Imaging oxidative stress in brains of chronic methamphetamine users: A combined 1H-magnetic resonance spectroscopy and peripheral blood biomarker study

Sarah E Watling; Samantha Jagasar; Tina McCluskey; Jerry Warsh; Shawn G Rhind; Peter Truong; Sofia Chavez; Sylvain Houle; Junchao Tong; Stephen J Kish; Isabelle Boileau

doi:10.3389/fpsyt.2022.1070456

Imaging oxidative stress in brains of chronic methamphetamine users: A combined 1H-magnetic resonance spectroscopy and peripheral blood biomarker study

Front Psychiatry. 2023 Jan 10:13:1070456. doi: 10.3389/fpsyt.2022.1070456. eCollection 2022.

Authors

Sarah E Watling^{1

2}, Samantha Jagasar², Tina McCluskey^{2

3}, Jerry Warsh^{1

2

3

4

5}, Shawn G Rhind^{6

7}, Peter Truong², Sofia Chavez², Sylvain Houle^{2

3

4}, Junchao Tong^{2

3

4}, Stephen J Kish^{1

2

3

4

5}, Isabelle Boileau^{1

2

3

4

5}

Affiliations

¹ Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada.
² Brain Health Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada.
³ Campbell Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada.
⁴ Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
⁵ Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada.
⁶ Faculty of Kinesiology and Physical Education, University of Toronto, Toronto, ON, Canada.
⁷ Defence Research and Development Canada, Toronto Research Centre, Toronto, ON, Canada.

Abstract

Introduction: Preclinical data suggest methamphetamine (MA), a widely used stimulant drug, can harm the brain by causing oxidative stress and inflammation, but only limited information is available in humans. We tested the hypothesis that levels of glutathione (GSH), a major antioxidant, would be lower in the brains of chronic human MA preferring polysubstance users. We also explored if concentrations of peripheral immunoinflammatory blood biomarkers were related with brain GSH concentrations.

Methods: 20 healthy controls (HC) (33 years; 11 M) and 14 MA users (40 years; 9 M) completed a magnetic resonance spectroscopy (MRS) scan, with GSH spectra obtained by the interleaved J-difference editing MEGA-PRESS method in anterior cingulate cortex (ACC) and left dorsolateral prefrontal cortex (DLPFC). Peripheral blood samples were drawn for measurements of immunoinflammatory biomarkers. Independent samples t-tests evaluated MA vs. HC differences in GSH.

Results: GSH levels did not differ between HC and MA users (ACC p = 0.30; DLPFC p = 0.85). A total of 17 of 25 immunoinflammatory biomarkers were significantly elevated in MA users and matrix metalloproteinase (MMP)-2 (r = 0.577, p = 0.039), myeloperoxidase (MPO) (r = -0.556, p = 0.049), and MMP-9 (r = 0.660, p = 0.038) were correlated with brain levels of GSH.

Conclusion: Normal brain GSH in living brain of chronic MA users is consistent with our previous postmortem brain finding and suggests that any oxidative stress caused by MA, at the doses used by our participants, might not be sufficient to cause either a compensatory increase in, or substantial overutilization of, this antioxidant. Additionally, more research is required to understand how oxidative stress and inflammatory processes are related and potentially dysregulated in MA use.

Keywords: glutathione; inflammation; magnetic resonance spectroscopy; methamphetamine; oxidative stress; substance use disorder.

Grants and funding

R21 DA040066/DA/NIDA NIH HHS/United States