Gene-Environment Interplay in the Comorbidity of PTSD and Disordered Eating

创伤后应激障碍 (PTSD) 和饮食失调合并症中的基因-环境相互作用

• 批准号: 8644922
• 负责人: KAREN Suzanne MITCHELL
• 金额: $ 17.56万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-15 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8644922
• 关键词: Accounting; Address; Adolescent; Affect; Aging; Alcohol or Other Drugs use; Animal Model; Anxiety; Asthma; Award; Behavioral Genetics; Binge eating disorder; Biological Factors; Body Image; Boston; Bulimia; Cause of Death; Child; Chronic stress; Clinical Research; Collaborations; Commit; Comorbidity; DNA Methylation; Data Set; Development; Disease; Eating; Eating Behavior; Eating Disorders; Emotions; Ensure; Environment; Environmental Risk Factor; Epidemiologic Studies; Epidemiologist; Epigenetic Process; Equipment; Etiology; Exposure to; Female; Foundations; Future; Genes; Genetic; Genetic Predisposition to Disease; Goals; Healthcare Systems; Human; Impulsivity; Individual; Institution; Investigation; K-Series Research Career Programs; Learning; Letters; Libraries; Longitudinal Studies; Mediating; Medical; Mental Depression; Mentorship; Metabolic syndrome; Methodology; Methods; Modeling; Molecular Epidemiology; Molecular Genetics; Nature; Nurses' Health Study; Obesity; Outcome; Overweight; Parents; Participant; Pathway interactions; Pattern; Phenotype; Play; Population; Positioning Attribute; Post-Traumatic Stress Disorders; Prevalence; Prevention; Principal Investigator; Probability Samples; Psychiatric Diagnosis; Psychiatry; Psychologist; Psychology; Psychosocial Factor; Public Health; Recording of previous events; Research; Research Design; Research Personnel; Research Training; Resources; Risk; Role; Sampling; Series; Sex Characteristics; Solid; Specific qualifier value; Strategic Planning; Stress; Stroke; Substance Use Disorder; Surveys; Symptoms; Techniques; Technology; Testing; Time; Training; Training Programs; Trauma; Twin Multiple Birth; Twin Studies; United States; Universities; Vietnam; Weight; Woman; Work; binge type behavior; career; career development; depressive symptoms; design; gene environment interaction; genetic epidemiology; genome-wide; hypothalamic-pituitary-adrenal axis; innovation; insight; knowledge base; male; maternal stress; medical schools; meetings; multidisciplinary; network models; offspring; pre-doctoral; prenatal; prenatal stress; professor; psychobiology; psychogenetics; psychosocial; purging behavior; response

DESCRIPTION (provided by applicant): I am an Assistant Professor of Psychiatry at Boston University School of Medicine (BUSM) and a Clinical Research Psychologist in the National Center for Posttraumatic Stress Disorder (PTSD) at VA Boston Healthcare System. The proposed training plan of my K01 application, The Interplay of Genetic and Environmental Factors in the Comorbidity of PTSD and Disordered Eating, would greatly enhance my predoctoral training in psychology, behavioral genetics, and eating disorders. In order to accomplish my long- term goal of conducting genetically informed investigations of PTSD, eating and weight disorders, and related psychiatric comorbidity, I require training in advanced twin modeling methodology as well as molecular and genetic epidemiology research. A particular challenge of designing a 5-year training plan in psychiatric genetics is that the field changes quite rapidly. Thus, an overarching goal of this training plan, above and beyond learning specific techniques, is to build a solid foundation that will allow me to first keep up wih the moving target that is the field of psychiatric genetics and second to begin to design studies that will overcome some of the limitations of extant research. I propose a comprehensive training program in the etiology and psychobiology of PTSD, molecular genetics and genetic epidemiology, advanced twin modeling, network models of genetic and environmental factors, and epigenetics. This training will provide me with a strong knowledge base from which to generate hypotheses about psychiatric genetic mechanisms. For this career development award, I have carefully chosen a multidisciplinary mentorship team of top researchers in the fields of PTSD, eating disorders, and genetics. This mentorship, along with resources available at my institutions, will ensure that I have all the support necessary to meet my training and research goals. Both BUSM and VA Boston are committed to my career development and protected research time, as described in the attached letters. I will have unique access to facilities, resources, and collaborations at both outstanding institutions, including office space, libraries, and research equipment and technology. My overarching career goal is to apply the latest and best methods to the study of the genetic epidemiology of PTSD and disordered eating. This application will investigate the interplay of genetic and environmental factors in ther etiology and comorbidity. PTSD, a debilitating condition that affects 10.4% of women and 5% of men in the United States during their lifetimes, is highly comorbid with other medical and psychiatric diagnoses. In the National Comorbidity Survey-Replication study, 40% of women with lifetime BN and 26% of women with lifetime BED met criteria for lifetime PTSD, as did 66% of men with BN and 24% of men with BED. There are several psychosocial and genetic mechanisms that may account for PTSD - DE comorbidity. Trauma, which has been associated with bingeing and purging behaviors, may directly impact one's body image. In addition, PTSD and DE share common associated features, including alexithymia, emotion dysregulation, and impulsivity. DE behaviors also may serve as a means to self-medicate the symptoms of PTSD and associated negative affect. In addition, PTSD and DE likely share a common genetic vulnerability. However, there remains a need for investigation of genetic mechanisms of PTSD - DE comorbidity, as well as which of these mechanisms are common across disorders and those that are unique to the etiology of PTSD and DE. The proposed research will test three main models determine the nature of the comorbid relationship between PTSD and DE: 1) genetic vulnerability to PTSD and DE is triggered by trauma exposure, 2) PTSD and DE have common genetic and psychosocial vulnerabilities, and 3) prenatal maternal stress exposure leads to offspring epigenetic changes and DE. Three datasets will be used to address these three aims: 1) male participants in the Vietnam Era Twin Study of Aging (VETSA), 2) women from the Nurses Health Study II (NHS II), and 3) male and female offspring from the Avon Longitudinal Study of Parents and Children (ALSPAC). Study 1 will test a series of twin models to investigate the extent to which the covariance of PTSD and DE is due to shared genetic and environmental influences and estimate the impact of gene-environment interaction. Study 2 will estimate a network model of genetic and psychosocial variables associated with PTSD and DE. Study 3 will investigate whether maternal prenatal stress exposure is associated with offspring genome-wide DNA methylation changes and DE. In addition, this study will investigate whether these associations apply to the etiology of substance use and depressive symptomatology, as well as DE. The proposed work is innovative in that it uses several cutting-edge methodologies to investigate the interplay of genetic and environmental factors in the etiology and comorbidity of PTSD and DE. It is expected that these disorders will share several key genetic and psychosocial vulnerabilities. Further, it is expected that exposure to prenatal stress will be associated with offspring adolescent DE and that this relation will be mediated by DNA methylation changes. Findings will provide a foundation for future genetic studies, as well as treatment and prevention efforts. Further, these outcomes are expected to position the Principal Investigator to submit a competitive R01 by the fourth year of the award period.

