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

Abstract

ObjectiveAnxiety 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.MethodsSixteen 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.ResultsPD 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).ConclusionOur 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.

Brain Iron Homeostasis and Mental Disorders

“…Furthermore, it has been observed that individuals with PD and anxiety exhibit increased iron accumulation in the fear circuit of the brain. This finding suggests that the excessive iron buildup in this region may potentially contribute to the onset and development of anxiety symptoms in individuals with PD [103]. Moreover, rodent studies have reported that iron overload in the brain appears to accelerate anxiety-like behavior and mood.…”

The Irony of Iron: The Element with Diverse Influence on Neurodegenerative Diseases

“…Increased QSM values in the medial frontal cortex, anterior cingulate cortex, hippocampus, precuneus, and angular cortex are found in PD patients with anxiety, although such elevation may be related to longer duration of disease in these patients. Regardless, the QSM values of select brain regions were found to be positively correlated with the Hamilton anxiety rating scale (HAM-A) scores [125]. Nigral iron deposition was found to be higher in PD patients with freezing of gait (FOG) than in those without, correlating with the new freezing of gait questionnaire (nFOGQ) scores [112].…”

Iron Deposition in Parkinson’s Disease: A Mini-Review

“…One small-scale study found that increased R2* values in the RN and right amygdala are related to PD sleep disturbances, whereas elevated R2* values in the right amygdala and left hippocampus are associated with PD autonomic dysfunction (Kim et al 2021 ). Additionally, anxiety in PD is linked to increased iron accumulation within the neural circuits associated with fear in the brain (Chen et al 2023 ).…”