Genetic Mutations Cause Schizophrenia

Schizophrenia is a chronic, severe and disabling brain disorder. Exactly what causes it is unknown, but an international team of researchers has found a system of genetic mutations that may shed some light on the condition. Inherited alleles account for much of the genetic risk for schizophrenia. Researchers found that, in people with schizophrenia, genes worked in clusters to disrupt specific proteins in the brain that are linked to learning and memory. They discovered the “de novo” mutations by sequencing all the coding regions (exons) in the genome in more than 600 people with schizophrenia and their parents, looking for sequences that were not present in either parent. These mutations have a role in triggering schizophrenia. The findings are “striking,” says study co-leader Michael Owen, Dean of Research at Cardiff University School of Medicine and Director of the MRC Centre for Neuropsychiatric Genetics & Genomics, Cardiff University, because “there are now three papers implicating these post-synaptic gene sets in schizophrenia. This level of convergence is striking and unusual in schizophrenia genetics.” As for the findings’ impact on care of patients with schizophrenia, by discovering “that these mutations concentrate in genes that make proteins with particular functions in nerve cells, we hope and believe we are moving towards a knowledge of schizophrenia biology that will allow the identification of better treatments, as it has in cancer,” explains study co-author Michael O’Donovan, Deputy Director of the MRC Centre for Neuropsychiatric Genetics & Genomics, Cardiff University. “We also hope that by slowly filling up the knowledge vacuum regarding the causes of schizophrenia, we along with colleagues pursuing other important scientific endeavors will reduce the opportunity for unscrupulous or misguided people to peddle much of the nonsense about the origins of psychiatric disorder.” Approximately 1% of Americans—about 2.4 million people—have schizophrenia, but it occurs in 10% of people who have a first-degree relative with the condition. Symptoms of schizophrenia include hallucinations, paranoia and delusions. The research team will soon launch a program seeking to understand how the mutations impact brain function, particularly synaptic plasticity. Reference Fromer M, O’Donovan M, Owen M, Purcell S, et al. De novo mutations in schizophrenia implicate synaptic networks. Nature. 2014.