Neuro-Genetic Markers of SSRI Treatment Response in Social Anxiety Disorder

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DESCRIPTION (provided by applicant): Project Summary: Through this Mentored Patient-Oriented Research Career Development Award (K23), the long-term objective of the candidate is to gain proficiency in research on the neurobiology and treatment of social anxiety disorder (SAD). Although approximately half of patients with SAD fail to respond to first-line selective serotonin reuptake inhibitor (SSRI) treatment despite adequate dose and duration, little is known about the neurophysiological mechanisms underlying treatment efficacy. Converging evidence suggests that amygdala reactivity to social threat and a functional polymorphism on the serotonin transporter gene (5-HTTLPR) are potential biomarkers of SSRI treatment response. The proposed research training and project focus on elucidating the neuro-genetic basis of pharmacologic treatment response in SAD through the application of brain functional magnetic resonance imaging (fMRI) and pharmacogenetics. To accomplish this goal, the candidate will build on his strong background in brain imaging of emotions and gain additional mentoring by experts in the fields of clinical psychopharmacology, pharmacogenetics, and SAD. Furthermore, the candidate will participate in formal coursework and carry out a research project closely aligned with his research training goals. In the context of an open-label clinical trial of sertraline, this study proposes to perform pre- and post-treatment fMRI of amygdala reactivity to harsh/negative face stimuli and pre-treatment DNA genotyping of the 5- HTTLPR in 80 patients with generalized SAD and 40 matched healthy controls in order to examine the relationship between these neuro-genetic markers and treatment response. By implementing this research project and training plan, the candidate will gain sufficient knowledge and skills to become an independent translational clinical neuroscience investigator in the field of social anxiety disorder, and advance our knowledge on the effect of genes on neurophysiology and treatment of anxiety disorders. Relevance: Social anxiety disorder is a highly prevalent, disabling, and difficult-to-treat chronic mental illness. The primary goal of this research is to identify neurobiological markers of treatment responsiveness in order to save patients costly and lengthy trials of medications that are unlikely to be effective and guide treatment towards modalities that have a greater probability of success.