Is personality formation related to the immune system?

© Chelsea Beck

Leviathan Press:

Many people envy people with hyperthymesia, but in fact, the experience of hyperthymesia patients can be described as extremely painful: they may remember every meal they have eaten and every thing they have done in the past few decades... Even extremely painful memories are still vivid in their minds. The reason why humans have a forgetting mechanism in their brains since evolution is also a necessity for survival selection. It selectively stores memories to obtain the best experience.

Other psychologists believe that depression, for example, is not a disorder at all, but an evolutionary mechanism designed to benefit. The physical and mental conditions of depression seem to form an organized system. First, there is anhedonia, the inability to take pleasure in most activities. There is an increase in rumination, dwelling on the source of personal pain. But at the same time, certain types of analytical abilities are enhanced, such as self-insight, problem-solving, and the ability to prevent problems before they occur.

(www.ncbi.nlm.nih.gov/pmc/articles/PMC2734449/)

Therefore, perhaps just like the relationship between personality and the immune system discussed in today's article, it is difficult for us to simply judge whether the ability that individuals and groups have acquired at a high price is good or bad. When a bird is hungry, it risks being eaten and calls loudly. When it becomes a sincere signal of thirst for food, the mother will respond to it. In our human society, psychiatrists have long regarded the behavior of attempting suicide due to depression as a cry for help, but rather than considering this as a pathological form of seeking help, it is better to regard it as the result of a keen response to the surrounding environment.

Geneticist and immunologist Joshua Milner, a senior investigator at the National Institutes of Health, has a radical theory about the way our lives are shaped by subtle factors.

Milner argues that the same thing that protects us from microscopic invaders and makes us sneeze at pollen—the immune system—can make us happy, brave, and outgoing, or shy, anxious, and lonely, depending on certain genetic variants and the environment around us. All it would take to directly prove this theory is to place people in a biodome and observe them for decades.

© MedicineNet

Milner has been trying to help people understand how genes affect the immune system and how it sometimes causes abnormalities in the immune system to make us sick. He is the head of the Laboratory of Allergic Diseases and the Genetics and Pathogenesis Section of the Allergy Division at the National Institutes of Health. He and his team have discovered a rare gene mutation that makes people allergic to cold temperatures. More recently, they have discovered the genetic factors behind a variety of difficult and complicated diseases, including irritable bowel syndrome or chronic fatigue.

(www.nih.gov/news-events/news-releases/nih-scientists-find-cause-rare-immune-disease)

(undark.org/2017/07/24/mystery-diseases-syndromes-health-care/)

Milner didn’t want to study a specific disease or set of symptoms caused by an immune system gone rogue; instead, he wanted to shed light on something more general: “It could help us better understand human behavior and why people perform and differ in cognitive tasks.”

In short, Milner wanted to create a closed world where scientists could observe a diverse sample of people from birth to death. To find out how genetic traits of the immune system were related to the mind, researchers would need to track their social lives and intelligence. Of course, such an experiment would be highly unethical and logistically impossible.

Milner and his team found a pattern in their research. Some patients with rare genetic diseases often have behavioral or cognitive problems, such as anxiety or poor memory. This is not surprising. If you suffer from a chronic, poorly understood disease like Milner's patients, it is natural to feel depressed due to the great pressure.

But reports suggest deeper changes are taking place between the immune system and our brains.

The cells that make up the immune system use molecules to help protect us from external harm. One of these molecules is called interferon gamma . Interferon gamma is particularly useful in producing specific immune responses against serious infections caused by viruses, bacteria, and fungi. And another molecule produced by the immune system, called interleukin 4 , helps promote the production of immune cells that fight parasites such as tapeworms.

However, our bodies are very frugal and try to concentrate resources as much as possible. Therefore, when interleukin 4 or IL-4 is stimulated, the body will reduce interferon gamma; conversely, when interferon gamma is called upon, IL-4 is put on the back burner. In simple terms, IL-4 and interferon gamma represent two different pathways of the immune system, which are used to defend against threats that are "compatible" with them, and they act in opposition to each other.

This is where it gets tricky. Researchers led by Jonathan Kipnis at the University of Virginia have found that in animal studies on mice, mice without the interferon gamma receptor or unable to produce interferon gamma have severely antisocial tendencies. These studies have also shown that mice unable to produce IL-4 have severe memory and cognitive problems.

(www.nature.com/articles/nature18626)

(www.jimmunol.org/content/189/9/4213)

To reiterate here: interferon gamma may make animals more social, while IL-4 may help keep the mind sharp. This is perhaps another example of the body loving frugality: two genes with different purposes in the immune system and the brain.

The main question, Milner says, is whether this relationship holds true in humans. If IL-4 makes you smart and interferon gamma makes you popular, then fluctuations in either factor could lead to behavioral changes. If there is less interferon gamma, for example, our brains could compensate by cleverly keeping us away from other people (who might be carrying all sorts of infectious diseases), a kind of cognitive immune system.

© Super Freak

"It's not the immune system that prevents these diseases, it's your brain that prevents you from getting into a situation where you get the disease," Milner said. "That's a common belief -- that the brain can step in when the immune system may or may not be able to do it."

This is a hypothesis proposed by Milner and others, but there is currently no direct evidence to support the link between the immune system and behavior or cognition. However, there is some indirect evidence that this complex interaction exists in humans. IL-4 is also the main cause of our allergies. Too much IL-4 can make the immune system oversensitive and may overreact to harmless substances such as pollen and pet dander.

