Genetics of Fear and Anxiety Disorders

描述（由申请人提供）：本K08指导临床科学家发展奖旨在为John M. Hettema博士提供恐惧和焦虑障碍遗传学方面的高级研究培训。世界知名的精神病学遗传学研究人员Kenneth S. Kendler博士将作为Hettema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提供了丰富、刺激的环境。Hettema博士建议接受流行病学、统计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影像学。具体的研究目标包括i)使用纵向设计检验焦虑障碍自我报告测量的稳定性、可靠性和遗传性；Ii)确定在何种程度上观察到焦虑症之间的高合并症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、压力生活事件等；Iii)确定神经质与焦虑症的遗传相关性及其因果关系；Iv)阐明遗传和环境因素导致先前存在的焦虑障碍导致重度抑郁症风险增加，以及性别对这种关系的影响；V)了解人类恐惧条件反射的基因结构，以及这在多大程度上与恐惧症相同。此外，Hettema博士打算将在培训中获得的知识应用于设计试点研究，该研究将从弗吉尼亚双胞胎登记处的双胞胎遗传信息样本中实验得出的焦虑相关措施，并将这些数据与现有的自我报告焦虑措施数据库相结合。该研究培训计划将使Hettema博士在提案期结束时成为焦虑症遗传学的独立研究员，寻求通过将自我报告和实验得出的焦虑相关措施与联系和关联研究相结合，进一步扩展这项工作，以确定与焦虑症有关的遗传位点和大脑机制。

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.