In vivo evidence for dysregulation of mGluR5 as a biomarker of suicidal ideation

Proc Natl Acad Sci U S A. 2019 Jun 4;116(23):11490-11495. doi: 10.1073/pnas.1818871116. Epub 2019 May 13.

Abstract

Recent evidence implicates dysregulation of metabotropic glutamatergic receptor 5 (mGluR5) in pathophysiology of PTSD and suicidality. Using positron emission tomography and [18F]FPEB, we quantified mGluR5 availability in vivo in individuals with PTSD (n = 29) and MDD (n = 29) as a function of suicidal ideation (SI) to compare with that of healthy comparison controls (HC; n = 29). Volume of distribution was computed using a venous input function in the five key frontal and limbic brain regions. We observed significantly higher mGluR5 availability in PTSD compared with HC individuals in all regions of interest (P's = 0.001-0.01) and compared with MDD individuals in three regions (P's = 0.007). mGluR5 availability was not significantly different between MDD and HC individuals (P = 0.17). Importantly, we observed an up-regulation in mGluR5 availability in the PTSD-SI group (P's = 0.001-0.007) compared with PTSD individuals without SI. Findings point to the potential role for mGluR5 as a target for intervention and, potentially, suicide risk management in PTSD.

Keywords: PET; PTSD; mGluR5; suicidal ideation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Biomarkers / metabolism*
  • Brain / metabolism
  • Depressive Disorder, Major / metabolism
  • Female
  • Humans
  • Male
  • Positron-Emission Tomography / methods
  • Radiopharmaceuticals / metabolism
  • Receptor, Metabotropic Glutamate 5 / metabolism*
  • Suicidal Ideation
  • Suicide Prevention*

Substances

  • Biomarkers
  • GRM5 protein, human
  • Radiopharmaceuticals
  • Receptor, Metabotropic Glutamate 5