Brain’s ‘Accelerator’ and ‘Brake’ for anxiety Identified in Groundbreaking New Research
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Nearly one in five Americans experiences anxiety, and a new study from the University of Utah reveals a surprising source of the condition: not neurons, but immune cells in the brain.
Anxiety disorders are among the most prevalent mental health challenges in the United States, affecting approximately 20% of the population. Despite its widespread impact, the underlying biological mechanisms driving anxiety have remained largely elusive. Now, researchers have pinpointed two distinct groups of microglia – a type of immune cell in the brain – that act as opposing forces in regulating anxiety levels.
For decades, neurotransmitters like serotonin and GABA were considered the primary regulators of anxiety. However, this new research challenges that assumption. “This is a paradigm shift,” stated a lead researcher.”It shows that when the brain’s immune system has a defect and is not healthy, it can result in very specific neuropsychiatric disorders.” The study demonstrates that microglia, traditionally known for their role in fighting infection and clearing debris, play a far more nuanced and direct role in regulating emotional states.
The Two Faces of Microglia: Accelerators and Brakes
The research team initially observed that manipulating microglial activity impacted anxiety levels in mice. Interfering with a specific group, called Hoxb8 microglia, induced anxious behaviors. Surprisingly, fully disabling all microglia had the opposite effect – mice behaved normally. This led researchers to hypothesize that different microglial populations exert opposing influences.
To confirm this, they conducted a unique experiment: transplanting different types of microglia into mice lacking their own microglial cells. The results were striking.
Non-Hoxb8 microglia acted as an “accelerator” for anxiety. Mice receiving only these cells exhibited compulsive grooming and avoidance of open spaces – hallmark signs of heightened anxiety. In these mice,the anxiety response was perpetually activated,lacking any natural counterbalance.
Conversely, Hoxb8 microglia functioned as a “brake” on anxiety. Mice transplanted with only Hoxb8 microglia displayed no anxious behaviors. Crucially, when both types of microglia were present, the anxiety-promoting effects of the non-Hoxb8 cells were neutralized, resulting in normal behavior. “These two populations of microglia have opposite roles,” explained a senior author on the study. “Together, they set just the right levels of anxiety in response to what is happening in the mouse’s surroundings.”
Implications for Future Treatments
the findings have important implications for the advancement of novel anxiety treatments. Current psychiatric medications primarily target neurons. Though, this research suggests that modulating microglial activity could offer a new therapeutic avenue.
Researchers believe that therapies could be designed to “activate the brakes” – bolstering the function of Hoxb8 microglia – or “weaken the accelerator” – reducing the activity of non-Hoxb8 microglia. “This knowledge will provide the means for patients who have lost their ability to control their levels of anxiety to regain it,” one researcher noted.
While acknowledging that therapeutic applications are still years away, the team is optimistic. “We’re far from the therapeutic side,” cautioned a postdoctoral researcher, “but in the future, one could probably target very specific immune cell populations in the brain and correct them through pharmacological or immunotherapeutic approaches.This would be a major shift in how to treat neuropsychiatric disorders.” The study also notes that humans possess similar populations of microglia, suggesting the potential for translating these findings to human treatments.
Reference: van Deren DA, Xu B, Nagarajan N, Boulet AM, Zhang S, Capecchi MR. Defective Hoxb8 microglia are causative for both chronic anxiety and pathological overgrooming in mice.mol Psychiatry. 2025. doi: 10.1038/s41380-025-03190-y
