Utilizing Medical Internship to Identify Genetic Variation Associated with Depres

描述(由申请者提供)：这个辅导式职业发展奖旨在结合重点研究、个性化指导和教学计划，为候选人提供高级基因组学和纵向研究设计方面的培训。申请者已经完成了精神病学住院医师培训和博士学位，中心是涉及横断面数据的单一变异基因关联研究。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，进一步加深我们对严重抑郁症背后的遗传和环境因素的理解。应聘者建议在自己背景的基础上发展一套新的技能，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。在过去的十年里，人们对确定抑郁症发展过程中特定基因和压力之间的相互作用越来越感兴趣。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有很大差异2)回溯性设计3)由于统计交互作用的测试而失去力量。不幸的是，由于慢性压力的开始很难事先预测，而且每个人遇到的压力类型差异很大，所以很难设计出克服这些限制的方法。医学实习是专业医生培训的第一年，它呈现了一种独特的情况，在这种情况下，可以前瞻性地预测统一的慢性应激源的开始。本研究的第一个研究目的是：确定实习医生在实习压力开始后抑郁症状的纵向轨迹。这将使候选人能够实现研究的第一个培训目标：在纵向设计和分析技术方面奠定坚实的基础。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(单核苷酸多态和拷贝数变异)与实习压力在实习压力下抑郁症状水平和轨迹上的交互作用。这将使候选人能够实现研究的第二个培训目标：开发先进基因组工具方面的专业知识。 与公共健康相关：大约六分之一的美国人在生活中的某个时候会受到严重抑郁症的影响。根据世界卫生组织的数据，就疾病相关残疾而言，抑郁症很快将成为仅次于心脏病的第二大疾病。不幸的是，目前可用的抑郁症治疗方法只有部分有效。该项目旨在帮助发现新的生物途径，可以有针对性地开发更有效、更精确的抗抑郁药物治疗。

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.