Genetic trait triples odds of cocaine abuse

By Will Parker on December 22, 2010 in News

Twenty-percent of Caucasians appear to carry a genetic variant that substantially increases their odds of being susceptible to severe cocaine abuse leading to fatal overdosing, say researchers at Ohio State University. The new study, published in Neuropsychopharmacology, notes that only one-in-eight African Americans are affected by the variant.

The variant, characterized by one or both of two tiny gene mutations, alters the brain’s response to specific chemical signals. Among whites, one or both mutations were found in more than 40 percent of autopsy brain samples taken from people who had abused cocaine, compared to 19 percent of samples from people who lived drug-free.

The mutations – either alone or in combination – affect how dopamine modulates brain activity. Previous research has established that cocaine blocks dopamine transporters from absorbing dopamine after its release, leaving the chemical outside the brain cells and creating a feeling of euphoria.

In people who carry one or both of the mutations, the function of a gene responsible for transmitting dopamine signals in the brain is altered. Lead researcher Wolfgang Sadee speculates that this altered gene function sets up a vicious circle of chemical signals that could lead to a craving for a substance that can maintain elevated levels of dopamine in the brain.

“We now have both good biological rationale and clinical association showing that this has an impact on the way cocaine abuse might progress or might be initiated,” said Sadee. “We have found a frequent variant in one of the key candidate genes that can affect cocaine abuse, but more importantly, it also opens the avenue to explore how this variant affects response to therapies for a variety of psychiatric disorders that involve dopamine.”

Interestingly, the dopamine receptor D2 that is implicated in this study is also a primary target for nearly all antipsychotic drugs. Sadee speculates that the cocaine abuse gene variants might affect carriers’ response to pharmaceutical drugs as well. “We now have found that this gene contains frequent variants that affect some fundamental behavior. In some psychiatric disorders there are treatments that depend on the dopaminergic system, and only 50 percent are effective. So now the question becomes, would these [variants] together with another gene, predict whether or not somebody responds to these treatments or becomes worse?”