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The role of low subcortical iron, white matter myelin, and oligodendrocytes in schizophrenia: a quantitative susceptibility mapping and diffusion tensor imaging study.

作者信息

Vano Luke J, McCutcheon Robert A, Sedlacik Jan, Rutigliano Grazia, Kaar Stephen J, Finelli Valeria, Lobo Maria C, Berry Alaine, Statton Ben, Fazlollahi Amir, Everall Ian P, Howes Oliver D

机构信息

Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.

Psychiatric Imaging Group, MRC Laboratory of Medical Sciences, Hammersmith Hospital, London, UK.

出版信息

Mol Psychiatry. 2025 Sep 5. doi: 10.1038/s41380-025-03195-7.


DOI:10.1038/s41380-025-03195-7
PMID:40913112
Abstract

Iron-the most abundant magnetic brain substance-is essential for many biological processes, including dopamine and myelin synthesis. Quantitative susceptibility mapping (QSM) MRI has recently linked altered subcortical magnetic susceptibility (χ) to schizophrenia. Since χ is increased by iron and decreased by myelin, abnormal levels of either could underlie these QSM differences. In white matter tracts, magnetic susceptibility anisotropy (δχ) serves as a myelin-specific marker that is insensitive to iron content. To clarify the origin of case-control χ differences, we employed QSM in 85 individuals with schizophrenia, from first-episode mental health teams, and 86 healthy controls. A subset also underwent diffusion tensor imaging (DTI) to calculate subcortical tissue mean diffusivity, which inversely correlates with myelin concentration and fractional anisotropy. White matter δχ was calculated by combining QSM and DTI. Schizophrenia was associated with lower subcortical χ (d = -0.36, p = 0.023). This was significant in the caudate nucleus (d = -0.37, p = 0.037), putamen (d = -0.36, p = 0.037), globus pallidus (d = -0.57, p = 0.001), and SN-VTA (as previously reported). Additionally, schizophrenia was linked to higher subcortical mean diffusivity (d = 0.44, p = 0.018), and lower white matter δχ (d = -0.37, p = 0.047). These findings suggest that both subcortical iron and brain myelin levels are lower in schizophrenia. By comparing our voxelwise χ maps with postmortem gene expression data, we reveal that regions with lower subcortical χ in schizophrenia are enriched for oligodendrocyte-related genes (p < 0.001). As oligodendrocytes are both the most iron-rich brain cells and essential for myelin synthesis, our results implicate oligodendrocyte dysfunction in schizophrenia pathophysiology.

摘要

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本文引用的文献

[1]
Mesostriatal Dopaminergic Circuit Dysfunction in Schizophrenia: A Multimodal Neuromelanin-Sensitive Magnetic Resonance Imaging and [F]-DOPA Positron Emission Tomography Study.

Biol Psychiatry. 2024-10-15

[2]
Brain cell-type shifts in Alzheimer's disease, autism, and schizophrenia interrogated using methylomics and genetics.

Sci Adv. 2024-5-24

[3]
Quantitative Susceptibility Mapping MRI in Deep-Brain Nuclei in First-Episode Psychosis.

Schizophr Bull. 2023-9-7

[4]
Variability and magnitude of brain glutamate levels in schizophrenia: a meta and mega-analysis.

Mol Psychiatry. 2023-5

[5]
Perturbed iron biology in the prefrontal cortex of people with schizophrenia.

Mol Psychiatry. 2023-5

[6]
Decreased basal ganglia and thalamic iron in early psychotic spectrum disorders are associated with increased psychotic and schizotypal symptoms.

Mol Psychiatry. 2022-12

[7]
Integrating the Neurodevelopmental and Dopamine Hypotheses of Schizophrenia and the Role of Cortical Excitation-Inhibition Balance.

Biol Psychiatry. 2022-9-15

[8]
Where Actions Meet Outcomes: Medial Prefrontal Cortex, Central Thalamus, and the Basal Ganglia.

Front Behav Neurosci. 2022-7-5

[9]
Magnetic susceptibility anisotropy in normal appearing white matter in multiple sclerosis from single-orientation acquisition.

Neuroimage Clin. 2022

[10]
Phenotypic and genetic associations of quantitative magnetic susceptibility in UK Biobank brain imaging.

Nat Neurosci. 2022-6

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