In the brain’s communication system, nerve cells transmit messages across the synapse, the minute gap between cells. On the receiving end, the postsynaptic density (PSD) is a network of proteins suspected of playing a role in causing psychosis and mood disorders. Supported by a 2012 NARSAD Young Investigator Grant, Melanie Föcking, Ph.D., of the Royal College of Surgeons in Ireland, led the first research to identify specific PSD-associated genes and proteins linked to schizophrenia. The study was published on July 22nd in the journal Molecular Psychiatry.
To conduct the study, the research team, which included 2007 NARSAD Independent Investigator Grantee David R. Cotter, M.D., Ph.D., of the Royal College of Surgeons in Ireland, examined postmortem tissue samples of the anterior cingulate cortex—a brain region known to play a role in schizophrenia—taken from the brains of 20 people with schizophrenia and 20 healthy controls. The research took advantage of recent technological advances in genomics, the study of the entire genome, and proteomics, the large-scale study of proteins. Proteomic methods have greatly enhanced scientists’ ability to identify and quantify disease-associated protein changes from specific genes.
The investigation uncovered more than 700 proteins within the PSD, of which 143 were altered in the schizophrenia samples compared to the control samples. Among those 143, the team pinpointed a small subset as being clearly associated with the pathophysiology of schizophrenia, and then went on to identify the critical cellular processes in which these proteins are involved. Their findings were confirmed by information from other laboratories.
“This is the first study to characterize the differential protein expression within the PSD in schizophrenia,” reports Dr. Föcking. “We also provide data implicating PSD-associated genes in schizophrenia. Together the data provide robust complementary evidence implicating the PSD in schizophrenia and providing clues to new pathways as targets for new treatments.”