Utilizing Medical Internship to Identify Genetic Variation Associated with Depres

利用医学实习来识别与抑郁症相关的基因变异

• 批准号: 8164789
• 负责人: SRIJAN SEN
• 金额: $ 18.23万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2015-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8164789
• 关键词: Affect; American; Award; Biological; Bypass; Candidate Disease Gene; Chronic; Chronic stress; Data; Depressed mood; Development; Disease; Doctor of Philosophy; Environmental Risk Factor; Epidemiologic Studies; Etiology; Foundations; Gene Dosage; General Population; Genes; Genetic; Genetic Polymorphism; Genetic Variation; Genomics; Genotype; Goals; Heart Diseases; Individual; Internships; K-Series Research Career Programs; Life Stress; Longitudinal Studies; Major Depressive Disorder; Medical; Mental Depression; Mental disorders; Mentors; Mentorship; Methods; Neurobiology; Pathogenesis; Pathway interactions; Patients; Pattern; Physicians; Psychiatry; Reporting; Research; Research Design; Research Personnel; Residencies; Risk Factors; Role; Sampling; Series; Single Nucleotide Polymorphism; Stress; System; Techniques; Testing; Training; Variant; World Health Organization; career; depressive symptoms; design; disability; genetic association; improved; interest; longitudinal design; preclinical study; programs; promoter; prospective; psychologic; serotonin transporter; skills; stressor; tool

DESCRIPTION (provided by applicant): This Mentored Career Development Award seeks to combine a program of focused research, individualized mentorship and didactics to provide the candidate with the training in advanced genomics and longitudinal study design. The applicant has already completed psychiatry residency training and PhD centered around single variant genetic association studies involving cross-sectional data. His career goal is to become an independent investigator, conducting studies that further our understanding of the genetic and environmental factors underlying major depression in a manner that improves the lives of individuals suffering from this disorder. The applicant proposes to build on his background and develop a new set of skills necessary to achieve this career goal. The focused research part in the award will build on epidemiological studies that indicate that genes and life stress are two of the most important factors in the etiology of depression. Over the past decade, there has been growing interest in identifying interactions between specific genes and stress in the development of depression. Despite the excitement surrounding the initial studies, our ability to draw definitive conclusions is compromised by significant study design limitations: 1) substantial variation in the character and intensity of stress between subjects 2) retrospective design 3) loss of power due to tests of statistical interaction. Unfortunately, because the onset of chronic stress is so difficult to predict beforehand and because the type of stress encountered varies widely between individuals, designing methods to overcome these limitations has been difficult. Medical internship, the first year of professional physician training, presents a unique situation where the onset of a uniform, chronic stressor can be prospectively predicted. The first research aim of this study is: to identify longitudinal trajectories of depressive symptoms among medical interns after the onset of internship stress. This will allow the candidate to achieve the first training aim of the study: to develop a strong foundation in longitudinal design and analytic techniques. The second research aim of this study is: to evaluate the interaction between genetic variation (single nucleotide polymorphisms and copy number variants) in depression candidate pathways and internship stress on both the level and trajectory of depressive symptoms under the stress of internship. This will allow the candidate to achieve the second training aim of the study: to develop expertise in advanced genomic tools. PUBLIC HEALTH RELEVANCE: Major depression affects approximately 1 in 6 Americans at some point in their lives. According to the World Health Organization, depression will soon be second only to heart disease in terms of disease-associated disability. Unfortunately, depression treatments that are currently available are only partially effective. This project is designed to help uncover new biological pathways that can be targeted to develop more effective and more precise anti-depressant treatments.

描述（由申请人提供）：该指导性职业发展奖旨在将重点研究、个性化指导和教学计划结合起来，为候选人提供高级基因组学和纵向研究设计方面的培训。申请人已经完成了精神病学住院医师培训和博士学位，其重点是涉及横截面数据的单变异遗传关联研究。他的职业目标是成为一名独立研究者，开展研究，进一步了解重度抑郁症背后的遗传和环境因素，从而改善患有这种疾病的人的生活。申请人建议以自己的背景为基础，培养实现这一职业目标所需的一套新技能。该奖项的重点研究部分将建立在流行病学研究的基础上，这些研究表明基因和生活压力是抑郁症病因学中两个最重要的因素。在过去的十年中，人们越来越有兴趣确定特定基因与压力在抑郁症发展过程中之间的相互作用。尽管最初的研究令人兴奋，但我们得出明确结论的能力受到重大研究设计限制的影响：1）受试者之间压力的特征和强度存在巨大差异2）回顾性设计3）由于统计交互作用测试而失去动力。不幸的是，由于慢性压力的发作很难提前预测，而且个体之间所遇到的压力类型差异很大，因此设计克服这些限制的方法非常困难。医学实习是专业医生培训的第一年，它提供了一种独特的情况，可以前瞻性地预测统一的慢性压力源的发生。本研究的第一个研究目的是：确定医学实习生在实习压力出现后抑郁症状的纵向轨迹。这将使候选人能够实现该研究的第一个培训目标：在纵向设计和分析技术方面打下坚实的基础。本研究的第二个研究目的是：评估抑郁候选途径中的遗传变异（单核苷酸多态性和拷贝数变异）与实习压力之间的相互作用，以评估实习压力下抑郁症状的水平和轨迹。这将使候选人能够实现该研究的第二个培训目标：发展先进基因组工具的专业知识。 公共卫生相关性：大约六分之一的美国人在一生中的某个阶段受到重度抑郁症的影响。据世界卫生组织称，在与疾病相关的残疾方面，抑郁症很快将仅次于心脏病。不幸的是，目前可用的抑郁症治疗方法仅部分有效。该项目旨在帮助发现新的生物途径，从而开发出更有效、更精确的抗抑郁治疗方法。