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

GxE：单胺转运蛋白基因型和创伤相关精神病理学风险

• 批准号: 7485401
• 负责人: ANANDA B AMSTADTER
• 金额: $ 4.18万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-12 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7485401
• 关键词: Address; Adult; Affect; Alcohol or Other Drugs use; Alleles; Award; Basic Behavioral Science; Biological; Biological Markers; Candidate Disease Gene; Case-Control Studies; Comorbidity; Condition; DNA; DNA analysis; Data; Data Collection; Data Set; Data Sources; Digit structure; Disasters; Disease; Elderly; Epidemiologic Studies; European; Event; Exposure to; Florida; Funding; Gene Frequency; Genes; Genetic; Genetic Polymorphism; Genotype; Goals; Grant; Health Benefit; Hurricane; Incidence; Individual; Interdisciplinary Study; Intervention; Interview; Investigation; Knowledge; Letters; Link; Literature; Mails; Major Depressive Disorder; Mental Health; Mental disorders; Methodology; Methods; Military Personnel; Modeling; Morbidity - disease rate; National Institute of Mental Health; Neurobiology; Neurosciences; Other Finding; Outcome; Outcome Study; Participant; Pattern; Persons; Pharmacogenetics; Phenotype; Population; Population Heterogeneity; Post-Traumatic Stress Disorders; Predisposition; Prevalence; Prevention; Procedures; Process; Promoter Regions; Psychopathology; Public Health; Publishing; Range; Recording of previous events; Recruitment Activity; Research; Research Design; Research Priority; Risk; Role; Saliva; Sampling; Seasons; Soldier; Stress; Substance Use Disorder; Supervision; System; Telephone; Testing; Training; Trauma; Traumatic Stress Disorders; Twin Studies; Universities; Veterans; base; biological adaptation to stress; comparison group; disorder risk; experience; gene environment interaction; genetic variant; monoamine; mortality; novel strategies; programs; psychogenetics; resilience; response; stress related disorder; stressor; young adult

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.

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升高相关，例如创伤后应激障碍（PTSD）和重度抑郁症（MD）。这些表型是与发病率和死亡率风险增加相关的主要公共卫生问题。尽管已付出相当大的努力来确定风险和复原力的相关性，但仍有很大一部分差异无法解释。此外，精神病学遗传学研究在确定基因型对疾病表型的直接影响方面的能力参差不齐。因此，非常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。该项目的主要目标是根据 NIMH 神经科学和基础行为科学部 (DNBBS) 的研究重点，研究两个人群（遭受灾难和战斗的人群）中单胺转运蛋白基因与精神病理学之间的关系。使用环境相互作用（GxE）模型的候选基因。候选人的研究计划有两个方面。首先，她将分析赞助商 NIMH 资助的基于人口的 600 名受 2004 年大西洋飓风影响的成年佛罗里达人样本中的 DNA 样本 飓风季节。除了与 5-HTTLPR 相关的可行性分析和主要分析外，这些 DNA 数据实际上仍未得到研究，从而为该提案的主要目标提供了基础。由于这些数据是基于人群的，因此拟议的项目不仅解决了 DNBBS 确定精神障碍风险和恢复力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，候选人将以她的共同发起人 NARSAD/VAMC 资助的针对 300 名经历过战斗的退伍军人的药物遗传学研究为基础，该研究目前正在进行中。候选人将收集样本，提取 DNA，并对佛罗里达灾难样本中分析的单胺转运蛋白基因进行基因型样本，以研究单胺转运蛋白基因与退伍军人疾病表型之间的关系。通过检查 GxE 相互作用，该项目将评估创伤暴露与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以及与表型表达风险和/或应激反应系统的神经生物学相关的基因的调节。公共卫生相关性：该项目通过识别特定基因型来调节两个不同创伤暴露群体的压力源暴露与心理健康结果之间的关系，从而具有潜在的公共健康益处。拟议研究的结果将有助于识别在创伤事件发生后需要干预的人员。

项目成果

Does Interviewer Status Matter? An examination of Lay Interviewers and Medical Doctor Interviewers in an Epidemiological Study in Vietnam.

面试官的身份重要吗？

• 发表时间: 2010-08-01
• 作者: Amstadter, Ananda B;Richardson, Lisa;Acierno, Ron;Kilpatrick, Dean G;Gaboury, Mario T;Tran, Trinh Luong;Trung, Lam Tu;Tam, Nguyen Thanh;Tuan, Tran;Buoi, La Thi;Ha, Tran Thu;Thach, Tran Duc
• 通讯作者: Thach, Tran Duc

A Preliminary Examination of Thought Suppression, Emotion Regulation, and Coping in a Trauma Exposed Sample.

对创伤暴露样本中的思想抑制、情绪调节和应对的初步检查。

• 发表时间: 2008-10-01
• 作者: Amstadter, Ananda B;Vernon, Laura L
• 通讯作者: Vernon, Laura L

Posttyphoon prevalence of posttraumatic stress disorder, major depressive disorder, panic disorder, and generalized anxiety disorder in a Vietnamese sample.

越南样本中台风后创伤后应激障碍、重度抑郁症、恐慌症和广泛性焦虑症的患病率。

• DOI: 10.1002/jts.20404
• 发表时间: 2009-06
• 期刊: Journal of traumatic stress
• 影响因子: 3.3
• 作者: Amstadter, Ananda B.;Acierno, Ron;Richardson, Lisa K.;Kilpatrick, Dean G.;Gros, Daniel F.;Gaboury, Mario T.;Trinh Luong Tran;Lam Tu Trung;Nguyen Thanh Tam;Tran Tuan;La Thi Buoi;Tran Thu Ha;Tran Duc Thach;Galea, Sandro
• 通讯作者: Galea, Sandro

A Pre-/Post-Disaster Epidemiological Study of Mental Health Functioning in Vietnam's Da Nang Province Following Typhoon Xangsane.

台风 Xangsane 后越南岘港省心理健康功能的灾前/灾后流行病学研究。

• 发表时间: 2009-03-01
• 作者: Acierno, Ron;Amstadter, Ananda B;Gros, Daniel F;Richardson, Lisa;Kilpatrick, Dean G;Trung, Lam Tu;Tuan, Tran;Buoi, La Thi;Ha, Tran Thu;Thach, Tran Duc;Gaboury, Mario T;Tran, Trinh Luong;Tam, Nguyen Thanh;Seymour, Anne;Galea, Sandro
• 通讯作者: Galea, Sandro

Emotion regulation and anxiety disorders.

情绪调节和焦虑症。

• 发表时间: 2008
• 影响因子: 10.3
• 作者: Amstadter; Ananda
• 通讯作者: Ananda