Multimodal investigation of emotional reactivity as a predictor of later psychopathology in infants at risk for ASD

摘要 自闭症谱系障碍(ASD)以社交障碍、限制性和重复性为特征 行为。那些对社会缺陷负有遗传责任的人，包括自闭症患者和他们的未受影响的人 亲属内化和外化疾病的风险也很高。并存的情感因素的存在 而行为状况会损害适应功能，增加家庭压力，并与 精神科住院和住宿安置。确定内化和内化的风险因素 将自闭症儿童及其兄弟姐妹的疾病外部化将改善诊断实践 并推动实施预防性和早期干预措施。总体上进行广泛的研究 人口表明内化性和外部性障碍的先兆可以在前两个中识别出来 以情绪反应性(EReactive)升高或减弱的水平或强度为指标的寿命 对内部或外部触发因素作出的情绪反应。现有的，尽管有限的证据表明 患有自闭症的学步儿童和他们未受影响的兄弟姐妹在行为和行为上都表现出非典型的eReactive特征 生理水平，尽管证据不完整，它们的起源和与后来的联系 精神病理学在很大程度上是未知的。为了填补这一空白，我们建议前瞻性地研究 在患有自闭症儿童的150名年幼的兄弟姐妹中，由于家庭因素， 患有自闭症(HR)和30个低风险(LR)兄弟姐妹的风险很高。我们计划检查电子反应性到REAL- 世界触发者旨在引发恐惧、愤怒和喜悦，并评估社会性和非社会性的影响 使用最先进的多方法行为和方法在三种情绪中触发电子反应性 生理学方法。AIM 1将前瞻性评估HRASD组(ASD的兄弟姐妹)、HRATP (有发育困难的兄弟姐妹)和HRTD(没有发展挑战的兄弟姐妹)是 以对社会和非社会触发的电子反应的不同模式为特征的，通过行为和非社会触发来衡量 4个月至30个月的生理指标与LRTD组比较。该目标将澄清是否存在差异 对社交和非社交触发的情绪反应构成了自闭症的一个新的特征 ASD的表型。目标2将研究婴儿期eReactive的发展与预测关系 30个月时内化和外化症状的严重程度。糖尿病早期预测因子的识别 将问题内部化/外部化将有助于获得旨在改善 行为和情感上的挑战。符合研究领域标准研究框架 建议，项目(1)采用多层次分析，(2)调查消极和积极的情况 价态系统以及唤醒系统，以及(3)检查ASD风险的范围，长期目标为 提高ASD的诊断精度和发现新的治疗靶点和干预措施 在疾病的前驱症状和早期症状阶段。

SUMMARY Autism Spectrum Disorder (ASD) is characterized by social impairments and restricted and repetitive behaviors. Those with a genetic liability for social deficits, including individuals with ASD and their unaffected relatives are also at high risk for internalizing and externalizing conditions. The presence of comorbid affective and behavioral conditions impairs adaptive functioning, increases family stress, and is associated with psychiatric hospitalizations and residential placement. Identification of risk factors for internalizing and externalizing disorders amongst young children with ASD and their siblings would improve diagnostic practices and promote implementation of preventative and early interventions. Extensive research in the general population indicates that precursors of internalizing and externalizing disorders can be identified in the first two years of life as indexed by elevated or attenuated levels of Emotional Reactivity (eReactivity), or intensity of emotional reactions in response to internal or external triggers. Extant, albeit limited, evidence suggests that toddlers with ASD and their unaffected siblings exhibit atypical eReactivity profiles both on the behavioral and physiological levels, though the evidence is incomplete and both their origins and the links with later psychopathology are largely unknown. To fill this gap, we propose to prospectively examine the development of eReactivity from 4 to 30 months in 150 younger siblings of children with ASD, who, due to familial factors, are at high risk for developing ASD (HR) and 30 low-risk (LR) siblings. We plan to examine eReactivity to real- world triggers aimed to elicit fear, anger, and joy, and to evaluate the effects of the social and nonsocial nature of the triggers on eReactivity across the three emotions using a state-of-the-art multi-method behavioral and physiological approach. Aim 1 will evaluate prospectively whether the HRASD group (siblings with ASD), HRATP (siblings with developmental challenges), and HRTD (siblings without developmental challenges) are characterized by distinct patterns of eReactivity to social vs nonsocial triggers as measured by behavioral and physiological indices between 4 and 30 months compared to the LRTD group. The aim will clarify if differential emotional reactivity to social and nonsocial triggers constitutes an emerging characteristic of the autism phenotype in ASD. Aim 2 will examine predictive relationships between development of eReactivity in infancy and severity of internalizing and externalizing symptoms at 30 months. Identification of early predictors of internalizing/externalizing problems will facilitate access to early interventions aimed at amelioration of behavioral and emotional challenges. Consistent with the Research Domain Criteria research framework recommendations, the project (1) employs multiple levels of analysis, (2) investigates negative and positive valence systems as well as arousal systems, and (3) examines a spectrum of ASD risk with long-term goals of improving diagnostic precision in ASD and enabling discovery of novel treatment targets and interventions both during prodromal and early syndromal stages of the disorder.