Risk for Depression Stress and Neuroendocrine Function

描述(由申请人提供)：目前K23申请的目的是为候选人发展成为抑郁症发病机制中一名高效的独立临床研究员提供支持。一项全面的五年职业发展和研究计划将在劳伦斯·H·普莱斯博士的指导下进行。普莱斯博士是一位知名的资深科学家，在抑郁症的神经生物学研究方面拥有国际公认的专业知识，并拥有指导初级教职员工的丰富经验。此外，还组建了一个由主持人和顾问组成的小组，就拟议奖项的培训和研究部分提供专家指导。 职业发展计划经过精心设计，旨在提供以下领域的深入培训：抑郁症的神经生物学和下丘脑-垂体-肾上腺(HPA)轴、压力和逆境在抑郁症发病机制中的作用、抑郁症的神经心理学和神经内分泌功能，以及研究伦理和方法。此外，还将进行纵向方法方面的进一步培训，以准备在颁奖的第4-5年提交预期的纵向R01。这些领域的正规培训将通过校内和校外教学和课程、指导、研究、研究小组会议和参加国家研究会议的课程获得。 拟议的研究计划包括检查神经内分泌挑战测试的应激激素反应与抑郁症家族史和童年逆境史的关系。其次，我们将研究HPA失调与认知功能之间的关系。这项研究为深入了解抑郁症的发病机制以及早期应激和HPA轴的过度活动的影响提供了潜在的可能性。这项研究的结果，加上纵向研究的设计、实施和分析方面的培训，将构成将于第5年开始提交的R01的基础。这项R01建议将需要对儿童逆境、母亲情绪和焦虑障碍对神经内分泌功能障碍和精神病理学发展的影响进行前瞻性的纵向调查。

DESCRIPTION (provided by applicant): The purpose of the current K23 application is to provide support for the candidate's development into a highly productive independent clinical investigator in the pathogenesis of depression. A comprehensive five-year career development and research plan will be undertaken with the mentorship of Dr. Lawrence H. Price, an established senior scientist with internationally recognized expertise in neurobiological investigations of depression and extensive experience mentoring junior faculty. In addition, a team of comentors and consultants has been assembled to provide expert guidance in the training and research components of the proposed award. The Career Development Plan has been carefully designed to provide in-depth training in the following domains: the neurobiology of depression and the hypothalamic-pituitary-adrenal (HPA) axis, the role of stress and adversity in the pathogenesis of depression, the neuropsychology of depression and neuroendocrine function, and research ethics and methodology. In addition, further training in longitudinal methodology will be undertaken in preparation for a prospective, longitudinal R01 submission in Year 4-5 of the award. Formal training in these areas will be obtained through a curriculum of intramural and extramural didactics and coursework, preceptorships, research, research group meetings, and participation in national research meetings. The proposed research plan involves an examination of stress hormone responses to neuroendocrine challenge tests in relation to family history of depression and history of childhood adversity. Secondly, associations between HPA dysregulation and cognitive functioning will be investigated. This study offers the potential for substantial insight into the pathogenesis of depression and the effects of early-life stress and hyperactivity of the HPA axis. Results of this study, in combination with training in the design, implementation, and analysis of longitudinal studies, will comprise the basis of an R01 to be submitted at the beginning of Year 5. This R01 proposal will entail a prospective longitudinal investigation of the effects of childhood adversity and maternal mood and anxiety disorders on the development of neuroendocrine dysfunction and psychopathology.