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

情绪和焦虑障碍困扰着超过20%的青少年和年轻人， 财政成本。面对战斗的晚期青少年/年轻成年服役人员有很大的创伤风险- 相关疾病，构成了一个理想的人群，以测试驱动这一假设的总体假设的预测。 中心更新：早期生活碎片化/不可预测性（FRAG）与早期 快感缺乏和相关精神健康症状的表现通过快乐-奖励的改变 这些回路预示着成年后精神病理学风险的增加。项目4的研究， 在建设性的评审建议的指导下，旨在为FRAG相关的作用提供证据 快感缺乏作为一种新的，未被怀疑的危险因素，精神病理学在一个脆弱的人口。 我们将利用一个大型的前瞻性和纵向队列的青少年后期/年轻人 海洋复原力研究（MRS）。MRS评估情绪和认知健康，包括 青少年服务中的快感缺失（在实验室、自我报告和临床评估的广泛组合中） 我们将招募800-1000名成员，以确定是否 自我报告的早期生活FRAG与成年后改变的心理健康轨迹有关。而 利用对MRS的丰富和广泛的评估，我们将测试三个假设： 1)FRAG，除了其他已建立的早期生活因素，预测快感缺乏在晚期 青春期/成年早期。(2)早期的FRAG和随后的快感缺失 青少年/成年早期增加了成人创伤相关精神病理学的风险。这 初步数据支持了这一预测，即部署前快感缺失预测PTS症状增加 部署后PTSD患病率增加（N=1972）。这一假设将探索临床 中心提出的FRAG和快感缺乏危险因素的意义和影响。(3)那个FRAG 快感缺乏通过异常的快乐-奖赏回路促进创伤相关的精神病理学。一个子集 目标1和2中确定的MRS参与者将被招募到4组， 风险（即结合早期生活FRAG和青少年/早期成人快感缺失），以及高或低水平的 PTS症状。所有人都将接受结构MRI、DTI和fMRI以及行为和认知功能检查。 类似于项目2和项目3的评估，以扩展FRAG的发展轨迹- 相关的电路变化和精神病理学到成年。 除了测试特定的中心假设，广泛的，纵向的情感和认知 MRS内的测量，加上数据驱动的MRI分析（成像核心），将使检查 FRAG在广泛的成人精神病理学轨迹中的作用。

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.