Increased Absolute Glutamate Concentrations and Glutamate-to-Creatine Ratios in Patients With Methamphetamine Use Disorders

Abstract

Introduction: Previous studies have indicated that changes in the concentration of glutamate and related metabolites may mediate the progression of addiction in patients with methamphetamine (MA) use disorders. In the present study, we utilized magnetic resonance spectroscopy (MRS) to investigate absolute glutamate concentrations and metabolite ratios in patients with MA addiction. We further analyzed the association between glutamate concentration and various clinical indicators.Methods: The present study included 31 unmedicated patients with clinically diagnosed MA dependence (mean age: 30.5 ± 8.0 years) and 32 age-matched healthy controls (mean age: 32.9 ± 8.2 years). Patients were evaluated using the Barratt Impulsiveness Scale (BIS-11). We also collected general information regarding the duration and dosage of drug use. Point-resolved spectroscopy was used to quantify the absolute concentrations of metabolites (glutamate, choline, N-acetylaspartate, glutamine, and creatine), as well as the ratio of metabolites to total creatine, using LCModel software. We then compared differences in glutamate levels and psychometric scores between the two groups.Results: Glutamate-to-creatine ratios in the brainstem were significantly higher in the MA group than in the control group (t = 2.764, p = 0.008). Glutamate concentrations in the brainstem were also significantly higher in the MA group than in the control group (t = 2.390, p = 0.020). However, no significant differences in the concentrations or ratios of other metabolites were observed between the two groups (all p > 0.05). Glutamate concentration was positively correlated with the duration of drug use (r = 0.401, p = 0.035) and the total dose of regular addiction (duration of addiction × regular addiction dose; r = 0.207, p = .040), but not with BIS-11 scores.Conclusions: Our findings indicated that glutamate levels in the brainstem are significantly elevated in patients with MA use disorders, and that these levels are significantly associated with the duration and dose of drug use.Such findings suggest that glutamate concentration can be used as an objective biological marker for evaluating/monitoring disease status and treatment efficacy in patients with MA dependence.

Revealing Metabolic Perturbation Following Heavy Methamphetamine Abuse by Human Hair Metabolomics and Network Analysis

“…In addition, the levels of more ion features were significantly altered in hair (103 and 18 in the positive and the negative ionization mode of untargeted MS, respectively) than in urine after MA self-administration, suggesting that hair may be a more suitable diagnostic specimen for evaluation of drug addiction [ 18 ]. Limited clinical studies have been performed to study the effect of MA exposure by analyzing specific target metabolites, such as glutamate [ 37 ] and n-acetyl-aspartate [ 38 ], in the brain.…”

Traumatic brain injury and methamphetamine: A double-hit neurological insult

“…Alternatively, in clinical studies, an investigation of the differences in glutamate concentration, among other metabolites, between untreated METH users and healthy individuals showed higher concentrations in the brainstem of the former group. These elevated levels were positively correlated with the duration and the total dose of drug use [152]. The glutamatergic upregulation observed post-TBI mimics the neurochemical state described in METH consumers and can possibly prime the brain for drugseeking behaviors in prior users.…”

Activation of mGluR5 and NMDA Receptor Pathways in the Rostral Ventrolateral Medulla as a Central Mechanism for Methamphetamine-Induced Pressor Effect in Rats

“…VGluT1 might participate in the glutamate release after MA is applied [34]. In human MA-dependent users, the glutamate levels in the brainstem are significantly elevated, and the levels are associated with the duration and dose of MA use [35]. Using the whole-cell patch-clamp recording in rat primary cultured hippocampal neurons, the authors found that MA modulated presynaptic glutamate release in a dopamine-independent manner [36].…”