We know that stress—especially of the traumatic variety—can affect the shape and function of structures in the brain. For example, studies on survivors with post-traumatic stress disorder (PTSD) reveal that the amygdala (the almond-shaped threat and danger detection center of the brain) can actually enlarge in the presence of an ongoing, unmitigated survival response. Conversely, the hippocampus (a horseshoe-shaped entity adjacent to the amygdala responsible for consolidating memories) can shrink when an overactive stress response hijacks its functionality. Understandably, when brain structures malfunction, aberrant behaviors result: PTSD survivors often exhibit an exaggerated startle response, hyperarousal, and hypervigilance. Plus, they experience a maddening frustration with memory issues.

It makes sense: The neurophysiological response to trauma can alter the brain in ways that continually affect survivors’ behavior. Can the immune system have similar effects? Very possibly. Research published in the Journal of Neuroscience and Biological Psychiatry suggests that your immune system can alter both your mood and your behavior.

Last summer researchers at Ohio State University, led by John Sheridan, professor of oral biology and associate director of Ohio State’s Institute for Behavioral Medicine Research (IBMR), stumbled upon some interesting data: In the presence of prolonged stress, the brain (in a process that confirms two-way communication between the brain and the rest of the body) calls up cells from the immune system. Recruited by the brain’s stress signals to the bone marrow, monocytes (the largest of all white blood cells) travel to specific brain areas affected by the stressor and produce inflammation, which leads to anxiety-like behavior. Once they’ve traveled to the brain, monocytes don’t respond to the body’s natural anti-inflammatory steroids and evidence qualities that signify a more substantial inflammatory state.

Researchers discovered the effusion of monocytes in the brain related to stress by subjecting mice to stressors that mirrored causes of “fight or flight” in humans. What scientists found was that the level of anxiety-like symptoms corresponded to increased levels of monocytes in the mice’s brains. Furthermore, these cells encircled blood vessels and infiltrated tissue in areas of the brain associated with fear and anxiety, such as the prefrontal cortex, amygdala, and hippocampus. Although the presence of monocytes did affect the animals’ behavior, it did not cause damage to the brain tissue.

The significance of the data lies in the accepted concept of the neurobiology of mood disorders, which primarily focuses on the idea of behavioral conditioning. The Ohio State University findings, however, suggest that something outside the central nervous system can also have a significant effect on behavior. These results set the stage for the more recent findings from a new set of experiments also led by Sheridan—findings that seem to reinforce the implications of the original data.

In the new research, mice were subjected to the same type of “fight or flight” chronic stress, allowed to recover, and then (24 days later) subjected to a single acute stressor—to which some magnificently overreacted by quickly returning to a biologically and behaviorally chronic stressed state. The crown jewel in this experiment was the difference between mice that did and didn’t have spleens. I’ll explain.

Likened to a large lymph node, the spleen’s many jobs include filtering the blood, holding a reserve of blood, and acting as a warehouse for half the body’s monocytes. Once called up from the bone marrow, monocytes are stored on standby in the spleen, from which they can be launched when the next stressor occurs. In the case of the experiment, mice whose spleens (and, hence, the activated monocytes) were removed showed zero signs of any significant stress response reactivation. Why is this relevant? Because it illustrates the spleen’s role in providing lodging for sensitized immune cells and their subsequent effect on the mood and behavior of the subject.

Since they have been conducted only with mice, the experiments’ results have limitations. Still, the research and its implications about the immune system’s involvement in the stress response open ideas about the underlying cellular mechanisms related to the effects of stress. They also offer possible new ways of helping humans who get caught in the loop of a sensitized immune system and its triggers—not, of course, by removing their spleens but perhaps by finding ways to subdue the sensitized monocytes so the immune system stress response becomes mediated.

When it comes to healing the effects of stress, then, part of the problem may very well hide out, of all places, in your spleen.