Mapping person-specific and spatially precise white matter development to transdiagnostic psychopathology and polygenic risk - psychiatric disorders are increasingly conceptualized as disorders of…

The National Institute of Mental Health awarded The Trustees of the University of Pennsylvania $110,228 under the Mental Health Research Grants program (CFDA 93.242) on November 4, 2026, to map person-specific and spatially precise white matter development to transdiagnostic psychopathology and polygenic risk in adolescents.

The research characterizes within-individual, along-tract white matter development in relation to transdiagnostic psychiatric symptoms and evaluates whether associations are strongest in superficial white matter regions adjacent to higher-order association cortices. The work leverages the longitudinal Adolescent Brain Cognitive Development study, which includes 11,875 participants ages 9–16 with multi-shell diffusion MRI, clinical, and genotype data. The recipient assesses how polygenic risk scores for transdiagnostic psychiatric illness relate to spatially precise white matter microstructure metrics and whether polygenic risk effects are concentrated in superficial white matter regions. The study aims to identify brain regions where protracted white matter maturation links to transdiagnostic symptoms and genetic risk for psychiatric illness.

Performance occurs in Philadelphia, Pennsylvania, with an ultimate completion date of May 31, 2029. The award is a project grant under NIMH's Mental Health Research Grants program, which supports competitive research projects not exceeding five years addressing the Institute's mission to transform understanding and treatment of mental illnesses through basic and clinical research.

Mapping person-specific and spatially precise white matter development to transdiagnostic psychopathology and polygenic risk - psychiatric disorders are increasingly conceptualized as disorders of brain development. White matter (WM) structure develops rapidly in adolescence and has been linked to many psychiatric illnesses. However, the neurobiological mechanisms linking WM development, transdiagnostic psychiatric symptoms, and genetic risk for psychopathology remain poorly understood. This proposal tests the central hypothesis that transdiagnostic psychiatric symptoms and genetic risk will be associated with WM that undergoes the most protracted development: superficial regions of WM tracts connected to higher-order association cortices. We will leverage the large, longitudinal adolescent brain cognitive development (abcd) study (n=11,875; ages 9-16), which includes multi-shell diffusion MRI, clinical, and genotype data. In aim 1, we will characterize within-individual, along-tract WM development and we will evaluate whether associations with transdiagnostic symptoms are strongest in superficial WM regions adjacent to higher-order association cortices. In aim 2, we will assess how polygenic risk scores (PRS) for transdiagnostic psychiatric illness relate to spatially precise WM microstructure metrics. We will assess whether PRS effects are strongest in superficial WM regions adjacent to higher-order association cortices. Together, this work will identify brain regions where protracted WM maturation is linked to transdiagnostic symptoms and genetic risk, advancing our understanding of how WM development is related to symptomatology and genetic liability for trans-diagnostic psychiatric illness.