As one of the leaders of an international research consortium, Mount Sinai School of Medicine researchers have discovered that several common genetic variants contribute to a person's risk of schizophrenia and bipolar disorder, or manic-depressive illness. Two just-released studies provide new evidence that 11 genomic regions have a strong correlation with mental illness, including six areas not previously discovered. The researchers also found that some of these DNA variations contribute to both diseases.
The findings provide fresh insight into the causes of these diseases and may lead to new, more effective treatment options. The data are published in the September 18 issue of Nature Genetics.
"Schizophrenia and bipolar disorder are debilitating illnesses affecting millions of people around the world, and existing therapies for these people are ineffective as long-term options," said Pamela Sklar, MD, PhD, Chief of the Division of Psychiatric Genomics in the Department of Psychiatry and Professor of Psychiatry at Mount Sinai School of Medicine and lead author on the bipolar study. "We have been hard at work trying to determine genetic risk for these diseases so that we can intervene earlier and develop new therapies with which to treat them. Through this research, we are an important step closer to making that possible."
In the first study, the investigators used the DNA of 7,481 individuals with bipolar disorder and 9,250 healthy individuals to look at millions of DNA sites that are known to have different genetic sequences. In the second study, another team evaluated the same DNA sites in more than 17,000 people with schizophrenia. In these two genome-wide association studies, the scientists found several of these DNA sites – also known as DNA variants, or SNPs – in different genes and pathways showed strong association evidence with the diseases, some with bipolar disorder, some with schizophrenia, and some with both.
"Until recently, psychiatric research has understood the genetic basis of mental illness only very poorly," said Shaun Purcell, MD, Associate Professor of Psychiatry at Mount Sinai School of Medicine and co-author with Dr. Sklar on the schizophrenia study. "Our research has helped us begin to elucidate the genetic structure of bipolar disorder and schizophrenia, and will, we hope, provide a new foundation to build upon in improving treatments and the quality of life of these patients."
Schizophrenia and bipolar disorder are common and often devastating brain disorders. Some of the most prominent symptoms in schizophrenia are persistent delusions, hallucinations, and cognitive problems. Bipolar disorder is characterized by episodes of severe mood problems including mania and depression. Both affect about one percent of the world's population and usually strike in late adolescence or early adulthood.
Despite the availability of treatments, these illnesses are usually chronic, and response to treatment is often incomplete, leading to prolonged disability and personal suffering. Family history, which reflects genetic inheritance, is a strong risk factor for both schizophrenia and bipolar disorder, and it has generally been assumed that dozens of genes, along with environmental factors, contribute to disease risk.
"This research represents a significant step forward in understanding the genetic risk factors behind mental illness, paving the way for a new era in psychiatry," said Dennis S. Charney, MD, Anne and Joel Ehrenkranz Dean of Mount Sinai School of Medicine and the Executive Vice President for Academic Affairs of The Mount Sinai Medical Center. "Mount Sinai has a long history of psychiatric research dating back more than 100 years, and psychiatric genomics is emerging as an increasingly critical area for earlier intervention and better treatments for these diseases. We are pleased to be leading the charge in this area."
Source: The Mount Sinai Hospital / Mount Sinai School of Medicine