Neuroimaging and Genetic Study of Inhibited Temperament

抑制气质的神经影像学和遗传学研究

• 批准号: 7583923
• 负责人: JENNIFER URBANO BLACKFORD
• 金额: $ 14.18万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2013-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7583923
• 关键词: Adolescent; Affect; Affective; Amygdaloid structure; Anxiety; Anxiety Disorders; Area; Brain; Child; Complement; Complex; Consultations; Corticotropin-Releasing Hormone; Dependence; Development Plans; Disease; Dopamine; Emotional; Emotions; Event; Face; Fright; Functional Magnetic Resonance Imaging; Genes; Genetic; Genotype; Glucocorticoids; Hormones; Image; Intervention; Knowledge; Measurement; Measures; Mental disorders; Mentored Research Scientist Development Award; Mentorship; Methods; Modeling; Mood Disorders; Moods; Neuroanatomy; Neurotic Disorders; Neurotransmitters; Norepinephrine; Personality; Persons; Phenotype; Physiology; Predisposition; Prevention strategy; Primary Prevention; Quality of life; Recovery; Research; Research Training; Rewards; Risk; Risk Factors; Role; Serotonin; Stress; System; Temperament; Testing; Training; Training Programs; Universities; Variant; alcohol use disorder; career development; cohort; daily functioning; depression; emotional factor; experience; gamma-Aminobutyric Acid; genetic risk factor; negative mood; neuroimaging; novel; positive mood; psychogenetics; public health relevance; relating to nervous system; response; skills; social; trait

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.

描述（由申请人提供）：这是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的专业知识，以研究精神病的气质脆弱性。抑制的气质是对新朋友，地方或以恐惧和回避的反应的倾向。这种可遗传的，有助于保存和建立的表型是社交焦虑症（SAD）和抑郁症的危险因素。最近的研究为抑制气质的遗传危险因素和神经脆弱性提供了初步证据，但仍然需要一种全面的，综合的观点。一项在单个队列中具有多个测量水平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，以进一步了解我们对增加风险的机制的理解。研究计划：候选人建议在抑制气质中对遗传，神经和情绪因素进行研究。将使用一种极端不一致的表型方法，导致两个不同的气质组。遗传危险因素将通过与单胺能神经递质和应力激素系统相关的等位基因变异来衡量。将使用与事件相关的fMRI新颖性范式来评估杏仁核和相关paralimbic区域的大脑功能。心情，个性，焦虑和抑郁症将被衡量。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影像学和遗传学所需的技能，并将包括：神经影像学方法和分析，时间动态分析，神经解剖学和生理学，复杂性状的遗传方法以及统计遗传学。焦虑/情绪障碍，气质，成像，精神遗传学和统计遗传学领域的专家将提供指导和咨询。这项培训和研究经验计划将为候选人提供必要的深度和知识，成为一种独立的情感神经科学家，专注于识别，定量和阐述气质如何增加精神病的风险。公共卫生相关性：SAD是一种影响1500万人的常见精神病，通常与其他焦虑症，情绪障碍和酒精使用障碍合并。 SAD可能是一种严重而令人衰弱的疾病，对日常运作和生活质量的影响影响。了解抑制性质如何增加SAD的风险将为开发鉴定方法，新颖的干预措施以及具有这些气质脆弱性的儿童和青少年精神病的主要预防策略提供新的信息。