Glutamatergic system abnormalities in posttraumatic stress disorder

Psychopharmacology (Berl). 2015 Dec;232(23):4261-8. doi: 10.1007/s00213-015-4052-5. Epub 2015 Aug 22.


Rationale: Accumulating evidence suggests involvement of the glutamatergic system in the biological mechanisms of posttraumatic stress disorder (PTSD), but few studies have demonstrated an association between glutamatergic system abnormalities and PTSD diagnosis or severity.

Objective: We aimed to examine whether abnormalities in serum glutamate and in the glutamine/glutamate ratio were associated with PTSD diagnosis and severity in severely injured patients at risk for PTSD and major depressive disorder (MDD).

Methods: This is a nested case-control study in TPOP (Tachikawa project for prevention of posttraumatic stress disorder with polyunsaturated fatty acid) trial. Diagnosis and severity of PTSD were assessed 3 months after the accidents using the Clinician-Administered PTSD Scale. The associations of glutamate levels and the glutamine/glutamate ratio with diagnosis and severity of PTSD and MDD were investigated by univariate and multiple linear regression analyses.

Results: Ninety-seven of 110 participants (88 %) completed assessments at 3 months. Serum glutamate levels were significantly higher for participants with full or partial PTSD than for participants without PTSD (p = 0.049) and for participants with MDD than for participants without MDD (p = 0.048). Multiple linear regression analyses showed serum glutamate levels were significantly positively associated with PTSD severity (p = 0.02) and MDD severity (p = 0.03). The glutamine/glutamate ratio was also significantly inversely associated with PTSD severity (p = 0.03), but not with MDD severity (p = 0.07).

Conclusions: These findings suggest that the glutamatergic system may play a major role in the pathogenesis of PTSD and the need for new treatments targeting the glutamatergic system to be developed for PTSD.

Keywords: Accident; Depression; Glutamate; Glutamine; Posttraumatic stress disorder.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers / blood
  • Case-Control Studies
  • Depressive Disorder, Major / blood
  • Depressive Disorder, Major / diagnosis
  • Depressive Disorder, Major / psychology
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Glutamic Acid / blood*
  • Glutamine / blood*
  • Humans
  • Male
  • Middle Aged
  • Stress Disorders, Post-Traumatic / blood*
  • Stress Disorders, Post-Traumatic / diagnosis*
  • Stress Disorders, Post-Traumatic / psychology


  • Biomarkers
  • Glutamine
  • Glutamic Acid