Study: AS may increase risk of schizophrenia, and vice versa
More research needed to determine potential underlying mechanisms
A new study based on genetic data suggests that ankylosing spondylitis (AS) is significantly associated with an increased risk of schizophrenia, and vice versa.
According to the researchers, “this study showed support for a causal link between autoimmune diseases” — specifically AS — and schizophrenia. The team called for further studies to identify any potential underlying mechanisms connecting the two conditions.
The study, “Causality between autoimmune diseases and schizophrenia: a bidirectional Mendelian randomization study,” was published in the journal BMC Psychiatry.
AS is an autoimmune disease marked by inflammation of the spaces between the vertebrae, or the bones of the spine, which causes symptoms like back pain and stiffness. Inflammation of the sacroiliac joints, where the base of the spine connects to the pelvis, is a hallmark sign of AS.
Previous studies have suggested a bidirectional link between schizophrenia and autoimmune disorders, meaning that one affects the risk of the other, and vice versa.
However, results remain conflicting, and “the true causal [cause-and-effect] connection between the disorders may be obscured by [potential influencing] factors, selection bias [when patients included in studies are not chosen at random], and study limitations,” the researchers wrote. Selection bias occurs when participants in a study are not chosen at random, and may therefore not be representative of the target population, influencing the results.
Genetic data show potential link between risk of schizophrenia, AS
In this study, a team of researchers in China set out to better understand the association between each of 10 autoimmune diseases, including AS, and schizophrenia. The other autoimmune diseases were multiple sclerosis (MS), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), type 1 diabetes, psoriasis, celiac disease, and inflammatory bowel disease (IBD).
To that end, the researchers turned to a statistical method, called Mendelian randomization, that uses genetic information to assess the causal relationship between a risk factor and an outcome. In this case, genetic predisposition to either an autoimmune disease or schizophrenia was a risk factor, and for each, respectively, an outcome.
The analysis was based on data from people of European descent culled from genome-wide association studies, known as GWAS. These large studies collect genetic and clinical information from thousands of people to establish genetic changes linked to the risk of a certain clinical feature, such as a disease.
For AS, the researchers analyzed data from 9,069 AS patients and 13,578 people without the disease, who served as controls.
GWAS studies for schizophrenia included a discovery group of 52,017 cases and 75,889 controls, and a replication group, to confirm the findings of the discovery group, of 33,640 cases and 43,456 controls.
The results showed that genetically predicted AS was significantly associated with a greater than 10% increased risk of developing schizophrenia. However, celiac disease, type 1 diabetes, and SLE were each significantly linked to a lower risk of schizophrenia, and no association was found between the other autoimmune diseases and the risk of schizophrenia.
This is the first research that we are aware of that uses [genetics] technology to comprehensively evaluate the bidirectional causal relationship between autoimmune diseases and [schizophrenia]. … The results of our study indicate that patients with AS are at a higher risk of developing [schizophrenia] in the future, and vice versa.
When the researchers looked at whether a genetic predisposition for schizophrenia would impact the risk for these autoimmune disorders, they found that schizophrenia was significantly linked with a higher risk of AS, by 11%.
Genetically predicted schizophrenia was also significantly associated with an increased risk of IBD and psoriasis, by 12% to 13%. In the replication group, celiac disease was found to be a protective factor against schizophrenia.
“This is the first research that we are aware of that uses [Mendelian randomization] technology to comprehensively evaluate the bidirectional causal relationship between autoimmune diseases and [schizophrenia],” the researchers wrote. “The results of our study indicate that patients with AS are at a higher risk of developing [schizophrenia] in the future, and vice versa.”
Overall, these findings provide some scientific support for a causal link between schizophrenia and autoimmune conditions, per the team. However, the fact that the study only involved people of European ancestry “limits the applicability of our findings to other populations,” the team noted.
Further is needed, per the researchers.
“To gain a better understanding of the mechanisms underlying the development of immune-mediated schizophrenia, additional research is required to identify potential mechanisms,” the team concluded.
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