[WARNING: This article will partly tackle depression and its effects. If you need help, please seek professional advice.]
The World Health Organization estimates that around 264 million people worldwide suffer from depression. It can hinder productivity in individuals and create distance between members of social circles, like families and friends. At worst, severe depression can cause individuals who suffer from it to consider extreme measures such as self-harm to help alleviate their negative experiences. As such, it is vital for doctors and researchers to identify the key factors that affect an individual’s mental health; doing so can improve what we know about our own minds, helping us diagnose those that need to escape it.
It has been known that there exists a link between inflammation and depression; several autoimmune conditions have been linked to higher rates of mood disorders, and previous studies have shown that patients with both depression and severe inflammation were unlikely to respond to treatments via antidepressants. However, discussions and debates are still ongoing to find out what exact mechanism might associate the two seemingly distant phenomena in our bodies. A team of researchers, however, may have determined a crucial link between the two events: histamine, a neurotransmitter involved with our body’s immune response. The study was published in the Journal of Neuroscience.
In the study, the team created serotonin-measuring microelectrodes, and implanted them in the hippocampus of mice. (The hippocampus in humans plays an important role in consolidating short-term memory into long-term memory, as well as spatial memory for navigational purposes.) Serotonin, or the “feel-good molecule,” is a neurotransmitter commonly associated with stabilizing one’s mood; as such, some antidepressants like selective serotonin uptake inhibitors (SSRIs) may target them by inhibiting reabsorption into the brain, allowing serotonin to linger just a bit longer and improving a person’s mood.
Afterwards, the researchers injected an immunotoxin called lipopolysaccharide (LPS) into the mice’s brains in one group, then a saline solution to another control group of mice. The first group’s exposure to LPS immediately triggered their immune response. The microelectrode also immediately detected a drop in serotonin levels in the mice, further cementing their hypothesis. It is also known that LPS is unable to cross the blood-brain barrier; thus, the team has ruled out the possibility of LPS directly affecting serotonin levels in the brain. For comparison, the control group’s serotonin levels remained stable and unchanged.
Upon further examination, they observed that histamine was also triggered by the immune response from exposure to LPS, which then proceeded to inhibit the release of serotonin—the histamine attached itself to inhibitory receptors in serotonin neurons, which they say might have caused the drop in serotonin detected by the microelectrodes. To counter this effect, the team injected SSRIs to the mice. The SSRIs had a much lesser effect on LPS-exposed mice compared to those in the control group. The team believes that the SSRIs hindered the brain’s ability to clear histamine within itself, further inhibiting the effects of serotonin. Finally, the team injected histamine-reducing drugs to the mice, returning their serotonin levels to normal—and, according to the team, confirming their hypothesis. The inhibitor receptors in the serotonin neurons are also present in human brains; this, the researchers say, implies that the results of this experiment may translate to humans as well.
According to lead author Parastoo Hashemi, their study “shines a spotlight on histamine as a potential key player in depression.” “This, and its interactions with the ‘feel-good molecule’ serotonin, may thus be a crucial new avenue in improving serotonin-based treatments for depression.” However, they also believe that depression is very much a “heterogeneous disorder,” and the mechanism described in the study is unlikely to be the sole cause of depression. They believe, however, that should the results in the study be translated to humans in further studies, it can lead the way to developing new ways of treating depression.
Said Hashemi: “Inflammation is a whole-body response and is therefore hugely complex. Depression is similarly complex, and the chemicals involved are affected in myriad ways by both genetic and environmental factors. Thus we need to look at more complex models of depression behaviors in both mice and humans to get a fuller picture of both histamine and serotonin’s roles in depression.”
Bibliography
- Brogan, C. (2021, August 17). Histamine could be a key player in depression, according to study in mice. Imperial College London. Retrieved September 7, 2021, from https://www.imperial.ac.uk/news/228353/histamine-could-player-depression-according-study/
- Haridy, R. (2021, August 17). Histamine may be a missing link connecting inflammation and depression. New Atlas. Retrieved September 7, 2021, from https://newatlas.com/science/histamine-inflammation-depression-serotonin-brain-imperial-college/
- ScienceDaily. (2021, August 17). Histamine could be a key player in depression, according to study in mice. ScienceDaily. Retrieved September 7, 2021, from https://www.sciencedaily.com/releases/2021/08/210817111404.htm
- World Health Organization. (2020, January 30). Depression. World Health Organization. Retrieved September 7, 2021, from https://www.who.int/news-room/fact-sheets/detail/depression
- Hersey, M., Samaranayake, S., Berger, S. N., Tavakoli, N., Mena, S., Nijhout, H. F., Reed, M. C., Best, J., Blakely, R. D., Reagan, L. P., & Hashemi, P. (2021). Inflammation-induced histamine impairs the capacity of escitalopram to increase hippocampal extracellular serotonin. Journal of Neuroscience, 41(30), 6564–6577.
