Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn

RCSI Researchers Discover Clues to New Pathways for Treatment of Schizophrenia

03 October 2014
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. Melanie Föcking, Ph.D. & RCSI Lecturer in Psychiatric Neuroscience led the first research to identify specific PSD-associated genes and proteins linked to schizophrenia. The study was published in the journal Molecular Psychiatry.

The research team examined a brain region known to play a role in schizophrenia and the research team utilised 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 provides clues to new pathways as targets for new treatments.”

Dr Melanie Focking was supported by a 2012 NARSAD Young Investigator Grant and by the Health Research Board. Prof David Cotter from the Department of Psychiatry, RCSI was the senior author and Health Research Board grant PI and Dr Gerard Cagney from Conway Institute of Biomolecular and Biomedical Research, University College Dublin was also a senior author on the paper.

Additional authors on the paper were Dr Lorna Lopez, Dr Jane English, Annemarie Wolff, Elizabeth Brindley, and Mr Patrick Dicker, Department of Epidemiology and Public Health, RCSI; and and Kieran Wynne, Conway Institute of Biomolecular and Biomedical Research, University College Dublin.