Too much salt doesn't just affect your heart -- it may also impact your mood.
Scientists discovered that high-salt diets in mice led to depression-like behavior through immune system activity. Cutting out certain immune cells reversed the symptoms, pointing to new ways we might treat or even prevent depression.
High-Salt Diet Linked to Depression
A new study in The Journal of Immunology reveals that eating a high-salt diet may trigger depression-like symptoms, at least in mice. Researchers found that excessive salt intake ramps up levels of a protein called IL-17A, which has also been linked to depression in human studies.
"This work supports dietary interventions, such as salt reduction, as a preventive measure for mental illness. It also paves the way for novel therapeutic strategies targeting IL-17A to treat depression," shared Dr. Xiaojun Chen, a researcher at Nanjing Medical University who led the study. "We hope these findings encourage discussions on salt consumption guidelines," said Dr. Chen.
The team also uncovered the role of a specific type of immune cell known as gamma-delta T cells, or γδT cells. These cells were responsible for nearly 40 percent of IL-17A production in the salt-fed mice. When the scientists removed these cells, the depression-like symptoms noticeably improved, highlighting another potential path for treatment.
Widespread Salt Consumption and Public Health Risks
High salt intake is extremely common in the modern Western diet. Some fast food meals contain up to 100 times more salt than the same dish prepared at home. While too much salt is already known to increase the risk of heart disease, autoimmune issues, and neurological conditions, its potential impact on mental health is becoming harder to ignore.
Depression is already one of the most serious public health challenges, affecting around 15 to 18 percent of people during their lifetime. It also ranks among the top 10 causes of death in the United States. Scientists have long suspected that salty diets may play a role, but the connection wasn't well understood until now.
In this new study, mice were fed either a standard diet or a high-salt diet for five weeks. The mice that consumed extra salt showed clear signs of reduced motivation and activity, classic indicators of depression in animal models. This strengthens the case that salt doesn't just affect the heart and kidneys. It may also be influencing the brain.
IL-17A Confirmed as a Depression Driver
Given the already established role of IL-17A in the development of depression, the research team also investigated whether HSD induced IL-17A production in mice. HSD increased IL-17A levels in the spleen, blood, and brain, correlating with anxiety- and depression-like behaviors. However, when mice that could not produce IL-17A were fed an HSD, depression-like symptoms were not observed, confirming the role of IL-17A in developing depression-like symptoms.
These findings corroborate epidemiological evidence that HSD correlates strongly with more severe depression and studies in people demonstrating that low sodium intake is closely associated with good mood.
Implications for Future Depression Therapies
The researchers hope these findings encourage further research into immune-mediated mechanisms of depression and pave the way for novel therapeutics targeting IL-17A or γδT cells. Dr. Chen and their team plan to validate these findings in humans while also investigating the mechanisms by which HSD activates γδT17 cells leading to increased HSD.
Reference: "High-salt diet drives depression-like behavior in mice by inducing IL-17A production" by Di Lu, Wenjie Chen, Wenhui Sun, Chuan Wei, Xuan Xie, Na Li, Haiyan Yan, Ying Chen, Yue Wu, Zhigang Lei, Lei Xu, Jifeng Zhu, Yalin Li, Chuan Su, Wei Li, Sha Zhou and Xiaojun Chen, 22 March 2025, The Journal of Immunology.
DOI: 10.1093/jimmun/vkaf019