Neural Phenotypes of Females with Autism Spectrum Disorder

描述（由申请人提供）：自闭症谱系障碍（ASD）影响美国88名儿童中的1名，但这种疾病在男孩中比女孩更常见。ASD在男孩中的患病率是女孩的5倍，男孩的患病率为1/54， 252女孩虽然这种不同的性别比例是ASD研究中重复性最高的发现之一，但ASD的性别差异仍然知之甚少。女性ASD的神经病理学研究不足，因为ASD样本招募的研究通常反映了强烈的男性偏见的疾病。本研究的目的是评估一个大型的，性别平衡的学龄前儿童ASD队列，以阐明女性ASD的神经表型，并确定ASD神经病理学的性别差异。儿童将在诊断时（2-3岁）入组，并纵向随访两年。将在研究入组时进行成像，然后在另外两个年度时间点进行成像，并将在第一个和第三个MRI时间点进行两次行为测试。成像将包括结构、弥散加权和静息状态功能连接，以实现以下目标：1）评估ASD核心缺陷背后的神经系统的性别差异，2）调查这些神经系统中大脑生长轨迹的性别差异，3）以确定不同的神经表型亚群和病因因素或行为结果之间的关联。全面了解ASD的女性表型是一个紧迫而及时的主题，正如国家努力将研究引向这一主题所表明的那样。该研究方案响应了机构间自闭症协调委员会（IACC）评估自闭症女性的战略计划，以及美国国立卫生研究院妇女健康研究办公室的使命，以加强和提高与影响女性的疾病，障碍和状况有关的研究。

DESCRIPTION (provided by applicant): Autism spectrum disorder (ASD) affects 1 in 88 children in the United States, but the disorder is much more common in boys than in girls. The prevalence of ASD in boys is 5 times higher than in girls, with a rate of 1 in 54 for boys and 1 in 252 for girls. Although this disparate sex ratio is among the most highly replicated findings in studies of ASD, sex differences in ASD remain poorly understood. The neuropathology of ASD in females is understudied because ASD samples recruited for research studies typically reflect the strong male bias of the disorder. The goal of this study is to evaluate a large, sex-balanced cohort of preschool-aged children with ASD in order to elucidate the neural phenotypes of females with ASD and to identify sex-differences in the neuropathology of ASD. Children will be enrolled at the time of diagnosis (2-3 years of age) and followed longitudinally for two years. Imaging will be carried out at study enrolment and then at two additional annual time points and behavioral testing will be conducted twice, in conjunction with the first and third MRI time points Imaging will include structural, diffusion-weighted and resting state functional connectivity in order to accomplish the following aims: 1) to evaluate sex differences in the neural systems that underlie core deficits in ASD 2) to investigate sex differences in brain growth trajectories in these neural systems and 3) to identify associations between distinct neural phenotypic subgroups and etiologic factors or behavioral outcomes. A comprehensive understanding of the female phenotype of ASD is a pressing and timely topic, as indicated by national efforts to direct research towards this topic. This program of research responds to the Interagency Autism Coordinating Committee (IACC) strategic plan to evaluate females with ASD as well as the mission of the NIH Office of Research on Women's Health to strengthen and enhance research related to diseases, disorders and conditions that affect females.