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

Natalia García-San-Martín, Richard AI Bethlehem, Patricia Segura, Agoston Mihalik, Jakob Seidlitz, Isaac Sebenius, Claudio Alemán-Morillo, Lena Dorfschmidt, Golia Shafiei, Sarah E. Morgan, Miguel Ruiz-Veguilla, Rosa Ayesa-Arriola, Javier Vázquez-Bourgon, Bratislav Misic, John Suckling, Benedicto Crespo-Facorro and Rafael Romero-García ()
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Natalia García-San-Martín: University of Seville
Richard AI Bethlehem: University of Cambridge
Patricia Segura: University of Seville
Agoston Mihalik: University of Cambridge
Jakob Seidlitz: The Children’s Hospital of Philadelphia
Isaac Sebenius: University of Cambridge
Claudio Alemán-Morillo: University of Seville
Lena Dorfschmidt: The Children’s Hospital of Philadelphia
Golia Shafiei: The Children’s Hospital of Philadelphia and Penn Medicine
Sarah E. Morgan: University of Cambridge
Miguel Ruiz-Veguilla: Health Institute Carlos III
Rosa Ayesa-Arriola: Health Institute Carlos III
Javier Vázquez-Bourgon: Health Institute Carlos III
Bratislav Misic: McGill University
John Suckling: University of Cambridge
Benedicto Crespo-Facorro: Health Institute Carlos III
Rafael Romero-García: University of Seville

Nature Communications, 2025, vol. 16, issue 1, 1-13

Abstract: Abstract 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.

Date: 2025
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DOI: 10.1038/s41467-025-63792-6

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