GxE: Monoamine Transporter Genotypes and Risk of Trauma-Related Psychopathology

描述（由申请人提供）：创伤性事件暴露与一系列心理健康问题的风险增加有关，如创伤后应激障碍（PTSD）和重度抑郁症（MD）。这些表型是与发病率和死亡率增加风险相关的主要公共卫生问题。尽管已经付出了相当大的努力来确定风险和恢复力的相关性，但很大比例的方差仍然无法解释。此外，精神病学遗传学研究在确定基因型对疾病表型的直接影响的能力方面存在分歧。因此，迫切需要新的方法来检查这些关系，为风险和恢复力模型提供信息。该项目的主要目标，直接按照NIMH神经科学和基础行为科学部门（DNBBS）的研究重点，是使用候选基因通过环境相互作用（GxE）模型来检查两个人群（灾难和战斗暴露）中单胺转运体基因与精神病理之间的关系。候选人的研究计划有两个方面。首先，她将分析她的赞助人的DNA样本，这些样本来自于由nimh资助的600名受2004年大西洋影响的成年佛罗里达人

DESCRIPTION (provided by applicant): Traumatic event exposure is associated with elevated risk of a range of mental-health problems such as posttraumatic stress disorder (PTSD) and major depressive disorder (MD). These phenotypes are major public health problems associated with an increased risk of morbidity and mortality. Although considerable effort has been given to identify correlates of risk and resilience, a high percentage of variance remains unexplained. Further, psychiatric genetic investigations have been mixed in their ability to identify direct effects of genotypes on disorder phenotypes. Therefore, the need is high for novel approaches to examining these relationships to inform models of risk and resilience. The primary objective of this project, directly in accordance with the research priorities of the NIMH Division of Neuroscience and Basic Behavioral Sciences (DNBBS), is to examine the relationship between monoamine transporter genes and psychopathology in two populations (disaster- and combat-exposed) using a candidate gene by environment interaction (GxE) model. The candidate's research plan is two fold. First, she will analyze DNA samples from her sponsor's NIMH-funded population-based sample of 600 adult Floridians affected by the 2004 Atlantic hurricane season. Aside from feasibility analyses and major analyses relating to the 5-HTTLPR, these DNA data remain virtually unstudied, thereby providing the basis of the primary aim of this proposal. As these data are population based, the proposed project not only addresses the DNBBS's priority of identifying biological markers of risk and resilience of mental disorders, but also allows for investigation of genetic variants among ethnically diverse populations. Second, the candidate will build upon her co-sponsor's NARSAD/VAMC funded pharmacogenetic study of 300 combat-exposed veterans, which is currently underway. The candidate will collect samples, extract DNA, and genotype samples for the monoamine transporter genes analyzed in the Florida disaster sample to investigate the relationship between monoamine transporter genes and disorder phenotypes in veterans. By examining GxE interactions this project will assess whether relations between trauma exposure and mental health phenotypes are moderated by candidate genes identified in previous GxE studies, as well as genes identified with phenotypic expression risk and/or the neurobiology of stress response systems. PUBLIC HEALTH RELEVANCE: This project has potential public health benefits by identifying specific genotypes that moderate the relation between stressor exposure and mental health outcomes in two distinct trauma exposure groups. Findings from the proposed research would aid in identifying persons in need of intervention in the aftermath of a traumatic event.