Background There is growing recognition that connectome architecture shapes cortical and sub-cortical grey matter atrophy across a spectrum of neurological and psychiatric diseases. Whether connectivity contributes to tissue volume loss in schizophrenia in the same manner remains unknown.Methods Here we relate tissue volume loss in patients with schizophrenia to patterns of structural and functional connectivity. Grey matter deformation was estimated in a sample of N = 133 individuals with chronic schizophrenia (48 female, 34.7 ± 12.9 years) and N = 113 controls (64 female, 23.5 ± 8.4 years). Deformation-based morphometry (DBM) was used to estimate cortical and subcortical grey matter deformation from T1-weighted MR images. Structural and functional connectivity patterns were derived from an independent sample of N = 70 healthy participants using diffusion spectrum imaging and resting-state functional MRI.Results We find that regional deformation is correlated with the deformation of structurally- and functionally-connected neighbours. Distributed deformation patterns are circumscribed by specific functional systems (the ventral attention network) and cytoarchitectonic classes (limbic class), with an epicenter in the anterior cingulate cortex.Conclusions Altogether, the present study demonstrates that brain tissue volume loss in schizophrenia is conditioned by structural and functional connectivity, accounting for 25-35% of regional variance in deformation.

Spatial patterning of tissue volume loss in schizophrenia reflects brain network architecture