People With Autoimmune Disorders More Likely To Have Psychosis, Research Shows

Andy

Retired committee member
Although previous research indicates that there exists a correlation between autoimmune disorders and psychosis, conflicting findings have made it difficult for researchers to reach definitive conclusions about the relationship between the two. Prompted by this, researchers from King’s College London conducted a meta-analysis of 30 studies, containing data of 25 million people total.

Their findings were published in the peer-reviewed journal Biological Psychiatry. Titled, “Associations Between Non-Neurological Autoimmune Disorders and Psychosis,” the meta-analysis was authored by Alexis E. Cullen, Scarlett Holmes, Dan W. Joyce, Matthew J. Kempton, Thomas A. Pollak, Graham Blackman, Robin M. Murray, Philip McGuire, and Valeria Mondelli.

King’s College London researchers focused on autoimmune disorders that affect the peripheral system. In particular, the focus was on disorders that target the body, as opposed to the brain, in order to see whether autoimmune disorders that target the body could still affect the mind.
https://www.inquisitr.com/4964404/p...more-likely-to-have-psychosis-research-shows/
 
Surely what this actually suggests is that psychiatrists are more likely to diagnose psychosis in people who have an autoimmune disorder, probably because of the incompetence (inability to understand, believe in or treat) of other doctors resulting in more people with autoimmune conditions being given referrals.
 
Plus ça change, plus c'est la même chose.

Women are far more likely to develop autoimmune disorders than men. If GPs and other doctors become familiar with the idea that women are more likely to become psychotic than men it just gives them yet another reason not to take women seriously and plonk them in the mental health waste basket.
 
I've often wondered why it is that women are so much more likely to get autoimmune disorders than men. I came across a possible reason very recently (I didn't keep a link, sorry). It was suggested that the immune systems in men and women work differently because women are made to carry "foreign bodies" i.e. babies. Men aren't - their immune systems only have to worry about "number one". So the immune system in men probably works "better" than the immune system in women, and this is by design.
 
I've often wondered why it is that women are so much more likely to get autoimmune disorders than men. I came across a possible reason very recently (I didn't keep a link, sorry). It was suggested that the immune systems in men and women work differently because women are made to carry "foreign bodies" i.e. babies. Men aren't - their immune systems only have to worry about "number one". So the immune system in men probably works "better" than the immune system in women, and this is by design.

Nice try Arnie! We all know its caused by a wandering womb.
 
It was suggested that the immune systems in men and women work differently because women are made to carry "foreign bodies" i.e. babies. Men aren't - their immune systems only have to worry about "number one". So the immune system in men probably works "better" than the immune system in women, and this is by design.

I think there may be a clearer story than this. Babies are not foreign bodies to the immune system despite the longstanding myth. The placenta attaches itself to the uterine endometrium but it never poses an invasive threat because the chorionic villi are not programmed to invade any deeper. Invasion only occurs if the embryonic tissue is itself cancerous (choriocarcinoma). The mother's immune system does not recognise the baby as a foreign body because every time a maternal lymphocyte or macrophage comes in to contact with a cell in the baby it will carry off whatever information it gathers to the babies immune system, not the mother's. And the baby's immune system is programmed to ignore its own cells.

Where the baby comes in to the difference between male and female immune function is that mothers have to make antibodies for themselves and for their babies, because the baby cannot learn to make antibodies to germs while it is in the uterus and if it did not have antibodies from mother it would hit a thousand different potentially dangerous microbes on its day of birth.

In fact, just as males are useless in general, it could be argued that antibodies are pretty irrelevant to adult males, who can survive pretty well on their learned T cell responses. But females have to go on making antibodies in case they get pregnant and a baby needs some.

Males and females have the same quantities of antibody in the blood but experiments on small mammals suggest that females may be better at making specific antibody responses to microbes than males. It seems likely that the exposure to oestrogen that makes someone female supercharges the B cell response in some way, although I have never heard anyone give a precise account of what way.

That would explain why females are specifically more susceptible to true B cell driven autoimmunity (not psoriasis or ankylosing spondylitis). From my perspective the key susceptibility factors are likely to be the rate of random generation of new antibody types with new B cells and the efficiency of selection of good ones. Something in females increases susceptibility by about three times for most B cell driven diseases. Interestingly for lupus it is nine times (three squared) suggesting that the difference acts twice in the pathway.

