The broad structure of psychopathology in the All of Us Research Program

Given substantial comorbidity among, and considerable heterogeneity within, psychiatric diagnoses, researchers have suggested alternative systems for classifying psychopathology. The Hierarchical Taxonomy of Psychopathology (HiTOP) is a recently proposed framework for understanding mental disorders based on how symptoms and diagnoses tend to cluster across individuals. While the model is grounded in existing research and supported by recent meta-analytic evidence, its structure has not yet been directly tested using large, representative clinical datasets. In this study, we used electronic health record (EHR) data to examine the overall organization of mental disorders as proposed by HiTOP, with the goal of informing future research on biological and environmental risk factors as well as important life outcomes.

Data were drawn from the All of Us Research Program, a landmark nationwide US biobank initiative designed to advance population-scale health research, and included participants' psychiatric diagnoses and sociodemographic correlates as documented in their EHRs. A total of 127,963 participants and 39 primary diagnoses were identified. We analyzed patterns of co-occurrence among psychiatric diagnoses to identify broader psychopathology dimensions, assess the overall structure of mental disorders, and clarify the placement of conditions that have been inconsistently categorized in past research. Several competing dimensional models were compared based on their statistical fit and complementary assessments of factor strength, specificity, and reproducibility.

A model identifying six broad and correlated dimensions - Fear, Distress, Externalizing, Substance Use, Thought Problems, and Neurodevelopmental Disorders - provided the best fit to the data. This structure was highly consistent across analyses and showed strong split-half replicability and meaningful associations with relevant clinical and demographic characteristics.

These findings support a 6-factor model of psychopathology that broadly resembles major dimensions in the HiTOP framework. By addressing key gaps in the literature, this study advances our understanding of the structure and correlates of mental disorders. The results offer a foundation for more nuanced investigations into the etiology, progression, and treatment of mental health conditions.