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Could controlling histamine become a novel treatment for depression?

Inflammation can inhibit the effect of antidepressants, with histamine the primary reason. Does this pave the way for new treatments?

A man expressing sadness with his head in his hands. Image by Tellmeimok. (CC BY-SA 4.0)
A man expressing sadness with his head in his hands. Image by Tellmeimok. (CC BY-SA 4.0)

A potential treatment for depression is being tested out and the results, based on an animal model, are so far promising. The treatment is based on the control of histamine levels, and it has been developed at Imperial College London.

The scientific inquiry reveals that bodily inflammation dampens levels of a ‘feel-good molecule’ and antidepressants’ ability to boost them (or the natural process of serotonin release to control a person’s mood). Critical to the inflammation process is the release of histamine. The research team set out to assess whether controlling histamine levels will make antidepressants wok more effectively.

With inflammation there is a release of histamine in the body. Histamine increases blood flow to an affected area so that immune cells research the desired target. In most cases this is designed to help the body fight infections. However, sometimes the immune system will work against the body.

Furthermore,  long-term and acute inflammation have been linked to depression. This is perhaps because inflammation is also associated with stress, allergic responses and several chronic diseases including diabetes and obesity.

Histamine is a chemical created in the body that is released by white blood cells into the bloodstream when the immune system is defending against a potential allergen.

All of this means that patients diagnosed with depression and who experience severe inflammation may not respond well to antidepressants, making the depression harder to treat.

Many types of common antidepressants are selective serotonin reuptake inhibitors. While these are often successful, where there are elevated levels of histamine the ability of the antidepressant to work is much reduced.

This finding was drawn from a study whereby serotonin-measuring microelectrodes (for fast scan cyclic voltammetry) were placed into the hippocampus of the brains of mice, looking at an area known to regulate mood. By elevating inflammation in half of the mice by injecting bacterial endotoxin (lipopolysaccharide) the effect of elevated histamine upon serotonin levels was measured the scientific theory about the role of histamine was confirmed.

The study was then repeated and this time histamine reducing drugs were used to control the chemical levels in the mice injected with the bacterial toxin. On this occasion, serotonin levels remained far higher.

Based on the findings, additional research will be performed to see if the findings are translatable to humans and whether a novel treatment can be developed.

The research appears in the Journal of Neuroscience, in a paper titled “Inflammation-Induced Histamine Impairs the Capacity of Escitalopram to Increase Hippocampal Extracellular Serotonin.”

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Written By

Dr. Tim Sandle is Digital Journal's Editor-at-Large for science news. Tim specializes in science, technology, environmental, and health journalism. He is additionally a practising microbiologist; and an author. He is also interested in history, politics and current affairs.

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