Neurodevelopmental Mechanisms linking Childhood Adversity with Adolescent Psychopathology: Pubertal Timing and Cortical-Limbic Circuitry

项目总结(30行) 暴露于童年逆境(CA)会增加患精神病的风险。一个始终如一 记录在案的女性接触CA的后果是青春期开始年龄更早。青春期早期计时 女性也与情绪和焦虑症的风险增加有关--尽管 青春期早期的时间通过什么传递精神病理学的风险还不是很清楚。在男性中，非 正常的青春期(即早或晚)青春期与精神病理的风险有关，但CA的相关性 对男性青春期时机的研究很少。在非正常年龄暴露于性激素可能 改变神经发育的方式，增加青少年精神病理学的脆弱性。然而，几乎没有 研究考察了CA如何影响青春期时机，CA和青春期时机如何影响大脑 发展，以及这些因素最终如何可能有助于精神病理学的风险。更少 研究已经检验了男性和女性这些途径是否以及如何不同。建议数 研究解决了这些差距，目的是确定CA、青春期时机和 大脑发育会影响青少年患精神病的风险。首先，拟议的工作将审查 在青春期男性和女性中，CA的不同维度如何影响青春期的时间。第二，我们将 调查不规范的青春期发育时间是否是解释CA和 青春期男女的精神病理学。第三，我们将调查青春期时间是否与 皮质-边缘环路的改变在早期CA与精神病理学的关系中起中介作用 青春期女性。数据将来自两个样本。前两个目标将进行大范围的考察， 全国有代表性的6,483名13-17岁青少年参加了全国 共病调查--青少年样本(NCS-A)。这个样本将让我们调查不同之处 CA的维度影响青春期计时，以及青春期计时是否是连接CA和 青春期男女的精神病理学。第二个样本来自正在进行的纵向 从3岁开始每年对300名儿童进行跟踪调查。数据将从最近一波浪潮中提取， 年龄10-11岁，受试者在完成恐惧条件反射任务期间完成fMRI扫描。本研究 将允许检查青春期时间和CA暴露的变化如何影响皮质-边缘回路 最终，是青少年精神病理学。这些研究的结果将提供对这些途径的洞察 CA、青春期时机和大脑发育通过这些因素对青少年的精神病理学做出贡献。这 该奖项将为这位在青春期拥有强大临床神经科学背景的候选人提供 儿童期逆境、青春期发育和青春期神经发育模型的培训 促进她向独立研究事业的过渡。

PROJECT SUMMARY (30 lines) Exposure to childhood adversity (CA) is associated with elevated risk for psychopathology. One consistently documented consequence of CA exposure in females is earlier age of pubertal onset. Early pubertal timing in females is also associated with elevated risk for mood and anxiety disorders—although the mechanisms through which early pubertal timing conveys risk for psychopathology are not well understood. In males, non- normative (i.e., early or late) pubertal timing is associated with risk for psychopathology, but associations of CA with pubertal timing in males have rarely been studied. Exposure to sex hormones at a non-normative age may alter neural development in ways that enhance vulnerability for adolescent psychopathology. However, scant research has examined how CA influences pubertal timing, how CA and pubertal timing impact brain development, and how these factors might ultimately contribute to risk for psychopathology. Even less research has examined whether and how these pathways might differ for males and females. The proposed studies address these gaps, with the goal of identifying mechanisms through which CA, pubertal timing, and brain development influence risk for psychopathology in adolescents. First, the proposed work will examine how different dimension of CA influence pubertal timing, in adolescent males and females. Second, we will investigate whether non-normative pubertal timing is a mechanism explaining the association between CA and psychopathology in adolescent males and females. Third, we will investigate whether pubertal timing-related changes in cortical-limbic circuitry mediate the association between CA and psychopathology in early adolescent females. Data will come from two samples. The first two aims will be examined in a large, nationally-representative sample of 6,483 adolescents aged 13-17 years who participated in in the National Comorbidity Survey-Adolescent Sample (NCS-A). This sample will allow us to investigate how different dimensions of CA influence pubertal timing and whether pubertal timing is a mechanism linking CA and psychopathology in adolescent males and females. The second sample comes from an ongoing longitudinal sample of 300 children followed annually from age 3 years. Data will be drawn from the most recent wave, at age 10-11 years where participants are completing fMRI scanning during a fear conditioning task. This study will permit examination of how alterations in pubertal timing and CA exposure impact cortical-limbic circuitry and, ultimately, adolescent psychopathology. The results of these studies will provide insight into the pathways through which CA, pubertal timing and brain development contribute to adolescent psychopathology. This award will provide the candidate, who has a strong background in clinical neuroscience in adolescence, with training in childhood adversity, pubertal development, and neurodevelopment models of adolescence to facilitate her transition to an independent research career.