Not “just” crazy – Some psychoses caused by autoimmunity

Antibodies defend the body against bacterial, viral, and other invaders. But sometimes the body makes antibodies that attack healthy cells. In these cases, autoimmune disorders develop. Immune abnormalities in patients with psychosis have been recognized for over a century, but it has been only relatively recently that scientists have identified specific immune mechanisms that seem to directly produce symptoms of psychosis, including hallucinations and delusions. In other words, some forms of psychoses might just be an autoimmune disorder.

Testing this ‘immune hypothesis’ researchers detected antibodies to the dopamine D2 receptor or the N-methyl-D-aspartate (NMDA) glutamate receptor in a subgroup of children experiencing their first episode of psychosis, but no such antibodies in healthy children. Both are key neural signaling proteins that have previously been implicated in psychosis.

“The antibodies we have detected in children having a first episode of acute psychosis suggest there is a distinct subgroup for whom autoimmunity plays a role in their illness,” said Dr. Fabienne Brilot, senior author.

It almost seems like a dirty trick. For decades psychiatrists have administered drugs that stimulate dopamine D2 receptors or block NMDA receptors. These drugs may briefly produce side effects that resemble symptoms of psychotic disorders, including changes in perception, delusions, and disorganization of thought processes. The current findings suggest that people may develop antibodies that affect the brain in ways that are similar to these psychosis-producing drugs.

“This study adds fuel to the growing discussions about the importance of antibodies targeting neural proteins and it raises many important questions for the field. Do these antibodies simply function like drugs in the brain or do they ‘attack’ and damage nerve cells in some ways?” questioned Dr. John Krystal, Editor of Biological Psychiatry.

“Also, are these antibodies producing symptoms in everyone or do they function as a probe of an underlying, perhaps genetic, vulnerability for psychosis?”

Importantly, work is advancing rapidly in this area. Less than a decade ago, anti-NMDA receptor encephalitis was first identified, a disease characterized by inflammation of the brain that causes acute psychiatric symptoms including psychosis. It is commonly misdiagnosed as schizophrenia or bipolar disorder, but is a form of treatable brain inflammation caused by antibodies that attack the brain’s NMDA receptors.

“The data from this study suggests that better interventions are possible, providing hope that major disability can be prevented for the subset of children experiencing acute psychosis with antibodies,” Brilot added.

“These findings also contribute significantly to an emerging acceptance in the field of the involvement of autoimmune antibodies in neurological diseases.”

“Combined, these investigations are providing a better understanding of the biology of psychiatric and neurological diseases, as well as pointing to novel treatment approaches for children with these debilitating illnesses.”

It is… more than just a little frustrating that with research such as this we are still treating people who suffer from mental health conditions like pariahs in society today. Especially in the case of individuals who suffer openly like cases of schizophrenia or other psychoses, who truthfully can’t help themselves. A perfect personal story about this would be about my friends brother who suffers from schizophrenia and is now in prison for it.

We didn’t just ignore the fact that ebola was going around, we fought to treat and contain it. Why can we get that sort of response for something that is contagious, but at best ignore or shame a person suffering from a mental illness, and at worse lock them away for something that is not their fault? Whatever the reason, it is good to see research being done and maybe even hope for a certain subgroup suffering like this. As for the rest of us, maybe it’s time to think, how would you want to be treated if it was you “going crazy?”

Sources:
Pathmanandavel, K., Starling, J., Merheb, V., Ramanathan, S., Sinmaz, N., Dale, R., & Brilot, F. (2015). Antibodies to Surface Dopamine-2 Receptor and N-Methyl-D-Aspartate Receptor in the First Episode of Acute Psychosis in Children Biological Psychiatry, 77 (6), 537-547 DOI: 10.1016/j.biopsych.2014.07.014