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

Author

Listed:
  • Natalia García-San-Martín

    (University of Seville
    University of Cambridge)

  • Richard AI Bethlehem

    (University of Cambridge)

  • Patricia Segura

    (University of Seville)

  • Agoston Mihalik

    (University of Cambridge)

  • Jakob Seidlitz

    (The Children’s Hospital of Philadelphia
    The Children’s Hospital of Philadelphia and Penn Medicine
    University of Pennsylvania)

  • Isaac Sebenius

    (University of Cambridge
    University of Cambridge)

  • Claudio Alemán-Morillo

    (University of Seville)

  • Lena Dorfschmidt

    (The Children’s Hospital of Philadelphia
    The Children’s Hospital of Philadelphia and Penn Medicine
    University of Pennsylvania)

  • Golia Shafiei

    (The Children’s Hospital of Philadelphia and Penn Medicine
    University of Pennsylvania)

  • Sarah E. Morgan

    (University of Cambridge
    University of Cambridge
    King’s College London)

  • Miguel Ruiz-Veguilla

    (Health Institute Carlos III
    Virgen del Rocío University Hospital
    University of Seville)

  • Rosa Ayesa-Arriola

    (Health Institute Carlos III
    University of Cantabria)

  • Javier Vázquez-Bourgon

    (Health Institute Carlos III
    University of Cantabria)

  • Bratislav Misic

    (McGill University)

  • John Suckling

    (University of Cambridge
    Peterborough NHS Foundation Trust)

  • Benedicto Crespo-Facorro

    (Health Institute Carlos III
    Virgen del Rocío University Hospital
    University of Seville
    University of Cantabria)

  • Rafael Romero-García

    (University of Seville
    University of Cambridge
    Health Institute Carlos III
    University of Seville)

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.

Suggested Citation

  • 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 & M, 2025. "Reduced brain structural similarity is associated with maturation, neurobiological features, and clinical status in schizophrenia," Nature Communications, Nature, vol. 16(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-63792-6
    DOI: 10.1038/s41467-025-63792-6
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