Tinnitus can range from mildly irritating to severely distressing. For some people, the nonstop noise creates anxiety and disrupts daily life. Researchers estimate that as many as 14% of people globally experience the condition, with many cases considered severe.

A team from Oregon Health & Science University and Anhui University in China studied mice and found that increasing serotonin levels in the brain also increased behaviors associated with tinnitus.

Serotonin and Tinnitus Connection

The findings could have important implications for people living with tinnitus, especially those taking antidepressants that affect serotonin levels, said co-senior author Laurence Trussell, Ph.D., professor of otolaryngology in the OHSU School of Medicine and a scientist at the OHSU Vollum Institute and Oregon Hearing Research Center.

"People with tinnitus should work with their prescribing physician to find a drug regimen that gives them a balance between relief of psychiatric symptoms like depression and anxiety, while minimizing the experience of tinnitus," Trussell said. "This study highlights the importance of clinicians recognizing and validating patient reports of medication-associated increases in tinnitus."

The medications discussed in the study include selective serotonin reuptake inhibitors, commonly known as SSRIs. These antidepressants are widely prescribed for moderate to severe depression and anxiety because they raise serotonin levels in the brain.

Researchers have long suspected serotonin played a role in tinnitus, but the exact mechanism remained unclear.

"We've suspected that serotonin was involved in tinnitus, but we didn't really understand how," said co-author Zheng-Quan Tang, Ph.D., of Anhui University in China. "Now, using mice, we've found a specific brain circuit involving serotonin that goes straight to the auditory system, and found that it can induce tinnitus-like effects. When we turned that circuit off, we were able to ameliorate the tinnitus significantly.

"This gives us a much clearer picture of what's going on in the brain -- and points toward new possibilities for treatment."

Tang began the project while working as a postdoctoral scholar in Trussell's laboratory.

Brain Circuit Linked to Ringing Ears

The new work builds on earlier research published in 2017.

In the latest study, scientists used optogenetics, a technique that uses fiber optics and light to activate specific brain cells. By targeting neurons that produce serotonin, the researchers were able to trigger activity in regions of the brain involved in hearing. They then measured how the mice responded using a modified auditory startle test.

"When you stimulate these serotonergic neurons, we can see that it stimulates activity in the auditory region in the brain," Trussell said. "We also saw that animals then behaved as if they were hearing tinnitus. In other words, it's producing symptoms that we would expect to be experienced as tinnitus in humans."

According to the researchers, the findings match reports from some patients who say their tinnitus becomes more intense while taking serotonin-boosting medications such as SSRIs.

Future Tinnitus Treatments

"Our study suggests a delicate balance," Trussell said. "It may be possible to develop cell- or brain region-specific drugs that steer the elevation of serotonin in some brain regions but not others. In that way, it may be possible to separate the beneficial and important effects of the antidepressant from the potentially harmful effects on hearing."

Trussell's research was supported by the National Institutes of Health through award RO1DC004450. The authors noted that the findings and conclusions are solely their responsibility and do not necessarily reflect the official views of the NIH.