May 12, 2020
Researchers may have determined why men are more likely to develop schizophrenia but are rarely diagnosed with lupus, an autoimmune disease that overwhelmingly affects women.
Such sex disparities are common in disease pathology. In this case, the answer lies in the interplay of genes and sex, according to a study published in the journal Nature.
Researchers found that the C4 gene increases a person's risk for schizophrenia, a mental disorder. But it also protects against lupus and Sjögren’s syndrome, both autoimmune diseases. And the gene's effects are more pronounced among men.
"The sex differences and vulnerabilities for some illnesses are extremely striking and scientists have puzzled over this issue for decades," researcher Steven McCarroll, director of genomic neurobiology at the Broad Institute of MIT and Harvard, told STAT. "There hasn't always been a good biological explanations for this, even though sex has an enormous effect."
Researchers hope that a better understanding of these mechanisms can help improve treatment for these diseases. By genotyping patients to identify the number of C4 gene copies they have, doctors may be able to determine a more appropriate medication dose.
The study analyzed the genomes of 1,265 people and additional genetic data from 6,700 people with lupus and 11,500 controls.
Researchers found people who carry the highest amounts of the C4 gene were seven times less likely to develop lupus and 16 times less likely to develop Sjögren’s syndrome. But they were 1.6 times more likely to develop schizophrenia.
The study's findings affirmed a prevailing theory that there is a strong association between schizophrenia and autoimmune disease. A complement protein produced by the C4 gene in response to foreign invaders also appears to play an important role.
Scientists believe that immune cells sometimes mistake debris from injured cells for a pathogen. When there are less complement C4 proteins, this debris tends to linger longer, potentially causing greater confusion. That prompts immune cells to launch an attack, leading to autoimmune diseases.
Researchers found women between the ages of 20 and 50 had fewer complement proteins than men of the same age. That's when lupus tends to manifest.
Men in their early 20s have the highest risk of developing schizophrenia. And this is when their complement C4 proteins are at their highest levels.
Still, the nature of all these connections are not completely clear. Earlier studies have suggested that people with autoimmune diseases were more, not less, likely to develop certain psychotic disorders like schizophrenia.
The C4 gene isn't the only player in the development of these complex diseases, the researchers noted. Hormones and behavior also can play a role.
To complicate matters, some women who have early onset of lupus and Sjögren’s syndrome test negative for the complement protein.