描述（由申请人提供）：我是波士顿大学医学院（BUSM）的精神病学助理教授，也是VA波士顿医疗保健系统国家创伤后应激障碍（PTSD）中心的临床研究心理学家。我的K 01申请的拟议培训计划，遗传和环境因素在创伤后应激障碍和饮食失调的并发症中的相互作用，将大大提高我在心理学，行为遗传学和饮食失调方面的博士前培训。为了完成我的长期目标，进行遗传知情的调查创伤后应激障碍，饮食和体重障碍，以及相关的精神科合并症，我需要培训先进的双胞胎建模方法以及分子和遗传流行病学研究。设计一个为期5年的精神遗传学培训计划的一个特殊挑战是，该领域的变化相当迅速。因此，除了学习特定的技术之外，本培训计划的总体目标是建立一个坚实的基础，使我能够首先跟上精神病遗传学领域的移动目标，其次开始设计研究，以克服现有研究的一些局限性。我建议在PTSD的病因学和心理生物学，分子遗传学和遗传流行病学，先进的双胞胎建模，遗传和环境因素的网络模型，和表观遗传学的综合培训计划。这项培训将为我提供一个强大的知识基础，从中产生关于精神病遗传机制的假设。对于这个职业发展奖，我精心挑选了一个由创伤后应激障碍，饮食失调和遗传学领域的顶级研究人员组成的多学科指导团队。这种指导，沿着在我的机构可用的资源，将确保我有所有必要的支持，以满足我的培训和研究目标。BUSM和VA波士顿都致力于我的职业发展和保护研究时间，如所附信件中所述。我将有独特的访问设施，资源和合作，在这两个优秀的机构，包括办公空间， 图书馆、研究设备和技术。我的总体职业目标是将最新和最好的方法应用于PTSD和饮食失调的遗传流行病学研究。这项申请将调查的相互作用，遗传和环境因素的病因和并发症。创伤后应激障碍是一种使人衰弱的疾病，在美国一生中影响10.4%的女性和5%的男性，与其他医学和精神病诊断高度共病。在全国科摩罗调查-复制研究中，40%的终生BN女性和26%的终生BED女性符合终生PTSD标准，66%的BN男性和24%的BED男性也符合PTSD标准。有几种心理社会和遗传机制可以解释PTSD-DE合并症。创伤，这一直与暴饮暴食和净化行为，可能会直接影响一个人的身体形象。此外，PTSD和DE有共同的相关特征，包括述情障碍、情绪失调和冲动。DE行为也可能作为一种手段来自我掩饰PTSD的症状和相关的负面影响。此外，PTSD和DE可能具有共同的遗传脆弱性。然而，仍然需要研究PTSD-DE合并症的遗传机制，以及这些机制中哪些是跨疾病常见的以及那些是PTSD和DE病因学所特有的。拟议的研究将测试三个主要模型，以确定PTSD和DE之间共病关系的性质：1）PTSD和DE的遗传脆弱性是由创伤暴露引发的，2）PTSD和DE具有共同的遗传和心理社会脆弱性，3）产前母体压力暴露导致后代表观遗传变化和DE。三个数据集将用于解决这三个目标：1）越南时代双胞胎老龄化研究（VETSA）的男性参与者，2）护士健康研究II（NHS II）的女性，以及3）雅芳父母和子女纵向研究（ALSPAC）的男性和女性后代。研究1将测试一系列双胞胎模型，以调查PTSD和DE的协方差在多大程度上是由于共享的遗传和环境影响，并估计基因-环境相互作用的影响。研究2将评估与PTSD和DE相关的遗传和心理社会变量的网络模型。研究3将调查母体产前应激暴露是否与后代全基因组DNA甲基化变化和DE相关。此外，本研究还将调查这些关联是否适用于物质使用和抑郁性精神病学以及DE的病因学。拟议的工作是创新的，因为它使用了几个尖端的方法来调查的遗传和环境因素在PTSD和DE的病因和共病的相互作用。预计这些疾病将共享几个关键的遗传和心理社会脆弱性。此外，预计产前应激与后代青少年DE相关，这种关系将通过DNA甲基化变化介导。这些发现将为未来的遗传学研究以及治疗和预防工作提供基础。此外，这些结果预计将使主要研究者在授予期的第四年提交竞争性R 01。