Adolescent anxiety disorders, e.g., social phobia, are common, cause significant impairment, and predict risk of anxiety disorders and depression in adulthood. Patients with social phobia exhibit biases toward threat and inappropriate fear responses to social stimuli. Abnormal threat biases and fear responses learned early may be more resistant to treatment than fears learned later in life. Understanding how these biases are learned in adolescents will provide insights for developing treatments. Fear conditioning, a learning process that associates "threat" with a neutral stimulus, and extinction, a learning process that associates "safety" with the previously conditioned stimulus might explain how these threat biases are learned in anxiety. Threat appraisal biases in social phobia may emerge from patients'difficulty in learning how to discriminate social "threat" from "safety". In addition, extinction-related processes may depend on brain regions that mature later in development, such as the ventromedial prefrontal cortex (vmPFC). The research objective of this application is to characterize neural perturbations associated with threat appraisal when recalling the extinction memory. The current proposal is the first effort to study the neural regions mediating threat biases during extinction recall in healthy development and adolescent social phobia. Our research group developed a fear conditioning paradigm using an ecologically valid source of threat (i.e., a "screaming lady") to study fear learning and a paradigm using morphed faces to examine threat appraisal during extinction recall. Using these two tasks, differences in normal and adolescent social anxiety are expected in vmPFC activation in response to threat appraisal during extinction recall. In addition, it is expected that vmPFC activation predicts treatment response in adolescents with social anxiety. The rationale for the proposed research is that data regarding neural perturbations in threat appraisal during extinction recall in adolescents with and without anxiety disorders will provide the basis for novel behavioral treatments. This proposal is consistent with Dr. Jennifer C. Britton's broad research goals, which include understanding neural dysfunction in pediatric anxiety and using that knowledge to inform the development of novel treatments. Through this Pathway to Independence Award, Dr. Britton will acquire clinical and development research training in pediatric anxiety at the National Institute of Mental Health. This training is necessary for Dr. Britton to become an independent investigator who studies the neural correlates of pediatric anxiety. Dr. Britton will extend the findings of the proposed work to study questions concerning disorder-specificity, comorbid disorders, and the development of these neural perturbations and will develop novel behavioral treatments to target these regions.

Public Health Relevance

. Pediatric anxiety disorders, like social phobia, are common and predict both adult anxiety and mood disorders. This functional magnetic resonance imaging study is the first to examine the neural regions mediating the recall of fear and extinction learning during normal development and in adolescents with social phobia. Understanding the pathophysiology early in the course of social phobia can inform the development of effective treatments, thereby, impacting the mental health of both youth and adults.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Transition Award (R00)
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Special Emphasis Panel (NSS)
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Garriock, Holly A
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University of Miami Coral Gables
Schools of Arts and Sciences
Coral Gables
United States
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Chen, Gang; Saad, Ziad S; Britton, Jennifer C et al. (2013) Linear mixed-effects modeling approach to FMRI group analysis. Neuroimage 73:176-90
Britton, Jennifer C; Grillon, Christian; Lissek, Shmuel et al. (2013) Response to learned threat: An FMRI study in adolescent and adult anxiety. Am J Psychiatry 170:1195-204