Trajectories of structure-function coupling in human brain networks from birth to adolescence and their relationship to transdiagnostic psychopathology

The National Institute of Mental Health awarded the University of North Carolina at Chapel Hill $124,128 on December 15, 2025, under the Mental Health Research Grants program (CFDA 93.242) to characterize trajectories of structure-function coupling in human brain networks from birth through adolescence and examine relationships to transdiagnostic psychopathology.

The project leverages the UNC Early Brain Development Study, a longitudinal dataset with ten timepoints of diffusion and resting-state functional neuroimaging spanning two weeks to 16 years in the same individuals. The research will measure psychiatric outcomes at ages 6, 10, and 16 using the General Psychopathology Factor to capture transdiagnostic risk for psychopathology. Approximately 40 percent of enrolled infants carried increased risk for future psychopathology due to factors such as premature birth or maternal mental illness, positioning the dataset for examination of how structure-function coupling changes across development in relation to long-term psychiatric outcomes.

Performance takes place in Chapel Hill, North Carolina, with the period of performance extending through December 14, 2031. The award is classified as a Project Grant.

Abstract

Half of all lifetime mental health disorders are present by adolescence, but the neural mechanisms underlying these disorders, particularly in the period leading up to adolescence, are still poorly understood. Early life and early adolescence are theorized to be sensitive periods characterized by large changes in structural (white matter-based) and functional (activity-based) brain networks and during which individuals are at increased vulnerability for later psychopathology. The correspondence between structural and functional connectivity, termed structure-function (s-f) coupling, also changes across development and, critically, relates to psychopathology. However, no studies have yet examined how s-f coupling changes across both sensitive periods in the same individuals, and IT is unknown how s-f coupling relates to risk for psychopathology that transcends diagnostic boundaries (i.e., transdiagnostically). The proposed study will leverage the UNC early brain development study (ebds), a unique dataset consisting of 10 timepoints of diffusion and resting-state functional neuroimaging data spanning two weeks to 16 years in the same individuals. This study will characterize trajectories of s-f coupling between birth and 16 years and will measure psychiatric outcomes at ages 6, 10, and 16 using the general psychopathology factor (p-factor), which captures transdiagnostic risk for psychopathology. Critically, 40% of infants in the ebds dataset were at increased risk for future psychopathology at enrollment (e.g., due to premature birth, maternal mental illness). Therefore, this dataset is ideally suited for a longitudinal study examining transdiagnostic outcomes. With these unique data, this project will be the first to establish how s-f coupling changes across development within individuals and how these changes relate to transdiagnostic psychopathology. To accomplish these goals, this project will: 1) characterize longitudinal trajectories of s-f coupling from birth to adolescence, 2) determine what features of s-f coupling in early childhood, middle childhood, and adolescence relate to transdiagnostic psychopathology cross-sectionally, and 3) determine how trajectories of s-f coupling from birth to adolescence predict transdiagnostic psychopathology in adolescence. Through the results of these aims, this study will not only advance our knowledge of neurodevelopmental trajectories across childhood and adolescence, but IT will also contribute to the identification of early neural markers of future transdiagnostic psychopathology. This essential early work may guide future clinical practice to improve outcomes for children of all ages. The expertise of an exceptional mentorship team combined with a unique dataset and top-tier resources available at the university of north carolina at chapel hill will allow the trainee to use this research project and training plan to prepare for a productive career as a physician-scientist applying advanced neuroimaging analysis to study typical and atypical neurodevelopment.