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

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 (<i>n</i> = 29) and MDD (<i>n</i> = 29) as a function of suicidal ideation (SI) to compare with that of healthy comparison controls (HC; <i>n</i> = 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 (<i>P</i>'s = 0.001-0.01) and compared with MDD individuals in three regions (<i>P</i>'s = 0.007). mGluR5 availability was not significantly different between MDD and HC individuals (<i>P</i> = 0.17). Importantly, we observed an up-regulation in mGluR5 availability in the PTSD-SI group (<i>P</i>'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.