Coordinated cortical thickness alterations across six neurodevelopmental and psychiatric disorders

Nat Commun. 2022 Nov 11;13(1):6851. doi: 10.1038/s41467-022-34367-6.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Attention
  • Cerebellum
  • Cerebral Cortex / pathology
  • Connectome*
  • Humans
  • Magnetic Resonance Imaging
  • Mental Disorders*