Researchers at Houston Methodist believe that a significant number of people diagnosed with schizophrenia or bipolar disorder may actually have a treatable immune system condition. A new research study could have a significant impact on the millions diagnosed with schizophrenia or bipolar disorder, including many homeless.
The study was inspired by the 2007 discovery of anti-NMDA receptor encephalitis, a disease that causes symptoms similar to schizophrenia or bipolar disorder but can be treated with existing immunotherapy medications.
“We suspect that a significant number of people believed to have schizophrenia or bipolar disorder actually have an immune system disorder that affects the brain’s receptors,” said Joseph Masdeu, M.D., Ph.D., the study’s principal investigator and a neurologist with the Houston Methodist Neurological Institute. “If true, those people have diseases that are completely reversible – they just need a proper diagnosis and treatment to help them return to normal lives.”
The immune system normally produces antibodies to attack foreign substances in the body, such as bacteria. When this process goes wrong, antibodies are produced that attack receptors in the brain, causing the receptor to stop listening to the signals being sent to it. In cases of anti-NMDA receptor encephalitis, antibodies attack N-methyl-D-aspartate (NMDA) receptors in the brain.
Conditions that cause the brain’s receptors to stop functioning properly are often mistaken for schizophrenia or bipolar disorder because these diseases are associated with a decrease in activity of the NMDA receptors, which control how someone thinks, makes decisions, and perceives the world around them. Classic schizophrenia and bipolar disorder symptoms seen in anti-NMDA receptor encephalitis and similar conditions include hearing voices and paranoia.
“We know that nearly 1 percent of the U.S. population – or more than 3.5 million people – have schizophrenia,” Masdeu said. “Another 2.6 percent of American adults have bipolar disorder. What we don’t know is how many of these patients actually have one of these treatable immune system disorders.”
The study will enroll 150 patients diagnosed with schizophrenia or bipolar disorder and 50 healthy people between the ages of 18 and 35 who are willing to undergo a spinal tap to collect a small amount of their cerebral spinal fluid, which will be screened for the presence of antibodies attacking NMDA and other receptors. If abnormal antibodies are discovered, researchers will notify the patient or caregiver, so that they may consider asking their health care provider about treatment options, such as using existing drugs that could suppress the production of the attacking antibodies.
Masdeu plans to use study results to develop more sensitive tests to aid in the detection of attacking antibodies. He first began researching possible autoimmune causes of schizophrenia in the early 2010s while working at the National Institutes of Health and published early papers on the subject. Masdeu is now collaborating with Josep Dalmau, M.D., Ph.D., who first described how antibodies can attack NMDA receptors.