Scientists have made a breakthrough in the study of the molecular mechanisms of schizophrenia pathogenesis, with findings published in the Oct. 10 issue of the Journal of Neuroscience. The discovery may lead researchers to develop new treatment options for schizophrenia. Features of schizophrenia include hallucinations and deterioration of learning and memory abilities, and these symptoms usually appear in late adolescence or early adulthood. Efforts to identify the causes of the disorder are complex, as research has not confirmed that any single genetic mutation is strongly associated with the disorder. But recently, Dr. Laurie Earls and his colleagues at St. Jude Children’s Research Hospital found that 22q11 deletion leads to an increased risk of schizophrenia by studying a rare genetic disorder called 22q11 deletion syndrome. Approximately 30 percent of people with 22q11 deletion syndrome will develop schizophrenia, and 22q11 deletion syndrome is one of the strongest risk factors for schizophrenia disorders. In previous studies of 22q11-deficient mice, the Zakharenko research group found that nerve cells undergo changes in the function of the brain’s hippocampal learning and memory centers, with progressive loss of function with age. In this new study, the scientists confirmed that similar molecular changes are present in patients with schizophrenia, so they focused on the genes that promote changes in nerve cell function. In previous studies, the Zakharenko research group found that abnormal communication between nerve cells and cognitive dysfunction were associated with elevated levels of proteins that regulate calcium levels in certain Serca2 nerve cells. The above abnormalities were only detectable in 22q11-deficient mice over the course of their lives as they aged. In the current study, researchers found that changes in the gene Dgcr8 could explain the mechanism by which Dgcr8 produces the small molecules of RNA that keep Serca2 neuronal cells normal. In the absence of Dgcr8, proteins that regulate calcium levels in Serca2 neurons are elevated. By adding these gene Dgcr8 molecules to the hippocampal gyrus of animals with 22q11 deletion, the researchers were able to restore Serca2 function and reduce the genetic defect. The researchers also analyzed autopsy reports of brain tissue from schizophrenia patients and found that Serca2 function was also abnormal in schizophrenia patients without 22q11 deletion. zakharenko believes these data suggest that Serca2 may be a new therapeutic target for schizophrenia.