When Sodium Is Missing, Fear Is Surplus: The Hidden Chemistry Of Anxiety
- Lidi Garcia
- Jul 2
- 4 min read
Chronic hyponatremia is when the sodium level in the blood is low for a long time. This condition, previously thought to have no major symptoms, can cause anxiety and mood swings because it affects chemicals in the brain, such as serotonin and dopamine. A study in mice showed that correcting the sodium level improved these symptoms. This reinforces the importance of treating hyponatremia to protect mental health.
Hyponatremia is a medical condition characterized by low sodium levels in the blood. Sodium is an essential mineral for the proper functioning of the body, as it helps maintain the balance of fluids inside and outside the cells and is important for the transmission of nerve impulses and muscle function.
For a long time, hyponatremia, especially when it occurs chronically (i.e., over a long period of time), was considered a problem without significant symptoms, since the brain is able to adapt to the low sodium environment.
However, more recent research, such as the study carried out by Professor Yoshihisa Sugimura's team at Fujita University of Health in Japan, indicates that this brain adaptation has a cost: it can generate changes in behavior and even psychological symptoms, such as anxiety.
The study in question aimed to understand whether chronic hyponatremia (CHC) could be linked to the emergence of anxiety-like behaviors and how this occurs in the brain.
To do this, scientists created a mouse model that simulated a human condition called syndrome of inappropriate antidiuresis (SIAD), a common cause of hyponatremia.
They did this by administering a substance called desmopressin, which mimics the hormone vasopressin, and offering a liquid diet, which led the mice to develop chronic hyponatremia.
During the experiments, it was possible to observe that animals with low levels of sodium in their blood presented more typical anxiety behaviors in behavioral tests used in science to evaluate this type of emotion, such as the light/dark transition test (which measures fear of open and illuminated environments) and the open field test (which evaluates the willingness to explore new spaces).
In addition to the behavioral tests, the researchers also analyzed the mice's brains and discovered something interesting: the levels of two neurotransmitters that are very important for mood and emotions, serotonin and dopamine, were reduced in the amygdala, an area of the brain that plays a central role in processing fear and anxiety.
Example of a behavioral test for anxiety. Open and unprotected areas are translated as dangerous. Anxiety is related to the excessive fear of being in these areas. The more time the mouse spends in the open and unprotected areas, the less anxiety it has.
In addition, the scientists observed a decrease in the activity of a protein called ERK, which is involved in regulating emotional responses. This suggests that low blood sodium levels interfere with brain chemistry in a way that can increase anxiety.
One of the most important points of the study was the demonstration that these changes are reversible. When the researchers stopped administering desmopressin and returned to offering a solid diet, the mice's sodium levels returned to normal.
As a consequence, anxiety-like behaviors decreased and the levels of serotonin, dopamine and the activity of the ERK protein in the amygdala also normalized. These results indicate that appropriate treatment of chronic hyponatremia not only corrects the physical problem of low sodium, but can also alleviate psychological symptoms such as anxiety, improving patients' quality of life.
In summary, this study reinforces the importance of identifying and treating chronic hyponatremia effectively. It also paves the way for new therapeutic approaches that consider the impact of hyponatremia on the brain and behavior, as well as its effects on the body as a whole.
For physicians and healthcare professionals, this means paying attention not only to laboratory tests, but also to the emotional and behavioral signs of patients with this condition.
READ MORE:
Chronic Hyponatremia Potentiates Innate Anxiety-Like Behaviors Through the Dysfunction of Monoaminergic Neurons in Mice
Haruki Fujisawa, Nobuhiko Magara, Shogo Nakayama, Sachiho Fuse, Naoko Iwata, Masaya Hasegawa, Hisayoshi Kubota, Hirotaka Shoji, Satoko Hattori, Hideo Hagihara, Hidetsugu Fujigaki, Yusuke Seino, Akihiro Mouri, Tsuyoshi Miyakawa, Toshitaka Nabeshima, Atsushi Suzuki, and Yoshihisa Sugimura
Mol Neurobiol (2025)
Abstract:
Hyponatremia is the most common clinical electrolyte disorder. Once thought to be asymptomatic in response to adaptation by the brain, recent evidence suggests that chronic hyponatremia (CHN) may induce neurological manifestations, including psychological symptoms. However, the specific psychological symptoms induced by CHN, the mechanisms underlying these symptoms, and their potential reversibility remain unclear. Therefore, this study aimed to determine whether monoaminergic neurotransmission is associated with innate anxiety-like behaviors potentiated by CHN in a mouse model of CHN secondary to the syndrome of inappropriate antidiuresis. In the present study, using a mouse model of the syndrome of inappropriate antidiuresis presenting with CHN, we showed that the sustained reduction of serum sodium ion concentrations potentiated innate anxiety-like behaviors in the light/dark transition and open field tests. We also found that serotonin and dopamine levels in the amygdala were significantly lower in mice with CHN than in controls. Additionally, phosphorylation of extracellular signal-regulated kinase (ERK) in the amygdala was significantly reduced in mice with CHN. Notably, after correcting for CHN, the increased innate anxiety-like behaviors, decreased serotonin and dopamine levels, and reduced phosphorylation of ERK in the amygdala were normalized. These findings further underscore the importance of treating CHN and highlight potential therapeutic strategies for alleviating anxiety in patients with CHN, which will improve their quality of life.
Comments