Researchers at the Hebrew University of Jerusalem explored how immune system activation sparks inflammation and how this inflammatory response can influence mood. Their work, published in Brain, Behavior and Immunity, offers evidence that inflammatory processes can steer depressive states by altering signaling in the brain. The findings emphasize a clear link between immune activity and the regulation of mood, suggesting that mood disorders may arise from immune-driven changes in neural communication rather than a simple neurotransmitter deficit alone.
Traditionally, depression has been explained by imbalances in brain chemicals such as serotonin and norepinephrine. Yet many patients do not respond to standard antidepressants, prompting scientists to look beyond the classic model. In recent years, chronic systemic inflammation has gained attention as a potential engine of depressive symptoms, presenting a broader view of how mood disorders can develop and persist in the body.
To understand the breadth of this link, researchers analyzed the 100 most cited papers on depression and inflammation. They found that treatments which stimulate the immune system, including some cancer and hepatitis therapies, can trigger mood symptoms. Activation of protective immune mechanisms always involves inflammation, and this activation can influence neural circuits related to motivation, energy, and mood regulation.
Experiments indicate that even low-dose immune stimulants, and the resulting immune imbalance, can produce depressive-like symptoms in healthy individuals. The results suggest that these mood changes may be countered by anti-inflammatory medications or conventional antidepressants that help restore balance in inflammatory signaling and neurotransmitter systems.
Stress, a major factor in depression, is also linked to brain inflammation. When stress occurs, microglia, the brain’s own immune cells, become activated and can remain altered with repeated exposure. Over time, these changes can contribute to ongoing inflammatory states and worsen mood symptoms, creating a feedback loop that makes recovery more challenging.
In their review, scientists note that certain groups appear more vulnerable to inflammation-related depression. The elderly, individuals living with chronic diseases, and people who endured difficult childhood events show higher susceptibility. This pattern underscores the need for a personalized approach to treatment, which may include anti-inflammatory strategies or microglia-targeted techniques, tailored to each person’s health history and life experience.
Earlier research has connected the gut with stress responses through the gut-brain axis, indicating that gut health and microbial balance can influence inflammation and mood. This broader view of psychoneuroimmunology adds depth to the inflammation–depression picture and points toward integrated care strategies that address both gut health and brain function for mood improvement.