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、地方或事物感到恐惧和回避的倾向。这种可遗传的、进化上保守的、既定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风险因素和神经脆弱性提供了初步证据，但仍需要全面、综合的观点。在单个队列中进行多个测量水平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： 候选人提议对抑制气质中的遗传、神经和情感因素进行研究。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基因相关的等位基因变异来衡量。将使用激活和时间动力学以及事件相关的功能磁共振成像新颖范例来评估杏仁核和相关旁边缘区域的大脑功能。情绪、性格、焦虑和抑郁都会被测量。针对遗传、神经和情感变量差异的组间测试将通过遗传、神经和情感因素之间相互关系的分析模型测试来补充。职业发展计划：范德比尔特大学的培训将强调神经影像和遗传学所需的技能，包括：神经影像方法和分析、时间动力学分析、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、影像学、精神遗传学和统计遗传学领域的专家将提供指导和咨询。该培训和研究经验计划将为候选人提供必要的深度和广度的知识，使其成为一名独立的情感神经科学家，专注于识别、量化和阐述气质如何增加精神疾病的风险。公共健康相关性：SAD 是一种常见的精神疾病，影响着 1500 万人，并且通常与其他焦虑症、情绪障碍和酒精使用障碍共存。 SAD 可能是一种严重且使人衰弱的疾病，会影响日常功能并降低生活质量。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、新颖的干预措施和初级预防策略提供新的信息。