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The World Health Organization estimates that schizophrenia affects 20 million people worldwide. Other sources suggest that the actual number is three or more times that.

And people with schizophrenia are two to three times more likely to die prematurely, largely because of preventable illnesses and suicide. So it's considered a serious global health issue. Medications and treatment programs can help people, but they don't always.

And while they can relieve symptoms, they cannot cure them. The thing is, it's proven hard to develop better treatments because, well, we don't actually know what schizophrenia is. We don't know how it develops, or what exactly causes it.

But a hypothesis that the immune system is a major player has been gaining traction. And if it's right, it could give doctors new ways to treat schizophrenia, or even prevent it from developing in the first place. People with schizophrenia have a different interpretation of reality than most of us – they experience hallucinations, delusions, and disruptions in typical thought processes.

And though there's no medical test that can confirm a person has schizophrenia, there tend to be some structural differences in the brains of people who receive the diagnosis. In particular, several regions vary in size from what's expected. And initially, scientists thought that such abnormalities were neurodevelopmental — meaning, they grew that way in utero and during childhood.

Though, some scientists thought they might be neurodegenerative instead — the result of deterioration of brain tissue later on. And over the past fifteen years or so, the scales have been slowly shifting that way. Some research suggests that both processes are involved.

But the increased emphasis on the role of degenerative processes has brought a decades-old hypothesis back to the forefront. See, if schizophrenia arises or progresses because of a loss of brain tissue, then the question becomes why that tissue is disappearing. And growing evidence suggests that may be the result of a person's immune system attacking their brain.

In other words, schizophrenia may be an autoimmune condition. There's lots of evidence that the immune system is somehow involved in at least some schizophrenia cases. Like, the symptoms of schizophrenia are often tied to inflammation, one of the ways the immune system can try to thwart what it sees as unwelcome guests in the body.

Inflammation isn't bad, per se. It can be part of a healthy immune response to pathogens. It's just that you don't want too much of a good thing.

And that seems to be what's happening. People with schizophrenia have higher levels of inflammatory markers in their blood, for example. Whether that's because inflammation causes schizophrenia or the other way around isn't clear.

But some experts believe that inflammation in the body could signal changes to the brain which, in turn, trigger or exacerbate schizophrenia symptoms. That may also explain why infections in general increase the likelihood of someone developing schizophrenia. Infections can result in the blood-brain barrier becoming permeable, allowing inflammation into the brain.

Like, a 2011 study that looked at over three million people in Denmark found that being hospitalized for an infection increased a person's risk of developing schizophrenia by 60%. And infections have been known to trigger autoimmune conditions, too. In fact, in that same 2011 study, people who were hospitalized for an infection and had had an autoimmune condition at some point were more than twice as likely to develop schizophrenia.

And by itself, having an autoimmune condition increased the risk of schizophrenia by 29%. That's a common theme. Decades of research has found a lot of overlap between schizophrenia and autoimmune diseases.

Though there are some notable exceptions, overall, the likelihood of developing schizophrenia is higher in people with autoimmune disorders, and vice versa. Even having a parent or sibling with an autoimmune condition can raise a person's risk of schizophrenia by 20%. And as far back as the 1970s, doctors noticed that people with schizophrenia have a lot of central nervous system autoantibodies, or antibodies that bind to their own cells in their brain and spinal cord.

These are a hallmark of certain kinds of autoimmune disease. So it may be that the symptoms of schizophrenia also stem from the immune system attacking the body — or, in this case, immune cells in the brain overstepping. Multiple studies have noted that the central nervous system's immune cells, called microglia, tend to be more active in people with schizophrenia.

And among other things, these cells play a huge role in synaptic pruning — the process by which the brain eliminates unneeded connections. Pruning happens to all of us, but it seems like the brains of people with schizophrenia prune more than they should, which may explain why some parts end up smaller. And researchers might finally be zeroing in on exactly what triggers microglia to get so snippy.

A January 2020 study in mice found that coaxing cells to overproduce one protein in the complement system — a part of the immune system that boosts the response to pathogens — was enough to send microglia into overdrive. That led to overeager synaptic pruning and schizophrenic symptoms. There may be more than one thing that sets microglia off, of course.

Which is why a person's immune system, genes, developmental conditions in utero, and reaction to psychological stress can all converge to trigger the condition. But, the connection between autoimmunity and schizophrenia is pretty convincing. And if an overactive immune system is a big part of schizophrenia, then effective treatments could lie in getting it to calm down.

For instance, scientists are already trying to figure out whether therapies that target autoantibodies in the brain can help people with schizophrenia. And it turns out that NSAIDs — pain relievers and fever reducers that also reduce inflammation — can help treat the symptoms of schizophrenia in tandem with traditional antipsychotic medications. Eventually, we may even be able to predict who will develop schizophrenia based on immunological markers — or prevent symptoms from developing altogether.

In the meantime, just knowing about the overlap between autoimmunity and schizophrenia could make a big difference. The authors of one study urged clinicians not to automatically dismiss complaints that might be symptoms of autoimmune disease as hallucinations or delusions. And hopefully, the more we unravel the role of autoimmunity in schizophrenia, the better equipped we'll be to help tens of millions of people worldwide.

Thanks for watching this episode of SciShow Psych! If you're hungry to learn more about autoimmune conditions, you can pop over to our main SciShow channel to watch our episode explaining why they're more common in women. But don't forget to click that subscribe button and ring the notification bell first!

Here on SciShow Psych, we're all about brains — so if you want to understand yours a bit better, you won't want to miss an episode. [ ♪OUTRO ].