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

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<sub>4</sub>β<sub>2</sub>) 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.

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Publication Details

Journal
Molecular Psychiatry
Published
2024-09-12
DOI
https://doi.org/10.1038/s41380-024-02724-0
Citations
12
Primary Topic
Functional Brain Connectivity Studies
Type
article
Field-Weighted Citation Impact
4.11

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article

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

Rosa Ayesa‐Arriola, Anthony S. David, Richard A. I. Bethlehem, Miguel Ruíz-Veguilla et al.
12 citations
Molecular Psychiatry
Functional Brain Connectivity Studies
4.11
article

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

Rosa Ayesa‐Arriola, Anthony S. David, Richard A. I. Bethlehem, Miguel Ruíz-Veguilla, Aaron Alexander‐Bloch, Rafael Romero-García, John Suckling, Kate Merritt, Benedicto Crespo‐Facorro, Javier Vázquez-Bourgón, Golia Shafiei, Edward Thomas Bullmore, Bratislav Mišić, Jakob Seidlitz, Víctor Ortiz‐García de la Foz, Isaac Sebenius, Lena Dorfschmidt, Natalia García-San-Martín, Sarah E. Morgan, Ágoston Mihalik, Claudio Alemán-Morillo
article en
12 citations

Abstract

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<sub>4</sub>β<sub>2</sub>) 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.

Molecular PsychiatryVol. 30(4)
Montreal Neurological Institute and Hospital (CA), Universidad de Cantabria (ES), Children's Hospital of Philadelphia (US), King's College London (GB), University of Cambridge (GB), Centro de Investigación Biomédica en Red de Salud Mental (ES), Marqués de Valdecilla University Hospital (ES), Institute of Mental Health (GB), Instituto de Investigación Marqués de Valdecilla (ES), Instituto de Biomedicina de Sevilla (ES), Cambridgeshire and Peterborough NHS Foundation Trust (GB), Lifespan (US), Hospital Universitario Virgen del Rocío (ES), Medical Research Network (US), University College London (GB), McGill University (CA), Universidad de Sevilla (ES), University of Pennsylvania (US)
Universidad de Sevilla, Junta de Andalucía, Medical Research Council, Agencia Estatal de Investigación
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