Pupil Size and Circadian Salivary Variations in Autism Spectrum Disorder

描述(申请人提供)：本项目旨在研究患有自闭症谱系障碍的2-5岁儿童的皮质醇和α-淀粉酶的昼夜节律及其与紧张性瞳孔大小的关系。目前应用的目的是探索下丘脑和去甲肾上腺素系统的非侵入性测量，以确定它们在自闭症儿童产生非典型自主神经反应中的参与。此外，这项建议试图确定这些措施是否可以洞察自闭症的潜在神经损害，以及这些措施最终是否可以用于在生命早期识别这种障碍。这些任务包括测量(A)休息时的瞳孔大小，以及(B)唾液皮质醇和α-淀粉酶在两天内的白天变化。之前有报道称，自闭症患者自主神经活动和睡眠困难的非典型基线水平表明交感神经活动水平升高。然而，研究发现，与心率等其他自主神经指标相比，瞳孔反应更可靠，受噪音的影响更小。此外，最近发现，与对照组相比，患有自闭症的2-5岁儿童在休息时瞳孔更大，面部更小。下丘脑和去甲肾上腺素系统都有助于自主神经系统的控制，并有助于保持适当的警觉水平，为中枢神经系统对传入的信息做出反应做好准备。自闭症患者被发现具有高水平的去甲肾上腺素和低水平的皮质醇，但这些反应被认为是非典型的，因为与抽血相关的高压力。因此，测量唾液中去甲肾上腺素和下丘脑系统的相关性，分别是α-淀粉酶和皮质醇，提供了一种对这些系统的非侵入性测量。提供的试点数据显示了在整个清醒状态下测量α-淀粉酶的判别能力。这些措施将在两天内分别对20名确诊为自闭症谱系障碍的儿童、20名唐氏综合症儿童和20名典型发育儿童进行治疗。公共卫生相关性：该项目寻求确定在自闭症中产生非典型自主神经反应所涉及的神经化学系统，从而为公共卫生提供两个潜在的贡献。首先，自主神经和唾液测量可能提供自闭症的潜在早期标记，因为这些非侵入性测量可以在婴儿期用于确定发生疾病的可能性。其次，确定导致非典型自主神经反应的神经化学成分可能会导致确定自闭症患者的神经损害，这种损害可能是其他损害的主要原因，并可能导致针对防止这种损害引起一连串影响的药物和/或行为干预。

DESCRIPTION (provided by applicant): This project proposes a study of the circadian rhythms of cortisol and alpha-amylase and their relationship to tonic pupil size in two to five year old children with Autism Spectrum Disorder. The aim of the current application is to explore non-invasive measures of both the hypothalamic and norepinephrine systems to determine their involvement in producing atypical autonomic responses in children with autism. In addition, this proposal seeks to determine whether such measures could provide insight into potential neural impairment in autism, and if these measures could eventually be used to identify the disorder early in life. The tasks include measurement of (a) pupil size at rest, and (b) daytime variations in salivary measures of cortisol and alpha-amylase across two days. Atypical baseline levels of autonomic activity and sleep difficulties have been previously reported in persons with autism and indicate a heightened level of sympathetic activity. However, pupillary responses have been found to be more reliable and less influenced by noise than other autonomic measures such as heart rate. In addition, pupil size has recently been found to be larger at rest and smaller to human faces in two to five year old children with autism than controls. Both the hypothalamic and norepinephrine systems contribute to the control of the autonomic nervous system and help to maintain appropriate levels of alertness to prepare the CNS to respond to incoming information. Persons with autism have been found to have heightened levels of norepinephrine and lower levels of cortisol, but these responses have been suggested to be atypical due to heightened stress associated with blood draw. Therefore, measurement of the salivary correlates of the norepinephrine and hypothalamic systems, alpha-amylase and cortisol respectively, provide a non-invasive measure of these systems. Pilot data are presented that show the discriminant ability of the measurement of alpha-amylase throughout the waking state. These measures will be taken on two separate days on a group of 20 children with a diagnosed Autism Spectrum Disorder, 20 children with Down Syndrome, and 20 typically-developing children. PUBLIC HEALTH RELEVANCE: This project seeks to determine the neurochemical systems involved in producing the atypical autonomic responses in autism, and thus provides two potential contributions to public health. First, the autonomic and salivary measures could provide potential early markers of autism, as these non-invasive measures could be used during infancy to determine the probability of developing the disorder. Second, determination of the neurochemical component responsible for atypical autonomic responses could lead to identification of a neural impairment in autism that is potentially primary to other impairments, and could lead to pharmacological and/or behavioral interventions targeted at preventing this impairment from causing a cascade of effects.