There is an urgent need to derive quantitative measures based on coherent neurobiological dysfunctions or ‘biotypes’ to enable stratification of patients with depression and anxiety. We used task-free and task-evoked data from a standardized functional magnetic resonance imaging protocol conducted across multiple studies in patients with depression and anxiety when treatment free (n = 801) and after randomization to pharmacotherapy or behavioral therapy (n = 250). From these patients, we derived personalized and interpretable scores of brain circuit dysfunction grounded in a theoretical taxonomy. Participants were subdivided into six biotypes defined by distinct profiles of intrinsic task-free functional connectivity within the default mode, salience and frontoparietal attention circuits, and of activation and connectivity within frontal and subcortical regions elicited by emotional and cognitive tasks. The six biotypes showed consistency with our theoretical taxonomy and were distinguished by symptoms, behavioral performance on general and emotional cognitive computerized tests, and response to pharmacotherapy as well as behavioral therapy. Our results provide a new, theory-driven, clinically validated and interpretable quantitative method to parse the biological heterogeneity of depression and anxiety. Thus, they represent a promising approach to advance precision clinical care in psychiatry. Personalized brain circuit measures quantified using a new imaging technology in 801 patients with depression and anxiety identify six biotypes with unique symptoms, behaviors and responses to different types of treatment.

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A study involving 801 patients with depression and anxiety used fMRI data to identify six distinct brain circuit biotypes. These biotypes demonstrate unique patterns of brain connectivity and activation and correlate with symptoms and treatment responses. The research suggests that personalized brain circuit scores can help stratify patients for more effective precision treatments in psychiatry.

Personalized brain circuit scores identify clinically distinct biotypes in depression and anxiety