One of the most compelling hypotheses in scientific research today is the growing belief that psychiatric disorders are potentially related to immune system irregularities. A team from King's College London has added substantial weight to that idea with a massive meta-analysis confirming that people with autoimmune disorders are consistently more likely to develop psychotic disorders.

It's becoming increasingly clear that psychiatric disorders such as schizophrenia and psychosis are not conditions that can be simply localized to the brain. A recent large-scale observational study following over one million subjects for 30 years found a striking correlation between stress-related disorders such as PTSD and subsequent autoimmune disease.

This new study from King's College London takes a broader, more meta approach, gathering data from 31 previously published studies, ultimately including over 25 million individuals. The goal of the analysis was to better understand the presence of a correlation between non-neurological autoimmune disorders, such as psoriasis or coeliac disease, and the prevalence of psychosis or schizophrenia.

"Our study shows that overall, people with any autoimmune disorder are around 40 percent more likely to develop psychotic disorders such as schizophrenia," explains lead researcher Alexis Cullen. "The finding that psychosis is associated with non-neurological autoimmune disorders, which are not known to directly target the brain, is particularly important."

The scale of this meta-study undeniably limits how detailed the final results can be but the researchers do note that the strength of the connection between autoimmune disorders and psychosis varies depending on the disease. Out of the 37 non-neurological autoimmune disorders tracked in the study pernicious anaemia, pemphigoid and psoriasis were among the most significantly correlated with psychosis.

Interestingly, the study found two autoimmune disorders displayed notable negative associations with psychosis: ankylosing spondylitis and rheumatoid arthritis. This result follows on from a long-observed phenomenon finding lower rates of rheumatoid arthritis in patients with schizophrenia.

An in-depth genetic study from the University of Pennsylvania last year found eight genes that seem to be implicated in both rheumatoid arthritis and schizophrenia. It is hypothesized that variants in the expressions of those particular genes make a person susceptible to either one or the other condition, but not both.

The researchers of this new study suggest there may be a variety of factors that underlie the connection between autoimmune disorders and psychosis.

"Inflammation is one likely candidate given that people with psychosis show higher levels of inflammatory markers than healthy individuals, and inflammation is a core feature of autoimmune disorders," suggests Cullen. "However, other factors such as shared genes, autoantibodies targeting brain proteins, and infectious agents might also play a role."

As with all observational studies of this type, there are limitations to the kinds of conclusions one can reach. Despite the large scope of the study, it is still unclear what mechanism could explain this connection. The researchers suggest that more granular studies are needed to home in on specific mechanisms and any bidirectional connections between autoimmune disorders and psychosis.

Despite this, Cullen does note that the new study does suggest that closer monitoring for early signs of psychosis in patients suffering from specific autoimmune diseases is warranted.

"This is important," says Cullen, "because we know that early intervention can improve clinical outcomes for people in the initial stages of a psychotic disorder."

The study was published in the journal Biological Psychiatry.