Inflammation is a key feature of depression

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New research suggests this depression and inflammation are biologically linked, a finding that may have important implications for patients whose condition does not respond to antidepressant treatment.

In the largest examination ever conducted of genetic, environmental, lifestyle, and medical factors of inflammation in major depressive disorder (MDD), levels of the key marker of C-reactive protein (PCR) inflammation went be superior in patients with depression than in those with mental illness.

This was true after adjusting for socio-demographic factors such as age, sex, body mass index (BMI), alcohol consumption, early life trauma, socioeconomic status, and physical health: evidence that there is a fundamental biological mechanism in operation.

The co-author of the study, Carmine Pariante, MD, Kings College London, London, UK, said there may be cause and effect elements in the presence of inflammation in patients with depression.

“We know that patients with depression may have profound changes in all aspects of the body, primarily associated with stress responses. Therefore, immune system activation is present in depression, possibly because it is along with other responses. to stress, ”he told an informative report

The study was published online May 14 al American Journal of Psychiatry.

Break a vicious cycle

In animal models, stress stimulates the entire immune system, including the bone marrow, which leads to overactive production of immune cells.

Humans with depression also produce more white blood cells, particularly monocytes. The release of these important immune cells into the bloodstream causes one more response anywhere else in the body.

Inflammation is an immune response to infection or other stresses in the body. Elevated levels of inflammation are associated with autoimmune disorders and can be risk factors for cardiovascular disease or other illnesses.

“Then the circulating immune factors can go back and influence the brain. They change the blood-brain barrier or move through the blood-brain barrier or transmit the signal (information) through the blood). Brain barrier and perpetuate depressive systems by changing the function of the brain areas responsible for the interpretation of emotions, ”said Pariante, a professor of biological psychiatry at the Institute of Psychiatry, Psychology and Neuroscience at Kings College London.

All of this results in a negative feedback loop in which inflammation makes the body believe it is threatened, produces a more robust and perpetual immune response, or exacerbates depressive symptoms.

“That’s why it’s so important to understand what’s going on, but also to break that vicious cycle, because then we could change the outcome and potentially improve the treatment of these patients,” he said.

The findings indicate that there may be an advantage in including anti-inflammatory drugs in the treatment regimens of patients with MDD whose condition does not respond to antidepressants. Lifestyle and diet changes, such as adding high doses fish oil Supplements and an increase in exercise could also help, Pariante said.

In part, this is because inflammation decreases the effectiveness of antidepressants by reducing the brain’s production of mood-determining chemicals, such as serotonin.

“We need to remember that about a third of patients with depression do not respond to any of the medications available, so we are a long way from having a silver bullet that can help all patients with depression,” he said.

He noted that even if only a few patients with MDD could be helped with the addition of an anti-inflammatory, it would be a “really important step forward.”

A new finding

For the study, researchers analyzed blood samples, genetic data and physical and health questionnaires collected by the UK Biobank, an information database of more than half a million British participants who were recruited from 2006 to 2010.

The study compared 26,894 patients who had been diagnosed with lifelong MDD with 59,001 control people who had no known mental disorder.

Although the researchers found a link between genetic predisposition to depression – as indicated by a polygenic risk score – and higher levels of inflammation, this association disappeared when they were removed from the analysis. ‘BMI and smoking.

This contrasted with autoimmune disorders such as rheumatoid arthritis, in which the association between genetic risk and inflammation was maintained after correcting behavioral factors.

Pariante said it was a new finding.

“Here we have shown that the genetic contribution to inflammation in depression comes primarily from eating and smoking habits,” said co-professor Cathryn Lewis, head of the Center for Social Psychiatry, Genetics and Development at the Institute of Psychiatry. Psychology and Neurosciences. , King’s College London.

“This finding is important to help us better understand depression,” he said.

Previous studies have shown that patients with depression have high levels of inflammation, but no study has been as large as it is today or dealt with such a wide range of causative factors.

Pariante said the results may also have implications in patients with long-term COVID, many of whom suffer from exhaustion or depression.

“Research on the long COVID-19 is still in its infancy. There is much more discussion than the actual data,” he said in response to a question from Medscape Medical News. Some studies have indicated that patients experiencing higher levels of inflammation during SARS-CoV-2 infection were more likely to have mental disorders 3 to 6 months after having COVID-19.

“So it’s definitely this biological pathway through which high levels of inflammation change the way the brain works, induce symptoms … that are relevant to fatigue, for example, or lack of motivation or “Willingness to participate in social activity. This could be relevant for some people with long COVID,” Pariante said.

As before reported per Medscape Medical News, a study published online April 6 a The Lancet showed that one-third of the 236,379 survivors of COVID-19 in a U.S. database were diagnosed with at least 1 of 14 psychiatric or neurological disorders over a 6-month period. Disease rates ranging from depression to stroke they were much higher among those who required hospital admission.

The authors cited several limitations of the study, including the fact that lifelong depression was diagnosed in participants 6 to 10 years after blood samples were collected and that CRP analysis was based on a single blood sample.

I am J Psychiatry. Published online May 14, 2021. Summary

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