Depression: Histamine identified as a possible cause

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Histamine interacts with serotonin

Depression is the most widespread mental illness in the world. The exact causes of depression are still not sufficiently understood. Recent research now suggests that histamines released in the body may play a role in its development.

Researchers at Imperial College London and the University of South Carolina suggest that the release of the protein molecule histamine affects the uptake of serotonin. Serotonin is a neurotransmitter that is largely responsible for our mood. According to the research findings, histamine may play a greater role in the development of depression than previously thought. The study was recently presented in The Journal of Neuroscience.

What are histamines?

Like serotonin, histamine is a so-called biogenic amine – a molecule that is formed during the breakdown and conversion of protein. Histamine is present in many foods, especially perishable foods, and is also produced by the body itself.

What is the function of histamines?

When inflammation occurs in the body, histamines are released to increase blood flow to the area in question. As a result, the area with better blood flow is flooded with immune cells. This effect helps the body fight infection.

Inflammation seems to promote depression

Inflammation occurs in the body not only from infections, however, but also from stress and allergic reactions, as well as chronic diseases such as diabetes, obesity, cancer and neurodegenerative diseases. Acute and long-term inflammation have been linked to depression in previous studies. The current research provides a possible explanation for this link.

“Inflammation may play a major role in depression, and there is already strong evidence that patients suffering from both depression and severe inflammation are most likely to be unresponsive to antidepressants,” confirms study lead author Dr. Parastoo Hashemi of the Imperial Department of Bioengineering.

Is histamine a key player in depression?

“Our work shines a spotlight on histamine as a possible major player in depression,” Dr. Hashemi points out. The discovered interactions with the “feel-good” molecule serotonin could have a critical impact on serotonin-based treatments for depression.

Serotonin to alleviate depression.

Serotonin is a neurotransmitter in the brain that affects our mood. Treatment of depression with antidepressants often involves so-called serotonin reuptake inhibitors (SSRIs), which ensure that serotonin can circulate in the brain longer, improving mood when treatment is successful.

SSRIs ineffective in some individuals

However, there are also individuals in whom serotonin reuptake inhibitors have no effect. The reasons for the lack of effect have been unclear until now. Scientists already suspected that interactions in chemical messengers or neurotransmitters could be responsible.

Serotonin levels measured in real time

With this in mind, the research group analyzed the relationship between histamine, serotonin and serotonin reuptake inhibitors in a mouse model. They inserted microelectrodes to measure serotonin in the animals’ hippocampus. This area of the brain is largely responsible for regulating mood. This allowed the researchers to measure the mice’s serotonin levels in real time.

Serotonin levels dropped within minutes

Subsequently, one group of mice received an injection with pro-inflammatory lipopolysaccharide, while the control group was administered a saline solution. Serotonin levels in the brain dropped within minutes due to the toxin, while they remained the same in the control mice. According to the researchers, this is evidence of how quickly inflammatory reactions in the body affect the brain and influence serotonin levels. Since lipopolysaccharide cannot cross the blood-brain barrier, a direct effect on the brain is ruled out, they said.

Histamine attaches to serotonin receptors

In further investigations, the research team was able to prove that histamine was released in the brain as a result of the inflammatory reaction. The histamine accumulated on receptors on the serotonin neurons, inhibiting serotonin uptake. Because these inhibitory receptors are also present on human serotonin neurons, the results are very likely to translate to humans, the team points out.

In addition, the team showed that administration of SSRIs increased serotonin levels less in the mice with inflammatory response than in the control mice. The researchers suspect that this is because the histamines abolished the serotonin-increasing effect. This suspicion was solidified when administration of histamine-reducing drugs increased serotonin levels in the animals with inflammatory responses.

Improved treatment of depression in prospect

Overall, the research suggests that an interaction between histamine and serotonin may have an impact on depression and its treatment. Measuring these substances could improve the diagnosis of depression and identify people who are unlikely to respond to SSRIs. The effects of certain antidepressants could also be enhanced by histamine-reducing drugs. Before this can happen, it must be confirmed that the interactions behave in the same way in humans.

 

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