A 2017 study showed that people with above-average IQs (a measure of intelligence with well-established flaws) tend to have more allergies and develop disorders that impair healthy social skills, such as autism or anxiety. Another 2018 study found that well-educated young people with allergies tended to have better spatial reasoning and more gray matter in their brains than non-allergic people. And a 2019 study found that raising people's levels of histamine, another key mediator of allergies, can have both negative and positive effects on their long-term memory skills.

(www.sciencedirect.com/science/article/pii/S0160289616303324#!)

(www.nature.com/articles/s41598-018-21985-8)

(www.eurekalert.org/news-releases/819619)

© The University of Virginia

Normally, figuring that out would require a lot of incremental research, much of which would rely on animal studies, which can never definitively prove effects on humans. But in Milner's imaginary lab, we can get a lot closer.

In his imagination, if the scientists at the Biodome found that people with higher levels of IL-4 were generally more intelligent but less sociable, we would have evidence that the protein affects the mind. Conversely, if people with higher levels of interferon gamma were less intelligent but more sociable, we would also be able to prove a relationship. But collecting such data would surely be difficult.

"What makes this research difficult is that we need genetic information from large populations, along with validated tests of cognitive and social outcomes," Milner explained.

Intelligence and social skills are complex variables, so someone with strong short-term memory or spatial reasoning may be better at solving puzzles, but that doesn't necessarily make them smarter in other areas. Likewise, extroversion isn't the only factor associated with good social skills.

How large this study group needs to be, genetically speaking, depends on the types of people that can be recruited.

“You need hundreds or thousands of people or hundreds of mild cases with rare mutations, which is not easy to find,” Milner said.

It would be nice to find some people who are genetically particularly sensitive to interferon gamma or IL-4, but genes are not everything. How a person's genes interact with the environment is also an important factor. In animal experiments, mice are not treated for infections or allergic reactions. But in the real world, infections and allergic triggers happen all the time, which trigger the production of more interferon gamma or IL-4, respectively. Therefore, these events and their frequency can also affect cognitive and social abilities.

What really makes this experiment nearly impossible is the processes it involves. There are so many variables that need to be tracked simultaneously, and a dedicated team of scientists would need to closely observe a large number of volunteers very early in their lives. Even more impractical is that scientists would have to observe a group of people not just for their entire lives, but for generations. I told Milner that his ideal experiment sounds like a serious version of the 1996 Pauly Shore classic Bio-Dome (and the real-life closed environment system that inspired that movie), and he graciously accepted the comparison.

Stills from the movie Biodome. © Inverse

Biosphere 2: Located in Oracle, north of Tucson, Arizona, USA, it is an artificial closed ecosystem built by Edward P. Bass and others. It covers an area of ​​13,000 square meters and is about 8 stories high. It is a dome-shaped sealed steel frame glass building. "Biosphere 2" was built between 1987 and 1989. It was used to test whether and how humans could live and work in a closed biosphere, and also explored the possible uses of closed ecosystems in future space colonization. © Joseph Sohm Getty Images

“The biodome will be very useful,” Milner said, adding that it will allow researchers to closely examine the interaction between environment and genes.

He gives the example of “we can have people with allergies go in there, so we can see what happens when allergic substances pass through their veins, but you also want to involve people without allergic disease.” For people who respond poorly to interferon gamma, the biome could also carefully control the types of bacteria they are exposed to, including those that could cause infection, he adds.

The closest scientists can actually get, he argues, is people with unusually rare mutations that make them either highly susceptible to interferon gamma and IL-4 or deficient in one type of receptor or the other. Milner and others have begun designing these studies. But because these people are by definition rare and often have a wide variety of diseases, it’s hard to use their findings as typical. Still, Milner believes the theory is worth pursuing.

“Is it possible that these genetic differences have no effect on our behavior? I would find that unlikely,” he said. “They have to affect something.”

Milner repeatedly points out that if these traits of the immune system and their relationship to the mind do exist, we shouldn’t view them as some kind of good or bad judgment. Better memory skills, coupled with a greater response to IL-4, might make you better at taking tests, but perhaps more anxious or antisocial. On the other hand, if you have a particularly strong response to interferon gamma, you might be less susceptible to colds and more outgoing, but at the cost of being the worst member of the weekly trivia night (of course, these examples are gross simplifications).

Most importantly, the interferon gamma/IL-4 theory shows that we are governed by the invisible forces in our lives, which are entangled with each other and have confusing sources.

Milner said:

The way the real world works isn’t simple, but experiments like this could help explain some of our tendencies in behavior. When responding to the threat of infection, do genetics predispose us to react differently to it? Do we get more anxious about different things? Does genetics influence our political leanings? Do we perceive threats differently based on our ability to fight off infection? Think of all the clues you could take from this.

For example, several studies have found that conservative-leaning people are more likely than liberals to express disgust and fear of pollution. At the same time, these people are more likely to worry about immigrants who look different. If we don’t excuse the behavior itself, then it may be more worthwhile to explore whether our genes and immune systems can help humans explain our worst impulses.

(www.sciencedirect.com/science/article/abs/pii/S109051381200116X)

By Ed Cara

Translation/Big Guy

Proofreading/Sesame filling teeth gap

Original article/gizmodo.com/a-lifelong-biodome-experiment-could-reveal-how-the-immu-1831010959

This article is based on the Creative Commons License (BY-NC) and is published by Da Guy on Leviathan

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