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Related Experiment Video

Updated: Apr 5, 2026

Developing Neuroimaging Phenotypes of the Default Mode Network in PTSD: Integrating the Resting State, Working Memory, and Structural Connectivity
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Glutamatergic system abnormalities in posttraumatic stress disorder.

Daisuke Nishi1,2, Kenji Hashimoto2,3, Hiroko Noguchi1,2

  • 1Department of Psychiatry, National Disaster Medical Center, 3256 Midoricho, Tachikawa, Tokyo, 190-0014, Japan.

Psychopharmacology
|August 22, 2015
PubMed
Summary

Elevated serum glutamate and altered glutamine/glutamate ratios are linked to posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) severity in trauma patients. These findings highlight the glutamatergic system

Keywords:
AccidentDepressionGlutamateGlutaminePosttraumatic stress disorder

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Area of Science:

  • Neuroscience
  • Psychiatry
  • Biochemistry

Background:

  • The glutamatergic system is implicated in the neurobiology of posttraumatic stress disorder (PTSD).
  • Limited research has established a direct link between glutamatergic system dysfunction and PTSD diagnosis or symptom severity.
  • Severely injured patients are at high risk for developing PTSD and major depressive disorder (MDD).

Purpose of the Study:

  • To investigate the association between serum glutamate levels, the glutamine/glutamate ratio, and the diagnosis and severity of PTSD.
  • To examine the relationship between these biomarkers and the diagnosis and severity of major depressive disorder (MDD) in trauma-exposed individuals.

Main Methods:

  • A nested case-control study was conducted within the TPOP trial.
  • Diagnosis and severity of PTSD and MDD were assessed 3 months post-trauma using the Clinician-Administered PTSD Scale.
  • Univariate and multiple linear regression analyses were employed to assess associations between glutamate levels, the glutamine/glutamate ratio, and PTSD/MDD outcomes.

Main Results:

  • Serum glutamate levels were significantly higher in participants with PTSD compared to those without (p = 0.049).
  • Elevated serum glutamate was also observed in participants with MDD versus those without (p = 0.048).
  • Higher serum glutamate positively correlated with PTSD severity (p = 0.02) and MDD severity (p = 0.03).
  • A lower glutamine/glutamate ratio was significantly associated with increased PTSD severity (p = 0.03).

Conclusions:

  • The glutamatergic system plays a significant role in the pathophysiology of PTSD.
  • Findings suggest potential therapeutic targets within the glutamatergic system for PTSD treatment.
  • Further research is warranted to explore novel interventions for PTSD based on glutamatergic modulation.