Social anxiety disorder is a common, chronic, and debilitating disorder, which typically begins during adolescence, and is associated with developmental risk factors, including childhood inhibited temperament. Previous studies have examined neural substrates of social anxiety disorder and inhibited temperament in adults, and found key differences in brain activation in the amygdala, bed nucleus of the stria terminalis (BNST), and dorsal anterior cingulate cortex (dACC). These differences in brain activation may represent neural risk factors for social anxiety disorder. However, it is crucial to determine if these risk factors are present early in development, in children at high risk for developing social anxiety disorder (inhibited temperament). In order to study changes in neural circuitry in high-risk children, we will focus on anticipatory processing - a key psychological process in social anxiety disorder and inhibited temperament. Prior to a social event, an individual may experience anticipatory worry, accompanied by physiological arousal, including sweating, shaking, and heart racing. A prior study by our lab examined differences in brain activation during anticipation of aversive social stimuli in adults and found that when adults with an inhibited temperament were anticipating viewing fear faces, they had increased activation in the amygdala and BNST, and decreased activation in the dACC. In the proposed project, we will test for differences during anticipation of viewing negative social stimuli between children at hig risk for developing social anxiety disorder (inhibited temperament) and those at low risk (uninhibited temperament) with a functional MRI task we have used successfully in young adults. We hypothesize that high-risk children will show differences in brain activation during anticipation of viewing fear faces, including increased amygdala and BNST activation, and decreased dACC activation. Because differences in brain activation between groups may be related to differences in connectivity between brain regions, we will also test for group differences in connectivity between the amygdala and dACC. We expect that children at high-risk for developing social anxiety disorder will decreased connectivity between the amygdala and the dorsal anterior cingulate cortex. The project sponsors will be Dr. Jennifer Blackford-an expert in inhibited temperament and fMRI-and Dr. Uma Rao-a nationally recognized expert on child psychopathology. I will be trained in neuroimaging techniques and child psychopathology via direct mentoring by Dr. Blackford and Dr. Rao, as well as independent studies with Dr. Bruce McCandliss and Dr. Baxter Rogers (consultants). I will also gain other experimental skills through coursework, independent studies, and seminars. The skills I gain during this fellowship will help to prepare me for a successful career as a physician- scientist, focused the neurodevelopment of anxiety disorders in children and adolescents.

Public Health Relevance

Neural substrates of social anxiety disorder in adults have been identified;however, neural substrates of risk for social anxiety disorder have yet to be found. Anticipation is a key psychological process in social anxiety disorder. The proposed project will determine neural substrates of anticipation in children at high risk for developing social anxiety disorder.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
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Special Emphasis Panel (ZRG1)
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Sarampote, Christopher S
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Vanderbilt University Medical Center
Schools of Medicine
United States
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Avery, S N; Clauss, J A; Blackford, J U (2016) The Human BNST: Functional Role in Anxiety and Addiction. Neuropsychopharmacology 41:126-41
Clauss, Jacqueline Alexandra; Benningfield, Margaret M; Rao, Uma et al. (2016) Altered Prefrontal Cortex Function Marks Heightened Anxiety Risk in Children. J Am Acad Child Adolesc Psychiatry 55:809-16
Clauss, J A; Avery, S N; Blackford, J U (2015) The nature of individual differences in inhibited temperament and risk for psychiatric disease: A review and meta-analysis. Prog Neurobiol 127-128:23-45
Clauss, Jacqueline A; Seay, April L; VanDerKlok, Ross M et al. (2014) Structural and functional bases of inhibited temperament. Soc Cogn Affect Neurosci 9:2049-58
Avery, Suzanne N; Clauss, Jacqueline A; Winder, Danny G et al. (2014) BNST neurocircuitry in humans. Neuroimage 91:311-23
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
Clauss, Jacqueline A; Avery, Suzanne N; VanDerKlok, Ross M et al. (2014) Neurocircuitry underlying risk and resilience to social anxiety disorder. Depress Anxiety 31:822-33