Psychosis: Link to brain inflammation antibodies raises new treatment hope

For the first time, researchers reveal that some people presenting with a first episode of psychosis have specific antibodies in their blood. The antibodies are the same ones known to cause encephalitis or brain inflammation. The discovery raises the question of whether the removal of these antibodies could be an effective treatment for psychosis as it is for encephalitis.

The researchers - led by Belinda R. Lennox, a professor in the department of psychiatry at the University of Oxford in the United Kingdom - report their findings in The Lancet Psychiatry.

Psychosis is a condition that affects the mind, where there is some loss of contact with reality. Thoughts, feelings, and perceptions are disturbed to the point where it becomes difficult to tell the difference between what is real and what is not.

Symptoms of psychosis include false beliefs or delusions and hallucinations - seeing and hearing things that others do not. Other symptoms include inappropriate behavior and incoherent speech. Becoming ill in this way is called a psychotic episode.

A person in a psychotic episode may also experience anxiety, depression, disrupted sleep, lack of motivation, and social withdrawal. They may struggle to function.

There is no specific cause of psychosis. It can be a symptom of mental illnesses such as schizophrenia or bipolar disorder. Other causes include sleep deprivation, some medical conditions, some prescription medications, and abuse of alcohol, marijuana, or other drugs.

The new study shows that certain antibodies are present in the blood of a significant minority of people presenting with a first episode of psychosis.

The antibodies are the same ones that cause encephalitis - a life-threatening inflammation of the brain - and include some that act against a neural or nerve cell protein called the NMDA receptor (NMDAR).

Antibodies against NMDAR 'might be relevant' to psychosis

Previous studies have already fueled discussion about the role antibodies targeting neural proteins may play in psychosis. For example, a study reported in 2015 of children experiencing their first episode of psychosis, also found links to an antibody response to NMDAR.

Fast facts about psychosis

  • In the United States, an estimated 3 percent of people will experience psychosis at some time in their lives
  • About 100,000 American teenagers and young adults experience first-episode psychosis each year
  • Many people who receive early treatment never have another psychotic episode.

Learn more about psychosis

For their study, Prof. Lennox and colleagues recruited 228 people with first-episode psychosis from Early Intervention in Psychosis services from across England. The patients gave blood samples within the first 6 weeks of treatment. The researchers also tested samples from a comparison group of healthy people - the controls.

The results showed that seven (3 percent) patients had NMDAR antibodies, compared with none of the controls.

The other antibodies did not differ between groups. There was no difference in the symptoms or course of psychosis between the patients with the NMDAR antibodies and those without.

The researchers conclude that: "Some patients with first-episode psychosis had antibodies against NMDAR that might be relevant to their illness, but did not differ from patients without NMDAR antibodies in clinical characteristics."

Prof. Lennox and her team have successfully treated a number of patients with psychosis who test positive for these antibodies. They used an experimental immunotherapy that targets the antibodies.

One of the patients, called Sarah, says she is now regaining all her previous functioning following two infusions of immune drugs.

Sarah received the therapy 3 years following a "devastating psychotic episode" that left her with memory, sleep, temperature, and emotional control problems. "My mood was in total flux," she says, "swinging from hallucinations and insomnia to sleeping all day and getting severely depressed."

"The next important step for this study is to work out whether removing the antibodies will treat psychosis in the same established way as is now used for encephalitis. To do this the research team are starting a randomized controlled trial of immune treatment in people with psychosis and antibodies, starting in 2017."

Prof. Belinda R. Lennox

Discover how researchers pinpointed rare genetic risk variants for schizophrenia.

    Prevalence and clinical characteristics of serum neuronal cell surface antibodies in first-episode psychosis: a case-control study, Belinda R. Lennox et al., The Lancet Psychiatry, doi:10.1016/S2215-0366(16)30375-3, published online 7 December 2016, abstract.

    University of Oxford news release, accessed 9 December 2016.

    Additional source: NIH National Institute of Mental Health Questions & Answers about Psychosis, accessed 9 December 2016.