Longitudinal Associations Between White Matter Microstructure and Psychiatric Symptoms in Adolescence

ObjectiveAssociations between psychiatric problems and white matter (WM) microstructure have been reported in childhood and adolescence. Yet, a deeper understanding of this relation has been hampered by a dearth of well-powered longitudinal studies and a lack of explicit examination of the bidirectional associations between brain and behavior. We investigated the temporal directionality of WM microstructure and psychiatric symptom associations from late childhood to early adolescence. MethodsIn this observational study, we leveraged the worlds largest single- and multi-site cohorts of neurodevelopment: the Generation R and Adolescent Brain Cognitive Development Studies (total n scans = 11,400). We assessed psychiatric symptoms with the Child Behavioral Checklist as broad-band Internalizing and Externalizing scales, and as syndrome scales (e.g., Anxious/Depressed). We quantified WM with Diffusion Tensor Imaging, globally and at a tract level. We used cross-lagged panel models to test bidirectional associations of global and specific measures of psychopathology and WM microstructure, meta-analyzed results across cohorts, and used linear mixed-effects models for validation. ResultsWe did not identify any robust longitudinal associations of global WM microstructure with internalizing or externalizing problems across cohorts (confirmatory analyses). We observed similar findings for longitudinal associations between tract-based microstructure with internalizing and externalizing symptoms, and for global WM microstructure with specific syndromes (exploratory analyses). ConclusionUni- or bi-directionality of longitudinal associations between WM and psychiatric symptoms was not robustly identified. We propose several explanations for these findings, including interindividual differences, the use of longitudinal approaches, and smaller effects than expected.