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

伊拉克和阿富汗战争的退伍军人经常面临长期和频繁的部署， 他们更严重的心理创伤（PT）和创伤性脑损伤（TBI）的风险。认知是强烈的 与在职业和社会角色中发挥作用的能力有关，这是退伍军人的关键方面。 康复活动. PT和TBI导致认知能力下降，对这些人的影响最大 有遗传倾向和更大的创伤暴露。据我们所知， 退伍军人在执行功能和记忆方面经历的战区创伤量， 认知功能，或这些经验与神经可塑性相关基因的相互作用， 认知障碍的风险受到的关注相对较少。 这个职业发展奖（CDA-1）的目的是更好地了解如何方面的 战斗创伤和遗传学与认知变化有关，因此，将退伍军人置于长期风险之中。 损伤本研究的目的是：1）评估创伤暴露的哪些方面 (e.g., PT，TBI）与认知功能相关; 2）检查脑源性 神经营养因子（BDNF）和载脂蛋白E（ApoE），以确定其对认知的直接影响， 遗传变异是否调节与创伤暴露和认知的关联;以及3）整合 创伤史、认知和遗传变异，以最有效地表征退伍军人的表型。 随着时间的推移，存在功能性残疾和生活质量差的风险（探索性）。萨博医生会完成 这些目标通过对来自功能障碍预测因子的纵向研究的数据进行二次分析来实现。 残疾在后9/11退伍军人（I 01 RX 000304; PI迈耶）进行的VISN 17中心， 优秀的研究返回战争退伍军人。退伍军人（n=308; 68%男性; 62%白人） 完成了简短的神经心理电池评估记忆和执行功能，一个临床 访谈评估TBI，PT的自我报告测量，并提供唾液样本进行遗传筛查。 该CDA-1将为推进Szabo博士成为独立VA研究的目标提供支持 一位心理学家，从事创新研究，研究如何改善生活质量和功能， 创伤暴露作为一个临床心理学研究员，在潮湿的实验室环境中接受培训，这个项目是一个 Szabo博士先前工作的自然延伸，整合了心理和生物因素， 创伤相关的损伤研究和培训目标将使萨博博士能够更好地评估如何 创伤暴露使退伍军人面临长期功能障碍的风险。她还将 获得遗传学和基因与环境相互作用的培训，目标是将遗传学 她现在和未来的研究调查萨博博士的培训计划包括动手，说教， 专业发展培训，以实现这些目标。拟议CDA-1的具体培训目标 包括指导：1）统计建模方法; 2）遗传学，包括基因分型; 3）研究 行政、道德和拨款写作。她的指导团队整合了以下领域的专家： 具有指导初级研究者的丰富经验的研究（Steven纳尔逊博士和Eric Meyer博士， 共同主要导师;博士内森Kimbrel和基思杨，共同导师;博士拉克什瓦尔Guleria， Timothy Elliott，A.亚历山大博让，顾问）。通过研究和培训的目的， Szabo博士将有能力开发CDA-2，重点关注本CDA中确定的亚组- 1.启动一项独立的研究，检查潜在的治疗目标，以提高质量 生活和功能在退伍军人。此外，她将获得更大的技能， 适用于大型数据集，例如百万退伍军人计划。这辆CDA-1将为萨博博士 具有解决退伍军人面临的复杂问题所需的跨学科技能。

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.