Prefrontal Glutamate Neurotransmission in PTSD: A Novel Approach to Estimate Synaptic Strength in Vivo in Humans

Authors

Lynnette A Averill
Lihong Jiang
Prerana Purohit
Anastasia Coppoli
Christopher L Averill
Jeremy Roscoe
Benjamin Kelmendi
Henk M De Feyter
Robin A de Graaf
Ralitza Gueorguieva
Gerard Sanacora
John H Krystal
Douglas L Rothman
Graeme F Mason
Chadi G Abdallah

Language

English

Publication Date

1-1-2022

Journal

Chronic Stress

DOI

10.1177/24705470221092734

PMID

35434443

PMCID

PMC9008809

PubMedCentral® Posted Date

4-11-2022

PubMedCentral® Full Text Version

Post-print

Abstract

Background: Trauma and chronic stress are believed to induce and exacerbate psychopathology by disrupting glutamate synaptic strength. However, in vivo in human methods to estimate synaptic strength are limited. In this study, we established a novel putative biomarker of glutamatergic synaptic strength, termed energy-per-cycle (EPC). Then, we used EPC to investigate the role of prefrontal neurotransmission in trauma-related psychopathology.

Methods: Healthy controls (n = 18) and patients with posttraumatic stress (PTSD; n = 16) completed 13C-acetate magnetic resonance spectroscopy (MRS) scans to estimate prefrontal EPC, which is the ratio of neuronal energetic needs per glutamate neurotransmission cycle (VTCA/VCycle).

Results: Patients with PTSD were found to have 28% reduction in prefrontal EPC (t = 3.0; df = 32, P = .005). There was no effect of sex on EPC, but age was negatively associated with prefrontal EPC across groups (r = -0.46, n = 34, P = .006). Controlling for age did not affect the study results.

Conclusion: The feasibility and utility of estimating prefrontal EPC using 13C-acetate MRS were established. Patients with PTSD were found to have reduced prefrontal glutamatergic synaptic strength. These findings suggest that reduced glutamatergic synaptic strength may contribute to the pathophysiology of PTSD and could be targeted by new treatments.

Keywords

PTSD, depression, glutamate, synaptic strength, stress, trauma

Published Open-Access

yes

Recommended Citation

Averill, Lynnette A; Jiang, Lihong; Purohit, Prerana; et al., "Prefrontal Glutamate Neurotransmission in PTSD: A Novel Approach to Estimate Synaptic Strength in Vivo in Humans" (2022). Staff and Researcher Publications. 11.
https://digitalcommons.library.tmc.edu/clinic_pub/11