Researchers at the University of Seville have identified the possible origins of structural damage in the brains of patients with schizophrenia spectrum disorders (SSDs). These are regions that show the greatest morphological alterations in the early stages of the disease compared to neurotypical people of the same sex and age. The study also also found that people with SSD have significant reductions in structural similarity between different regions of the temporal, cingulate and insular lobes.
A growing number of studies support the hypothesis that psychiatric conditions initially emerge as structural alterations in specific brain regions and subsequently spread to other areas through brain connectivity. SSDs are characterised by atypical brain maturation, such as reduced volume, area and thickness of the cerebral cortex. These alterations, associated with cognitive deficits and severe symptoms, follow a pattern that reflects disconnection within specific brain networks.
The structural similarity between different cortical regions can be estimated using networks based on Morphometric Inverse Divergence (MIND), a methodology that uses characteristics derived from structural magnetic resonance imaging (MRI), such as volume, surface area and cortical thickness. These networks quantify the degree of morphological similarity between different pairs of regions, where decreased MIND values indicate less structural similarity, which can be interpreted as greater morphological disconnection between the pairs.
Applying this recent methodology, MIND networks were constructed for 195 healthy controls and 352 individuals with SSD. Compared to healthy patients, these latter group showed significant reductions in structural similarity, mainly in the temporal, cingulate and insular lobes. These decreases were more pronounced in individuals with a poorer clinical status, defined by greater cognitive impairment and more severe symptoms. The alterations were mainly located in higher-order association areas, which mature later and are fundamental for complex cognitive functions.
The study also identified the possible origins, or epicentres, of structural damage, defined as regions showing the greatest morphological alterations in the early stage of the disease compared to the expected values for neurotypical individuals of the same sex and age.
Finally, 46 neurobiological characteristics were related to the MIND networks, revealing that regions with lower similarity in individuals with SSD have a high presence of astrocytes and neurotransmitters, such as dopamine and serotonin, as well as reduced metabolism and cortical microstructure.
These findings provide evidence of the complex interaction between structural similarity, maturation processes and underlying neurobiology in determining the clinical status of individuals with SSD. This approach could contribute to the development of structural biomarkers and personalised therapeutic strategies based on each patient’s biological and clinical profile.