Pre-treatment clinical and gene expression patterns predict developmental change in early intervention in autism.
Pre-treatment clinical and gene expression patterns predict developmental change in early intervention in autism.
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DOI：
10.1038/s41380-021-01239-2
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发表时间：
2021-12
影响因子：
11
通讯作者：
Pierce K
中科院分区：
文献类型：
--
作者：
Lombardo MV;Busuoli EM;Schreibman L;Stahmer AC;Pramparo T;Landi I;Mandelli V;Bertelsen N;Barnes CC;Gazestani V;Lopez L;Bacon EC;Courchesne E;Pierce K
早期发现和干预被认为是促进自闭症儿童获得更好结果的关键，但治疗开始时的年龄对结果的影响却知之甚少。虽然语言能力等临床特征已被证明可以预测治疗结果，但基因组水平的信息是否以及如何预测治疗结果尚不清楚。利用一群自闭症儿童，他们在很小的时候就接受了同样的标准化干预，并提供了血液样本，我们发现非常早的治疗参与(即24个月)在控制治疗时间的同时会带来更大的收益。治疗前的临床行为测量预测了早期干预期间技能成长率的21%的变化。治疗前的血液白细胞基因表达模式也预测了技能增长的速度，占治疗斜率差异的13%。结果表明，295个基因可以优先驱动这一效应。这些与治疗相关的基因在蛋白质水平上高度相互作用，在自闭症死后皮质组织中富集组蛋白和乙酰化差异基因，并在对社会交流和语言发展重要的各种皮质下和皮质区域正常高表达。这项工作表明，在早期干预的背景下，治疗前的生物学和临床行为特征对于预测发育变化是重要的，与组蛋白乙酰化相关的个体化治疗前生物学特征可能是关键。
Early detection and intervention are believed to be key to facilitating better outcomes in children with autism, yet the impact of age at treatment start on the outcome is poorly understood. While clinical traits such as language ability have been shown to predict treatment outcome, whether or not and how information at the genomic level can predict treatment outcome is unknown. Leveraging a cohort of toddlers with autism who all received the same standardized intervention at a very young age and provided a blood sample, here we find that very early treatment engagement (i.e., <24 months) leads to greater gains while controlling for time in treatment. Pre-treatment clinical behavioral measures predict 21% of the variance in the rate of skill growth during early intervention. Pre-treatment blood leukocyte gene expression patterns also predict the rate of skill growth, accounting for 13% of the variance in treatment slopes. Results indicated that 295 genes can be prioritized as driving this effect. These treatment-relevant genes highly interact at the protein level, are enriched for differentially histone acetylated genes in autism postmortem cortical tissue, and are normatively highly expressed in a variety of subcortical and cortical areas important for social communication and language development. This work suggests that pre-treatment biological and clinical behavioral characteristics are important for predicting developmental change in the context of early intervention and that individualized pre-treatment biology related to histone acetylation may be key.
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影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
25
作者：
Gazestani, Vahid H.;Pramparo, Tiziano;Lewis, Nathan E.
通讯作者：
Lewis, Nathan E.
自闭症谱系障碍（ASD）、精神分裂症和双相情感障碍中全转录组异构体水平失调
影响因子：
56.9
作者：
Gandal, Michael J.;Zhang, Pan;Geschwind, Daniel H.
通讯作者：
Geschwind, Daniel H.
影响因子：
25
作者：
Cohen, Michael X.;Schoene-Bake, Jan-Christoph;Weber, Bernd
通讯作者：
Weber, Bernd
影响因子：
--
作者：
Bacon, Elizabeth C;Dufek, Sarah;Courchesne, Eric
通讯作者：
Courchesne, Eric