Exploring Links between Genotypes, Phenotypes, and Clinical Predictors of Response to Early Intensive Behavioral Intervention in Autism Spectrum Disorder.
Exploring Links between Genotypes, Phenotypes, and Clinical Predictors of Response to Early Intensive Behavioral Intervention in Autism Spectrum Disorder.
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DOI：
10.3389/fnhum.2013.00567
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发表时间：
2013-09-11
影响因子：
2.9
通讯作者：
Walter A
中科院分区：
文献类型：
--
作者：
Eapen V;Crnčec R;Walter A
自闭症谱系障碍（ASD）是最常见的家族性精神障碍之一。双胞胎和家庭研究表明，同卵一致性率为70-90%，异卵一致性约为10%，一级亲属的风险增加20倍以上。尽管自闭症遗传学取得了重大进展，但行为和认知表型的不同方面与其潜在的遗传倾向性之间的关系仍不清楚。这是复杂的异质性自闭症，存在于遗传和表型水平。鉴于这种异质性，寻找同质实体并将其与特定基因型联系起来的一种方法是追求内表型。来自神经影像学、眼动追踪和电生理学研究的证据支持这样一种假设，即基于遗传易感性，ASD出现于一个发育级联过程，在这个过程中，对社会刺激的注意力缺陷导致与主要照顾者的互动受损。这导致负责社会认知的神经回路发育异常，进而对依赖于这些早期过程的后期行为和功能领域产生不利影响，例如语言发展。这种模型产生了异质性的临床表型，并且也得到了研究的支持，表明早期治疗可以获得更好的临床结果。强化的ASD早期行为干预后的治疗反应也明显不同；然而，对临床表型的特定因素所知相对较少，这些因素可能预测对当前行为治疗的反应。本文综述了有关ASD行为干预反应的基因型、表型和预测因素的文献，并提出了未来研究的建议，以探索这些因素之间的联系，从而更好地识别ASD，提高ASD的治疗效果。
Autism spectrum disorder (ASD) is amongst the most familial of psychiatric disorders. Twin and family studies have demonstrated a monozygotic concordance rate of 70–90%, dizygotic concordance of around 10%, and more than a 20-fold increase in risk for first-degree relatives. Despite major advances in the genetics of autism, the relationship between different aspects of the behavioral and cognitive phenotype and their underlying genetic liability is still unclear. This is complicated by the heterogeneity of autism, which exists at both genetic and phenotypic levels. Given this heterogeneity, one method to find homogeneous entities and link these with specific genotypes would be to pursue endophenotypes. Evidence from neuroimaging, eye tracking, and electrophysiology studies supports the hypothesis that, building on genetic vulnerability, ASD emerges from a developmental cascade in which a deficit in attention to social stimuli leads to impaired interactions with primary caregivers. This results in abnormal development of the neurocircuitry responsible for social cognition, which in turn adversely affects later behavioral and functional domains dependent on these early processes, such as language development. Such a model begets a heterogeneous clinical phenotype, and is also supported by studies demonstrating better clinical outcomes with earlier treatment. Treatment response following intensive early behavioral intervention in ASD is also distinctly variable; however, relatively little is known about specific elements of the clinical phenotype that may predict response to current behavioral treatments. This paper overviews the literature regarding genotypes, phenotypes, and predictors of response to behavioral intervention in ASD and presents suggestions for future research to explore linkages between these that would enable better identification of, and increased treatment efficacy for, ASD.
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影响因子：
3.7
作者：
Bruining H;de Sonneville L;Swaab H;de Jonge M;Kas M;van Engeland H;Vorstman J
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影响因子：
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发表时间：
1994-07-01
影响因子：
7.6
作者：
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通讯作者：
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