June 15, 2023 | Scientists and clinicians have been looking for behavioral predictors of suicide for decades now, and yet the most reliable detection method remains self-disclosure by individuals who feel life is not worth living. The work of trying to understand the brain mechanisms behind suicide is a newer, “burgeoning bubble” of research to better foresee who is in peril of taking their own life, according to Audreyana Jagger-Rickels, Ph.D., principal investigator in the National Center for Post-Traumatic Stress Disorder (PTSD) at the Veteran Affairs (VA) Boston Healthcare System and assistant professor of psychiatry at Boston University.
The focus of her suicide research is the functional connectivity between brain networks involved in cognitive control and self-referential thought processing as well as connectedness in the right amygdala, a brain region important for fear learning and trauma. As most recently reported in the Journal of Affective Disorders, (DOI: 10.1016/j.jad.2023.04.061), functional MRI imaging shows evidence of aberrant connectivity in the amygdala after a suicide attempt that is absent beforehand.
That opens a lot more questions than it answers, Jagger-Rickels is quick to share. “We don’t really understand what a suicide attempt means for an individual, but we do know that having a history of suicide attempt already puts you at higher risk for suicide in the future.” Among the possible explanations is that the events surrounding the suicide attempt or the associated emotional arousal—potentially related to amygdala activity—raises a person’s overall suicide risk profile.
Surprisingly, brain markers of suicide risk have not been heavily investigated, particularly in veterans who are about 1.5 times more vulnerable than the general population, she says. But the tide has been slowly turning following publication of a comprehensive review of suicide research published in 2016 by the American Psychological Association (Psychological Bulletin, DOI: 10.1037/bul0000084) finding that experts’ ability to predict who is at risk for suicide hasn’t significantly improved over the last 50 years.
For Jagger-Rickels, the long-term vision here is to nail down the linkage between functional connectivity in the brain with cognitive behavior to lessen the dependency on self-reporting by at-risk individuals. As suicide statistics suggest, not everyone is inclined or comfortable disclosing suicidal thoughts or tendencies in their hour of need, she says.
“Hopefully in the future we will be able to identify them before that point and... facilitate the delivery of evidence-based interventions,” continues Jagger-Rickels. At-risk individuals could be guided to useful treatments without the need for costly trips to an MRI scanner.
Psychiatric literature discusses the role of suicide stigma and self-disclosure and some of it suggests the problem is a bit worse with veterans because of their desire to excel and do right by their brothers and sisters in arms, she says. Despite concerted efforts to destigmatize mental health issues, at-risk individuals may want to avoid psychiatric hospitalization or other unwelcome reactions from friends, family, or clinicians to their emotional struggles.
Typically, people who have a history of suicide attempt or are reporting suicidal thoughts or behaviors also have higher symptoms of depression, anxiety, and PTSD, says Jagger-Rickels, in explaining the importance of having a psychiatric control group with those set of symptoms in research studies. This gives researchers greater confidence that differences seen in brain functional connectivity are unique to suicide rather than heightened psychiatric distress or severity.
In previous work, Jagger-Rickels worked with colleagues to identify the two connectivity brain markers of suicide risk thanks to participants in the longitudinal cohort study at the Translational Research Center for Traumatic Brain Injury and Stress Disorders (TRACTS) of the VA Boston Healthcare System that measures brain, cognitive, physical and psychological health. As a part of that study, veterans completed a resting functional MRI scan measuring the intrinsic communication between brain regions and networks.
To learn if the biomarkers might correspond to the suicide attempt itself, a new sample of 598 post-9/11 deployed veterans who reported a suicide attempt for the first time during a follow-up assessment were then identified from TRACTS. Another group with equivalent symptoms of depression and PTSD, but who did not report a suicide attempt, were simultaneously identified.
Finding ways other than self-disclosure to identify people at risk is an emerging theme in the overall suicide research field, Jagger-Rickels says. For example, researchers in Matthew Nock’s lab at Harvard University has developed the Death Implicit Association Test that measures suicide risk based on the time it takes to categorize words on a screen into categories.
On the treatment front, promising work is now occurring using brief cognitive-behavioral therapy for suicide prevention, she adds. One of the big questions to emerge from the pandemic is whether the approach works virtually as well as in person, which has initial support from a study that published in Cognitive and Behavioral Practice (DOI: 10.1016/j.cbpra.2020.12.001).
Where Jagger-Rickels sees the therapy-developing potential of the connectivity biomarkers in the brain is to guide use of techniques such as real-time neurofeedback and transcranial magnetic stimulation (TMS) that are related to brain activation and how brain regions communicate with one another. TMS, which uses a magnetic pulse to activate or inhibit certain brain regions, has proven to be an effective treatment for people with treatment-resistant depression, she explains, and in the future could perhaps also find a role in alleviating suicidal thoughts and behaviors.
Theoretically, real-time neurofeedback could also be used to monitor changes in connectivity as affected individuals complete a task or practice mindfulness to find the most helpful approach for any given situation. Personalized treatments could thereby be designed to modulate targeted brain responses linked to suicide risk.