Pathogenic mechanisms in post-bereavement psychopathology: Contributions of gene-environment interplay, psychosocial factors, and cognitive ability in two population-based cohorts

项目总结/摘要 超过75%的青少年在上大学时会经历亲密朋友的死亡， 300万儿童将在18岁之前经历父母一方的死亡（或相当于每一个儿童中有一个儿童死亡）。 教室）。童年丧亲会增加精神病理学的风险，这本身就会产生负面影响 在整个生命周期中。现有的临床试验数据提供了初步证据， 预防性干预可以显著减少精神病理学。然而，进一步发展 预防性干预受到对损失后时间模式的有限理解的阻碍 精神病理学，以及遗传易感性，发育时间，认知能力， 心理社会变量和环境暴露。此应用程序描述了一系列指导 培训和研究活动，将解决这些限制，我准备领导综合， 发展知情，财团为基础的研究，以发现强大的新方法，以防止 暴露后精神病理学，符合NIMH战略计划1.2和2.1。总体目标是 K23应用程序，这是我追求长期目标的下一步，是为了增强我的临床背景 心理学和心理社会因素，在终身精神病学，多基因 流行病学和汇集的联盟科学使用两个精心挑选的人口为基础的纵向 队列，雅芳父母和孩子纵向研究（ALSPAC; n= 14，541）和R代（GR; n= 9，778）。我的总体假设是，确定影响风险的致病机制， 青年丧亲后的精神病理学将最终为有效的预防和治疗提供信息。 减少暴露后精神病理学负担的干预措施。拟议的研究战略使用 一个生物心理社会模型，在主题上联系了三个具体目标：（目标1）描述发病特征， 离散他律模式的损失后精神病理学;（目的2）了解生物的影响， (sex、性别）、社会心理因素（社会支持、父母关系）和认知因素（认知能力）对 丧亲后精神病理学;和（目的3）调查抑郁症的多基因风险是否相互作用 会增加丧亲后精神病理学的风险建议的理由 研究表明，考虑到生物学、心理社会学和认知因素的联合影响， 对谁最容易受到损失后精神病理学的影响有了深入的了解，从而提高了 预防不良后果。我的成功将为研究独立性建立关键技能， 在该奖项的第4年提交R 01，重点关注新颖而强大的新方法， 了解和预防暴露后的精神病理学。

PROJECT SUMMARY/ABSTRACT Over 75% of all adolescents will experience the death of a close friend by the time they reach college age, and 3 million children will experience the death of a parent by the age of 18 (or the equivalent of one child in every classroom). Childhood bereavement increases risk for psychopathology, which itself exerts negative effects across the lifespan. Available clinical trial data provide preliminary evidence that risk of post-exposure psychopathology can be significantly reduced by preventative interventions. However, further development of preventative interventions is hampered by limited understanding of temporal patterns of post-loss psychopathology, as well as the joint effects of genetic liability, developmental timing, cognitive ability, psychosocial variables, and environmental exposures. This application describes a sequence of mentored training and research activities that will address these limitations by preparing me to lead integrative, developmentally-informed, consortium-based research to discover powerful new approaches to preventing post-exposure psychopathology, consistent with NIMH strategic plans 1.2 and 2.1. The overall objective for this K23 application, which is the next step in pursuit of my long-term goal, is to augment my background in clinical psychology and psychosocial factors with mentored training in lifespan psychiatric epidemiology, polygenic epidemiology and pooled consortium science using two carefully selected population-based longitudinal cohorts, the Avon Longitudinal Study of Parents and Children (ALSPAC; n=14,541) and Generation R (GR; n=9,778). My overarching hypotheses is that identifying pathogenic mechanisms that influence the risk for post-bereavement psychopathology in youth will ultimately inform effective preventative and treatment interventions that reduce the burden of post-exposure psychopathology. The proposed research strategy uses a biopsychosocial model that thematically links three Specific Aims: (Aim 1) to characterize the onset and discrete heteronomous patterns of post-loss psychopathology; (Aim 2) to understand the influence of biological (sex, gender), psychosocial (social support, parental relationships) and cognitive factors (cognitive ability) on post-bereavement psychopathology; and (Aim 3) to investigate whether polygenic risk for depression interacts with bereavement to increase risk for post-bereavement psychopathology. The rationale for the proposed research is that considering the joint effects of biological, psychosocial, and cognitive factors will yield a more robust knowledge of who is most vulnerable to post-loss psychopathology, thus resulting in greater ability to prevent adverse outcomes. My success will build critical skills for research independence and generate pilot findings to submit an R01 in Year 4 of this award that focuses on novel and powerful new approaches to understanding and preventing post-exposure psychopathology.