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

描述（由申请人提供）：这个指导职业发展奖旨在结合联合收割机的重点研究，个性化的指导和教学计划，为候选人提供先进的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住院医师培训和博士学位，主要围绕涉及横断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的调查员，进行研究，以改善患有这种疾病的个人的生活的方式，进一步了解重性抑郁症的遗传和环境因素。申请人建议建立在他的背景和发展一套新的技能，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中最重要的两个因素。在过去的十年中，人们越来越感兴趣的是确定特定基因和压力之间的相互作用在抑郁症的发展。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）受试者之间压力的性质和强度存在实质性差异2）回顾性设计3）由于统计相互作用的测试而失去功效。不幸的是，由于慢性压力的发作很难事先预测，而且由于个体之间遇到的压力类型差异很大，因此很难设计出克服这些限制的方法。医学实习，专业医师培训的第一年，提出了一个独特的情况下，一个统一的，慢性应激源的发病可以前瞻性地预测。本研究的第一个目的是：探讨医学实习生在实习压力发生后，其忧郁症状的纵向发展轨迹。这将使候选人实现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：评估抑郁候选通路中的基因变异（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对实习压力下抑郁症状水平和轨迹的影响。这将使候选人实现研究的第二个培训目标：发展先进基因组工具的专业知识。

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.