Mental illness: The autoimmune connection

The College of Psychiatrists of Ireland Spring Conference featured a talk by Prof Belinda Lennox of the Department of Psychiatry at the University of Oxford, UK. Prof Lennox delivered a presentation titled ‘Autoimmune causes of mental illness and the challenge (and opportunity) for psychiatry’.

In her address, Prof Lennox outlined the growing body of evidence suggesting that a subset of severe mental illnesses may have an autoimmune origin. 

She referred to the discovery of neuronal cell surface antibodies that are considered pathogenic in patients with limbic encephalitis, often with prominent psychiatric symptoms, she said. Removal of the antibody results in clinical improvement, and often remission, but the relevance of the same antibodies in patients with purely psychiatric presentations is more controversial.

Screening for antibodies and subsequent treatment is not readily available.

In her talk, Prof Lennox attempted to address these uncertainties, including the challenges and opportunities for psychiatrists and other doctors.

Prof Lennox provided examples of diseases that have an autoimmune basis and told the attendees: “I want to highlight the curious lack of association with rheumatoid arthritis [and mental illness]. If you have schizophrenia, you have half the risk of having rheumatoid arthritis compared to other people. It’s fascinating and we still don’t know why that is.”

She highlighted research that looked at this phenomenon from another angle. “If you have a pre-existing autoimmune condition, you then have an increased risk of developing schizophrenia, and that risk is increased with each infection that you have,” said Prof Lennox. “So, in a stepwise fashion, the more infections you have, the greater your risk of developing schizophrenia.” This risk is increased even more if a patient has a pre-existing autoimmune disorder, she explained.

Prof Lennox gave an overview of a screening study she is conducting with colleagues to identify antibodies in patients and shared research involving plasma exchange as a treatment approach.

“Fifteen years ago, along with a neurologist, I started treating patients with any illness if they had an antibody and had not improved with symptomatic treatment. And we decided we will offer a treatment trial with plasma exchange.

“We described how people got better,” she continued. “I saw young people with profound presentations who were catatonic and couldn’t tolerate antipsychotics… they had plasma exchange and within a week, their illness melted away without other treatments. It melted away and stayed away, so they didn’t have to be transferred back to the psychiatric ward at all.”

Prof Lennox commented: “If you have autoimmune encephalitis and an antibody, and you get treated in less than six weeks, you get a lot better than if that treatment is delayed….

“If there is anything in the patient’s clinical history that makes you suspicious that they have autoimmune encephalitis; if they have had a problem with movements or catatonia; if they have had a recently-diagnosed tumour; if there is a possibility of a paraneoplastic syndrome; if they have had an adverse response to antipsychotics…. If the patient has severe disproportionate cognitive dysfunction, a decreased level of consciousness or new-onset seizures, then you should have this in mind and you should test for antibodies.”

She also warned that there can be a lot of false-negatives in serum antibody blood tests, so clinicians should also be prepared to do more investigations. “And the number one way to do this, unfortunately, is a lumbar puncture,” she said.

“That is the most useful investigation because if there is no inflammation, that is reassuring. But if there is inflammation, we really need to do more.”