CentileBrain: A Normative Modeling Framework for Brain Health and Disease

ABSTRACT With this proposal we launch the "ENIGMA CentileBrain: A Normative Modeling Framework for Brain Health and Disease," an international initiative spearheaded by the ENIGMA Consortium. The absence of a standardized normative reference values for neuroimaging phenotypes is a major limitation in brain research in contrast to all other medical fields where biological measures (such as blood glucose or pressure) are assessed against established norms. This proposal addresses this gap by leveraging empirically validated normative models derived from geographically and ethnoracially diverse MRI datasets, covering brain morphology, white matter microstructure, and resting-state functional connectivity. This comprehensive approach includes cross-sectional and longitudinal multimodal neuroimaging data from over 50,000 healthy controls, multimodal neuroimaging data and polygenic risk scores from five major psychiatric disorders (schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorders and substance use disorder), and novel polygenic predictors of brain phenotypes developed by ENIGMA-Genetics group. Our aims are to: (1) establish and disseminate CentileBrain as the largest public access platform of normative models of multimodal neuroimaging measures; (2) quantify the influence of genetic and non-genetic features (i.e., body mass index, cognition, socioeconomic status) on normative models of brain morphometry, white matter microstructure, and resting-state connectivity; and (3) map multivariate deviations from normative reference values within and across the five major psychiatric disorders. This study addresses NIMH funding priorities to characterize age-related changes across the lifespan in diverse populations and identify biomarkers of mental illness across the lifespan.