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Quantitative susceptibility mapping of deep brain nuclei in 22q11.2 deletion syndrome
(Frontiers Media SA, 2026-01-09)
Nestor Muñoz
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Marisleydis García
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Analía Cuiza
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Angeles Tepper
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Javiera Vásquez
<jats:sec> <jats:title>Background</jats:title> <jats:p>22q11.2 Deletion Syndrome (22q11.2 DS) confers a high risk to dopamine-related disorders such as schizophrenia and Parkinson’s disease. These disorders have recently been associated with abnormal iron concentrations in deep brain nuclei. In this study we hypothesized that abnormal iron concentrations may also appear in deep brain nuclei of individuals with 22q11.2 DS.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>We analyzed iron concentrations in four dopamine-related nuclei (caudate, putamen, substantia nigra, and globus pallidus) of 32 individuals, including adolescents and adults, carriers of the 22q11.2 DS and 49 healthy controls. For all individuals, we characterized iron concentrations in each region by quantifying R2* values and using a recently developed technique called Quantitative Susceptibility Mapping (QSM). We used linear mixed models to analyze potential differences between 22q11.2 DS individuals and our control group, considering brain region, age, sex, laterality, volume size, and framewise-displacement as fixed-effect covariates and individuals’ intercepts as random effects.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>All individuals showed age-related increases in R2* values and susceptibility within dopaminergic nuclei (caudate, putamen, and substantia nigra). However, individuals with 22q11.2 DS showed a significantly lower rate of increase compared to healthy control group. This suggests that, over time, individuals with 22q11.2 deletion syndrome accumulate less iron in these nuclei than healthy controls.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Individuals with 22q11.2 DS present lower iron accumulation in dopaminergic areas, such as substantia nigra, caudate and putamen, relative to healthy controls. These findings suggest a possible association between a dopaminergic dysfunction and abnormal iron accumulation.</jats:p> </jats:sec>
1
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Longitudinal changes in striatocortical connectivity in first-episode psychosis associated with the emergence of treatment resistance
(Springer Science and Business Media LLC, 2025-08-16)
Angeles Tepper
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Javiera Vásquez
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Camila Díaz Dellarossa
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Juan Pablo Ramirez-Mahaluf
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Juan Aguirre
1
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Human development, inequality, and their associations with brain structure across 29 countries
(Royal College of Psychiatrists, 2025)
Vicente Medel
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Luz M. Alliende
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Richard Bethlehem
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Jakob Seidlitz
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Grace Ringlein
2
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Quantitative Susceptibility Mapping MRI in Deep-Brain Nuclei in First-Episode Psychosis
(2023)
Marisleydis García Saborit
;
Alejandro Jara
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Néstor Muñoz
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Carlos Milovic
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Angeles Tepper
<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>Psychosis is related to neurochemical changes in deep-brain nuclei, particularly suggesting dopamine dysfunctions. We used an magnetic resonance imaging-based technique called quantitative susceptibility mapping (QSM) to study these regions in psychosis. QSM quantifies magnetic susceptibility in the brain, which is associated with iron concentrations. Since iron is a cofactor in dopamine pathways and co-localizes with inhibitory neurons, differences in QSM could reflect changes in these processes.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>We scanned 83 patients with first-episode psychosis and 64 healthy subjects. We reassessed 22 patients and 21 control subjects after 3 months. Mean susceptibility was measured in 6 deep-brain nuclei. Using linear mixed models, we analyzed the effect of case-control differences, region, age, gender, volume, framewise displacement (FD), treatment duration, dose, laterality, session, and psychotic symptoms on QSM.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>Patients showed a significant susceptibility reduction in the putamen and globus pallidus externa (GPe). Patients also showed a significant R2* reduction in GPe. Age, gender, FD, session, group, and region are significant predictor variables for QSM. Dose, treatment duration, and volume were not predictor variables of QSM.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Reduction in QSM and R2* suggests a decreased iron concentration in the GPe of patients. Susceptibility reduction in putamen cannot be associated with iron changes. Since changes observed in putamen and GPe were not associated with symptoms, dose, and treatment duration, we hypothesize that susceptibility may be a trait marker rather than a state marker, but this must be verified with long-term studies.</jats:p> </jats:sec>
Scopus© Citations 1 1
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Abnormal nodal and global network organization in resting state functional MRI from subjects with the 22q11 deletion syndrome
(2021)
Teuntje A. D. Pelgrim
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Matthijs G. Bossong
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Analía Cuiza
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Luz María Alliende
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Carlos Mena
<jats:title>Abstract</jats:title><jats:p>The 22q11 deletion syndrome is a genetic disorder associated with a high risk of developing psychosis, and is therefore considered a neurodevelopmental model for studying the pathogenesis of schizophrenia. Studies have shown that localized abnormal functional brain connectivity is present in 22q11 deletion syndrome like in schizophrenia. However, it is less clear whether these abnormal cortical interactions lead to global or regional network disorganization as seen in schizophrenia. We analyzed from a graph-theory perspective fMRI data from 40 22q11 deletion syndrome patients and 67 healthy controls, and reconstructed functional networks from 105 brain regions. Between-group differences were examined by evaluating edge-wise strength and graph theoretical metrics of local (weighted degree, nodal efficiency, nodal local efficiency) and global topological properties (modularity, local and global efficiency). Connectivity strength was globally reduced in patients, driven by a large network comprising 147 reduced connections. The 22q11 deletion syndrome network presented with abnormal local topological properties, with decreased local efficiency and reductions in weighted degree particularly in hub nodes. We found evidence for abnormal integration but intact segregation of the 22q11 deletion syndrome network. Results suggest that 22q11 deletion syndrome patients present with similar aberrant local network organization as seen in schizophrenia, and this network configuration might represent a vulnerability factor to psychosis.</jats:p>
1Scopus© Citations 2
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Country-level gender inequality is associated with structural differences in the brains of women and men
(2023)
André Zugman
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Luz María Alliende
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Vicente Medel
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Richard A.I. Bethlehem
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Jakob Seidlitz
<jats:p>Gender inequality across the world has been associated with a higher risk to mental health problems and lower academic achievement in women compared to men. We also know that the brain is shaped by nurturing and adverse socio-environmental experiences. Therefore, unequal exposure to harsher conditions for women compared to men in gender-unequal countries might be reflected in differences in their brain structure, and this could be the neural mechanism partly explaining women’s worse outcomes in gender-unequal countries. We examined this through a random-effects meta-analysis on cortical thickness and surface area differences between adult healthy men and women, including a meta-regression in which country-level gender inequality acted as an explanatory variable for the observed differences. A total of 139 samples from 29 different countries, totaling 7,876 MRI scans, were included. Thickness of the right hemisphere, and particularly the right caudal anterior cingulate, right medial orbitofrontal, and left lateral occipital cortex, presented no differences or even thicker regional cortices in women compared to men in gender-equal countries, reversing to thinner cortices in countries with greater gender inequality. These results point to the potentially hazardous effect of gender inequality on women’s brains and provide initial evidence for neuroscience-informed policies for gender equality.</jats:p>
Scopus© Citations 38 5

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