Summary: There is some sound evidence that metabolic inflammation is among the significant drivers of the rise in depression. Even so, the role of chronic inflammation in how depression starts is still little studied.
Depression is a complex mental disease with many causes. It used to be a rare disease until the middle of the 20th century. Now, about 75 years later, it is one of the most common mental health problems. So why has this rise happened? Is growing mental stress enough to explain it? Probably not.
We are likely missing something. Unlike metabolic disorders, depression is hard to diagnose. That is because there is no specific test or biomarker (a measurable sign in the body). Doctors diagnose it mostly by talking with and watching the patient. That means many cases are missed, and the real numbers are much higher.
So could metabolic inflammation be a main force behind the rise of depression? Could it also drive other mental health problems and neurodegenerative diseases (diseases that wear down the brain)? That is quite likely.
Figure 1 Depression, historical trend
Look at the two graphs above. The rise in depression rates matches the rise in metabolic disorders like diabetes.
It may be hard to say how, and how much, depression is linked to metabolic disorders. Still, more and more studies now suggest that metabolic inflammation may be a significant, if not the main, driver of depression risk.
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Of course, depression has many sides. Not everyone with depression has a metabolic disorder. Still, metabolic inflammation may be a significant factor behind the rise of depression.
Analysis of the 2009-2010 National Health and Nutrition Examination Survey (NHANES) data found that about 41% of people with depression in the US had metabolic syndrome. One-third of all people with depression had high CRP (a blood marker of inflammation).
But CRP is not the only sign of metabolic inflammation. A normal CRP does not mean there is no inflammation. Researchers now think metabolic inflammation is present in about half of all people diagnosed with depression.
New studies show that cytokines are high in all people with obesity. These are chemicals that fuel inflammation. They have a significant effect on mood and mental health. In people with obesity, cytokines stay high all the time. It appears that metabolic inflammation disrupts the production of neurotransmitters and the signals they carry.
So far, science knows little about how metabolic inflammation may cause depression. Most evidence comes from animal studies. Larger studies in people are still needed. We also need better biomarkers that can flag depression risk in people with metabolic inflammation.
The link between depression and metabolic inflammation also runs both ways. Metabolic syndrome raises depression risk, and the opposite is also true. People with depression go through changes in appetite and body weight. So they are more likely to get metabolic disorders, and the inflammation that comes with them.
So it is time to rethink and redefine depression. We must start looking at how chronic inflammation drives disease. We must understand the role of metabolic inflammation in depression. We also need to know this kind of inflammation better. Some common blood tests cannot be trusted to find it.
Knowing the role of metabolic inflammation in depression may even help us diagnose it better. It may help find reliable biomarkers. Those could flag the risk and even track how the disease moves.
In our interventional pain management practice, we use these insights to treat chronic pain and its effects on mental health. That makes treatment more complete.
Where metabolic inflammation and mood are tangled together, weight is one input we can change. We address it through physician-led medical weight loss.
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Frequently asked questions
Is depression linked to inflammation?
Yes. Metabolic inflammation is a significant factor behind the rise in depression. Researchers now think it is present in about half of all people diagnosed with depression. Cytokines are chemicals that fuel inflammation. In people with obesity they stay high all the time. They affect mood and mental health. Metabolic inflammation also seems to disrupt the production of neurotransmitters (the brain’s chemical messengers) and the signals they carry.
Is metabolic syndrome linked to depression?
Yes. An analysis of 2009-2010 National Health and Nutrition Examination Survey (NHANES) data found that about 41% of people with depression in the US had metabolic syndrome. One-third had high CRP. Not everyone with depression has a metabolic disorder, but the overlap is large. And the rise in depression rates tracks the rise in metabolic disorders such as diabetes.
Does a normal CRP test rule out inflammation?
No. CRP is not the only marker of metabolic inflammation, so a normal CRP does not mean inflammation is absent. Some common blood tests cannot be trusted to find it. That is why researchers are looking for better biomarkers. They want ones that flag depression risk in people with metabolic inflammation and track how it moves.
Can depression cause weight gain and metabolic problems?
Yes. The link runs both ways. Metabolic syndrome raises the risk of depression, and depression raises the risk of metabolic disorders. People with depression go through changes in appetite and body weight. That makes metabolic disorders, and the inflammation that comes with them, more likely.
Why has depression become so common?
Depression was a rare disease until the middle of the 20th century. About 75 years later, it is one of the most common mental health problems. Rising mental stress alone does not explain the jump. The rise in depression matches the rise in metabolic disorders such as diabetes. That points to metabolic inflammation as a significant, if not the main, driver.
Dr. Gurpreet Singh Padda, MD, MBA, MHP
