Anyone who suffers from tinnitus constantly hears annoying ringing in their ears. For many of those affected, the disease is accompanied by depression and anxiety. But a study shows that medications that are intended to alleviate psychological symptoms could also increase tinnitus. Experiments on mice suggest that the neurotransmitter serotonin, known as the happiness hormone, activates neuronal circuits that promote ringing in the ear. So-called selective serotonin reuptake inhibitors (SSRIs), an established therapy against depression, can therefore be counterproductive when it comes to tinnitus.
Around 14 percent of people worldwide are affected by tinnitus. Without external noise, they hear constant whistling, ringing, hissing or buzzing in their ears, which can severely limit their quality of life. Many of those affected also suffer from depression and anxiety. An established treatment for these mental illnesses are so-called selective serotonin reuptake inhibitors (SSRIs). They ensure that the “happiness hormone” serotonin remains available in the brain for longer.
There have already been indications that these medications can also affect ringing in the ears. Clinical studies have even tested whether they might be suitable as a treatment for tinnitus. But the hoped-for success did not materialize: “Some patients even reported that their tinnitus got worse,” explains a team led by Meng-Ting Yu from Anhui University in China. Even people who did not previously suffer from tinnitus sometimes experienced ringing in the ears when treated with SSRIs.
Circuits out of balance
In order to get to the bottom of the underlying mechanisms, Yu and her team have now examined the processes in the brain using mice in which they artificially induced tinnitus. They discovered that the serotonin system in the brains of the tinnitus mice is actually disturbed. Key auditory brain regions were hyperactive and showed similar signal patterns to those in people suffering from tinnitus. Using optogenetic methods, the researchers specifically stimulated serotonin-producing nerve cells in these regions and analyzed the changes in the brain and behavior of the mice.
“Stimulating serotonergic neurons increases hyperactivity in the auditory area of the brain,” reports co-author Laurence Trussel from Oregon Health and Science University in Portland. “The behavior of the animals indicated that they were actually hearing ringing in their ears.” In one test, the mice were able to hear external noises, but no longer perceived silence as such. “In other words: it causes symptoms that we would interpret as tinnitus in humans.” However, if the researchers inhibited the serotonin signaling pathways in the auditory brain regions of the mice, the signs of tinnitus in the animals’ brains and behavior decreased.
Targeted therapies
“This study underscores the importance of medical professionals recognizing and taking seriously patient reports of medication-related exacerbations of tinnitus,” says Trussel. “People with tinnitus should work with their healthcare provider to find medication therapy that strikes a balance between relieving psychiatric symptoms such as depression and anxiety and minimizing tinnitus symptoms.”
From the researchers’ point of view, the new findings on the brain circuits involved could also help to find new treatment options. “It might be possible to develop cell- or brain-region-specific drugs that increase serotonin levels in certain brain regions but not in others,” says Trussel. “In this way, it could be possible to separate the positive and important effects of the antidepressant from the potentially harmful effects on hearing.”
Source: Meng-Ting Yu (Anhui University, Hefei, China) et al., Proceedings of the National Academy of Sciences, doi: 10.1073/pnas.2509692123