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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01MH083052-05
Application #
8231412
Study Section
Child Psychopathology and Developmental Disabilities Study Section (CPDD)
Program Officer
Wynne, Debra K
Project Start
2008-04-01
Project End
2013-09-30
Budget Start
2012-04-01
Budget End
2013-09-30
Support Year
5
Fiscal Year
2012
Total Cost
$144,648
Indirect Cost
$10,715
Name
Vanderbilt University Medical Center
Department
Psychiatry
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
Blackford, Jennifer Urbano; Clauss, Jacqueline A; Avery, Suzanne N et al. (2014) Amygdala-cingulate intrinsic connectivity is associated with degree of social inhibition. Biol Psychol 99:15-25
Avery, Suzanne N; Clauss, Jacqueline A; Winder, Danny G et al. (2014) BNST neurocircuitry in humans. Neuroimage 91:311-23
Benningfield, Margaret M; Blackford, Jennifer U; Ellsworth, Melissa E et al. (2014) Caudate responses to reward anticipation associated with delay discounting behavior in healthy youth. Dev Cogn Neurosci 7:43-52
Edmiston, Elliot Kale; Blackford, Jennifer Urbano (2013) Childhood maltreatment and response to novel face stimuli presented during functional magnetic resonance imaging in adults. Psychiatry Res 212:36-42
Watkins, Tristan J; Raj, Vidya; Lee, Junghee et al. (2013) Human ecstasy (MDMA) polydrug users have altered brain activation during semantic processing. Psychopharmacology (Berl) 227:41-54
Williams, Lisa E; Blackford, Jennifer Urbano; Luksik, Andrew et al. (2013) Reduced habituation in patients with schizophrenia. Schizophr Res 151:124-32
Charboneau, Evonne J; Dietrich, Mary S; Park, Sohee et al. (2013) Cannabis cue-induced brain activation correlates with drug craving in limbic and visual salience regions: preliminary results. Psychiatry Res 214:122-31
Blackford, Jennifer Urbano; Clauss, Jacqueline A (2013) Dr. Blackford and Ms. Clauss reply:. J Am Acad Child Adolesc Psychiatry 52:319-20
Blackford, Jennifer Urbano; Allen, Amil H; Cowan, Ronald L et al. (2013) Amygdala and hippocampus fail to habituate to faces in individuals with an inhibited temperament. Soc Cogn Affect Neurosci 8:143-50
Salomon, Ronald M; Karageorgiou, John; Dietrich, Mary S et al. (2012) MDMA (Ecstasy) association with impaired fMRI BOLD thalamic coherence and functional connectivity. Drug Alcohol Depend 120:41-7

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