Depression is one of the most common mental health conditions in the world. According to global estimates, more than 280 million people are living with depression. The illness can affect nearly every part of a person’s life.
Many people with depression feel deeply sad, emotionally empty, or hopeless for long periods of time. Others lose interest in hobbies, family life, work, or social activities they once enjoyed.
Depression can also cause physical symptoms such as extreme tiredness, poor sleep, appetite changes, and difficulty concentrating. In severe cases, it can even increase the risk of self-harm and suicide.
As depression becomes more common around the world, scientists are working hard to understand what happens inside the brain during this illness.
Most treatments available today focus on chemicals in the brain called neurotransmitters, especially serotonin. Antidepressant drugs are designed to change the balance of these chemicals to improve mood and emotional stability.
However, these medicines do not work well for everyone. Researchers say only about half of patients experience strong improvement after taking antidepressants. Some people also develop unpleasant side effects, including stomach problems, headaches, weight changes, sleep issues, or increased anxiety.
Because of this, scientists are searching for new biological systems inside the brain that may play an important role in depression.
A new study from researchers at the Institute for Basic Science, also known as IBS, may have uncovered one of those hidden systems. The research team was led by scientists C. Justin Lee and Boyoung Lee. Their findings were published in the journal Science Advances.
The researchers discovered that stress may change special sugar structures inside the brain, and these changes may help trigger depression. This discovery opens a completely new direction for understanding mental illness.
The team focused on a biological process called glycosylation. This is a natural process where tiny sugar chains attach themselves to proteins. These sugar chains help proteins work properly and keep brain cells healthy.
Scientists already know that glycosylation is involved in diseases such as cancer and Alzheimer’s disease, but much less is known about its role in mental health conditions.
To investigate further, the researchers used advanced technology to examine proteins inside the brains of mice that had been exposed to long-term stress. Chronic stress in mice is commonly used in scientific research because it can create behaviors that resemble depression in humans.
The scientists studied nine different regions of the brain. They found that stress caused major changes in sugar chains, especially in an area called the prefrontal cortex. This part of the brain is extremely important because it helps control emotions, social behavior, planning, and decision-making.
One of the biggest discoveries involved a process called sialylation. During this process, a substance called sialic acid is added to sugar chains. This helps stabilize proteins and allows brain cells to communicate properly.
The researchers found that stressed mice had lower levels of an enzyme called St3gal1. This enzyme is responsible for helping the sialylation process happen normally.
To better understand whether this enzyme was directly connected to depression, the team carried out two important experiments.
In the first experiment, the scientists reduced St3gal1 levels in healthy mice that had not been exposed to stress. Surprisingly, those mice began showing behaviors linked to depression. They became more anxious, less motivated, and less interested in normal activities even though they had not experienced chronic stress.
In the second experiment, the researchers increased St3gal1 levels in mice that had already been exposed to stress. Those mice showed fewer signs of depression and behaved more normally. This strongly suggested that St3gal1 plays an important role in either causing or reducing depressive symptoms.
The team then explored what was happening inside the brain at a deeper level. They discovered that low St3gal1 levels made it harder for nerve cells to connect and communicate with each other properly.
One important protein affected by this process was neurexin 2, also known as NRXN2. This protein acts like a support system that helps brain connections stay stable.
When NRXN2 became unstable, communication between brain cells was disrupted. The researchers believe this breakdown in communication may contribute to emotional problems and depressive behavior.
Researcher Boyoung Lee explained that the study provides clear evidence that sugar chains in the brain are closely linked to depression.
This is important because most current treatments only focus on neurotransmitters such as serotonin or dopamine. The new findings suggest there may be entirely different biological pathways involved in mental illness.
The researchers believe this discovery could eventually lead to better ways to diagnose depression and create more effective treatments. Instead of only targeting neurotransmitters, future medicines might also target sugar-related processes inside the brain.
Director C. Justin Lee said the findings could have broader importance beyond depression alone. He believes the same brain pathways may also play a role in other serious mental health conditions such as post-traumatic stress disorder, commonly known as PTSD, and schizophrenia.
Although more research is still needed before new treatments become available, the study gives scientists an exciting new direction to explore. It also gives hope to millions of people worldwide who continue to struggle with depression despite current treatment options.
By uncovering the hidden role of sugar structures in the brain, researchers may eventually develop safer and more effective ways to help people recover from mental illness in the future.
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The study is published in Science Advances.
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