NEUROCIRCUITRY UNDERLYING RISK AND RESILIENCE TO SOCIAL ANXIETY DISORDER
Contract grant sponsor: National Institute of Mental Health; Contract grant numbers: K01-MH083052, JUB; F30-MH097344, JAC; T32-MH018921; Contract grant sponsor: National Institute on Drug Abuse; Contract grant numbers: K12-DA000357, MMB; R21-DA031441, RLC; R21-DA033341, RLC; Contract grant sponsor: Eunice Kennedy Shriver National Institute of Child Health and Human Development; Contract grant number: R21-HD053766, RLC; Contract grant sponsor: Vanderbilt Institute for Clinical and Translational Research (NCRR); Contract grant number: UL1-RR024975; Contract grant sponsor: National Center for Advancing Translational Sciences; Contract grant number: 2-UL1-TR000445–06; Contract grant sponsor: Vanderbilt Medical Scholars Program (NIH); Contract grant number: TL1-RR024978; Contract grant sponsor: Vanderbilt Medical Scientist Training Program (NIGMS); Contract grant number: T32-GM07347; Contract grant sponsor: Vanderbilt University Institute of Imaging Science.
Almost half of children with an inhibited temperament will develop social anxiety disorder by late adolescence. Importantly, this means that half of children with an inhibited temperament will not develop social anxiety disorder. Studying adults with an inhibited temperament provides a unique opportunity to identify neural signatures of both risk and resilience to social anxiety disorder.
Functional magnetic resonance imaging (fMRI) was used to measure brain activation during the anticipation of viewing fear faces in 34 young adults (17 inhibited, 17 uninhibited). To identify neural signatures of risk, we tested for group differences in functional activation and connectivity in regions implicated in social anxiety disorder, including the prefrontal cortex, amygdala, and insula. To identify neural signatures of resilience, we tested for correlations between brain activation and both emotion regulation and social anxiety scores.
Inhibited subjects had greater activation of a prefrontal network when anticipating viewing fear faces, relative to uninhibited subjects. No group differences were identified in the amygdala. Inhibited subjects had more negative connectivity between the rostral anterior cingulate cortex (ACC) and the bilateral amygdala. Within the inhibited group, those with fewer social anxiety symptoms and better emotion regulation skills had greater ACC activation and greater functional connectivity between the ACC and amygdala.
These findings suggest that engaging regulatory prefrontal regions during anticipation may be a protective factor, or putative neural marker of resilience, in high-risk individuals. Cognitive training targeting prefrontal cortex function may provide protection against anxiety, especially in high-risk individuals, such as those with inhibited temperament.