Immunotherapies for Schizophrenia and Bipolar Disorder Not Quite Ready for Prime Time


The intersection between the immune system and psychiatric illness has been a long time coming and still has a long way to go, said Mark Weiser, M.D., at APA’s 2018 Annual Meeting.

“There are many hypotheses about the origins of schizophrenia but few are strongly based on conclusive data,” said Weiser, a professor of psychiatry at Tel Aviv University and chief psychiatrist at Sheba Medical Center. “Inflammation was put forward as one possibility as far back as the 1870s, linked to typhoid, malaria, or influenza, and it is drawing more attention again today.”

Recent epidemiology has found environmental effects on risk that could involve the immune system, such as being born or raised in an urban area, being born in the winter, having antibodies to Toxoplasmosis gondii, or maternal exposure to influenza, said Weiser, who is also associate director for treatment trials at the Stanley Medical Research Institute in Kensington, Md. One of the 108 genes recently associated with schizophrenia is related to the immune system.

Schizophrenia and autoimmune diseases often have a similar age of onset and follow a relapsing-remitting course. Abnormal levels of certain cytokines have been documented in patients with schizophrenia.

With that background, researchers around the world have been testing drugs to learn their effects on the symptoms of schizophrenia, mostly producing indifferent results in small trials, said Weiser. For instance, an initial study of the antibiotic minocycline indicated positive effects on positive and negative symptoms, but a second study found no improvement.

Similar discouraging outcomes have been recorded as well for acyclovir, aspirin, azithromycin, fingolimod, methotrexate, N-acetyl cysteine, intravenous immunoglobulins, and monoclonal antibodies. However, one intriguing observation has been that patients with high levels of C-reactive protein (CRP), a biomarker for inflammation, have seemed to do better in some of these trials.

A second speaker in the session described a study of probiotics to explore their effects on patients with mania. Faith Dickerson, Ph.D., M.P.H., and colleagues at Sheppard Pratt Health System in Towson, Md., randomized 66 patients admitted to the hospital for symptoms of mania. In addition to their regular psychiatric medications, half the patients also received a probiotic containing nonpathogenic anaerobic bacteria previously shown to modulate the immune system response. It was thought that use of the probiotics might change the inflammatory response in the gut to harmful antigens.

In fact, patients on the probiotic had about a 2.5-times reduction in the rate of rehospitalization in the six months after hospital discharge, said Dickerson. However, results showed no difference in the severity of psychiatric symptoms, perhaps because the monthly monitoring schedule did not capture briefer, more acute episodes mania.

Mikhail Pletnikov, M.D., Ph.D., a professor of psychiatry, neuroscience, and molecular and comparative pathobiology at Johns Hopkins University, described his initial work in mice in parallel with human trials like Dickerson’s. Gaps in the field exist, and researchers need to expand the limited neurobiological and immunological understanding and learn the mechanisms of action.

“Animal models can provide a more sensitive test system for preclinical evaluation of probiotics and for identifying the mechanisms of probiotics action,” he said.

Maybe it’s a long way from the gut to the brain, but the session hints at a start on the winding path through the immune system that may—someday—lead to a better understanding of mental illness and ways to treat it.

(Image: iStock/xubingruo)