Cross-sectional Exploration of the Relationship Between Glutamate Abnormalities and Tic Disorder Severity Using Proton Magnetic Resonance Spectroscopy

Phenomics. 2022 Aug 16;3(2):138-147. doi: 10.1007/s43657-022-00064-z. eCollection 2023 Apr.

Abstract

Glutamate (Glu) has been reported to be closely related to the pathophysiology of Tic Disorders (TD). By using proton magnetic resonance spectroscopy (1H-MRS), we aimed to investigate the relationship between in vivo Glu levels and the severity of TD. We performed a cross-sectional study in medication-free patients with TD and healthy controls aged between 5 and 13 years using 1H-MRS at 3 T. First, we measured the Glu levels in both patients and controls and observed the difference in subgroups, including mild TD patients and moderate TD patients. We then examined the correlations between the Glu levels and clinical features of the patients. Finally, we assessed the diagnostic value of 1H-MRS and the influencing factors. Our results show that the Glu levels in the striatum of all patients with TD were not significantly different from those of the healthy controls. Subgroup analysis revealed that the Glu levels in the moderate TD group were higher than those in the mild TD group and healthy controls. The correlation analysis showed that Glu levels are strongly positive correlated with TD severity. The optimal cutoff value of Glu levels to differentiate mild tics from moderate tics was 1.244, with a sensitivity of 88.2% and a specificity of 94.7%. Multiple linear regression models revealed that the severity of TD is one of the important factors that affect Glu levels. We conclude that Glu levels are mainly associated with the severity of tics, thus it could serve as a key biomarker for TD classification.

Keywords: Glutamate levels; Magnetic resonance spectroscopy; Striatum; Tic Disorders.