The Gut-Brain Axis and Suicide Attempts: New Markers for Assessment and Prevention

Predicting suicide risk based on clinical symptoms alone remains a challenge, particularly among people living with major depressive disorder (MDD). While depression is strongly associated with suicide attempts, not everyone with severe symptoms goes on to attempt suicide, and warning signs can vary widely from person to person. For this reason, researchers have been exploring whether biological markers (i.e., measurable signals in the body) might help clarify periods of heightened vulnerability. One area of growing interest is the immune system. Increasing evidence suggests that inflammation and immune-related processes may be linked to mood disorders and suicidal behavior, though these relationships are complex and not yet fully understood. Studying how specific immune markers differ across clinical groups may help researchers better understand when suicide risk is elevated and guide future prevention strategies, without assuming any single marker tells the whole story.

With support from her AFSP-funded grant, Dr. Faith Dickerson examined blood levels of matrix metalloproteinase-9 (MMP-9), an enzyme involved in inflammation and brain-related processes, in 186 adults hospitalized with major depressive disorder and 79 adults without a psychiatric diagnosis. Among those with MDD, the researchers compared individuals who had made a suicide attempt within the past month, those with no recent attempt (including people with and without a past attempt), and a non-psychiatric comparison group. Dr. Dickerson found that elevated MMP-9 levels were most strongly associated with a recent suicide attempt, rather than with depression alone or with a distant history of attempts. Individuals with MDD who had not attempted suicide recently showed MMP-9 levels similar to those without a psychiatric disorder. This pattern remained even after accounting for depression severity, medication use, substance use history, body mass index, and other clinical factors. While the study does not show that MMP-9 causes suicide attempts, it suggests that immune-related changes may be particularly relevant during periods of acute risk. The findings point toward the potential value of biological markers like MMP-9 in future research aimed at identifying high-risk windows and developing more targeted, timely suicide prevention approaches.

Citation: Dickerson, F., Katsafanas, E., Origoni, A., Rowe, K., Khan, S., Mukhtar, F., Yang, S., Splan, V.W., Yolken, R., Levels of Matrix Metalloproteinase 9 (MMP-9) are Elevated in Persons with Major Depressive Disorder Who Have Had a Recent Suicide Attempt, Brain, Behavior, & Immunity - Health, https://doi.org/10.1016/j.bbih.2025.101163