Molecular and micro-architectural mapping of gray matter alterations in psychosis.

Autor: García-San-Martín N; Department of Medical Physiology and Biophysics, University of Seville, Seville, Spain., Bethlehem RAI; Department of Psychology, University of Cambridge, Cambridge, UK., Mihalik A; Department of Psychiatry, University of Cambridge, Cambridge, UK., Seidlitz J; Department of Child and Adolescent Psychiatry and Behavioral Science, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.; Lifespan Brain Institute, The Children's Hospital of Philadelphia and Penn Medicine, Philadelphia, PA, USA.; Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Sebenius I; Department of Psychiatry, University of Cambridge, Cambridge, UK., Alemán-Morillo C; Department of Medical Physiology and Biophysics, University of Seville, Seville, Spain., Dorfschmidt L; Department of Child and Adolescent Psychiatry and Behavioral Science, The Children's Hospital of Philadelphia, Philadelphia, PA, USA., Shafiei G; Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Ortiz-García de la Foz V; Department of Psychiatry, Marqués de Valdecilla University Hospital, IDIVAL, School of Medicine, University of Cantabria, Santander, Spain.; Biomedical Research Center in Mental Health Network (CIBERSAM), Health Institute Carlos III, Madrid, Spain., Merritt K; Division of Psychiatry, Institute of Mental Health, UCL, London, UK., David A; Division of Psychiatry, Institute of Mental Health, UCL, London, UK., Morgan SE; Department of Psychiatry, University of Cambridge, Cambridge, UK.; Department of Computer Science and Technology, University of Cambridge, Cambridge, UK.; School of Biomedical Engineering and Imaging Sciences, King's College London, London, UK., Ruiz-Veguilla M; Biomedical Research Center in Mental Health Network (CIBERSAM), Health Institute Carlos III, Madrid, Spain.; Mental Health Service, Virgen del Rocío University Hospital, Seville, Spain.; Instituto de Biomedicina de Sevilla (IBiS) HUVR/CSIC, University of Seville, Seville, Spain., Ayesa-Arriola R; Department of Psychiatry, Marqués de Valdecilla University Hospital, IDIVAL, School of Medicine, University of Cantabria, Santander, Spain.; Biomedical Research Center in Mental Health Network (CIBERSAM), Health Institute Carlos III, Madrid, Spain., Vázquez-Bourgon J; Department of Psychiatry, Marqués de Valdecilla University Hospital, IDIVAL, School of Medicine, University of Cantabria, Santander, Spain.; Biomedical Research Center in Mental Health Network (CIBERSAM), Health Institute Carlos III, Madrid, Spain., Alexander-Bloch A; Department of Child and Adolescent Psychiatry and Behavioral Science, The Children's Hospital of Philadelphia, Philadelphia, PA, USA., Misic B; Montreal Neurological Institute, McGill University, Montreal, QC, Canada., Bullmore ET; Department of Psychiatry, University of Cambridge, Cambridge, UK., Suckling J; Department of Psychiatry, University of Cambridge, Cambridge, UK.; Peterborough NHS Foundation Trust, Peterborough, UK., Crespo-Facorro B; Department of Psychiatry, Marqués de Valdecilla University Hospital, IDIVAL, School of Medicine, University of Cantabria, Santander, Spain.; Biomedical Research Center in Mental Health Network (CIBERSAM), Health Institute Carlos III, Madrid, Spain.; Mental Health Service, Virgen del Rocío University Hospital, Seville, Spain.; Instituto de Biomedicina de Sevilla (IBiS) HUVR/CSIC, University of Seville, Seville, Spain., Romero-García R; Department of Medical Physiology and Biophysics, University of Seville, Seville, Spain. rr480@cam.ac.uk.; Department of Psychiatry, University of Cambridge, Cambridge, UK. rr480@cam.ac.uk.; Biomedical Research Center in Mental Health Network (CIBERSAM), Health Institute Carlos III, Madrid, Spain. rr480@cam.ac.uk.; Instituto de Biomedicina de Sevilla (IBiS) HUVR/CSIC, University of Seville, Seville, Spain. rr480@cam.ac.uk.
Jazyk: angličtina
Zdroj: Molecular psychiatry [Mol Psychiatry] 2024 Sep 12. Date of Electronic Publication: 2024 Sep 12.
DOI: 10.1038/s41380-024-02724-0
Abstrakt: The psychosis spectrum encompasses a heterogeneous range of clinical conditions associated with abnormal brain development. Detecting patterns of atypical neuroanatomical maturation across psychiatric disorders requires an interpretable metric standardized by age-, sex- and site-effect. The molecular and micro-architectural attributes that account for these deviations in brain structure from typical neurodevelopment are still unknown. Here, we aggregate structural magnetic resonance imaging data from 38,696 healthy controls (HC) and 1256 psychosis-related conditions, including first-degree relatives of schizophrenia (SCZ) and schizoaffective disorder (SAD) patients (n = 160), individuals who had psychotic experiences (n = 157), patients who experienced a first episode of psychosis (FEP, n = 352), and individuals with chronic SCZ or SAD (n = 587). Using a normative modeling approach, we generated centile scores for cortical gray matter (GM) phenotypes, identifying deviations in regional volumes below the expected trajectory for all conditions, with a greater impact on the clinically diagnosed ones, FEP and chronic. Additionally, we mapped 46 neurobiological features from healthy individuals (including neurotransmitters, cell types, layer thickness, microstructure, cortical expansion, and metabolism) to these abnormal centiles using a multivariate approach. Results revealed that neurobiological features were highly co-localized with centile deviations, where metabolism (e.g., cerebral metabolic rate of oxygen (CMRGlu) and cerebral blood flow (CBF)) and neurotransmitter concentrations (e.g., serotonin (5-HT) and acetylcholine (α 4 β 2 ) receptors) showed the most consistent spatial overlap with abnormal GM trajectories. Taken together these findings shed light on the vulnerability factors that may underlie atypical brain maturation during different stages of psychosis.
(© 2024. The Author(s).)
Databáze: MEDLINE
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