Alterations in brain iron deposition with progression of late-life depression measured by magnetic resonance imaging (MRI)-based quantitative susceptibility mapping.

Background: Previous studies have revealed abnormality of iron deposition in the brain of patients with depression. The progression of iron deposition associated with depression remains to be elucidated. Methods: This is a longitudinal study. We explored brain iron deposition with disease progression in 20 patients older than 55 years with depression and on antidepressants, using magnetic resonance imaging (MRI)-based quantitative susceptibility mapping (QSM). Magnetic susceptibility values of the whole brain were compared between baseline and approximately one-year follow-up scans using permutation testing. Furthermore, we examined the relationship of changes between the susceptibility values and disease improvement using Spearman's partial correlation analysis, controlling for age, gender, and the visit interval. Results: Compared to the initial scan, increased magnetic susceptibility values were found in the medial prefrontal cortex (mPFC), dorsal anterior cingulate cortex (dACC), occipital areas, habenula, brainstem, and cerebellum (P<0.05, corrected). The susceptibility values decreased in the dorsal part of the mPFC, middle and posterior cingulate cortex (MCC and PCC), right postcentral gyrus, right inferior parietal lobule, right precuneus, right supramarginal gyrus, left lingual gyrus, left dorsal striatum, and right thalamus (P<0.05, corrected). Notably, the increase in susceptibility values at the mPFC and dACC negatively correlated with the changes in depression scores, as calculated using the Hamilton Depression Scale (HAMD) (r=-0.613, P=0.009), and the increase in susceptibility values at the cerebellum and habenula negatively correlated with the changes in cognitive scores, which were calculated using the Mini-Mental State Examination (MMSE) (cerebellum: r=-0.500, P=0.041; habenula: r=-0.588, P=0.013). Additionally, the decreased susceptibility values at the white matter near the mPFC (anterior corona radiata) also correlated with the changes in depression scores (r=-0.541, P=0.025), and the decreased susceptibility values at the left lingual gyrus correlated with the changes in cognitive scores (r=-0.613, P=0.009). Conclusions: Our study identified brain areas where iron deposition changed with the progression of depression while on antidepressants. The linear relationship of changes in the magnetic susceptibility values in the mPFC, dACC, and some subcortical areas with changes in depression symptoms and cognitive functions of patients is highlighted. Our results strengthen the understanding of the alterations of brain iron levels associated with disease progression in patients with late-life depression.