Psychological stress unfortunately is a poorly defined concept: one person facing a stressor may cope admirably, and in fact even thrive and get a buzz from that stressor; you only need to look at people engaging in high risk sports to appreciate that. I used to do things like that when young and healthy: I'd seek out the buzz from facing risky activities, like for example irresponsible boy-racer driving. Whereas for another person, the same stressor may be highly perturbing and nerve-wracking, and even mentally damaging. A great deal depends on the brain's ability to cope with stress, and when people say something is stressful, it depends as much on their brain make-up as it does on the external life stressor itself. The same stressor can be an exhilarating buzz for one person, and a nightmare for the next. Whether it is a buzz or a nightmare can depend on genetics, but also in my experience, on infectious pathogen status. When I caught the virus that later seemed to triggered my ME/CFS, it first caused a chronic sore throat and some other chronic physical symptoms, but at around two months after first contracting the virus, it induced some really horrible neuropsychological symptoms: significant anxiety (generalized anxiety disorder), anhedonia, loss of desires, blunted affect (weak emotions), depression, worsening memory. There was increased fatigue, but not yet what would consider ME/CFS. And as this virus spread to friends and family (my chronic sore throat appeared to be constantly shedding the virus), I observed it was able to trigger these same mental symptoms in a number of people, especially severe generalized anxiety disorder. So my response to the virus was not unique or idiosyncratic. Although most people had milder mental symptoms than I did. Once my brain had been affected by this virus, my ability to cope with any stressors plummeted. Whereas before I'd enjoyed facing challenging stressors, all of a sudden, my brain and mind just could not cope with these. The effects of this virus on the brain (possibly mediated via a neuroinflammatory immune response) dramatically altered the way I handle stress. Consequently I started avoiding any form of stressor, because I felt my mind was just not able to cope. I was not working at the time, so fortunately it was easy to cocoon myself away from all stressors; but if I had been working, I am sure it would have been a disaster, and I would have come tumbling down in flames, as I would not have been able to cope with anything, and my work colleagues would have probably perceived me as having a nervous breakdown. This is I think what happens when people have a nervous breakdown: the cliche of nervous breakdown is someone in a high flying job, doing very well, then all of a sudden they find they cannot cope, and are totally stressed out by everything — whereas before they loved the challenging stressors. The cliche explanation of the average man in the street is that his stressful job itself caused the nervous breakdown; but your average man in the street will often create some psychological explanation for such events, because that's all he understands. He does not have the background in biology to understand the complexities of the body and brain. But most likely these people caught some sort of infection, perhaps asymptomatically so that they do not even know that they contracted a new microbe, and then that pathogen starts altering their brain mechanics, and suddenly makes them vulnerable to stress and unable to cope with stressors. Hence the "nervous breakdown". But going back to your statement that increased psychological stress causes increased microglial activity and neuroinflammation: depending on how the study was conducted, if you are simply asking people whether they feel stressed, and then measuring neuroinflammation, that's a flawed study because as explained, whether you feel stress or not from a stressor depends on the health of your brain, which may in turn depend on the infections in your body and your immune response to them. Thus if you find in a study that people who report high stress have neuroinflammation, that does not prove that the stressors caused the neuroinflammation; it may be that a chronic viral infection caused the neuroinflammation, which in turn leads to inability to cope with stressors, and thus a constant feeling of being stressed.