, CA USA
[16] Kennedy Krieger Inst, Baltimore, MD USA
关键词
autism; development; neurochemistry; genetics; animal models;
D O I
10.1038/sj.mp.4001499
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:646 / 663
页数:18
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