Some research suggests that depression is the second leading cause of disability worldwide, affecting over 350 million people across the globe.
Typical symptoms of depression include an inability to feel joy, persistent hopelessness, and in some cases, self-harm or suicidal thoughts. Understanding this condition is often difficult, and it is still wrongly associated by many with a moral or mental weakness. However, recent research indicates that depression may, in part, stem from dysfunction in the immune system — in other words, not all causes are purely psychological.
Studies have shown a link between depression and elevated levels of inflammatory cytokines, such as IL-6 (interleukin-6). But the relationship is complex: which comes first? Does a rise in IL-6 (perhaps due to aging or other inflammatory conditions) trigger depression? Or does depression cause IL-6 to increase? While researchers have tried to answer this, the direction of the relationship remains unclear.
We do know that depression has a strong impact on both immune and inflammatory systems. People suffering from depression are at greater risk for heart disease and early death. Even healthy individuals with depression are more likely to develop heart conditions, and those with heart disease are more prone to depression. In fact, people suffering from both conditions are four times more likely to die within six months of a heart attack than those with heart disease alone.
To investigate the potential connection further, a team of scientists in the UK collaborated with pharmaceutical researchers to explore whether treating the immune system could help relieve depression. The study is led by Professor Ed Bullmore, head of psychiatry at the University of Cambridge.
“We haven’t made the progress we had hoped in treating depression over the past 20 years,” says Bullmore. “If you see a doctor for depression today, you're likely to be offered cognitive behavioral therapy (CBT) or prescribed antidepressants that haven't changed much since the 1960s.”
He explains that most antidepressants work by increasing serotonin levels, a neurotransmitter that affects mood. But these drugs don’t work for everyone. Only about a third of patients experience full recovery with current treatments, another third show only partial improvement, and the rest show no response at all.
Initial results from this new study — consistent with other research — suggest that a significant subset of people with treatment-resistant depression have higher levels of inflammation. This suggests a clear link between inflammation and depressive symptoms. More importantly, it raises the question: Is the inflammation causing the depression?
To answer that, researchers have studied animal behavior, such as in mice. These animals behaved normally until they were injected with inflammation-triggering proteins. Afterwards, they began showing clear signs of depression, measured through controlled lab experiments.
In humans, people undergoing treatment for conditions like hepatitis C, which often involves inflammatory medications, tend to develop depression — even if they’ve never had it before. Similarly, individuals with chronic inflammatory diseases like arthritis often experience depression, and anti-inflammatory drugs have shown antidepressant effects that go beyond simply easing physical symptoms.
So, if inflammation causes depression — potentially by interfering with serotonin production — what causes the inflammation in the first place?
There are many possible triggers. Inflammation is the body's natural response to infection, but it can also result from stress and unhealthy lifestyle habits. Some research even suggests that children exposed to frequent infections or traumatic life events are more prone to depression later in life.
Professor Carmine Pariante of King’s College London explains: “For people exposed to early-life stress, the immune system becomes hypersensitive. Later in life, when they face emotional stress, their inflammatory response overreacts, making them more vulnerable to depression.”
Even people who have never experienced depression might recognize the pattern. A bad case of the flu or a cold often begins with loss of appetite, fatigue, brain fog, and a strong desire to just lie on the couch — all typical depressive symptoms. This happens because the body’s inflammatory response to infection can trigger mood changes.
This study aims to investigate the immune system in depressed patients and test anti-inflammatory drugs to see if they improve symptoms. If these drugs — many of which are already developed for other conditions — prove effective, this could dramatically speed up the development of new treatments.
Such progress could also revive pharmaceutical interest in psychiatric drug development, a field many companies have abandoned in recent years due to its complexity.
“We're starting to understand depression in a broader biological context,” says Pariante. “Rather than focusing solely on the brain or psychological factors, we’re recognizing that the immune system plays a major role. This shift is crucial for developing entirely new treatments.”
This new understanding also challenges the stigma surrounding depression. Bullmore adds: “It’s not fair to tell someone suffering from depression that it’s just in their head. Depression is a physical illness too — like any other health condition.”
He continues: “Some people say mental health isn't a medical issue, and new drugs aren’t the answer. But it’s unlikely that 350 million people are all depressed for the same reasons. If we can identify how inflammation causes depression in some cases, we can create effective new treatments for those who don’t respond to current options.”
While these findings are still in the early stages, if anti-inflammatory treatments prove effective, it could be a major breakthrough. “We’re not promising a miracle cure,” Bullmore says, “but it could represent a significant step forward — especially for patients who have exhausted other options.”
