Reduced brain structural similarity is associated with maturation, neurobiological features, and clinical status in schizophrenia

Schizophrenia spectrum disorders (SSD) are characterized by atypical brain maturation, including reduced structural similarity between regions. However, the maturational and neurobiological underpinnings of the complex interactions between abnormal development and network reorganization remain poorly characterized. Using structural MRI data from 195 healthy controls (HC) and 352 individuals with SSD, we constructed individual Morphometric INverse Divergence (MIND) networks. Compared to HC, individuals with SSD exhibited reduced structural similarity in the temporal and cingulate lobes, with more pronounced reductions in individuals exhibiting a ‘poor’ clinical status (more impaired cognitive functioning and more severe symptomatology). These alterations in MIND networks were associated with cortical hierarchy and maturational events, locating MIND reductions in higher-order association areas that predominantly mature later. Finally, we mapped 46 neurobiological features from healthy individuals onto MIND networks revealing a high presence of neurotransmitters, astrocytes, and microglia, along with decreased metabolism and microstructure, in regions with reduced similarity in SSD. Taken together, these findings provide evidence on the complex interplay between structural dysconnectivity, maturational events, and the underlying neurobiology in determining clinical status of individuals with SSD.