Medical Internship as a Model to Find Gene x Stress Interactions in Depression

医学实习作为寻找抑郁症中基因与压力相互作用的模型

• 批准号: 8278523
• 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/8278523
• 关键词: Affect; American; Award; Biological; Bypass; Candidate Disease Gene; Chronic; Chronic stress; Data; 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; Modeling; 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.

描述（由申请人提供）：这一指导的职业发展奖旨在结合一个集中研究，个性化指导和教学法，为候选人提供高级基因组学和纵向研究设计的培训。申请人已经完成了精神病学居住培训和博士学位，围绕涉及横断面数据的单个变异遗传关联研究。他的职业目标是成为一名独立研究者，进行研究，以进一步了解重大抑郁症的遗传和环境因素，以改善患有这种疾病的人的生活的方式。申请人建议以其背景为基础，并开发一套新的技能，以实现这一职业目标。该奖项的重点研究部分将基于流行病学研究，表明基因和生命压力是抑郁症病因中最重要的两个因素。在过去的十年中，人们对确定特定基因与压力之间的相互作用的兴趣越来越大。尽管最初的研究引起了人们的兴奋，但我们得出明确结论的能力受到重大研究局限性的损害：1）受试者之间的应力和应力强度的实质性差异2）回顾性设计3）由于统计相互作用的测试而导致的权力损失。不幸的是，由于慢性压力的发作很难事先预测，并且由于个人之间遇到的压力类型的变化很大，因此设计克服这些局限性的方法很困难。医疗实习是专业医师培训的第一年，它提出了一种独特的情况，可以预测统一，慢性压力源的发作。这项研究的第一个研究目的是：在实习压力开始后，确定医疗实习生中抑郁症状的纵向轨迹。这将使候选人能够实现研究的首个培训目的：在纵向设计和分析技术方面建立强大的基础。这项研究的第二个研究目的是：评估抑郁症候选途径中遗传变异（单核苷酸多态性和拷贝数变异）之间的相互作用，以及在实习压力下的抑郁症状水平和轨迹上的实习压力。这将使候选人能够实现研究的第二个培训目标：发展高级基因组工具方面的专业知识。