Translating Across Circuits and Genetics Toward Progress in Fear- and Anxiety-Related Disorders

Abstract

Anxiety and fear-related disorders are common and disabling, and they significantly increase risk for suicide and other causes of morbidity and mortality. However, there is tremendous potential for translational neuroscience to advance our understanding of these disorders, leading to novel and powerful interventions and even to preventing their initial development. This overview examines the general circuits and processes thought to underlie fear and anxiety, along with the promise of translational research. It then examines some of the data-driven "next-generation" approaches that are needed for discovery and understanding but that do not always fit neatly into established models. From one perspective, these disorders offer among the most tractable problems in psychiatry, with a great deal of accumulated understanding, across species, of neurocircuit, behavioral, and, increasingly, genetic mechanisms, of how dysregulation of fear and threat processes contributes to anxiety-related disorders. One example is the progressively sophisticated understanding of how extinction underlies the exposure therapy component of cognitive-behavioral therapy approaches, which are ubiquitously used across anxiety and fear-related disorders. However, it is also critical to examine gaps in our understanding between reasonably well-replicated examples of successful translation, areas of significant deficits in knowledge, and the role of large-scale data-driven approaches in future progress and discovery. Although a tremendous amount of progress is still needed, translational approaches to understanding, treating, and even preventing anxiety and fear-related disorders offer great opportunities for successfully bridging neuroscience discovery to clinical practice.

Keywords: Amygdala; Anterior Cingulate; Anxiety Disorders; Fear Extinction; GWAS; Posttraumatic Stress Disorder.