SAN DIEGO – Researchers are looking at the potential role that autoimmune reactions, such as inflammation, play in the pathogenesis of schizophrenia, both with and without comorbid substance use.
“What we see is evidence of autoimmune involvement through the lifespan in schizophrenia,” explained Brian Miller, MD, PhD, of the department of psychiatry at Augusta (Georgia) University. “We know there is a bidirectional association between schizophrenia and autoimmune disorders, [where] starting with either increases the chances of the other occurring comorbidly.”
Previous studies have shown that adding anti-inflammatory agents to second-generation antipsychotics has been associated with greater symptomatic improvement in schizophrenia than with second-generation antipsychotics alone. Now, Dr. Miller and his colleagues are conducting a randomized, controlled study using the systemic immunotherapy siltuximab to see if adjunct anti-inflammatory treatments can improve cognition in schizophrenia. They are using the monoclonal antibody instead of nonsteroidal anti-inflammatory drugs because of its precise ability to target specific autoimmune pathways, according to Dr. Miller.
In addition, Dr. Miller and his colleagues conducted a post-hoc analysis of data from the CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness) study to determine if there was a difference between those patients with comorbid substance in schizophrenia, compared with those without. He and his coinvestigators found in a post-hoc analysis that the higher the level of certain inflammatory markers, the higher the Positive and Negative Syndrome Scale (PANSS) psychopathology score in people who’d tested positive for marijuana use at baseline.
The results, he said, beg the question about whether trial inclusion criteria for schizophrenia research need revisiting.
“What we really need to do is investigate, in a well-controlled, well-designed, prospective sample of patients who have this substance use comorbidity, [whether] we see alterations in these immune markers, and then how they vary over the course of illness,” Dr. Miller explained in a video interview at the International Congress on Schizophrenia Research. “It’s an important selection bias that as a field we’ve ignored. Maybe that’s a population that is enriched for some kind of immune dysfunction that might be targeted by some kind of anti-inflammatory or other immunotherapy strategy.”
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