Exploring brain glutathione and peripheral blood markers in posttraumatic stress disorder: a combined [1H]MRS and peripheral blood study

Sarah E Watling; Shawn G Rhind; Jerry Warsh; Duncan Green; Tina McCluskey; Junchao Tong; Peter Truong; Sofia Chavez; J Don Richardson; Stephen J Kish; Isabelle Boileau

doi:10.3389/fpsyt.2023.1195012

Exploring brain glutathione and peripheral blood markers in posttraumatic stress disorder: a combined [1H]MRS and peripheral blood study

Front Psychiatry. 2023 Jun 2:14:1195012. doi: 10.3389/fpsyt.2023.1195012. eCollection 2023.

Authors

Sarah E Watling^{1

2}, Shawn G Rhind^{3

4}, Jerry Warsh^{1

2

5

6

7}, Duncan Green^{1

2}, Tina McCluskey^{2

5}, Junchao Tong^{2

5

6}, Peter Truong², Sofia Chavez², J Don Richardson^{8

9

10

11}, Stephen J Kish^{1

2

5

6

7}, Isabelle Boileau^{1

2

5

7}

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 Faculty of Kinesiology & Physical Education, University of Toronto, Toronto, ON, Canada.
⁴ Defence Research and Development Canada, Toronto Research Centre, Toronto, ON, Canada.
⁵ Campbell Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada.
⁶ Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
⁷ Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada.
⁸ The MacDonald Franklin Operational Stress Injury (OSI) Research Centre, Lawson Health Research Institute, London, ON, Canada.
⁹ Department of Psychiatry, Western University, London, ON, Canada.
¹⁰ Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada.
¹¹ St. Joseph's London Operational Stress Injury (OSI), Parkwood Institute, St. Joseph's Health Care, London, ON, Canada.

Abstract

Introduction: Oxidative stress has been implicated in psychiatric disorders, including posttraumatic stress disorder (PTSD). Currently, the status of glutathione (GSH), the brain's most abundant antioxidant, in PTSD remains uncertain. Therefore, the current study investigated brain concentrations of GSH and peripheral concentrations of blood markers in individuals with PTSD vs. Healthy Controls (HC).

Methods: GSH spectra was acquired in the anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex (DLPFC) using MEGA-PRESS, a J-difference-editing acquisition method. Peripheral blood samples were analyzed for concentrations of metalloproteinase (MMP)-9, tissue inhibitors of MMP (TIMP)-1,2, and myeloperoxidase (MPO).

Results: There was no difference in GSH between PTSD and HC in the ACC (n = 30 PTSD, n = 20 HC) or DLPFC (n = 14 PTSD, n = 18 HC). There were no group differences between peripheral blood markers (P > 0.3) except for (non-significantly) lower TIMP-2 in PTSD. Additionally, TIMP-2 and GSH in the ACC were positively related in those with PTSD. Finally, MPO and MMP-9 were negatively associated with duration of PTSD.

Conclusions: We do not report altered GSH concentrations in the ACC or DLPFC in PTSD, however, systemic MMPs and MPO might be implicated in central processes and progression of PTSD. Future research should investigate these relationships in larger sample sizes.

Keywords: glutathione; magnetic resonance spectroscopy; metalloproteinase (MMP); myeloperoxidase (MPO); posttraumatic stress disorder (PTSD); psychiatric disorder.

Grants and funding

Funded by the Department of National Defence and Canadian Institute for Military and Veteran Health Research (CIMVHR) through a sub-award to IB.