Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.06.11.147009v1?rss=1 Authors: Parkes, L., Moore, T. M., Calkins, M. E., Cook, P. A., Cieslack, M., Roalf, D. R., Wolf, D. H., Gur, R. C., Gur, R. E., Satterthwaite, T. D., Bassett, D. S. Abstract: Psychopathology is hypothesized to be rooted in neurodevelopment. However, clinical and biological heterogeneity, and a focus on case-control approaches, have made it difficult to link specific forms of psychopathology to abnormalities of neurodevelopment. Here, we modeled the normative neurodevelopment of brain structure in 1,393 youths aged 8 to 22 years from the Philadelphia Neurodevelopmental Cohort. Normative neurodevelopment of cortical thickness and volume was estimated using Gaussian Process Regression in 410 healthy individuals. Deviations from normative neurodevelopment were estimated in the remaining 983 individuals who reported lifetime psychopathology. Next, we modeled six orthogonal psychopathology dimensions: overall psychopathology, anxious-misery, externalizing disorders, fear, positive psychotic symptoms, and negative psychotic symptoms. Psychopathology dimensions were correlated with regional deviations from normative neurodevelopment. Finally, we performed conventional case-control comparisons of deviations in a group of individuals with depression and a group with attention-deficit hyperactivity disorder (ADHD). Psychopathology dimensions were associated with spatially varied patterns of deviations from normative neurodevelopment. In particular, greater overall psychopathology was associated with neurodevelopmentally advanced volume reductions in ventromedial prefrontal, inferior temporal, dorsal anterior cingulate, and insula cortices, all regions consistently implicated in a range of putatively distinct disorders. Furthermore, case-control comparisons of deviations revealed spatially overlapping group-level effects for depression and ADHD, which diminished when controlling for overall psychopathology. Together, our results demonstrate that case-control comparisons are confounded by overall psychopathology, rendering them unlikely to yield meaningful biomarkers. Instead, the neural underpinnings of psychopathology may be better elucidated by integrating dimensional models of psychopathology with models of normative neurodevelopment. Copy rights belong to original authors. Visit the link for more info