Genetics of Fear and Anxiety Disorders

描述(申请人提供)：这项K08指导临床科学家发展奖建议为约翰·M·赫特玛博士提供恐惧和焦虑症遗传学方面的高级研究培训。世界著名的精神病学遗传学研究员肯尼斯·S·肯德勒博士将担任赫特马博士的主要赞助人。培训将在弗吉尼亚联邦大学的弗吉尼亚精神病学和行为遗传学研究所进行，该研究所为培训和研究的进行提供了丰富、刺激的环境。赫特玛博士建议接受流行病学、统计学和分子遗传学方面的培训，以及测量焦虑相关特征的实验方法，包括心理生理学和神经成像。具体的研究目标包括：i)使用纵向设计检验焦虑症自我报告测量的稳定性、可靠性和遗传性；ii)确定焦虑症之间观察到的高共病程度是由它们之间共有的遗传和环境因素决定的，包括特定的个体风险因素，如性别、早期环境、应激性生活事件等；iii)确定神经质和焦虑症之间的遗传相关性以及它们之间的因果关系；iv)阐明由先前存在的焦虑症引起的严重抑郁风险增加的遗传和环境因素以及性别对这种关系的影响；V)了解人类恐惧条件反射的遗传结构，以及这在多大程度上与恐惧症相同。此外，赫特马博士打算将培训中获得的知识应用于设计先导性研究，将弗吉尼亚双胞胎登记处的双胞胎样本中与焦虑相关的实验数据结合起来，将这些数据与现有的自我报告焦虑量表数据库结合起来。这项研究培训计划将允许赫特玛博士在建议书结束时成为焦虑症遗传学方面的独立研究员，寻求通过将自我报告和实验得出的与焦虑相关的测量方法与连锁和关联研究相结合，进一步扩展这项工作，以确定与焦虑症相关的遗传基因和大脑机制。

DESCRIPTION (provided by applicant): This K08 Mentored Clinical Scientist Development Award proposes to provide advanced research training in the genetics of fear and anxiety disorders for Dr. John M. Hettema, M.D., Ph.D. Dr. Kenneth S. Kendler, M.D., a world renowned researcher in psychiatric genetics, will serve as Dr. Hettema's primary sponsor. The training will take place at the Virginia Institute for Psychiatric and Behavioral Genetics of Virginia Commonwealth University, which provides a rich, stimulating environment for the conduct of training and research. Dr. Hettema proposes to receive training in epidemiology, statistical and molecular genetics, and experimental methods for measuring anxiety-related traits, including psychophysiology and neuroimaging. Specific research objectives include i) examining the stability, reliability, and heritability of self-report measures in anxiety disorders using a longitudinal design; ii) determine the extent to which the high comorbidity observed between the anxiety disorders is determined by genetic and environmental factors shared between them, including specific individual risk factors such as gender, early enviroment, stressful life events, etc.; iii) determine the genetic correlations between neuroticism and the anxiety disorders and the causal relations between them; iv) elucidate the genetic and environmental factors underlying the increased risk for major depression caused by pre-existing anxiety disorders and what effects gender has on this relationship; v) understand the genetic structure of fear conditioning in humans and to what extent this is shared with phobias. In addition, Dr. Hettema intends to apply knowledge gained in training to design pilot studies that incorporate experimentally derived anxiety-related measures from a genetically informative sample of twins from the Virginia Twin Registry, combining this data with the existing database of self-report anxiety measures. This research training plan will allow Dr. Hettema to emerge at the end of the proposal period as an independent researcher in the genetics of anxiety disorders, seeking to extend this work further by combining self-report and experimentally derived anxiety-related measures with linkage and association studies to identify genetic loci and brain mechanisms involved in the anxiety disorders.