Neurocircuitry of treatment in anxiety disorders

Understanding how treatments change neurobiology is critical to developing predictors of treatment response. This is especially true for anxiety disorders-the most common psychiatric disorders across the lifespan. With this in mind, we examined neurofunctional predictors of treatment response and neurofunctional changes associated with treatment across anxiety disorders.

PubMed/Medline was searched for prospective treatment studies that included parallel examinations of functional activation or connectivity (both task-based and resting state) in adults and youth with panic disorder and generalized, separation, and/or social anxiety disorders published before April 30, 2021. All studies examining baseline predictors or changes related to pharmacologic and psychotherapeutic treatment of DSM-TV and DSM-5 anxiety disorders were included. Demographic, clinical, and treatment data as well as neurofunctional outcomes were extracted and summarized.

Twenty-nine studies examined changes in functional activation and/or connectivity (56 treatment arms) related to treatment and twenty-three examined neurofunctional predictors of treatment response. Predictors of treatment response and treatment-related neurofunctional changes were frequently observed within amygdala-prefrontal circuits. However, immense heterogeneity and few replication studies preclude a cohesive neurofunctional treatment response model across anxiety disorders.

The extant literature describing neurofunctional aspects of treatment response in anxiety disorders is best viewed as a partially constructed scaffold on which to build a clinically translatable set of robust neuroimaging biomarkers that can be used to guide treatment and to select from available treatment. The construction of this understanding will require harmonization of analytic and task approaches, larger samples, and replication of component studies.