A new analysis suggests that schizophrenia may be caused by an interaction of genes and viruses in glia cells

A report in the open access journal BMC Psychiatry presents a new hypothesis that may explain the causes of the psychiatric disease, schizophrenia. The hypothesis hinges on glia, a special type of cell, which is important for the maintenance of the connections between brain cells. By re-examining previously published research the authors suggest that schizophrenia may be caused by a combination of defective genes, which result in deficiencies of a variety of growth factors in glia, and infection by viruses, which may further weaken the glia. They conclude that this “weakening” of glia may result in the breakdown of connections between different brain cells leading to the development of schizophrenia.

Schizophrenia is a severe disabling psychiatric disease, which affects approximately 1 percent of the population. People with schizophrenia often suffer terrifying symptoms such as hearing internal voices, feelings of extreme paranoia and an inability to distinguish reality from fantasy. It is clear that schizophrenia has a strong genetic component, however analysis of individual genes alone will not give us a full understanding the causes of schizophrenia.

Irving Gottesman, one of the authors of this paper and originator of the now widely accepted polygenic model of schizophrenia explains,

“The investigation of individual genes in isolation has its limitations since virtually all important biological phenomena, from normal brain functioning to schizophrenia, are the result of complex systems. What is needed is a systems approach for understanding the development of schizophrenia.”

This insight motivated Gottesman, and his colleagues Hans Moises and Tomas Zoega, to apply such an approach to previously published results of schizophrenia research.

Human brains are made up of two main types of cells, nerve cells, which carry electrical impulses around the brain and glia, which are important for the normal development of the brain in the young and the maintenance of nerve connections in adults. The authors argue that many of the genes implicated in the development of schizophrenia code for factors involved in the development of glia cells. In addition they hypothesize that some viral infections may cause additional weakening of glial cells, which in turn may lead to the disruption of brain cell connections and the development of schizophrenia.

“Epidemiological data indicate that all humans must harbor viruses in the glial cells of their brains, and since reproduction is a necessity for these viruses to survive, it seems reasonable to presume that they are reproducing at low levels in glial cells and that this results in an additional weakening of glial functioning”, explains Moises.

This new provocative hypothesis bridges the gap between several previously unrelated schizophrenia hypotheses, most notably the genetic, the neurodevelopmental and the virus hypotheses, thereby providing a unifying explanation for the development of schizophrenia. It is hoped that by testing this hypothesis in the laboratory, researchers will come up with new ways of treating this debilitating brain disease.

The new hypothesis is freely available in the peer-reviewed open access journal BMC Psychiatry

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