NEURO-GENETIC MARKERS OF SOCIAL ANXIETY DISORDER

点击翻译按钮获取中文摘要

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Social anxiety disorder, also known as social phobia, is an anxiety disorder characterized by excessive fear and/or avoidance of exposure to social situations that involve potential scrutiny by others. Little is known about the pathophysiologic mechanisms that underlie social anxiety disorder, although a neurobiologic basis is strongly suspected. While selective serotonin reuptake inhibitors (SSRI) are widely used in the treatment of social anxiety disorder (SAD), as many as half of the patients with the disorder fail to respond to this first-line treatment despite adequate dosage and duration. Little is known about the neurobiological factors that would predict which patients will or will not respond to respond to treatment, and thus, guidance towards optimal therapeutic strategies remain largely uninformed. Converging evidence suggests that two related biomarkers relevant to social anxiety may be involved in mediating the therapeutic response to SSRI treatment. They are: 1) amygdala reactivity to social threat, and 2) the serotonin transporter genetic polymorphism (5-HTTLPR). The overall goal of the proposed project is to investigate whether amygdala activation to socially salient stimuli/interactions and genetic variation in the serotonin transporter polymorphism are associated with response to SSRI treatment in SAD. In the context of an open-label clinical trial of sertraline, this study consists of pre- and post-treatment fMRI of amygdala reactivity and pre-treatment DNA genotyping of the 5-HTTLPR in 80 patients with generalized SAD and 80 matched healthy controls (HC) in order to examine the relationship between these neuro-genetic markers (brain response and 5-HTTLPR genotype) and treatment response.