I am not too excited about this study. As far as I know psoriasis and Grave's disease have nothing in common (psoriasis not being autoimmune) any more than hypertension or baldness. The obvious confounding factor, as someone has said, would be sample bias from diagnostic pathways.
 
I like to see research like this; it provides evidence that mental health conditions may be due to physical disease, rather than psychogenic factors.

Even these days, too many researchers in psychology and psychiatry search for psychogenic causes of mental health (which has never really led to much success in understanding the basis of illnesses such as schizophrenia or bipolar). And not enough researchers focus on biological causes of mental illness; although the younger generation do seem to have more interest in biological mechanisms.

This focus on psychogenic rather than biological causes of mental health stems in part from the fact that historically, medicine was not able to peer into the biochemical workings of the body, so psychogenic explanations were the only ones accessible. That has changed in recent decades, as medicine gets better and better at peering into the biological functioning of the body.

I think there needs to be a renaissance in mental health research, because whereas psychogenic factors play a huge role in normal psychology, personally I don't think they play anywhere near as important a role in abnormal psychology. I think if we are going to make inroads in understanding abnormal psychology, we need to get biological.

And we need to do this quickly, as mental health causes a huge amount of suffering, and there is currently an epidemic of mental health problems among school children in the UK: Children face mental health epidemic, say teachers.
 
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That would explain why females are specifically more susceptible to true B cell driven autoimmunity (not psoriasis or ankylosing spondylitis). From my perspective the key susceptibility factors are likely to be the rate of random generation of new antibody types with new B cells and the efficiency of selection of good ones. Something in females increases susceptibility by about three times for most B cell driven diseases. Interestingly for lupus it is nine times (three squared) suggesting that the difference acts twice in the pathway.

Interesting. Relapsing Polychondritis affects males and females equally. Perhaps that is more evidence pointing to it being a T-cell driven disease?
 
paper here:
https://www.biologicalpsychiatryjournal.com/article/S0006-3223(18)31630-5/fulltext

Found this bit interesting:
"The potential contribution of corticosteroid treatments to the association between NNAI disorders and psychosis has received relatively little attention. This is surprising given that there is robust evidence of glucocorticoid (i.e., cortisol) abnormalities among individuals with, and at-risk for, psychosis (75. Moreover, a recent population-based study reported increased risks for schizophrenia spectrum disorders among children/adolescents exposed to glucocorticoid treatment (76. Of particular relevance to our findings, corticosteroids are among the most common treatment types for psoriasis and pemphigoid (77, 78, 79), and some forms of autoimmune anaemia (80. However, corticosteroids are commonly used in the treatment of rheumatoid arthritis (81, which was negatively associated with psychosis. Thus, the contribution of corticosteroids to these associations is currently unclear."

I'm not sure about these meta-analysis studies generally though; it seems you can at least partially show correlations between any two things (not just medical issues) if you pick the right data.
 
Fascinating explanation, @Jonathan Edwards.

I was a bit excited about this study, because it followed so closely on the heels of that recent one examining individuals in first episode schizophrenia - the one that examined various blood markers of inflammation, and found them to be higher in those with schizophrenia. My brain isn't working well right now, so I can't remember the details. But the idea that the the body - not just the brain - plays a role in severe mental illness is fascinating.

There were two things that seemed persuasive for me.

First, the correlations were not always in the same direction. Which rules out some generic health factor that's driving everything, something linked to social class or whatever.

And second, its not depression, or anything wishy-washy like that, where people might throw the label in any time they think a patient is glummer than they should be. Its psychosis, which has a much more demanding set of diagnostic criteria. And psychosis is more commonly diagnosed in men than in women. So it runs against cultural biases (which are generally towards pathologising women's thoughts/feelings/behaviours more than men's).

I take your point, @Jonathan Edwards, that it doesn't give us any clues as to the mechanisms at play. But maybe its useful in guiding future investigations?
 
I just checked out the link between Graves disease and psychosis. It seems that there are specific reasons why the disruption of thyroid hormone levels caused by this autoimmune disease might cause psychosis. While there might be some general cause of a heightened risk of psychosis in autoimmune conditions, I think I'd want to be separating out the obvious ways specific conditions might be causing psychosis first.

