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

Background: This study presents large-scale normative models of white matter (WM) organization across the lifespan, using diffusion magnetic resonance imaging data from over 25,000 healthy individuals ages 0 to 100 years from multiple cohorts including the Human Connectome Project (HCP) Lifespan and UK Biobank. These models capture lifespan trajectories and interindividual variation in fractional anisotropy (FA), a marker of WM integrity.

Methods: By addressing non-Gaussian data distributions, self-reported race, and site effects, the models offer reference baselines across diverse ages 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 multiview sparse canonical correlation analysis.

Results: Our results reveal extensive WM heterogeneity in psychosis, which is not captured by group-level analyses, with key regions identified, including the right uncinate fasciculus and thalami.

Conclusions: These normative models offer valuable tools for individualized WM deviation identification, improving precision in psychiatric assessments. All models are publicly available for community use.