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/文摘

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.