Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, King's College, London, UK.
Mol Psychiatry. 2013 Apr;18(4):435-42. doi: 10.1038/mp.2012.102. Epub 2012 Jul 17.
Discovering novel treatments for Autism Spectrum Disorders (ASD) is a challenge. Its etiology and pathology remain largely unknown, the condition shows wide clinical diversity, and case identification is still solely based on symptomatology. Hence clinical trials typically include samples of biologically and clinically heterogeneous individuals. 'Core deficits', that is, deficits common to all individuals with ASD, are thus inherently difficult to find. Nevertheless, recent reports suggest that new opportunities are emerging, which may help develop new treatments and biomarkers for the condition. Most important, several risk gene variants have now been identified that significantly contribute to ASD susceptibility, many linked to synaptic functioning, excitation-inhibition balance, and brain connectivity. Second, neuroimaging studies have advanced our understanding of the 'wider' neural systems underlying ASD; and significantly contributed to our knowledge of the complex neurobiology associated with the condition. Last, the recent development of powerful multivariate analytical techniques now enable us to use multi-modal information in order to develop complex 'biomarker systems', which may in the future be used to assist the behavioral diagnosis, aid patient stratification and predict response to treatment/intervention. The aim of this review is, therefore, to summarize some of these important new findings and highlight their potential significant translational value to the future of ASD research.
发现自闭症谱系障碍 (ASD) 的新疗法是一项挑战。其病因和病理学在很大程度上仍然未知，该病症表现出广泛的临床多样性，且病例识别仍然仅基于症状。因此，临床试验通常包括具有生物学和临床异质性的个体样本。因此，“核心缺陷”（即所有 ASD 患者共有的缺陷）很难发现。然而，最近的报告表明，新的机会正在出现，这可能有助于为该病症开发新的治疗方法和生物标志物。最重要的是，现在已经确定了几个显著增加 ASD 易感性的风险基因变异体，其中许多与突触功能、兴奋抑制平衡和大脑连通性有关。其次，神经影像学研究增进了我们对 ASD 潜在“广泛”神经系统的理解；并显著提高了我们对与该病症相关的复杂神经生物学的认识。最后，最近开发的强大多元分析技术现在使我们能够使用多模态信息来开发复杂的“生物标志物系统”，这些系统将来可能用于协助行为诊断、辅助患者分层和预测对治疗/干预的反应。因此，本综述的目的是总结其中一些重要的新发现，并强调它们对 ASD 研究未来的潜在重要转化价值。
