Threading the Needle: Practical Considerations for Merging Theory-Driven Computational Psychiatry With Data-Driven Analytics to Enhance Precision Health at Scale.

The rapidly evolving field of computational psychiatry enables quantification of specific cognitive processes and their underlying mechanisms in a translational and potentially scalable manner, using a combination of data collection via mechanistically informed behavioral tasks and theory-driven mathematical modeling. In parallel, transdiagnostic, dimensional approaches to psychiatric diagnostics, such as the Research Domain Criteria and Hierarchical Taxonomy of Psychopathology, seek to facilitate links between clinical research and real-world clinical reality, which rarely respects traditional diagnostic boundaries. These two approaches are seldom combined. In addition, while most psychiatric disorders are defined by their longitudinal course, our ability to predict symptom trajectories and tailor treatments to the individual remains limited, in part due to a dearth of longitudinal data collected using assessments sensitive to individual change over time. To address these gaps, the recently launched IMPACT-Y (Individually Measured Phenotypes to Advance Computational Translation at Yale) study is collecting longitudinal data from a transdiagnostic cohort of 2400 individuals, using a combination of traditional clinical research methods (e.g., health records, standardized assessments) and more novel computational approaches (e.g., behavioral tasks with demonstrated sensitivity to latent constructs and to within-person change, spoken narrative data). Here, we discuss unique challenges and opportunities in study design and analysis considerations of IMPACT-Y. Incorporating both theory- and data-driven analytics, we hope that IMPACT-Y will provide an unprecedented resource for characterizing longitudinal trajectories of core computational psychiatry constructs (e.g., reward learning) within and between individuals for parsing heterogeneity beyond traditional diagnostic categories and for linking inter- and intraindividual clinical variability to underlying mechanisms.