The Effects of Early Life Stress on Neurodevelopment in Children and Adolescents

描述(由申请人提供)：早期生活压力(ELS)是一系列精神症状发展的重要风险因素，这些症状横跨多个诊断类别。然而，ELS导致这种高度脆弱性的机制却鲜为人知。鉴于美国每年有数百万例涉及涉嫌虐待儿童的转诊，至关重要的是，调查人员应专注于阐明ELS的神经发育后果，以及ELS相关的神经生物学功能变化导致精神病理学脆弱性的机制。重要的是，流行病学研究证明，过渡到青春期是ELS影响表现的关键时期；此外，从青春期开始，女性情绪障碍症状的发生率高于在儿童时期受到虐待的男性，这表明这些结果受到性别的影响。因此，在努力阐明ELS对神经生物学系统和精神病理学易感性的影响时，研究人员考虑青春期和性别的影响是至关重要的。拟议的项目旨在解决这些问题，研究ELS对神经回路、神经内分泌和认知过程成熟的影响，这些过程对心理健康至关重要，是负价、正价和唤醒/调节系统等特定RDoC结构的组成部分。由于ELS导致一系列精神疾病的易感性，阐明ELS对广泛的功能领域的影响，其中异常被假定为横跨各种精神病理学，将使我们能够更全面和综合地了解有ELS病史的儿童如何出现和表现出精神病理学的风险。此外，该项目的结果将在早期通知 旨在预防ELS长期后遗症的干预措施。

DESCRIPTION (provided by applicant): Early life stress (ELS) is a significant risk factor for the development of a range of psychiatric symptoms that cut across a number of diagnostic categories. The mechanisms through which ELS confers this heightened vulnerability, however, are poorly understood. Given that there are several million referrals involving alleged child maltreatment in the US each year, it is critical that investigators focus on elucidating the neurodevelopmental consequences of ELS and the mechanisms by which ELS-related changes in neurobiological function confer vulnerability for psychopathology. Importantly, epidemiological studies have documented that the transition to puberty is a critical period for the expression of the effects of ELS; moreover, beginning at puberty, there is a higher incidence of symptoms of emotional disorders in females than in males who were abused as young children, suggesting that these outcomes are moderated by gender. Therefore, in efforts to elucidate the effects of ELS on neurobiological systems and on vulnerability for psychopathology, it is vital that researchers consider the impact of both puberty and gender. The proposed project is designed to address these issues, examining the influence of ELS on the maturation of neural circuits and neuroendocrine and cognitive processes that are critical to psychological health, and that are integral to specific RDoC constructs of the Negative Valence, Positive Valence, and Arousal/Regulatory Systems. Because ELS confers vulnerability for a range of psychiatric illnesses, elucidating the effects of ELS on broad domains of function in which aberrations are posited to transect a variety of psychopathologies will allow us to develop a more comprehensive and integrative understanding of how risk for psychopathology emerges and is manifested in children with a history of ELS. Further, findings from this project will inform early interventions aimed at preventing the long-term sequelae of ELS.