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ORIGINAL RESEARCH article

Front. Psychiatry

Sec. Molecular Psychiatry

This article is part of the Research TopicBrain Iron in Neuropsychiatric DisordersView all articles

Quantitative susceptibility mapping of deep brain nuclei in 22q11.2 deletion syndrome

Provisionally accepted
Nestor MuñozNestor Muñoz1,2,3Marisleydis GarcíaMarisleydis García2,4Analía CuizaAnalía Cuiza5Angeles TepperAngeles Tepper5Javiera VásquezJaviera Vásquez5Juan Pablo Ramirez-MahalufJuan Pablo Ramirez-Mahaluf5Daniella BarbagelataDaniella Barbagelata5Juan AguirreJuan Aguirre5María Elisa MaldonadoMaría Elisa Maldonado5Claudia OrnsteinClaudia Ornstein5Rosemarie FritschRosemarie Fritsch5Gabriela RepettoGabriela Repetto5Carlos MilovicCarlos Milovic1,5Marcelo AndiaMarcelo Andia1,2Nicolas CrossleyNicolas Crossley1,5Cristian TejosCristian Tejos1,2,3*
  • 1Biomedical Imaging Center, Pontificia Universidad Católica de Chile, Santiago, Chile
  • 2Milennium Institute for Intelligent Healthcare Engineering, Santiago, Chile
  • 3Pontificia Universidad Catolica de Chile, Department of Electrical Engineering, Santiago, Chile
  • 4Universidad de Santiago de chile, Faculty of Engineering, Biomedical Engineering, Santiago, Chile
  • 5Pontificia Universidad Catolica de Chile, Department of Psychiatry, Santiago, Chile

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Background: 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. Methods: 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. Results: 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. Conclusions: 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.

Keywords: 22q11.2 deletion syndrome, magnetic susceptibility, MRI, Iron, deep-brain nuclei

Received: 24 Jun 2025; Accepted: 20 Nov 2025.

Copyright: © 2025 Muñoz, García, Cuiza, Tepper, Vásquez, Pablo Ramirez-Mahaluf, Barbagelata, Aguirre, Maldonado, Ornstein, Fritsch, Repetto, Milovic, Andia, Crossley and Tejos. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Cristian Tejos, ctejos@uc.cl

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Supplementary Material