Cortical Iron in Schizophrenia: A Quantitative Susceptibility Mapping and Diffusion Tensor Imaging MRI Study
Abstract
Background and Hypothesis
Cognitive and negative symptoms in schizophrenia remain poorly treated. Iron dysregulation has been implicated as a potential mechanism underlying cognitive dysfunction and schizophrenia. While elevated postmortem iron in Brodmann areas 10-11 has been linked to schizophrenia, this has not been assessed in vivo . We therefore used iron-sensitive MRI to test whether cortical iron is elevated in individuals with schizophrenia compared to healthy controls.
Study Design
We acquired quantitative susceptibility mapping (QSM) MRI to measure magnetic susceptibility (χ), a marker of iron, in 158 participants aged 18–45 (73 with schizophrenia and 76 matched healthy controls). As χ is reduced by myelin, we conducted diffusion tensor imaging (DTI) to assess mean diffusivity, an iron-insensitive marker also reduced by myelin.
Study Results
Primary analyses showed no significant case-control differences in χ in the whole cortex (p=0.675) or Brodmann areas 10–11 (p=0.537). Exploratory analyses examined χ for 362 cortical regions and a voxelwise analysis, correcting for multiple comparisons. Two left temporo-parieto-occipital (TPO) junction regions showed significantly elevated χ in schizophrenia: the posterior TPO junction (d=0.752, p<0.001) and the superior temporal visual area (d=0.638, p=0.033), which remained significant after adjusting for mean diffusivity and clinical covariates (p=0.001 and p=0.023, respectively). Voxelwise analysis confirmed elevated χ in schizophrenia in the left TPO junction (peak t=5.62).
Conclusions
This study provides the first in vivo evidence of elevated cortical iron in schizophrenia, suggesting regional iron accumulation may contribute to cortical pathology.
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