The findings of a recent study could potentially lead to new ways to predict risk for depression and treatments for the disease, using genome-wide association studies.
Major depression is one of the most common mental disorders in the U.S., according to the National Institute of Mental Health. In 2012, an estimated 16 million adults in the U.S. aged 18 or older had at least one major depressive episode in the past year, representing almost 7 percent of the population. “This report shows for the first time that genome-wide association studies – a method that has found risk genes from many important complex human disorders – can work for major depression,” said joint-senior author Kenneth S. Kendler, M.D., professor of psychiatry and human and molecular genetics at Virginia Commonwealth University School of Medicine. “With these genome-wide studies, as you identify more markers your ability to identify specific biological pathways to illness substantially improves.”
Prior studies have failed to identify replicated evidence for molecular genetic markers that predispose to risk for the disease. The new research suggested that an enzyme from a strain of DNA and a gene called SIRT1, a protein that gives energy to mitochondria, have a direct influence on depression. The research team speculated that the cause of depression might be the abnormal activity of SIRT1 in mitochondria and the DNA's enzyme effect on the human body. Scientists still do not fully understand how the enzyme functions in influencing the behavior of the SIRT1 gene with regard to mitochondria in order to cause depression when there are not enough genetic banks.
Kendler attributes the research’s success to the carefully designed study sample, which consisted of 5,303 Chinese women with recurrent major depression from 58 hospitals throughout China and 5,337 Chinese women in the control group. The study was limited to women because about 45 percent of the genetic liability to major depressive disorder is not shared between sexes. The women with depression in the study had to be at least 30 years old; have had two episodes of major depression; had no history of alcohol or drug abuse, bipolar illness, or psychosis; and have had all four grandparents of Han Chinese descent.
“It is likely that our study was successful because the patients we studied were relatively homogenous and severely ill,” Kendler said.
Citation: CONVERGE consortium, 'Sparse whole-genome sequencing identifies two loci for major depressive disorder', Nature 15 July 2015 doi:10.1038/nature14659