Fragmented early-life experiences, aberrant circuit maturation, emotional vulnerabilities

破碎的早期生活经历、异常的电路成熟、情感脆弱

• 批准号: 10379271
• 负责人: Victoria B Risbrough
• 金额: $ 51.64万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-06-17 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10379271
• 关键词: Adolescence; Adolescent; Adolescent and Young Adult; Adult; Anhedonia; Anxiety; Anxiety Disorders; Automobile Driving; Behavior assessment; Biological; Child; Clinical; Clinical assessments; Cognitive; Coupled; Data; Development; Diagnosis; Disease; Emotional; Exhibits; Functional Magnetic Resonance Imaging; Health; Human; Image; Individual; Infant; Interview; Laboratories; Life; Life Experience; Longitudinal cohort; Magnetic Resonance Imaging; Maintenance; Measures; Mental Depression; Mental Health; Modeling; Mood Disorders; Online Systems; Outcome; Participant; Pathology; Patient Recruitments; Patient Self-Report; Play; Population; Post-Traumatic Stress Disorders; Prevalence; Prospective cohort; Psychopathology; Questionnaires; Rewards; Risk; Risk Factors; Rodent; Role; Severities; Structure; Suggestion; Symptoms; Telephone; Testing; Trauma; Vulnerable Populations; base; childhood adversity; clinically significant; cognitive testing; combat; cost; early adolescence; emerging adult; emotional symptom; novel; pleasure; predictive modeling; prospective; recruit; resilience; reward circuitry; service member; social; young adult

Mood and anxiety disorders afflict >20% of adolescents and young adults, with tremendous social and fiscal costs. Late adolescent/young adult service members facing combat are at significant risk for trauma- related disorders, constituting an ideal population to test predictions of the overarching hypothesis driving this Center renewal: that early-life fragmentation/unpredictability (FRAG) is associated with early manifestations of anhedonia and related mental health symptoms via alterations in pleasure-reward circuits which presage increased risk for psychopathology in adulthood. The studies of Project 4, guided by constructive Reviewer suggestions, aim to provide evidence for the role of FRAG-related anhedonia as a novel, unsuspected risk factor for psychopathology in a vulnerable population. We will leverage a large prospective and longitudinal cohort of late-adolescents/young adults recruited in the Marine Resiliency Study (MRS). MRS assessed emotional and cognitive health including anhedonia (within a broad battery of laboratory, self-report and clinical assessments) in young service members before a combat deployment and 3-6 month after it. We will recruit 800-1000 subjects to determine if self-report of early life FRAG is associated with altered mental health trajectories in adulthood. While capitalizing on rich and broad-based assessments of the MRS, we will test three hypotheses: 1) That FRAG, in addition to other established early-life factors, predicts anhedonia during late adolescence / early adulthood. (2) That early-life FRAG and subsequent anhedonia in late adolescence/early adulthood increases risk for adult trauma-related psychopathology. This prediction is supported by preliminary data that pre-deployment anhedonia predicts increased PTS symptoms and increased prevalence for PTSD after deployment (N=1972). This hypothesis will probe the clinical significance and impact of the Center-proposed FRAG and anhedonia risk factors. (3) That FRAG and anhedonia promote trauma-related psychopathology via aberrant pleasure-reward circuitry. A subset of MRS participants identified in Aims 1 & 2 will be recruited into 4 groups with either high or low levels of risk (i.e. combined early-life FRAG and adolescent /early adult anhedonia) and with either high or low levels of PTS symptoms. All will undergo structural MRI, DTI and fMRI and behavioral and cognitive assessments similar to those in Projects 2 and 3 to extend the developmental trajectories of FRAG- associated circuit changes and psychopathology to adulthood. In addition to testing specific Center hypotheses, the broad, longitudinal emotional and cognitive measures within MRS, coupled with data-driven MRI analyses (Imaging core), will enable examination of the role of FRAG in the trajectory of a broad spectrum of adult psychopathology.

情绪和焦虑症困扰着20%的青少年和年轻人，具有巨大的社会性和 财政成本。面临战斗的晚年青少年/年轻成年军人有极大的创伤风险- 相关的障碍，构成了一个理想的人群，以检验驱动这一现象的总体假设的预测 中心更新：早期生活碎片化/不可预测性(FRAG)与早期 快感快感改变对快感缺乏及相关心理健康症状的影响 预示着成年后精神病理风险增加的回路。项目4的研究， 在建设性的审查者建议的指导下，旨在为碎片相关的角色提供证据 在弱势人群中，快感缺乏是一种新的、未被怀疑的精神病理危险因素。 我们将利用一大批前瞻性和纵向的晚期青少年/年轻人 在海洋复原力研究(MRS)中招募。MRS评估了情绪和认知健康状况，包括 青年时期的快感缺乏症(在广泛的实验室、自我报告和临床评估中) 成员在战斗部署前和部署后3-6个月。我们将招募800-1000名受试者以确定 早期生活裂痕的自我报告与成年后心理健康轨迹的改变有关。而当 利用对MRS的丰富和广泛的评估，我们将测试三个假设： 1)除了其他已确立的早期生活因素外，该基因片段还预示着晚期快感缺乏 青春期[成年初期](2)早期精神分裂和随后的晚期快感缺乏 青春期/成年期早期增加了成人创伤相关精神病理的风险。这 初步数据支持这一预测，即部署前快感障碍预示PTS症状增加 部署后创伤后应激障碍患病率增加(N=1972)。这一假说将探索临床 中心提出的FRAG和快感缺乏危险因素的意义和影响。(3)该碎片和 快感缺乏症通过异常的愉悦-奖赏回路促进与创伤相关的精神病理。一个子集 在目标1和目标2中确定的MRS参与者中，将被招募到4个高水平或低水平的小组 风险(即早期生活崩溃和青春期/成人早期快感缺乏症)，并具有高水平或低水平的 PTS症状。所有患者都将接受结构磁共振成像、DTI和功能磁共振成像以及行为和认知 与项目2和项目3中的评估类似，以扩展框架的发展轨迹-- 与成年期相关的环路变化和精神病理学。 除了测试特定的中心假设外，广义的、纵向的情绪和认知 MRS内的测量，加上数据驱动的MRI分析(成像核心)，将使检查成为可能 在广泛的成人精神病理学的发展轨迹中所扮演的角色。