Neuroinflammation and Imminent Risk for Suicidal Behavior in Young Adults

Inflammation is our body’s way of protecting ourselves from adverse forces, like viruses. This also occurs in the brain, which impacts the way we think and feel. While previous research has suggested that neuroinflammation may play a role in suicide risk, its connection to stress-related suicidal ideation and negative mood remains unclear. The translocator protein (TSPO), a marker of neuroinflammation, has been found to be higher in individuals with depression, but its relationship to acute stress and suicidal ideation is unclear. Understanding how neuroinflammatory processes interact with daily stressors may tell us more about suicide risk.

In their AFSP-funded grant, Dr. Nadine Melhem and Dr. J. John Mann examined 53 adults with major depressive disorder (MDD), using PET-scan brain imaging to measure TSPO binding in the brain. A subset of 21 participants also completed a seven-day ecological momentary assessment (EMA), to track daily stress, mood, and suicidal ideation throughout each day. Results showed that higher TSPO binding was associated with more suicidal ideation and negative affect during stressful periods, but not in non-stressful periods. However, TSPO binding was not significantly associated with a history of suicide attempts, suggesting it may be more indicative of acute suicide risk rather than long-term vulnerability. These findings suggest that neuroinflammation may play a role in stress-related suicidal thoughts.

Citation: Herzog, S., Bartlett, E. A., Zanderigo, F., Galfalvy, H. C., Burke, A., Mintz, A., Schmidt, M., Hauser, E., Huang, Y. Y., Melhem, N., Sublette, M. E., Miller, J. M., & Mann, J. J. (2025). Neuroinflammation, Stress-Related Suicidal Ideation, and Negative Mood in Depression. JAMA psychiatry, 82(1), 85–93. https://doi.org/10.1001/jamapsychiatry.2024.3543