Why Do Infections of the Brain Only Make People Meaner?

The fact that on average the entire population of the globe has become more angry, unfriendly, and generally just bigger assholes is one aspect of the Covid-19 epidemic that is less remarked upon and studied then it should be. It is now well known that Covid-19 does enter into and replicate in the brains of infected animals, including humans, and that this causes inflammation and damage to nerve cells and can impact behavior in subtle and not so subtle ways. To take just on example from the animal kingdom when laboratory mice are infected with some strains of Covid-19 at a high enough inoculum level they develop a strange stunted gait or hiccup in the way they walk. Almost like they are trying to hop/jump instead of walk but somehow the signals for both are becoming mixed up in their brains resulting in a very bizarre, but indicative behavior. Those that display this behavior (almost) always die soon after. It is a very disturbing thing to see and our own human brain is instinctively repulsed by witnessing it. It falls so far outside the normal standard way of how we are "used" to seeing mice walk that it triggers a sort of revulsion, a primal revulsion is the best word I can use to describe it. If I were H.P. Lovecraft (not the racist dickhead one, but the master of eldritch horror one) I might call it a thing that should not be, and that would be a very good way to put it. There can also be changes in animal behavior in terms of what I would call their mental state. They can become more aggressive, they may attack each other for much smaller transgressions, those attacks may become more vicious, and they become much more self destructive and generally less concerned for their own or other animals well being overall. Of course, often times they are too sick to do any of these things, at least not very well.

Many or maybe even most humans infected with Covid-19 whether they show no symptoms, or become just a little sick or get very sick also exhibit behavioral changes during and post infection and, like with lab animals, they are all bad. More aggressive, less empathy, less sympathy, quicker to anger, more violent, etc. and so on. The question I have been asking myself since I first noticed and learned about this phenomenon is why is that the case? Why are all the behavioral changes as a result of Covid infections resulting in amplification of what I (and I would suggest most people) would consider negative emotional traits, and not also some positive ones, at least every once in a while? And, a bigger question, why is this also the case with every other virus that is known to infect the human brain? One would think that over the course of human history at some point a virus would evolve that could infect the human brain and result in amplification of positive traits. For instance make people more loving, more helpful, less prone to anger, calmer, more peaceful, etc. And yet, it never has, not once, at least that we know about.

The simple and obvious answer would be that negative traits like anger and aggression are much more advantageous from a human survival perspective and thus they have been selected for by evolutionary pressures over the millennia. It makes intuitive sense. When someone is sick, and if you have a brain infection you are very sick, you are very vulnerable to attack by other people and animals. Ramping up the fight or flight response would be a very smart thing to do from a survival perspective. Also, in terms of the what can happen biochemically when people experience brain damage it makes sense. Damage to the brain can trigger what is known as a cytokine storm, also called hypercytokinemia. It is a pathological reaction in humans and other animals in which the innate immune system causes an uncontrolled and excessive release of pro-inflammatory signaling molecules called cytokines. Cytokines are a normal part of the body's immune response to infection, but their sudden release in large quantities may cause multisystem organ failure and death. Incidentally cytokine storms may be caused by infectious or non-infectious etiologies, especially viral respiratory infections including various influenza viruses, SARS-CoV-1, SARS-CoV-2 (Covid-19), and other viruses and bacteria. A cytokine storm also can be triggered by conditions which have nothing to do with infections such as graft-versus-host disease.

Importantly for purposes of this discussion, cytokines are also known to be important in the neurobiology of aggression and rage. An increase in certain cytokines is associated with increased aggression and anger. This phenomenon was first noticed when clinical reports described increasing levels of hostility, anger, and irritability in patients who had received cytokine immunotherapy. At the same time their were other reports of a positive correlations between cytokine levels and aggressive behavior in non-patient populations. Since that time the link between increased levels of certain specific cytokines and higher levels of anger and aggressive behavior has been shown repeatedly in multiple laboratory studies using a variety of different animal models and humans.

For sure there are many other hypotheses that could be posited to account for the increased anger and aggression seen so often in persons with infections of the brain. However, I am much more interested in why the opposite never happens despite the fact that there seems to be no good reason(s) why it should/could not happen. Why do infections of the brain never result in making a person happier or nicer or more calm or more peaceful, etc? Taking the evolutionary argument approach I used earlier couldn't one just as easily make the case that a more calm person would have a better chance of surviving an infection of the brain than one all jacked up on anger and aggression which we know can cause persons to act irrationally and rashly and expend/waste a lot of energy that might be better put to use fighting off the infection. From a survival perspective those are all very bad things for a person to do when they are very sick. Remaining calm on the other hand, conserving energy, resting, we know is a very smart thing to do. Moreover, I would guess, though do not know for certain, that there are specific cytokines associated with calm and reserve and peaceful resting states.