Mood Disorders are Linked to Inflammation


Reasons for Suspecting Mood Disorders are Linked to Inflammation

On balance, it seems that mood disorders are linked to inflammation. World Health Organization (WHO) cites mood disorders as the leading cause of disability worldwide. Mood disorders affect over 20% of adults in the United States aged 18 to 49 years.  It is well-known that genetic and behavioral factors underpin these disorders. Researchers nowadays are investigating the links between the immune system and mood disorders. Previous studies found that inflammation can lead to depressive symptoms such as anhedonia and fatigue. Inflammation also plays a major role in certain nerve signals involved in mood regulation in depression and bipolar disorder.

Diagram showing that mood disorders are linked to inflammation bidirectionally
Mood disorders are linked to inflammation bidirectionally

It is well-known that in many physical diseases, such as cardiovascular disease and cancer, inflammation appears to play a role in the pathophysiology. Similar seems to be the case in major depressive disorder because those patients have the following inflammatory markers elevated in their blood:

  • Interleukin (IL)-6 and tumor necrosis factor (TNF)-α
  • C-reactive protein (CRP)
  • Chemokines
  • Cellular adhesion molecules

These inflammatory markers decrease with successful antidepressant therapy. Also, cytokine activation in flu-like illnesses produces the depressive symptoms of anhedonia, hypersomnia, social withdrawal, poor concentration, weakness, and bodily aches and pains.

What Exactly is Inflammation?

Inflammation is the response of our immune system to invading bacteria, viruses, toxins, or parasites. The immune system recruits proteins, cells, and tissues, including the brain, to attack these invaders.

The strategy is to mark off the injured portion of the body. Local inflammation makes the injured parts swollen, hot, and red. If the body does not localize the injury, then inflammation becomes systemic.

Pro-inflammatory factors lead to “sickness behaviors.” These include physical, cognitive and behavioral changes. Typically, the sick person experiences sleepiness, loss of appetite, fatigue, cognitive impairments, and slow reaction time.

This constellation of changes is adaptive. It forces us to sleep more to enhance healing and remain isolated so as not to spread infections.

Are Mood Disorders Linked to Inflammation? Yes.

A large-scale Danish study conducted in 2013 links mood disorders like depression directly to inflammation. It hypothesizes that mood disorders are the brain’s response to inflammation. They published this study in the June 2013 issue of JAMA Psychiatry.

The study found that an autoimmune disease increased the risk of a mood disorder by 45 percent. Any history of infection increased the risk of a mood disorder by 62 percent. There was also a history of hospitalization for infection in about one-third of people diagnosed with a mood disorder.

Yet another team of Danish researchers showed earlier in 2013 an association between elevated levels of a C-reactive protein in the blood and an “increased risk for psychological distress and depression in the general population”. The body produces C-reactive protein in response to inflammation. They also published this study in JAMA Psychiatry.

A 2011 study found the links between high levels of quinolinic acid and chronic depression and suicidal tendencies. And quinolinic acid is a by-product of inflammation. The researchers published this study in the Journal of Neuroinflammation.

So, the case seems strong that mood disorders are linked to inflammation.

Are Mood Disorders Linked to Inflammation? No.

Contrary to the above findings, the latest studies do not suggest that mood disorders are linked to inflammation. Rather, they show that mood disorders may lead to inflammation, and inflammation may not be a risk factor for the onset of mood disorders. These findings have come out in 2019 from Lausanne University Hospital and Bern University Hospital, in Switzerland and the National Institute of Mental Health in Maryland.

What they found is that there was an association between the current atypical subtype of major depressive disorder at baseline with increased levels of hsCRP at follow-up. But there was no association between inflammatory levels at baseline and atypical major depressive disorder at follow-up.

Hence, we could say that mood disorders are not linked to inflammation. However, these findings are specific to the atypical subtype of major depressive disorder. Bodily symptoms are present in this subtype, such as lack of sleep, decreased energy, and erratic eating behavior.

The earlier studies had studied the links between inflammation and mood disorders by focusing on dysthymia.


There is a lot of evidence that the immune system and inflammation, in particular, are responsible for the pathophysiology in a significant number of depressed patients. But remember that depression is not an inflammatory disorder and not every patient with depression has increased inflammation. We do not know the percentage of depressed patients in whom inflammation plays a role.

Note that increased inflammation not only occurs in mood disorders but also in multiple other psychiatric diseases, including anxiety disorders, personality disorders, and schizophrenia. But, the role that inflammation plays suggests several very promising anti-inflammatory therapies in mood disorders, including statins, aspirin, pioglitazone, and celecoxib. Regular aerobic exercise, drinking plenty of water, and stress management are the other proven ways to reduce inflammation.

We still need to examine in more depth and detail the extent of links between inflammation and mood disorders.


Mood Disorders are Linked to Inflammation
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Mood Disorders are Linked to Inflammation
A large-scale Danish study conducted in 2013 suggested that mood disorders like depression are directly linked to inflammation.
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