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

将童年逆境与青少年精神病理学联系起来的神经发育机制：青春期时机和皮质边缘回路

• 批准号: 9759987
• 负责人: Natalie L Colich
• 金额: $ 6.16万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-29 至 2020-09-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9759987
• 关键词: 10 year old; 3 year old; Acceleration; Address; Adolescence; Adolescent; Affective; Age; Amygdaloid structure; Animals; Anxiety Disorders; Award; Brain; Child; Clinical; Cognitive; Comorbidity; Complex; Data; Detection; Development; Dimensions; Exposure to; Extinction (Psychology); Female; Female Adolescents; Fright; Goals; Gonadal Steroid Hormones; High Prevalence; Human; Learning; Link; Male Adolescents; Mediating; Mental Health; Modeling; Mood Disorders; Neurophysiology - biologic function; Neurosciences; Participant; Pathway interactions; Phase; Play; Population Study; Psychopathology; Puberty; Research; Risk; Role; Sampling; Sex Differences; Stress; Surveys; Symptoms; System; Systems Theory; Testing; Training; Work; adolescent brain development; adolescent health; aged; boys; career; childhood adversity; conditioned fear; deprivation; emotion regulation; experience; functional MRI scan; girls; improved; insight; male; neural circuit; neurodevelopment; neuroimaging; pediatric trauma; peer; physical conditioning; population based; pubertal timing; sex; theories; trauma exposure; vulnerable adolescent

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.

项目概要（30行） 暴露于童年逆境（CA）与精神病理学风险升高相关。一个一贯 有记录的女性接触CA的结果是青春期开始的年龄更早。青春期提前时间 女性也与情绪和焦虑障碍的风险增加有关-尽管机制 青春期提前的时间传递精神病理学风险的机制尚不清楚。在男性中，非- 规范的（即，早或晚）青春期时间与精神病理学风险相关，但CA 与男性青春期时间的关系很少被研究。在非正常年龄接触性激素可能 改变神经系统的发育，从而增强青少年精神病理学的脆弱性。然而， 一项研究调查了CA如何影响青春期时间，CA和青春期时间如何影响大脑 发展，以及这些因素如何最终导致精神病理学的风险。更不 研究已经检查了这些途径是否以及如何在男性和女性之间存在差异。拟议 研究解决了这些差距，目标是确定CA，青春期时间， 大脑发育影响青少年精神病理学风险。首先，拟议的工作将审查 CA不同维度如何影响青春期男女的青春期时间。二是 调查非规范性青春期时间是否是解释CA与 青少年男女的精神病理学。第三，我们将调查青春期时间是否与 皮质-边缘系统的变化介导了CA和早期精神病理学之间的联系， 青春期的女性数据将来自两个样本。前两个目标将在一个大的， 全国代表性样本的6,483名青少年年龄在13-17岁，谁参加了全国 科摩罗青少年抽样调查。这个样本将使我们能够研究 CA的维度影响青春期的时间和青春期的时间是否是一个机制连接CA和 青少年男女的精神病理学。第二个样本来自一个正在进行的纵向调查， 从3岁起每年对300名儿童进行随访。数据将来自最近的一波， 年龄10-11岁，参与者在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暴露的改变如何影响皮质边缘电路 最后是青少年精神病理学这些研究的结果将提供深入了解的途径 通过CA，青春期时间和大脑发育有助于青少年精神病理学。这 该奖项将提供候选人，谁在青少年临床神经科学的强大背景， 儿童期逆境、青春期发育和青春期神经发育模型的培训， 帮助她过渡到独立的研究生涯。

项目成果

Distinctions between sex and time in patterns of DNA methylation across puberty.

青春期 DNA 甲基化模式中性别和时间的差异。

• DOI: 10.1186/s12864-020-06789-3
• 发表时间: 2020
• 期刊: BMC genomics
• 影响因子: 4.4
• 作者: Moore,SarahRose;Humphreys,KathrynLeigh;Colich,NatalieLisanne;Davis,ElenaGoetz;Lin,DavidTseShen;MacIsaac,JuliaLynn;Kobor,MichaelSteffen;Gotlib,IanHenry
• 通讯作者: Gotlib,IanHenry