Why existing psychiatric medicine does not work for some people diagnosed with bipolar disorder and other mental health conditions

Because of this autoimmune disorder!

Imagine you wake up in a hospital without a single memory of the last month. Doctors say you had a series of violent episodes and paranoid delusions. You'd become convinced you were suffering from bipolar disorder. Then, after a special test, a neurologist diagnoses you with a rare autoimmune disease called anti-NMDAR (Anti-N-methyl-d-aspartate receptor) encephalitis.

Anti-NMDAR encephalitis can lead to hallucinations, blackouts, and psychosis. It mostly affects women ages 25 to 35—the same age at which schizophrenia often presents itself. But what's happening in anti-NMDAR encephalitis is something else.

In anti-NMDAR encephalitis, antibodies bind to those receptors and prevent them from working. As an autoimmune response, the brain becomes inflamed—hence, it is thought as "Brain on Fire".

While some treatments are available, their effectiveness varies depending on symptom severity. New research  may explain why. In a recent study, researchers map how antibodies from three patients bind to NMDARs. The study is published in the journal Nature Structural & Molecular Biology.

The researchers find that the way in which each of the three antibodies binds to NMDARs differs. The discovery marks an important step in gaining a fuller understanding of anti-NMDAR encephalitis, a condition first diagnosed in 2008. Furthermore, it suggests personalized medicine may be critical for treating this disease.

Distinct binding patterns manifest in different functional regulation levels in NMDARs. This affects neuronal activities. So, different binding sites may correspond to variations in patients' symptoms. 

Uncovering those correlations could lead to more precise therapeutic strategies. Imagine, for example, that scientists identify several binding sites common among encephalitis patients. Pharmacologists could then design new drugs to target these sites. But that's not all. Personalized medicine could also mean more accurate diagnoses, say the experts.

It's still a rare disease, but it could be misdiagnosed or underdiagnosed. Therefore, we need to spread awareness. Could, for example, some schizophrenic patients have this disease? Could it be caused by antibodies?

Currently, it's said that anti-NMDAR encephalitis affects one in 1.5 million people. Yet, in time, we may find it's more common than previously assumed. That's a scary thought. However, it could explain why existing psychiatric medicine does not work for some people diagnosed with bipolar disorder and other mental health conditions—a huge revelation for patients as well as the families and therapists who care for them.

As science advances, we can identify several such new conditions which can be treated successfully.

Kevin Michalski et al, Structural and functional mechanisms of anti-NMDAR autoimmune encephalitis, Nature Structural & Molecular Biology (2024). DOI: 10.1038/s41594-024-01386-4