The impact of iron deposition on the fear circuit of the brain in patients with Parkinson’s disease and anxiety

OBJECTIVE: Anxiety is one of the most common psychiatric symptoms of Parkinson’s disease (PD), and brain iron deposition is considered to be one of the pathological mechanisms of PD. The objective of this study was to explore alterations in brain iron deposition in PD patients with anxiety compared to PD patients without anxiety, especially in the fear circuit. METHODS: Sixteen PD patients with anxiety, 23 PD patients without anxiety, and 26 healthy elderly controls were enrolled prospectively. All subjects underwent neuropsychological assessments and brain magnetic resonance imaging (MRI) examinations. Voxel-based morphometry (VBM) was used to study morphological brain differences between the groups. Quantitative susceptibility mapping (QSM), an MRI technique capable of quantifying susceptibility changes in brain tissue, was used to compare susceptibility changes in the whole brain among the three groups. The correlations between brain susceptibility changes and anxiety scores quantified using the Hamilton Anxiety Rating Scale (HAMA) were compared and analyzed. RESULTS: PD patients with anxiety had a longer duration of PD and higher HAMA scores than PD patients without anxiety. No morphological brain differences were observed between the groups. In contrast, voxel-based and ROI-based QSM analyses showed that PD patients with anxiety had significantly increased QSM values in the medial prefrontal cortex, anterior cingulate cortex, hippocampus, precuneus, and angular cortex. Furthermore, the QSM values of some of these brain regions were positively correlated with the HAMA scores (medial prefrontal cortex: r = 0.255, p = 0.04; anterior cingulate cortex: r = 0.381, p < 0.01; hippocampus: r = 0.496, p < 0.01). CONCLUSION: Our findings support the idea that anxiety in PD is associated with iron burden in the brain fear circuit, providing a possible new approach to explaining the potential neural mechanism of anxiety in PD.