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

项目摘要/摘要 超过75%的青少年在他们到大学年龄时会经历亲密朋友的死亡，而且 到18岁时，将有300万儿童经历单亲死亡(相当于每18岁中就有一个儿童死亡 教室)。童年丧亲会增加患精神病的风险，而精神病本身也会产生负面影响。 在整个生命周期内。现有的临床试验数据提供了暴露后风险的初步证据 通过预防性干预可以显著减少精神病理学的发生。然而，进一步发展 预防性干预受阻于对损失后时间模式的有限了解 精神病理学，以及遗传易感性、发育时机、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被指导的 培训和研究活动将解决这些限制，让我做好准备，领导 基于发展信息的研究，以发现有效的预防新方法 暴露后精神病理学，与NIMH战略计划1.2和2.1一致。这个项目的总体目标是 K23的申请，是我追求长期目标的下一步，是为了增加我的临床背景 心理学和心理社会因素与终生精神流行病学指导培训，多基因 流行病学和联合联合体科学使用两个精心选择的基于人群的纵向研究 队列，雅芳父母和孩子纵向研究(ALSPAC；n=14,541)和R代(GR； N=9,778)。我最重要的假设是，确定影响疾病风险的致病机制 青年丧亲后的精神病理学最终将为有效的预防和治疗提供信息 减轻暴露后精神病理学负担的干预措施。建议的研究策略使用 一个生物-心理-社会模型，从主题上将三个具体目标联系起来：(目标1)描述发病和 遗失后精神病理学的离散的他律模式；(目标2)了解生物学的影响 (性别、性别)、心理社会(社会支持、父母关系)和认知因素(认知能力) 丧亲后精神病理学；以及(目标3)调查抑郁症的多基因风险是否相互作用 丧亲会增加丧亲后精神病的风险。建议的理由是 研究表明，考虑生物、心理社会和认知因素的共同影响将产生更多的 对谁最容易受到损失后精神病理的深刻了解，从而使他们有更强的能力 防止出现不良后果。我的成功将培养研究独立性的关键技能，并产生飞行员 在该奖项的第四年提交R01的调查结果，重点是新的和强大的新方法 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.