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

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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.