What Is the Role of Immune Dysfunction in Schizophrenia? VA Researchers Seek to Find Out

By Annette M. Boyle

SAN ANTONIO — Can cytokines, the signaling proteins secreted by immune system cells, offer a way to prevent development of schizophrenia in susceptible individuals or keep psychosis from occurring in veterans with the disorder?

Dimitre Dimitrov, MD

Dimitre Dimitrov, MD, staff psychiatrist at the South Texas Veterans Health Care System and assistant professor at the University of Texas Science Center in San Antonio, thinks they just might.

Dimitrov and colleagues recently received a VA grant to try to identify a constellation of cytokines uniquely associated with schizophrenia.

“My goal is to identify specific cytokines active during an exacerbation of schizophrenia that correlate with psychosis. If we can identify the specific cytokines, we would have a signature of the disorder. Potentially, we would be able to prevent the occurrence of schizophrenia or its symptoms,” Dimitrov told US Medicine.

Dimitrov has been working toward this goal for years. Last fall, he and co-authors Nicole Braida, MD, chief of psychiatry services, South Texas Veterans Health Care System and Consuelo Walss-Bass, PhD, an associate professor in the department of psychiatry at the University of Texas Health Science Center, published an article in Psychiatric Times that presented evidence for immune system dysfunction in the development of schizophrenia. 

The Role of Inflammation

While the theory that inflammation plays a role in schizophrenia is far from new, recent research has provided additional evidence of the relationship, wrote Dimitrov and his colleagues in “The Link Between Immune System Dysregulation and Schizophrenia.” Among the evidence for the link is the significantly greater proportion of mononuclear macrophages present in the spinal fluid of patients with schizophrenia than in spinal fluid of controls, indicating a dysfunction in the blood-brain barrier.

When activated, these macrophages produce inflammatory cytokines. “Chronically activated macrophages, microglia, and T cells synthesize inflammatory compounds that destabilize the brain and lead to schizophrenia,” explained the authors. Positron emission tomography shows that “microglial cells — the macrophages of the brain — are activated during psychosis,” they added. Activated microglia also stimulate astrocyte production of serum S100B, a marker of inflammation in the brain that is elevated in patients with schizophrenia.

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