Coordinated cortical thickness alterations across six neurodevelopmental and psychiatric disorders
Meike D. Hettwer, Sara Larivière, Bo‐yong Park, Odile A. van den Heuvel, Lianne Schmaal, Ole A. Andreassen, Christopher R. K. Ching, Martine Hoogman, Jan K. Buitelaar, Daan van Rooij, Dick J. Veltman, Dan J. Stein, Barbara Franke, Theo G.M. van Erp, ENIGMA ADHD Working Group, ENIGMA Autism Working Group, Daan van Rooij, ENIGMA Bipolar Disorder Working Group, ENIGMA Major Depression Working Group, ENIGMA OCD Working Group, Odile A. van den Heuvel, ENIGMA Schizophrenia Working Group, Theo G.M. van Erp, Neda Jahanshad, Paul M. Thompson, Sophia I. Thomopoulos, Richard A. I. Bethlehem, Boris C. Bernhardt, Simon B. Eickhoff, Sofie L. Valk
Abstract
Neuropsychiatric disorders are increasingly conceptualized as overlapping spectra sharing multi-level neurobiological alterations. However, whether transdiagnostic cortical alterations covary in a biologically meaningful way is currently unknown. Here, we studied co-alteration networks across six neurodevelopmental and psychiatric disorders, reflecting pathological structural covariance. In 12,024 patients and 18,969 controls from the ENIGMA consortium, we observed that co-alteration patterns followed normative connectome organization and were anchored to prefrontal and temporal disease epicenters. Manifold learning revealed frontal-to-temporal and sensory/limbic-to-occipitoparietal transdiagnostic gradients, differentiating shared illness effects on cortical thickness along these axes. The principal gradient aligned with a normative cortical thickness covariance gradient and established a transcriptomic link to cortico-cerebello-thalamic circuits. Moreover, transdiagnostic gradients segregated functional networks involved in basic sensory, attentional/perceptual, and domain-general cognitive processes, and distinguished between regional cytoarchitectonic profiles. Together, our findings indicate that shared illness effects occur in a synchronized fashion and along multiple levels of hierarchical cortical organization.