VCU researchers identify gene with schizophrenia tie

By Lorraine Cichowski and Kenneth Kendler

RICHMOND, Va. – An international team of researchers led by Virginia Commonwealth University has identified a gene located in the middle of the short arm of Chromosome 6 that appears to be strongly associated with schizophrenia and related mental disorders.

The discovery, reported today in the online edition of The American Journal of Human Genetics, www.journals.uchicago.edu/AJHG/journal/, is the most significant finding to emerge so far in the 20-year study for the molecular causes of this debilitating, yet little understood, disease that affects as much as 1% of the adult population with hallucinations, delusions and other symptoms and is considered highly inheritable. About 24 million people worldwide have schizophrenia, according to the World Health Organization.

"We’re potentially at a turning point and could have a result that is important in unlocking some of the secrets of this tragic disease," said psychiatric geneticist Dr. Kenneth S. Kendler, co-director of the Virginia Institute for Psychiatric and Behavioral Genetics at VCU and founder and coordinator of the overall study. "Much more work is needed to confirm and extend our findings, but we’re cautiously optimistic that one or more variants in the dysbindin gene influence susceptibility to schizophrenia. This gene deserves more study."

The collaborative team assembled by Dr. Kendler, which included psychiatrists and geneticists from VCU, Queens University in Belfast, Northern Ireland, and the Health Research Board in Dublin, Ireland, studied 270 families in Ireland with at least two schizophrenic members each and genotyped 1,425 individuals. The study, which was funded by grants from the National Institute of Mental Health (NIMH), found strong associations between schizophrenia and related disorders and genetic markers in a gene called dysbindin, which is located on the "p," or short arm, of Chromosome 6.

"Dysbindin is the first schizophrenia gene to be identified using only the positional cloning, or linkage disequilibrium, approach. Given its probable synaptic location in the brain, one can easily imagine how defects in dysbindin might affect the efficiency of neurotransmitter signaling," said Dr. Richard E. Straub, a former VCU researcher who led the molecular team that produced the dysbindin finding. Dr. Straub is now with the Clinical Brain Disorders Branch of the NIMH in Bethesda, MD.

While multiple genetic factors have long been considered important in the causation of schizophrenia, researchers have been unable so far to identify specific genes that cause the disease. Some studies have produced evidence that linked specific genes to the disease, but not all of these results have been consistently replicated. As recently as April, an international, multi-research-institute effort to which Kendler and colleagues contributed reported that it had failed to replicate results from a study done in Canada in 2000 that had found promising evidence of a schizophrenia gene on the "q," or long arm, of Chromosome 1.

At least one international team already is at work on replicating the VCU results about the dysbindin gene on Chromosome 6. The team of investigators at the Virginia Institute for Psychiatric and Behavioral Genetics are continuing its research on this gene, looking for further mutations that might directly contribute to schizophrenia.

About VCU: Virginia Commonwealth University is ranked by the Carnegie Foundation as one of the nation’s top research universities. Located on two campuses in Richmond, Va., VCU enrolls about 25,000 students in more than 160 undergraduate, graduate, professional, doctoral and post-graduate certificate degree programs at 11 schools and one college. Sixteen graduate and professional programs have been ranked by U.S. News & World Reports as among the best of their kind in the nation. The VCU Health System is one of the leading academic medical centers in the country. VCU recently launched VCU Life Sciences, a comprehensive undergraduate and graduate program involving academic and medical faculty. In addition, the university is developing the Virginia Biotechnology Research Park in collaboration with business, civic and government leaders. For more, see http://www.vcu.edu/. The Virginia Institute for Psychiatric and Behavioral Genetics is located at the Biotech Park. The institute is a multi-disciplined, integrated research program of VCU’s departments of psychiatry and human genetics, focused on identifying genes and environments that cause psychiatric diseases and behavioral differences. For more, see http://www.vipbg.vcu.edu/.