Pupil Size and Circadian Salivary Variations in Autism Spectrum Disorder

描述（由申请人提供）：本项目提出了一项研究皮质醇和α-淀粉酶的昼夜节律及其与2至5岁自闭症谱系障碍儿童的紧张性瞳孔大小的关系。本申请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，以确定它们参与自闭症儿童产生非典型自主反应。此外，该提案旨在确定这些措施是否可以提供对自闭症潜在神经损伤的洞察力，以及这些措施是否最终可以用于在生命早期识别这种疾病。这些任务包括测量（a）静息时的瞳孔大小，和（B）两天内唾液皮质醇和α-淀粉酶测量值的日间变化。非典型的自主活动和睡眠困难的基线水平先前已在自闭症患者中报道，并表明交感神经活动水平升高。然而，已经发现瞳孔反应比其他自主测量（例如心率）更可靠并且受噪声影响更小。此外，最近发现，与对照组相比，患有自闭症的2至5岁儿童的瞳孔大小在休息时更大，而对人脸更小。下丘脑和去甲肾上腺素系统都有助于控制自主神经系统，并帮助维持适当的警觉水平，使CNS准备好对传入信息做出反应。自闭症患者的去甲肾上腺素水平升高，皮质醇水平较低，但这些反应被认为是非典型的，因为与抽血相关的压力增加。因此，分别测量去甲肾上腺素和下丘脑系统的唾液相关物α-淀粉酶和皮质醇，提供了这些系统的非侵入性测量。试点数据显示的判别能力的测量α-淀粉酶在整个清醒状态。这些措施将在两个不同的日子里对一组20名被诊断为自闭症谱系障碍的儿童，20名唐氏综合症儿童和20名发育正常的儿童进行。公共卫生相关性：该项目旨在确定参与产生自闭症非典型自主反应的神经化学系统，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以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展障碍的概率。第二，确定负责非典型自主反应的神经化学成分可能导致识别自闭症的神经损伤，这可能是其他损伤的主要原因，并可能导致针对防止这种损伤引起级联效应的药理学和/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.