Yale Study Investigates Biomarker that may Reveal PTSD Sufferers at Risk of Suicide

Much like fingerprints, “brainprints” can identify individuals with a high degree of accuracy.

More Americans are killing themselves every year than any time since the Second World War, according to the Centers for Disease Control and Prevention’s National Health Statistics. The rise in suicide rates is especially high among veterans suffering from post-traumatic stress disorder (PTSD), as reported by the National Vital Statistics System.

The link between suicide, PTSD, and major depressive disorder (MDD) is well known. However, scientists understand little about what occurs in the brain that connects trauma, thought, and action.

Margaret T. Davis, Assistant Professor in the Department of Psychiatry at Yale University, believes that the best potential solution for the ever-increasing suicide rates lies in better medication—especially for PTSD. “As a therapist, working with individuals with trauma related psychopathology, with PTSD… there’s really nothing you can do if something bad happens, and they’re in a place where they feel like they might need to attempt suicide…. So, the best solution, arguably, is for us to develop something pharmacological, something that they can have on board that will intervene on a neurobiological level and reduce their risk” Davis said. To date, the FDA has approved only two drugs for PTSD.

In Davis’s study, “Biomarker reveals PTSD sufferers at risk of suicide” published May 13, 2019 in the journal Proceedings of the National Academy of Sciences, she and a team of Yale researchers discovered a biological marker that appears linked to individuals with PTSD (but not in people with serious depression) most likely to contemplate suicide.

Researchers used PET imaging to measure levels of metabotropic glutamatergic receptor 5 (mGluR5), a protein receptor connected to anxiety and mood disorders, in individuals with PTSD and major depressive disorder (MDD).

“Ninety percent of the synapses in the brain are actually glutamatergic, so it makes a lot of sense to try to develop a treatment that’s potentially targeting a glutamate system. We know that glutamate has a lot to do with things that are really important to psychiatric disorders, including emotion regulation and fear conditioning, which is the biggest component of PTSD,” Davis said. Thus, Davis set out to conduct the first study investigating mGluR5 in humans with PTSD.

Conducted at the Yale PET Center and the Yale Translational Brain Imaging Lab, Davis’s team formed three distinct groups: healthy control (individuals with no history of psychiatric diagnosis), individuals with MDD but no PTSD, and individuals with PTSD—some with MDD and some without.

The researchers then compared the PET scan results across the diagnostic groups. Davis and her team noticed high levels of mGluR5 in individuals with PTSD and who experienced suicidal thoughts; they did not find such levels of mGluR5 in individuals with PTSD but no suicidal thoughts or in those with MDD—with or without suicidal thoughts.

“Our first big finding… was that mGluR5 availability”—the number of mGluR5 that the injected tracer was able to bind to—“was higher in individuals with PTSD relative to both healthy control and people with major depressive disorder. And that’s in regions that were relevant to PTSD and to suicidal behavior… so the frontal region and limbic region,” Davis said.

“Within PTSD, you see that people who on scan-day were thinking about suicide, who are having what we call suicidal-ideation, had significantly higher mGluR5 availability to those who were not having standard suicidal-ideation,” Davis added. mGluR5 availability was not higher in the healthy control group or in individuals contemplating suicide with MDD; the higher mGluR5 availability was just in those with PTSD.

Davis was quick to mitigate premature overexcitement: “I think it’s always important to emphasize that this is a first-step… But what we’ve got here are the first findings in humans that show real, live differences in mGluR5 availability. And that’s exciting.”

Next, Davis hopes to build upon this study’s findings and investigate suicidal behavior and mGluR5 availability in individuals with other trauma-related psychopathologies.

From this study, it became clear to Davis that “reducing suicidal behavior is not as simple as a one size fits all solution. We’re going to have to think about it differently for different groups of people.” Thus, she hopes to look trans-diagnostically at “suicidal behavior and mGluR5 to try to figure out if this is something that could potentially be used as a treatment for suicidal behavior in more than just PTSD. And if we can predict who it will work for and who it won’t,” Davis concluded.