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: 9393803
• 负责人: Natalie L Colich
• 金额: $ 6.02万
• 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/9393803
• 关键词: 10 year old; 3 year old; Acceleration; Address; Adolescence; Adolescent; Affective; Age; Amygdaloid structure; Animals; Anxiety Disorders; Award; Brain; Child; Childhood; 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 Characteristics; Stress; Surveys; Symptoms; Systems Development; Systems Theory; Testing; Training; Work; adolescent brain development; adolescent health; aged; boys; career; 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; 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.

项目摘要（30行） 暴露于儿童逆境（CA）与心理病理学风险升高有关。一个始终如一 女性CA暴露的后果是青春期发作的早期。青春期初期 女性还与情绪和焦虑症的风险升高有关，尽管机制 青春期早期的时机传达了心理病理学的风险。在男性中，非 正常（即早期或晚期）青春期时机与心理病理学的风险有关，但CA的关联 男性的青春期时机很少被研究。暴露于非规范年龄的性激素可能 以增强青少年心理病理脆弱性的方式改变神经发育。但是，很少 研究已经检查了CA如何影响青春期的时机，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心理病理的风险。更少 研究检查了男性和女性的这些途径是否可能有所不同。提议 研究解决了这些差距，目的是确定CA，青春期时机和 大脑发展影响青少年心理病理学的风险。首先，拟议的工作将检查 CA的不同维度如何影响青春期男性和女性的青春期时间。第二，我们会的 调查非规范性青春期时间是否是解释CA和CA之间关联的机制 青春期男性和女性的心理病理学。第三，我们将调查是否与青春期的时机有关 皮质膜电路的变化介导了早期CA与心理病理学之间的关联 青少年女性。数据将来自两个样本。前两个目标将在一个大的 6,483名青少年13-17岁的青少年的全国代表性样本 合并症调查 - 青春期样本（NCS-A）。该样本将使我们能够研究 CA的维度会影响青春期的时机，以及青春期的时机是否是连接CA和 青春期男性和女性的心理病理学。第二个样本来自正在进行的纵向 每年3岁的300名儿童的样本。数据将从最近的浪潮中获取 年龄10-11岁，参与者在恐惧调节任务期间完成了功能磁共振成像扫描。这项研究 将允许检查青春期的变化和CA暴露的变化如何影响皮层夹层电路 并最终是青春期的心理病理学。这些研究的结果将为途径提供洞察力 CA，青春期的时机和大脑发育有助于青少年的心理病理学。这 奖项将为候选人提供，他在青少年的临床神经科学方面具有良好的背景 童年青少年，青春期发展和青少年神经发育模型的培训 促进她过渡到独立研究职业。