Neural Dimensions of Threat Reactivity and Regulation for Understanding Anxiety

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DESCRIPTION (provided by applicant): The immediate goal of this project is to use functional imaging to define dimensional constructs for reactivity and regulation of potential threat, within the Negative Valence system of the Research Domain Criteria (RDoC). By using these constructs we ground the understanding of anxiety in neural mechanisms, rather than using pre-set diagnostic boundaries, which have inherent assumptions about the structure of anxiety symptoms. In our community, the experience of anxiety is prevalent, and costs $47 billion per year in care and lost time. A wide range of anxiety disorders share common symptoms of anxious arousal, and show hyper- reactivity of the amygdala in functional imaging studies, which we call excessive "Threat reactivity". Some of these disorders also involve a more generalized loss of adaption accompanied by more cognitive experiences of anxiety, such as apprehensive expectations. They show hypo-activation of the ventral-rostral anterior cingulate, which we call poor "Threat regulation". Given the commonalities in anxiety phenomena and imaging findings, our goal is to determine whether imaging-defined dimensions of Threat reactivity and regulation provide a primary organizing principle for distinguishing specific features of anxiety and mood symptoms, the behaviors they generate, and their impact on the real world capacity to function socially and at work. To do this we will recruit all people who come through a large community psychology clinic which attends to a broad spectrum of anxiety and mood-related symptoms. These participants will be unmedicated and studied using a coordinated battery of functional imaging, behavioral, self-report and genetic probes, with well established paradigms for threat reactivity and regulation. The immediate aim is to determine if imaging-defined dimensions of amygdala threat reactivity and anterior cingulate threat regulation relate to severity of anxiety symptoms, specifically anxious arousal and apprehensive expectations. A second aim is to determine how these dimensions also relate in a cohesive way to behavioral performance in emotional and cognitive domains since, for instance, disruptions to threat processing can temporarily impair cognitive control. The third aim of the study is to assess how the imaging-defined dimensions affect real world functions related to burden of illness, specifically social functioning, quality of life and work productivity. This will create a personalized medicine approach for the treatment of anxiety disorders that will lead to specific treatments most likely t result in remission of symptoms. Outcomes will result in conceptually valid constructs for understanding what neural mechanisms generate specific experiences of anxiety.