A neuroimaging study of twin pairs with autism

描述（由申请人提供）：自闭症是一种严重的神经发育障碍，其特征是明显的社交和沟通缺陷，行为和兴趣的限制和刻板模式，有证据支持其神经生物学和多基因基础。拟议的研究将建立在一项正在进行的NIMH资助的研究（R 01 MH 067005“一项基于人群的加州自闭症双胞胎研究”PI：Joachim Hallmayer）的基础上。这项基于人群的双胞胎研究的存在，至少有一个双胞胎患有自闭症，将提供前所未有的机会来研究遗传和非遗传因素对自闭症大脑解剖学和化学的相对影响。具体来说，从迄今为止完成遗传研究的120多对双胞胎样本中，我们将随机招募80对同性自闭症双胞胎，40对MZ和40对DZ。我们还将招募40名典型的同性双胞胎对照，20名MZ和20名DZ，与80名自闭症（双胞胎）先证者的年龄，性别和社会经济地位组成的样本进行组匹配。将获得所有参与者的高分辨率解剖、扩散张量和质子光谱扫描。本研究中收集的所有新数据将在上述正在进行的NIMH研究的广泛认知和行为测量的背景下进行评估。我们还将在拟定的影像学研究时收集其他临床指标，以提供神经解剖学和神经化学变量的更具体的协变量。总体目标是更好地了解自闭症患者的临床特征和神经生物学指标之间的联系，从而确定临床或生物学内表型，从而更好地描述和了解这种疾病。自闭症的双胞胎研究对于检查遗传和环境风险因素对这种疾病中观察到的神经生物学变化的相对贡献特别有用。提高我们对自闭症神经生物学和大脑行为相关性的理解将有助于开发更好的预测结果的程序，以及设计和实施更具针对性的治疗方法。公共卫生相关性：自闭症和自闭症谱系障碍是非常异质性和致残性的疾病，最近的估计表明这类疾病的患病率可能比以前认为的要高得多（NINDS，1983; Fombonne，2003）。成人结果研究表明，大约三分之二的自闭症成人仍然严重残疾，生活在完全依赖或半依赖状态，只有1 - 2%的人获得正常和独立的状态，有收入的就业，5 - 20%的人达到边缘正常状态（Young等人，1989年）。因此，我们继续寻求创新策略，使我们能够更好地了解这种疾病的神经生物学。自闭症的双胞胎研究是非常有益的，因为它们有助于检查遗传和环境风险因素对这种疾病中观察到的神经生物学变化的相对贡献。更好地了解自闭症的病理生理学将有助于制定有效的治疗策略，旨在针对社会和沟通缺陷的核心症状。

DESCRIPTION (provided by applicant): Autism is a severe neurodevelopmental disorder characterized by marked social and communication deficits, restricted and stereotyped patterns of behaviors and interests with evidence supporting its neurobiologic and polygenic basis. The proposed study will build on an ongoing NIMH-funded study (R01 MH 067005 "A population-based twin study of autism in California" PI: Joachim Hallmayer). The existence of this population-based study of twins, with at least one twin with autism, will provide unprecedented opportunities to examine the relative impact of genetic and nongenetics factors on brain anatomy and chemistry in autism. Specifically, from this sample of more than 120 twin pairs who completed the genetic study to date, we will randomly recruit 80 same-sex autism twin pairs, 40 MZ and 40 DZ. We will also recruit 40 typically developing same-sex twin pair controls, 20 MZ and 20 DZ, group-matched to the sample comprised by the 80 autistic (twin) probands for age, gender, and socioeconomic status. High resolution anatomical, diffusion tensor and proton spectroscopy scans will be obtained from all participants. All new data collected in this study will be evaluated in the context of extensive cognitive and behavioral measures available from the ongoing NIMH study described above. We also will collect additional clinical measures at the time of the proposed imaging investigation to provide more specific covariates for neuroanatomical and neurochemical variables. The overarching goal is to develop a better understanding of linkages among clinical features and neurobiological measures in individuals affected by autism, thus allowing the identification of clinical or biological endophenotypes that will lead to a better characterization and understanding of this disorder. Twin studies in autism are particularly informative for examining the relative contribution of genetic and environmental risk factors to neurobiologic variations observed in this disorder. Improving our understanding of the neurobiology of autism and brain behavior correlations will help in the development of better procedures for predicting outcome and the design and implementation of more targeted therapeutic approaches. PUBLIC HEALTH RELEVANCE: Autism and autism spectrum disorders are very heterogeneous and disabling conditions with recent estimates suggesting that the prevalence of this class of disorders may be considerably higher than previously thought (NINDS, 1983; Fombonne, 2003). Adult outcome studies indicate that about two thirds of autistic adults remain severely handicapped and live in complete dependence or semi-dependence, with only 1 to 2 percent acquiring a normal and independent status with gainful employment, and 5 to 20 percent achieving a borderline normal status (Young et al., 1989). Therefore, the quest continues to identify innovative strategies that will allow us to better understand the neurobiology of this disorder. Twin studies in autism are very informative since they facilitate the examination of the relative contribution of genetic and environmental risk factors to the neurobiologic changes observed in this disorder. A better understanding of the pathophysiology of autism will be instrumental in the development of effective therapeutic strategies that aim at targeting the core symptoms of social and communication deficits.