Psychological Trauma, Head Injury and Genetics: Detecting Changes in Cognition and Functioning in a Longitudinal Study of Veterans

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Veterans of the wars in Iraq and Afghanistan often face lengthy and frequent deployments, increasing their risk for more severe psychological trauma (PT) and traumatic brain injury (TBI). Cognition is strongly associated with the ability to function in occupational and social roles, which are key aspects of Veterans’ rehabilitation. PT and TBI contribute to cognitive decline, with the greatest impact on those individuals who have genetic predispositions and greater trauma exposures. To our knowledge, the impact of type or amount of warzone trauma experienced by a Veteran on executive functioning and memory, two aspects of cognitive functioning, or the interaction of these experiences with genes linked to neural plasticity and risk for cognitive disorders has received relatively little attention. The objective of this Career Development Award (CDA-1) is to better understand how aspects of combat trauma and genetics relate to changes in cognition and, thus, place Veterans at risk for long-term impairment. The research aims of this study are to: 1) evaluate what aspects of trauma exposure (e.g., PT, TBI) are associated with cognitive functioning; 2) examine associations between brain-derived neurotrophic factor (BDNF) and apolipoprotein E (ApoE) to determine their direct effects on cognition and whether genetic variation moderates associations with trauma exposure and cognition; and 3) integrate trauma history, cognition, and genetic variation to descriptively characterize phenotypes of Veterans most at risk for functional disability and poor quality of life over time (exploratory). Dr. Szabo will accomplish these aims by performing secondary analysis of data from a longitudinal study of predictors of functional disability among post-9/11 Veterans (I01RX000304; PI Meyer) conducted at the VISN 17 Center of Excellence for Research on Returning War Veterans. Veterans (n=308; 68% male; 62% Caucasian) completed brief neuropsychological batteries assessing memory and executive functioning, a clinical interview assessing TBI, self-report measures of PT, and provided saliva samples for genetic screening. This CDA-1 will provide support to advance Dr. Szabo’s goal of becoming an independent VA research psychologist with innovative research examining how to improve quality of life and functioning following trauma exposure. As a clinical psychology fellow with training in wet laboratory settings, this project is a natural extension of Dr. Szabo’s prior work integrating psychological and biological factors to understand trauma-related impairment. The research and training aims will allow Dr. Szabo to better assess how trauma exposure places Veterans at risk for trajectories of long-term functional impairment. She will also obtain training in genetics and gene-environmental interactions with the goal of incorporating genetics into her current and future research inquiries. Dr. Szabo’s training plan includes hands-on, didactic, and professional development training to achieve these goals. Specific training goals for the proposed CDA-1 include mentoring in: 1) statistical modeling methods; 2) genetics, including genotyping; and 3) research administration, ethics, and grant writing. Her mentoring team integrates experts in the proposed areas of study with extensive experience mentoring junior investigators (Dr. Steven Nelson and Dr. Eric Meyer, co-primary mentors; Drs. Nathan Kimbrel and Keith Young, co-mentors; Drs. Rakeshwar Guleria, Timothy Elliott, A. Alexander Beaujean, consultants). Through the research and training aims of this award, Dr. Szabo will be well positioned to develop a CDA-2 focused on subgroups identified in this CDA- 1 to launch an independent line of research that examines potential treatment targets to improve quality of life and functioning in Veterans. Additionally, she will emerge with a greater skillset that could be applied to large datasets, such as the Million Veteran Program. Together, this CDA-1 will equip Dr. Szabo with the interdisciplinary skills necessary to address the complex issues faced by Veterans.