Neuroimaging and Genetic Study of Inhibited Temperament

描述（由申请人提供）：这是一份指导研究科学家发展奖的申请，重点是发展神经影像学和遗传学方法方面的专业知识，以研究精神疾病的气质脆弱性。压抑气质是指对新的人、地方或事物有恐惧和回避的倾向。这种遗传的、进化保守的、成熟的表型是社交焦虑障碍（SAD）和抑郁症的一个危险因素。最近的研究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。在单一队列中进行多层次测量的研究将为开发抑制气质的基因型-表型关系模型提供必要的信息，以进一步了解增加风险的机制。研究计划：拟对抑制气质的遗传、神经、情感因素进行研究。将使用极端不一致的表型方法，导致两个不同的气质群体。遗传风险因素将通过与单胺能神经递质和应激激素系统相关的基因的等位变异来测量。杏仁核和相关旁缘区的脑功能将通过事件相关fMRI新范式的激活和时间动态来评估。情绪、性格、焦虑和抑郁将被测量。对遗传、神经和情感变量差异的组间测试将辅以对遗传、神经和情感因素之间相互关系的分析模型测试。职业发展规划：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和统计遗传学。焦虑/情绪障碍、气质、影像、精神遗传学和统计遗传学领域的专家将提供指导和咨询。本课程的培训和研究经验将为候选人提供必要的深度和广度知识，使其成为一名独立的情感神经科学家，专注于气质如何增加精神疾病风险的识别、量化和阐述。公共卫生相关性：SAD是一种常见的精神疾病，影响1500万人，通常与其他焦虑症、情绪障碍和酒精使用障碍合并症。SAD是一种严重的、使人衰弱的疾病，影响日常功能，降低生活质量。了解抑制性气质如何增加SAD的风险，将为开发具有这些气质脆弱性的儿童和青少年精神疾病的识别方法、新的干预措施和初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.