A cortical coordinate space of psychiatric vulnerability

COEX 

Overlapping psychopathological spectra may reflect an underlying, general liability for mental illness linked to shared risk factors and common alterations in neurodevelopmental processes. In three studies, we investigated how multi-scale features of brain organization shape topologically heterogeneous levels of transdiagnostic vulnerability. Combining meta-analytic cortical thickness maps of 6 major mental disorders with multi-scale data, we characterized a transdiagnostic cortical coordinate space framed by connectomic, cytoarchitectonic, and functional dimensions, along which synchronized brain alterations are organized. We identified low-dimensional cortical axes of co-alteration networks, which indicated that the likelihood of two brain regions to display synchronized illness effects, regardless of their location on the cortical landscape, is related to the degree to which these regions share cytoarchitectonic profiles and are engaged in similar functional tasks. Moreover, fronto-temporal epicenters emerged as potential connectome anchors of shared cortical alterations. We extended these observations towards symptom domains and explored a continuous coordinate space in which individuals with mental disorders are embedded based on the degree to which they express a combination of pathological brain imaging patterns – partly crossing categorical diagnoses. Last, we studied adaptation to transdiagnostic environmental risk factors during adolescence and found that adolescents’ vulnerability or resilience to environmental stressors varies during development. This intra-individual variability was tied to maturational trajectories of cortical myelination of association cortices, as well as microstructural and functional network re-organization. In my contribution, I will present multi-modal insights into brain organizational principles shaping transdiagnostic vulnerability.