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

基本信息

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
项目类别：
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

项目摘要

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.

项目摘要（30 行）童年时期的逆境（CA）与精神病理学风险升高有关。有记录的女性暴露于 CA 的后果是青春期开始时间提前。女性也与情绪和焦虑障碍的风险升高有关——尽管机制在男性中，青春期提前是否会带来精神病理学风险尚不清楚。正常（即早或晚）青春期时机与精神病理学风险相关，但 CA 与很少研究男性在非正常年龄接触性激素的情况。然而，改变神经发育以增强青少年精神病理学脆弱性的方法却很少。研究探讨了 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风险。研究已经检验了这些途径对于男性和女性是否存在差异以及如何存在差异。研究解决了这些差距，目标是确定 CA、青春期时机和首先，拟议的工作将研究大脑发育对青少年精神病理学风险的影响。 CA 的不同维度如何影响青春期男性和女性的青春期时间其次，我们将。研究非规范青春期时机是否是解释 CA 和第三，我们将调查青春期男性和女性的精神病理学是否与时间相关。皮质-边缘回路的变化介导早期 CA 与精神病理学之间的关联数据将来自两个样本，将在一个大的样本中进行检查。全国代表性样本 6,483 名 13-17 岁青少年参加了全国合并症调查 - 青少年样本 (NCS-A) 该样本将使我们能够研究有何不同。 CA 的维度影响青春期时机以及青春期时机是否是连接 CA 和青春期时机的机制第二个样本来自正在进行的纵向研究。从 3 岁起每年对 300 名儿童进行抽样调查，数据将从最近一波中抽取。年龄 10-11 岁，参与者在这项研究中完成 fMRI 扫描。将允许检查青春期时间的变化和CA暴露如何影响皮质边缘电路最终，青少年精神病理学的研究结果将提供对这些途径的深入了解。 CA、青春期时机和大脑发育有助于青少年精神病理学。该奖项将为具有丰富青春期临床神经科学背景的候选人提供儿童逆境、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研究生涯。

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Reward-circuit biomarkers of risk and resilience in adolescent depression.

青少年抑郁症风险和复原力的奖励回路生物标志物。

DOI：
10.1016/j.jad.2018.12.104
发表时间：
2019-03-01
期刊：
Journal of affective disorders
影响因子：
6.6
作者：
Adina S. Fischer;M. Ellwood;Natalie L. Colich;Anna C. Cichocki;T. Ho;I. Gotlib
通讯作者：
I. Gotlib

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：
发表时间：
2020-06-03
期刊：
影响因子：
4.4
作者：
Moore, Sarah Rose;Humphreys, Kathryn Leigh;Colich, Natalie Lisanne;Davis, Elena Goetz;Lin, David Tse Shen;MacIsaac, Julia Lynn;Kobor, Michael Steffen;Gotlib, Ian Henry
通讯作者：
Gotlib, Ian Henry

Associations of waking cortisol with DHEA and testosterone across the pubertal transition: Effects of threat-related early life stress.

整个青春期过渡期间清醒皮质醇与 DHEA 和睾酮的关联：与威胁相关的早期生活压力的影响。