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

描述(由申请人提供)：创伤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)和严重抑郁障碍(MD)。这些表型是与发病率和死亡率增加相关的主要公共卫生问题。尽管已经做出了相当大的努力来确定风险和韧性的相关性，但仍有很大比例的差异仍未得到解释。此外，精神病学遗传学研究在确定基因类型对障碍表型的直接影响的能力方面也存在差异。因此，迫切需要新的方法来检查这些关系，以便为风险和弹性模型提供信息。该项目的主要目标，直接根据NIMH神经科学和基础行为科学(DNBBS)分部的研究重点，利用候选基因与环境相互作用(GxE)模型，研究两个人群(灾难和战斗暴露)中单胺转运体基因与精神病理学之间的关系。候选人的研究计划有两个方面。首先，她将分析她的赞助商NIMH资助的以人口为基础的样本的DNA样本，这些样本包括600名受2004年大西洋气候影响的佛罗里达州成年人 飓风季节。除了可行性分析和与5-HTTLPR有关的主要分析外，这些DNA数据几乎仍未得到研究，从而为本提案的主要目标提供了基础。由于这些数据是以人群为基础的，拟议的项目不仅解决了DNBBS确定精神障碍风险和韧性的生物标记的优先事项，而且还允许调查不同种族人群中的遗传变异。其次，候选人将在她的联合赞助商NARSAD/VAMC资助的对300名战斗暴露的退伍军人进行的药物遗传学研究的基础上再接再厉，该研究目前正在进行中。候选人将收集样本，提取DNA和在佛罗里达州灾难样本中分析的单胺转运体基因的基因型样本，以调查退伍军人单胺转运体基因与疾病表型之间的关系。通过研究GxE的相互作用，该项目将评估创伤暴露和心理健康表型之间的关系是否受到先前GxE研究中确定的候选基因的调节，以及与表型表达风险和/或应激反应系统的神经生物学有关的基因的调节。公共卫生相关性：该项目通过确定在两个不同的创伤暴露组中调节应激源暴露与心理健康结果之间关系的特定基因类型，具有潜在的公共健康益处。拟议研究的结果将有助于确定创伤事件发生后需要干预的人。

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.