An international team of scientists has identified a gene mutation strongly linked to schizophrenia.They say that variations in the VIPR2 gene increases signaling in the vasoactive intestinal peptide pathway, which can be controlled by synthetic peptides, but therapeutic effect of these compounds are yet to be determined.
Details of the study are reported in “Duplications of the neuropeptide receptor gene VIPR2 confer significant risk for schizophrenia,” published in the February 23 online issue of Nature.
Over the past three years researchers discovered that copy number variants (CNVs) at many locations in the human genome resulted in significantly higher risk of schizophrenia. Those findings were the first conclusive evidence that rare mutations can cause schizophrenia but did not identify specific genes involved.
In the latest study, led by Jonathan Sebat, Ph.D., assistant professor of psychiatry and cellular and molecular medicine at the University of California, San Diego School of Medicine, researchers scanned for CNVs in the genomes of 8,290 individuals with diagnosed cases of schizophrenia and 7,431 healthy controls.
The study confirmed CNVs identified in earlier studies but also found that duplications at the tip of chromosome 7q were detected in individuals with schizophrenia at a rate 14 times higher than in healthy individuals. The duplications impact a gene coding for the vasoactive intestinal peptide receptor 2 (VIPR2), expressed in the nervous system including in the brain as well as blood vessels and the gastrointestinal tract.
Previous studies showed that VIPR2 helps to regulate the formation and activity of neurons in the brain. In mice, VIPR2 also has been found to play important roles in behavioral processes like learning and timing of daily activity.
The study next measured expression of the VIPR2 gene in blood cells from patients, finding that individuals with mutations had greater expression of VIPR2 and greater activity of the receptor. "This suggests that the mutations increase signaling in the vasoactive intestinal peptide pathway," explains Aiden Corvin, Ph.D., of the psychosis research group at Trinity College Dublin and co-author on the study.
"We know that this activity can be modulated by synthetic peptides and the next step is to see if these compounds have a therapeutic effect in mice or in cultured human cells that carry the VIPR2 gene mutation."
The psychosis research group was involved in study design, analysis, and data interpretation. Irish patients and their families from Trinity teaching hospitals contributed to the original test sample of 802 cases and 742 controls along with participants from Columbia University, Harvard, NYU, McLean, and University of Washington medical teaching hospitals.