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 alterations in structural similarity between regions. Using structural MRI data from 195 healthy controls (HC) and 352 individuals with SSD, we construct individual Morphometric INverse Divergence (MIND) networks. Compared to HC, individuals with SSD mainly exhibit reduced structural similarity in the temporal, cingulate, and insular lobes, being more pronounced in individuals exhibiting a ‘poor’ clinical status (more impaired cognitive functioning and more severe symptomatology). These alterations are associated with cortical hierarchy and maturational events, locating MIND reductions in higher-order association areas that mature later. Finally, we map 46 neurobiological features onto MIND networks, revealing a high presence of neurotransmitters and astrocytes, along with decreased metabolism and microstructure, in regions with reduced similarity in SSD. These findings provide evidence on the complex interplay between structural similarity, maturational events, and the underlying neurobiology in determining clinical status of individuals with SSD. Individuals with schizophrenia show reduced structural similarity in temporal, cingulate, and insular lobes, especially those with worse cognition and symptoms, affecting late maturing association areas with low metabolism and high neurotransmission.