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.

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 Michigan Ann Arbor
Schools of Medicine
Ann Arbor
United States
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MacNamara, Annmarie; Klumpp, Heide; Kennedy, Amy E et al. (2017) Transdiagnostic neural correlates of affective face processing in anxiety and depression. Depress Anxiety 34:621-631
Tadayonnejad, Reza; Klumpp, Heide; Ajilore, Olusola et al. (2016) Aberrant pulvinar effective connectivity in generalized social anxiety disorder. Medicine (Baltimore) 95:e5358
Klumpp, Heide; Fitzgerald, Daniel A; Piejko, Katherine et al. (2016) Prefrontal control and predictors of cognitive behavioral therapy response in social anxiety disorder. Soc Cogn Affect Neurosci 11:630-40
Nelson, Brady D; Fitzgerald, Daniel A; Klumpp, Heide et al. (2015) Prefrontal engagement by cognitive reappraisal of negative faces. Behav Brain Res 279:218-25
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
Gorka, Stephanie M; Fitzgerald, Daniel A; de Wit, Harriet et al. (2014) Cannabinoid modulation of amygdala subregion functional connectivity to social signals of threat. Int J Neuropsychopharmacol 18:
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
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
Phan, K Luan; Coccaro, Emil F; Angstadt, Mike et al. (2013) Corticolimbic brain reactivity to social signals of threat before and after sertraline treatment in generalized social phobia. Biol Psychiatry 73:329-36
Sripada, Chandra Sekhar; Phan, K Luan; Labuschagne, Izelle et al. (2013) Oxytocin enhances resting-state connectivity between amygdala and medial frontal cortex. Int J Neuropsychopharmacol 16:255-60

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