Glutamate Receptor Dysregulation and Suicidal Thoughts in PTSD

Post by Deborah Joye

What's the science?

Post-traumatic stress disorder is a condition in which individuals experience persistent anxiety, flashbacks, and intense fear after a traumatic event. People who experience PTSD are at higher risk for developing suicidal thoughts, but the reasons why are not understood. One potential target implicated in mood and stress disorders is metabotropic glutamate receptor type 5 (mGluR5), which moderates activity of other receptors critical for synaptic plasticity and emotional learning. Previous work has identified higher mGluR5 availability and an association between increased mGluR5 gene expression and suicide in individuals with PTSD. This week in PNAS, Davis, Esterlis and colleagues use positron emission tomography (PET) to demonstrate that suicidal PTSD individuals have more mGluR5 availability in frontolimbic regions than individuals with PTSD with no suicidal thoughts, those with major depression and healthy controls, suggesting that mGluR5 dysregulation may serve as a biomarker of suicidality in PTSD specifically.

How did they do it?

The authors recruited 29 individuals with PTSD, 29 individuals with major depression, and 29 healthy controls. Participants completed physical, psychiatric, and neurological examinations during their initial visit to establish their diagnosis and rule out any other major illnesses. Participants also filled out a report on the day of their scan in order to assess suicidal thoughts. Participants were injected with [18F]FPEB, a radioligand with high selectivity and specificity for mGluR5 (e.g., a radioactive substance that selectively binds to mGluR5). Individuals participated in a PET scan and data were analyzed in five key frontolimbic brain regions – the dorsolateral and ventromedial prefrontal cortices, the orbitofrontal cortex, the amygdala, and the hippocampus. The authors analyzed associations between mGluR5 availability and PTSD, depression, suicidal thoughts, and scores from mood and anxiety tests.

What did they find?

Overall, the authors found that mGluR5 availability was higher in individuals with PTSD with suicidal ideation relative to those without suicidal thoughts, those with major depression, and healthy controls. Availability of mGluR5 was not different between those with major depression and healthy controls. Higher mGluR5 availability was associated with suicidal ideation among individuals with PTSD, but not those with major depression. Scores on mood tests were positively correlated with mGluR5 availability in the PTSD group (higher scores mean more mood disturbance). Interestingly, mood test scores were inversely correlated with mGluR5 availability in the major depression group (more mood disturbance was associated with lower mGluR5). Specifically, more mood disturbance was associated with more mGluR5 availability in individuals with PTSD that also reported suicidal thoughts.

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What's the impact?

These findings confirm that mGluR5 is upregulated in the frontolimbic regions of individuals with PTSD relative to healthy controls. Notably, this study is the first to demonstrate that higher mGluR5 availability is associated with suicidal ideation specifically in individuals with PTSD but not depression. This study identifies mGluR5 as a possible biomarker and treatment target for intervention and management of suicide risk in individuals with PTSD.


Davis et al., In vivo evidence for dysregulation of mGluR5 as a biomarker of suicidal ideation, PNAS (2019). Access the original scientific publication here.