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

心理创伤、头部受伤和遗传学：在退伍军人的纵向研究中检测认知和功能的变化

• 批准号: 10266046
• 负责人: Yvette Zoltana Szabo
• 金额: --
• 依托单位: OLIN TEAGUE VETERANS CENTER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-11-01 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10266046
• 关键词: Address; Affect; Afghanistan; Alleles; Apolipoprotein E; Area; Attention; Award; Biological; Biological Factors; Brain-Derived Neurotrophic Factor; Caucasians; Centers of Research Excellence; Clinical; Clinical Psychology; Cognition; Cognition Disorders; Cognitive aging; Complex; Craniocerebral Trauma; Data; Data Analyses; Development; Disease; Ethics; Face; Funding; Genes; Genetic; Genetic Models; Genetic Predisposition to Disease; Genetic Screening; Genetic Variation; Genotype; Goals; Grant; Health; Impaired cognition; Impairment; Individual; Intervention; Interview; Iraq; K-Series Research Career Programs; Laboratories; Lead; Life; Link; Longitudinal Studies; Measures; Memory; Memory Loss; Mental disorders; Mentors; Methionine; Methods; Mission; Neurologic; Neuronal Plasticity; Neuropsychological Tests; Neuropsychology; Occupational; Outcome; Patient Self-Report; Phenotype; Positioning Attribute; Prevention; Process; Psychological Factors; Psychologist; Quality of Care; Quality of life; Recording of previous events; Recovery; Rehabilitation therapy; Reporting; Research; Research Personnel; Research Training; Risk; Role; Statistical Models; Subgroup; Time; Tissues; Training; Trauma; Traumatic Brain Injury; Variant; Veterans; War; Work; Writing; apolipoprotein E-3; apolipoprotein E-4; base; career; cognitive ability; cognitive change; cognitive function; cognitive performance; combat; combat trauma; design; executive function; experience; functional disability; functional outcomes; improved; innovation; large datasets; male; post 9/11; precision medicine; programs; prospective; psychobiologic; psychogenetics; psychological trauma; saliva sample; satisfaction; secondary analysis; skills; targeted treatment; trauma exposure; trauma symptom

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.

参加过伊拉克和阿富汗战争的退伍军人经常面临长时间和频繁的部署， 他们遭受更严重心理创伤（PT）和创伤性脑损伤（TBI）的风险很高。 与履行职业和社会角色的能力有关，这是退伍军人的关键方面 PT 和 TBI 会导致认知能力下降，对这些人的影响最大。 据我们所知，有遗传倾向和更大的创伤暴露的人。 退伍军人在执行功能和记忆力两个方面所经历的战区创伤的数量 认知功能的影响，或者这些经历与神经可塑性相关基因的相互作用 认知障碍的风险相对较少受到关注。 该职业发展奖 (CDA-1) 的目的是更好地了解 战斗创伤和遗传学与认知变化有关，因此使退伍军人面临长期风险 本研究的研究目的是：1）评估创伤暴露的哪些方面。 （例如，PT、TBI）与认知功能相关；2）检查脑源性之间的关联； 神经营养因子 (BDNF) 和载脂蛋白 E (ApoE)，以确定它们对认知和认知的直接影响 遗传变异是否会调节与创伤暴露和认知的关联；3）整合； 创伤史、认知和遗传变异最能描述退伍军人的表型 随着时间的推移，面临功能障碍和生活质量下降的风险（探索性）。 这些目标是通过对功能预测因子纵向研究的数据进行二次分析来实现的。 9/11 事件后退伍军人的残疾情况（I01RX000304；PI Meyer）在 VISN 17 中心进行 退伍军人研究卓越奖（n=308；68% 男性；62% 白人） 完成简短的神经心理学电池评估记忆和执行功能，临床 访谈评估 TBI、自我报告 PT 测量，并提供唾液样本进行基因筛查。 该 CDA-1 将为推进 Szabo 博士成为独立 VA 研究人员的目标提供支持 心理学家进行创新研究，研究如何改善生活质量和功能 作为一名接受过潮湿实验室环境培训的临床心理学研究员，这个项目是一个 萨博博士之前的工作的自然延伸，整合了心理和生物因素来理解 研究和培训目的将使萨博博士能够更好地评估与创伤相关的损伤。 创伤暴露使退伍军人面临长期功能障碍的风险。 获得遗传学和基因与环境相互作用的培训，以整合遗传学为目标 萨博博士的培训计划包括实践、教学和培训。 为实现这些目标而提出的专业发展培训 CDA-1。 包括以下方面的指导：1) 统计建模方法；2) 遗传学，包括基因分型；3) 研究； 她的指导团队汇集了拟议领域的专家。 研究具有指导初级研究人员的丰富经验（Steven Nelson 博士和 Eric Meyer 博士， 共同主要导师；Nathan Kimbrel 博士和 Keith Young 博士，Rakeshwar Guleria 博士； Timothy Elliott，A. Alexander Beaujean，顾问)。 获得该奖项后，Szabo 博士将有能力开发 CDA-2，重点关注该 CDA 中确定的亚组- 1 启动独立的研究系列，检查潜在的治疗目标以提高质量 此外，她还将掌握退伍军人的生活和职能，并拥有更强大的技能。 该 CDA-1 将应用于大型数据集，例如百万退伍军人计划。 具有解决退伍军人面临的复杂问题所需的跨学科技能。

项目成果

Measuring salivary markers of inflammation in health research: A review of methodological considerations and best practices.

• DOI: 10.1016/j.psyneuen.2020.105069
• 发表时间: 2021-03
• 期刊: Psychoneuroendocrinology
• 影响因子: 3.7
• 作者: Szabo YZ;Slavish DC
• 通讯作者: Slavish DC

Cortisol as a Biomarker of Alcohol Use in Combat Veterans: A Literature Review and Framework for Future Research.

皮质醇作为退伍军人饮酒的生物标志物：文献综述和未来研究框架。

• DOI: 10.1080/15504263.2020.1771504
• 发表时间: 2020
• 期刊: Journal of dual diagnosis
• 影响因子: 2.2
• 作者: Szabo,YvetteZ;Breeding,Tessa;Hejl,Christina;Guleria,RakeshwarS;Nelson,StevenM;Zambrano-Vazquez,Laura
• 通讯作者: Zambrano-Vazquez,Laura

MicroRNAs as biomarker and novel therapeutic target for posttraumatic stress disorder in Veterans.

• DOI: 10.1016/j.psychres.2021.114252
• 发表时间: 2021-11
• 期刊: Psychiatry research
• 影响因子: 11.3
• 作者: Gupta S;Guleria RS;Szabo YZ
• 通讯作者: Szabo YZ

Changes in Trauma-Related Cognitions and Emotions After Eliciting Moral Elevation: Examining the Effects of Viewing Others' Virtuous Behavior on Veterans with PTSD.

• DOI: 10.3389/frhs.2021.831032
• 发表时间: 2022-02-04
• 期刊: FRONTIERS IN HEALTH SERVICES
• 作者: McGuire, Adam P;Fagan, Joanna;Howard, Binh An N;Wurm, Annika;Szabo, Yvette Z
• 通讯作者: Szabo, Yvette Z