Neuroimaging and Genetic Study of Inhibited Temperament

描述(由申请人提供)：这是一个导师研究科学家发展奖的申请，重点是发展神经成像和遗传学方法方面的专业知识，以研究精神疾病的气质易感性。克制气质是一种对陌生人、新地方或新事物做出恐惧和回避反应的倾向。这种可遗传的、进化上保守的、成熟的表型是社交焦虑症(SAD)和抑郁症的危险因素。最近的研究已经为抑制气质的遗传风险因素和神经脆弱性提供了初步证据，但仍需要一个全面、综合的观点。一项在单个队列中进行多水平测量的研究将提供必要的信息，以开发抑制气质的基因型-表型关系模型，以进一步了解增加风险的机制。研究计划：应聘者提议对受抑制的气质中的遗传、神经和情绪因素进行研究。将使用极端不协调的表型方法，产生两个不同的气质组。遗传风险因素将通过与单胺类神经递质和应激激素系统相关的基因相关的等位基因变异来衡量。杏仁核和相关边缘旁区域的大脑功能将通过事件相关的fMRI新奇范式，使用激活和时间动力学进行评估。将对情绪、个性、焦虑和抑郁进行测量。对遗传、神经和情绪变量差异的组间测试将与遗传、神经和情绪因素之间相互关系的分析模型测试相辅相成。职业发展计划：范德比尔特大学的培训将强调神经成像和遗传学所需的技能，包括：神经成像方法和分析、时间动力学分析、神经解剖学和生理学、复杂特征的遗传方法以及统计遗传学。焦虑/情绪障碍、气质、成像、精神病学遗传学和统计遗传学领域的专家将提供指导和咨询。这项培训和研究经验的计划将为候选人提供必要的深度和广度的知识，以成为一名独立的情感神经学家，专注于识别、量化和阐述气质如何增加精神疾病的风险。公共卫生相关性：悲伤是一种常见的精神疾病，影响着1500万人，通常与其他焦虑障碍、情绪障碍和酒精使用障碍并存。悲伤可能是一种严重的、使人虚弱的疾病，会影响日常功能，降低生活质量。了解压抑的气质如何增加SAD的风险，将为开发识别方法、新的干预措施以及对具有这些气质易感性的儿童和青少年的精神疾病的一级预防策略提供新的信息。

DESCRIPTION (provided by applicant): This is an application for a Mentored Research Scientist Development Award with a focus on developing expertise in neuroimaging and genetics methods to study temperamental vulnerabilities for psychiatric disease. Inhibited temperament is the predisposition to respond to new people, places or things with fear and avoidance. This heritable, evolutionarily-conserved, and well-established phenotype is a risk factor for social anxiety disorder (SAD) and depression. Recent studies have provided preliminary evidence for genetic risk factors and neural vulnerabilities for inhibited temperament, but a comprehensive, integrated view is still needed. A study with multiple levels of measurement in a single cohort will provide the necessary information to develop models of the genotype-phenotype relationships in inhibited temperament to further our understanding of the mechanisms which increase risk. Research Plan: The candidate proposes to conduct a study of genetic, neural and emotional factors in inhibited temperament. An extreme discordant phenotype method will be used, resulting in two divergent temperament groups. Genetic risk factors will be measured by allelic variation associated with genes involved in monoaminergic neurotransmitter and stress hormone systems. Brain function in the amygdala and related paralimbic areas will be assessed using both activation and temporal dynamics with an event-related fMRI novelty paradigm. Mood, personality, anxiety and depression will be measured. Between-group tests for differences in genetic, neural and emotional variables will be complemented with analytic model testing of interrelationships between genetic, neural and emotional factors. Career Development Plan: Training at Vanderbilt University will emphasize skills necessary for neuroimaging and genetics and will include: neuroimaging methods and analysis, temporal dynamics analysis, neuroanatomy and physiology, genetic approaches to complex traits, and statistical genetics. Experts in the fields of anxiety/mood disorders, temperament, imaging, psychiatric genetics and statistical genetics will provide mentorship and consultation. This program of training and research experience will provide the candidate with the necessary depth and breadth of knowledge to become an independent affective neuroscientist focused on the identification, quantification and elaboration of how temperament increases risk for psychiatric disease. PUBLIC HEALTH RELEVANCE: SAD is a common psychiatric disease affecting 15 million people and is often comorbid with other anxiety disorders, mood disorders, and alcohol use disorders. SAD can be a serious and debilitating disease with impact on daily functioning and reduced quality of life. Understanding how inhibited temperament increases risk for SAD will provide new information for developing methods for identification, novel interventions, and primary prevention strategies for psychiatric disease in children and adolescents with these temperamental vulnerabilities.