Effects of Uric Acid on the Alterations of White Matter Connectivity in Patients with Major Depression

Abstract

Objective: Uric acid is a non-enzymatic antioxidant associated with depression. Despite its known protective role in other brain disorders, little is known about its influence on the structural characteristics of brains of patients with major depressive disorder (MDD). This study explored the association between uric acid and characteristics of white matter (WM) in patients with MDD.

Methods: A total of 32 patients with MDD and 23 healthy controls (HCs) were examined. All participants were scored based on the Beck Depression Inventory and Beck Anxiety Inventory at baseline. All patients were also rated with the Hamilton Depression Rating Scale. We collected blood samples from all participants immediately after their enrollment and before the initiation of antidepressants in case of patients. Tract-based spatial statistics were used for all imaging analyses.

Results: Lower fractional anisotropy (FA) and higher radial diffusivity (RD) values were found in the MDD group than in the HC group. Voxelwise correlation analysis revealed that the serum uric acid levels positively correlated with the FA and negatively with the RD in WM regions that previously showed significant group differences in the MDD group. The correlated areas were located in the left anterior corona radiata, left frontal lobe WM, and left anterior cingulate cortex WM.

Conclusion: The present study suggests a significant association between altered WM connectivity and serum uric acid levels in patients with MDD, possibly through demyelination.

Keywords: Antioxidants; Neuroimaging; Oxidative stress; Uric acid; White matter; Depressive disorder.

Figure 1.

Tract-Based Spatial Statistics analysis showing significant correlations (corrected p<0.05) between the serum uric acid levels and FA or RD values in the depression group. A: Voxels demonstrating significant positive correlations between the serum uric acid levels and FA values in the depression group are shown in red-yellow. B: Voxels demonstrating significant negative correlations between the serumuric acid levels and RD values in the depression group are shown in blue-lightblue. Only voxels showing significant differences between patients with depression and healthy controls are included. Results are shown overlaid on the Montreal Neurologic Institute 1-mm template (Z=-22 to Z=44) and the mean FA skeleton (green). A threshold-free cluster enhancement method was applied using a permutation-based inference tool for nonparametric statistics. The number of permutations was 10,000, and the left-right orientation is according to the radiological convention. ACC: anterior cingulate cortex, ACR: anterior corona radiata, L: left, WM: white matter, FA: fractional anisotropy, RD: radial diffusivity.