The Role of Pathogen Exposure

Macrophages often secrete cytokines in response to exposure to pathogens. Certain cytokines are elevated in patients with schizophrenia, indicating a role for infectious agents in development or triggering of the disorder. The authors note that pathogens might affect in utero development of the immune system, contributing to the etiology of schizophrenia. As evidence, children whose mothers contracted influenza while pregnant have a three-fold increase in risk of having schizophrenia. Maternal infection with rubella, varicella zoster, herpes and other viruses also has been associated with the development of schizophrenia.

Increases in cytokines caused by exposure to pathogens prenatally or in early childhood, particularly, may affect development of the brain and increase the risk of schizophrenia. Even later infection may contribute to development of the disorder. Mumps, meningitis, hepatitis C and toxoplasmosis in childhood or as an adult have all been implicated in schizophrenia.

In addition, some immune system genes that appear to have a role in schizophrenia also regulate the life cycle of several pathogens. “Understanding the interplay between gene function and pathogen exposure may help explain the role of gene-environment interactions in schizophrenia development,” noted the authors.

Recent studies have demonstrated an association between development of schizophrenia and specific variants of immune system genes. Pathogen exposure during early neurodevelopment may cause mutations that make individuals more susceptible to the disorder, while exposure later in life could determine the expression and severity of the symptoms.

Some pathogens might trigger symptoms by interfering with the function of neurotransmitters. “A number of viruses use the same receptors as are used for dopamine and can lead to psychosis,” Dimitrov said. Changes in the dopaminergic system have long been considered significant in the development of schizophrenia.

“The dopamine theory explains some symptoms of schizophrenia,” Dimitrov said. “The glutamatergic, abnormal immune function and neurodevelopmental theories explain some, too. I’m inclined to find something common to put it all together. The metabolism of tryptophan, which is affected by pro-inflammatory cytokines, could have an effect on a lot of receptors and explain many of the changes that occur. Maybe the theories are not mutually exclusive.”