Psychosis Crisis Associated with Thyrotoxicosis due to Graves' Disease

Differential diagnosis of psychosis crisis must include trauma, autoimmune diseases, drug abuse, iatrogenic causes, strokes, tumors, congenital disorders (velocardiofacial syndrome), metabolic disturbances, sepsis, neurological infections, Addison disease, hyperparathyroidism, temporal lobe epilepsy, NMDA autoantibodies-associated encephalopathy, and schizophrenia [15, 16]. This implies an adequate evaluation by a psychiatrist and a neurologist with specific treatment for each disease.
...
Psychosis crisis associated with hyperthyroidism is really unusual. In contrast, psychiatric manifestations are commonly associated with hypothyroidism in the form of “myxedema madness” or are related to a quick correction of high levels of thyroid hormones (fT4) [12]. However, even when psychosis could have an independent cause (e.g., a primary disease), thyrotoxicosis by itself could worsen psychiatric manifestations [13]. In fact, it seems that adrenergic hyperactivity observed in patients with hyperthyroidism could influence certain brain functions.

(I've included this next one mostly because I like the way the superstitious beliefs of the Nigerians are dismissed as silly so easily, while we know people with equally silly and unsupported beliefs about psychosomatic illness are regarded as pillars of the mental health establishment.)
Graves’ Thyrotoxicosis Presenting as Schizophreniform Psychosis: A Case Report and Literature Review
Similar to other parts of the world, Graves’ disease is the most common cause of thyrotoxicosis in Nigeria (1). Subtle neuropsychological symptoms such as anxiety, irritability, tremor, and insomnia are not uncommon in severe thyrotoxicosis, regardless of the cause. However, psychosis, as the first clinical presentation of Graves’ disease, is extremely rare. The first case of thyrotoxic psychosis was described over a century ago (2). Since then, many other cases have been reported, mostly from developed countries (3-5), while only one case of psychosis associated with Graves’ disease has been reported in Nigeria (6).

Superstitious beliefs about the causes of psychiatric disorders abound in Nigeria and other developing countries (7, 8). Mental diseases are often wrongly ascribed to witchcraft, evil spirits/demons, and nemesis. Consequently, treatment of most psychiatric disorders is first sought in unorthodox centers, such as herbal homes and prayer houses, leading to delayed patient admission and management with poor outcomes.

Herein, we report an unusual case of a 16-year-old female Nigerian with schizophreniform psychotic disorder, associated with Graves’ disease, who was believed to be possessed by demonic spirits and was kept in a prayer house ostensibly for "spiritual deliverance".
 
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That was an interesting read @Arnie Pye.

Words of such sense written in 1949...

No physician would attempt to diagnose lobar pneumonia or typhoid by the delirium they may produce, and likewise in myxoedema it is the disease which is the characteristic feature, not its mental manifestations.

The fact that recorded cases of myxoedema psychosis have closely resembled paranoia (CaseIandStol,1932), schizophrenia (Zondek and Wolfsohn, 1944), melancholia (Buschan,1896), or other orthodox psychoses does suggest that the common psychoses- schizophrenia, mania, melancholia, paranoia, and so on- may turn out to be not diagnoses in themselves, but manifestations of underlying organic disease.
 
the only people I know who have had hallucinations/delusions had Alzheimers/Parkinsons and my understanding is the hallucinations/delusions are a symptom of the underlying diseases in both cases

is there anything to say this isnt the case for most if not all people who have hallucinations/delusions - just because there isnt a current medical explaination..............
 
the only people I know who have had hallucinations/delusions had Alzheimers/Parkinsons and my understanding is the hallucinations/delusions are a symptom of the underlying diseases in both cases

I knew someone who developed delusions, paranoia and psychosis (and possibly hallucinations as well) as a result of developing sepsis.
 
That would explain why females are specifically more susceptible to true B cell driven autoimmunity (not psoriasis or ankylosing spondylitis).
That is the most interesting and reasonable explanation I have ever read. Thank you.

I have a question. Would that mean an imbalance of hormones, or even an induced imbalance via estrogenic drugs (yes, “the pill,” but especially the much more concentrated and now withdrawn diethlylstilbestrol) could also contribute to these types of autoimmune diseases?

Also, does that mean if there’s T cell clonal expansion in M.E. and this turns out to be a reliable finding, that men and boys are not getting diagnosed? (even worse than women and girls are not getting diagnosed, which is already super bad).
 
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