Does substance abuse cause depression, or does depression cause substance abuse? A study involving laboratory animals suggests that substance abuse could cause mood disorders, such as depression. Previous research indicates that the converse could be true -- i.e., that mood disorders cause substance abuse. About 20% or one in five American adults has a mental disorder, according to government estimates, and this group is more vulnerable to substance abuse and alcoholism. An article in the Journal of the American Medical Association reported that about half are affected by substance abuse, which means that 53% of drug abusers and 37% of alcoholics have a serious mental illness. Among those with bipolar disorders, 57% are also substance abusers, according to data from the Epidemiologic Catchment Area Survey. Those who have suffered a depressive episode within the past year are almost three times more likely to abuse alcohol, according to the U.S. Department of Health and Human Services. When people enter treatment for substance abuse, the mental illness has to be treated as a separate medical issue distinct from addiction. For this latest study, Dr. Eric Nestler and his colleagues at the Mount Sinai School of Medicine studied the effects of cocaine on the brains of mice. They found that cocaine use increased the animals' vulnerability to stress by causing changes in their brains. It was already known that histone methylation is associated with depression, and this new research found that cocaine use changed the levels of H3 lysine 9 dimethylation in a major reward center in the brains of the mice. Methylation of histones turns on the genes in DNA, and demethylation of histones turns them off. These processes are related to developing depression and stress-related disorders. "Our results provide fundamentally novel insight into how prior exposure to a drug of abuse enhances vulnerability to depression and other stress-related disorders," Dr. Nestler said. "Identifying such common regulatory mechanisms may aid in the development of new therapies for addiction and depression." This study appears in the journal Neuron.