Lifespan Normative Models of White Matter Fractional Anisotropy: Applications to Early Psychosis.

This study presents large-scale normative models of white matter (WM) organization across the lifespan, using diffusion MRI data from over 25,000 healthy individuals aged 0-100 years. These models capture lifespan trajectories and inter-individual variation in fractional anisotropy (FA), a marker of white matter integrity. By addressing non-Gaussian data distributions, race, and site effects, the models offer reference baselines across diverse ages, ethnicities, and scanning conditions. We applied these FA models to the HCP Early Psychosis cohort and performed a multivariate analysis to map symptoms onto deviations from multimodal normative models using multi-view sparse canonical correlation analysis (msCCA). Our results reveal extensive white matter heterogeneity in psychosis, which is not captured by group-level analyses, with key regions identified, including the right uncinate fasciculus and thalami. These normative models offer valuable tools for individualized WM deviation identification, improving precision in psychiatric assessments. All models are publicly available for community use.