This Mentored Patient-Oriented Career Development Award (K23) application is designed to advance the candidate's long-term career goal of becoming an independent clinician scientist to improve psychosocial treatment of social anxiety disorder (SAD), a major public health problem. SAD symptoms include excessive negative social-evaluative beliefs and attentional bias for threat-relevant stimuli (e.g., "harsh" faces). Neuroimaging evidence suggests SAD involves dysfunction in prefrontal regions that interact with limbic regions engaged in threat processing. Cognitive behavioral therapy (CBT) is a widely used first-line treatment in SAD;however, many do not fully recover with CBT. The cognitive component of CBT requires higher-order functions (e.g., ability to reframe a feared situation to make it less fearful). Therapeutic success is associated with reduction/elimination of negative beliefs and attentional bias even though modification of implicit bias is not a target of intervention. This has important implications for better understanding neural mechanisms of CBT. Specifically, it is not clear if reductions in negative beliefs and attentional bias are due to overlapping or relatively distinct prefrontal regions. The proposed project includes a hands-on pre/post-CBT functional magnetic resonance imaging (fMRI) study to elucidate specific neural mechanisms in SAD recovery. The candidate will build on her strong CBT background for SAD and gain mentoring by experts in the fields of brain imaging of emotion and emotion-cognition interactions (Drs. Phan, Liberzon);cognitive affective neuroscience (Drs. Phan, Abelson, Liberzon);attentional and cognitive probes of SAD and translational clinical trials (Drs. Gross, Amir);and psychotherapy outcome research (Drs. Himle, Rauch). Participants will comprise 50 patients with generalized SAD and 25 matched healthy controls. An attentional task to ignore harsh faces and a reappraisal task to reframe harsh faces will be used to examine the effects of CBT on prefrontal regions implicated in implicit and explicit emotion regulation, respectively. Short-term training goals are: 1) advanced training in Neuroimaging (fMRI) Research Methodology and Statistics, 2) increased knowledge in Cognitive Affective Neuroscience, and 3) advanced training in Psychosocial Treatment Clinical Trials Methodology. IMPACT: Social anxiety disorder is highly prevalent and disabling;a better understanding of CBT brain mechanisms and of individual differences in treatment response will improve our understanding of CBT thereby optimizing current interventions and contribute to the advancement of new, more refined therapies to increase the probability of therapeutic success.

Public Health Relevance

Cognitive behavioral treatment (CBT) is a widely used first-line treatment for social anxiety disorder (SAD), a prevalent, debilitating disorder. Although many do not fully recover from SAD with CBT, the specific mechanisms by which CBT exerts its therapeutic effects are unknown. The primary goal of this research is to discover the effects of CBT on brain function, particularly in relation to specific emotion regulation strategies implicated in CBT-namely, increased attentional control over threat stimuli and higher-order cognitive regulation of emotions evoked by threat-relevant stimuli. A better understanding of the brain mechanisms of CBT and of individual differences in treatment response in patients with SAD will improve our understanding of CBT mechanisms thereby optimizing current therapies and contributing to the advancement of improved therapies to increase the probability of therapeutic success.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Mentored Patient-Oriented Research Career Development Award (K23)
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Adult Psychopathology and Disorders of Aging Study Section (APDA)
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Chavez, Mark
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University of Illinois at Chicago
Schools of Medicine
United States
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Wheaton, Michael G; Fitzgerald, Daniel A; Phan, K Luan et al. (2014) Perceptual load modulates anterior cingulate cortex response to threat distractors in generalized social anxiety disorder. Biol Psychol 101:13-7
Klumpp, H; Fitzgerald, D A; Angstadt, M et al. (2014) Neural response during attentional control and emotion processing predicts improvement after cognitive behavioral therapy in generalized social anxiety disorder. Psychol Med 44:3109-21
Klumpp, Heide; Fitzgerald, Daniel A; Cook, Edwin et al. (2014) Serotonin transporter gene alters insula activity to threat in social anxiety disorder. Neuroreport 25:926-31
Klumpp, Heide; Fitzgerald, Daniel A; Phan, K Luan (2013) Neural predictors and mechanisms of cognitive behavioral therapy on threat processing in social anxiety disorder. Prog Neuropsychopharmacol Biol Psychiatry 45:83-91