New Brain Mechanisms Linked to Anxiety, OCD

A study in mice discovers new mechanisms that may be involved in anxiety and obsessive-compulsive disorder (OCD).

Nearly one in five (19.1%) adults in the United States has had an anxiety disorder in the past year, and one-third (31.1%) of Americans experience it at some time in their lives. Another 1.2% of U.S. adults suffer from OCD.

While researchers still do not fully understand brain mechanisms responsible for anxiety, neurons — the predominant brain cell type — are traditionally thought to control anxiety-related behaviors in mice.

However, previous research from the University of Utah Health discovered that a mutation in a gene called Hoxb8 caused mice to show signs of chronic anxiety and to groom themselves excessively. Unexpectedly, the researchers identified that the source of these behaviors was microglia, a type of brain cell. Accounting for only 10% of cells in the brain, microglia had been considered the brain’s "trash collectors" that disposed of dying neurons and abnormally shaped proteins.

Thus far, the researchers did not know how Hoxb8 microglia controlled behavior by communicating with specific neuronal circuits. In their new study published in the journal Molecular Psychiatry, the research team stimulated specific populations of microglia in the brain of lab mice.

When the laser triggered one subpopulation, Hoxb8 microglia, the mice became more anxious. When Hoxb8 microglia were stimulated in other parts of the brain, the mice groomed themselves. Previous research has shown that mice with OCSD-like behaviors can’t resist grooming themselves.

Targeting Hoxb8 microglia in yet another location produced multiple effects: the mice’s anxiety increased, they groomed themselves, and they froze, which is an indicator of fear. Whenever the scientists turned the laser off, the behaviors stopped.

Stimulating non-Hoxb8 and Hoxb8 microglia at the same time did not result in anxiety and OCSD-like behavior, suggesting that the two populations of microglia act like a brake and an accelerator. They balance each other out under normal conditions and induce a disease state when the signals are off-balance.

Results in animal studies may not apply to humans; therefore, further research is needed. Nevertheless, the researchers hope that their findings could eventually lead to new approaches for targeted therapies.

Anxiety disorders vs. OCD

Although OCD is no longer classified as a type of anxiety disorder, condition-related obsessions and compulsions can cause a lot of anxiety for a person with OCD. Nearly 76% of OCD cases are combined with anxiety disorders.

Anxiety disorders involve excessive fear or anxiety and are associated with physical symptoms such as muscle aches and tension, a noticeably strong, fast, or irregular heartbeat, dry mouth, and trembling or shaking. The intense feeling of anxiety can interfere with daily activities and cause people to try to avoid situations that trigger or worsen their symptoms.

People with OCD experience persistent and intrusive ideas or sensations (obsessions). To get rid of the thoughts, they engage in repetitive behaviors, also called compulsions. Such behaviors can significantly interfere with a person’s daily activities and social interactions.

Both conditions are treatable with psychotherapy or medication, or a combination of both.