He is hunting for autoimmunity in psychiatry

Could schizophrenia be an autoimmune disease? Yes, perhaps in some cases, says Mats Persson, clinical psychiatrist and associate professor of immunology at CMM at Karolinska Institutet.

Picture of Mats Persson wearing glasses in front of a brick wall.
Mats Persson Photo: Stefan Zimmerman

Mats Persson is on the lookout for autoantibodies in psychiatry. Among other things, he and his colleagues have studied samples from people who had a psychosis. Psychoses, in particular, are often discussed in current reasoning about autoimmunity in psychiatry. For example, it is known that people with the rheumatic system disease SLE may suffer from acute confusion and psychosis, probably as a result of autoimmune attacks in the brain.

Developed schizophrenia

One of the studies from Mats Persson's research group includes 53 people with first-time psychosis and 41 healthy control subjects. In all cases, blood plasma samples containing autoantibodies if present were exposed to more than 2,300 human protein fragments. It was found that eight of the patients with psychosis had autoantibodies against a protein called PAGE. No one in the control group had these autoantibodies. The patients were then monitored for an average of seven years. By then, 14 of them had developed schizophrenia. Five of them belonged to the patients who had autoantibodies to PAGE. Three patients with autoantibodies avoided new psychosis episodes.

But PAGE does not seem to be manifested in the brain. It seems to occur mainly in the testicles, as well as in, for example, the prostate, gastrointestinal tract and kidneys, Mats Persson explains.

To progress further, the researchers developed serum with the relevant autoantibodies using rabbits. Then the researchers tested this rabbit serum on tissue samples from human brains. And then the rabbit autoantibodies bound to them, in areas close to schizophrenia-relevant proteins.

Identify autoantibodies

It is possible that Mats Persson and his research group are about to identify autoantibodies that cause an autoimmune course of events in schizophrenia through cross-reactivity. Perhaps one can then imagine a future in which patients with psychosis are screened for these autoantibodies. If they are found to occur, these patients could be offered immunologic treatment.

“Yes, you might think that. But I don't think all schizophrenia is due to some immunological disturbance. I think, however, that it may turn out to be a large enough proportion for it to be relevant to consider them as a subgroup and treat them in a different way,” Mats Persson says.

Text: Annika Lund, first published in Swedish in the magazine Medicinsk Vetenskap nr 4/2020.