The central premise of precision medicine is that an individual’s unique physiologic characteristics play a significant role in disease vulnerability and response to specific therapies. To make progress toward precision medicine in psychiatry, it is critical to move beyond group-based studies that disregard individual variations as noise and, in the spirit of the Research Domain Criteria (RDoC) paradigm, interpret these variations in the context of the normal range of biological systems. This project will deliver a comprehensive normative reference atlas for brain microstructure across multiple brain regions and parameters, providing a quantitative framework for characterizing individual-level variations. This approach has the potential to advance clinical translation by enabling information about a patient’s brain microstructure to forecast the probability of psychiatric conditions, clinical outcomes, or treatment response
We focus on brain microstructure because postmortem and neuroimaging studies have implicated microstructural abnormalities in virtually all major psychiatric disorders. Using normative modeling (“brain growth charting”), we will generate a comprehensive reference atlas from archived multi-shell diffusion MRI (dMRI) data (>50,000 subjects, ages 10-100).
Aim I: To create normative models of brain microstructure as a framework to study psychiatric disorders at the individual participant level.
Aim III: To assess the extent and clinical relevance of individual variations in brain microstructure in early psychosis patients.
This work represents a pivotal step toward precision psychiatry, where patients are conceptualized based on their unique physiologic characteristics to guide medical decision-making.
