Mapping Neural Circuit Biotypes to Symptoms and Behavioral Dimensions of Depression and Anxiety

Abstract

Background: Despite tremendous advances in characterizing human neural circuits that govern emotional and cognitive functions impaired in depression and anxiety, we lack a circuit-based taxonomy for depression and anxiety that captures transdiagnostic heterogeneity and informs clinical decision making.

Methods: We developed and tested a novel system for quantifying 6 brain circuits reproducibly and at the individual patient level. We implemented standardized circuit definitions relative to a healthy reference sample and algorithms to generate circuit clinical scores for the overall circuit and its constituent regions.

Results: In new data from primary and generalizability samples of depression and anxiety (N = 250), we demonstrated that overall disconnections within task-free salience and default mode circuits map onto symptoms of anxious avoidance, loss of pleasure, threat dysregulation, and negative emotional biases-core characteristics that transcend diagnoses-and poorer daily function. Regional dysfunctions within task-evoked cognitive control and affective circuits may implicate symptoms of cognitive and valence-congruent emotional functions. Circuit dysfunction scores also distinguished response to antidepressant and behavioral intervention treatments in an independent sample (n = 205).

Conclusions: Our findings articulate circuit dimensions that relate to transdiagnostic symptoms across mood and anxiety disorders. Our novel system offers a foundation for deploying standardized circuit assessments across research groups, trials, and clinics to advance more precise classifications and treatment targets for psychiatry.

Keywords: Anxiety; Biotype; Clinical translation; Depression; Functional brain circuit imaging; Precision mental health.