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.
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.
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