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For decades, researchers have sought a definitive biological marker to confirm a diagnosis of schizophrenia, but have been unsuccessful. A review published last year in Schizophrenia Research concluded that the condition isn’t defined by a single cause, symptom, or biological mechanism, highlighting the complexity of the illness.
A potential shift in understanding schizophrenia began in 2007, when Josep Dalmau, a neurologist at the Autonomous University of Barcelona, and colleagues began publishing research on young patients experiencing delusions and sudden behavioral changes, including agitation and inappropriate laughter. Within days or weeks, these patients deteriorated, developing seizures, loss of consciousness, or difficulty breathing.
Dalmau discovered these patients had a form of encephalitis, or brain inflammation. Their immune systems had mistakenly identified the NMDA receptor – a brain protein affecting mood and memory – as foreign and were producing antibodies to attack it. When treated with immunotherapy, most of these young people recovered fully, some in less than a month.
Thomas Pollak, a neuropsychiatrist at King’s College London and the Maudsley Hospital, described treating patients with this condition as both “revealing” and “disturbing.” He explained, “Some of them looked exactly like the patients I saw on the psychiatric ward. It was very strange to see that a completely different pathway could lead to the same presentation.” This illness, named anti-NMDA receptor encephalitis, typically affects people in their twenties, similar to the age of onset for schizophrenia.
Susannah Cahalan detailed her experience with anti-NMDA receptor encephalitis in her 2012 autobiography, Insane: My Month of Madness. As the 217th person in the world diagnosed with the condition, she recounts oscillating between paranoid aggression and euphoria, but initially being misdiagnosed by some doctors as having a difficult psychiatric condition. She wrote, “If one of the best hospitals in the world took so long to reach this diagnosis, how many people are going untreated, diagnosed with a mental illness, or condemned to spend the rest of their lives in a nursing home or psychiatric ward?”
Since Dalmau’s initial discovery, scientists have identified over twenty additional antibodies linked to psychiatric symptoms. In 2020, a study with 28 authors published in The Lancet Psychiatry proposed a new category of illness, termed “autoimmune psychosis” – a milder or incomplete form of encephalitis manifesting only with psychiatric symptoms. This research suggests that some mental health conditions previously attributed to other causes may have an underlying immunological component.
Christopher Bartley, who investigates the role of immune dysfunction in mental illness at the National Institute of Mental Health in the United States, believes the twenty known antibodies may represent “just the tip of the iceberg.” He suggests numerous targets within the brain could be vulnerable to antibody attacks, potentially altering perception and behavior.
This may have been the case for Mary, whose story is detailed in a recent article in piauí magazine. Mary’s schizophrenia symptoms began to subside after she started treatment for lymphoma, a potentially fatal type of cancer, and underwent chemotherapy with rituximab, a medication that targets antibodies involved in the body’s immune response.
Christine, Mary’s daughter, asked one of her mother’s doctors, “She has a twenty-year psychiatric history. Have you ever heard of anything like this? Could any of the medications have caused this?” Omid Heravi, one of Mary’s oncologists, was also puzzled. “Medicine is very specialized; we don’t venture into other areas,” he explained. His initial thought was that the cancer medications might have had unexpected, beneficial side effects. “In medicine, not all side effects are negative,” he said.
Subscribers to piauí can read the full article here.
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