Gene variants increase risk of cocaine-induced paranoia

Yale scientists and colleagues at Boston University School of Medicine and the University of Connecticut have discovered genetic variants that increase the risk of paranoia in cocaine addicts and also seem to affect risk for cocaine dependence itself, although most of the molecular culprits that make some people more susceptible to cocaine dependence remain elusive.

In a study of almost 4,000 subjects of European or African descent published in the March edition of the Archives of General Psychiatry, the Yale researchers looked closely at an area of the genome that they had previously shown to be associated with cocaine dependence and cocaine-induced paranoia, a symptom common among many addicts.

Adoption, twin and family studies have shown that cocaine dependence has a strong genetic component. Scientists, including the Yale group, have previously shown that numerous individual gene variants confer increased risk of addiction to a range of abusable substances.

Yale researchers did a genetic analysis of 11 variants of the a-endomannosidase, or MANEA gene, which metabolises complex carbohydrates and which previously had been implicated in the researchers’ low-density genome-wide association study of drug dependence. Nine of the variants were linked to cocaine-induced paranoia among African Americans while six such variants were found among European Americans. Variants located in this area of the genome were also associated with cocaine dependence, but much less strongly than with cocaine-induced paranoia.

"We feel that these findings are of great interest because of the novelty of the physiological pathway involved," says Dr Joel Gelernter, professor of psychiatry, genetics and neurobiology, and director of the Division of Human Genetics in Psychiatry at the Yale University School of Medicine.

"This is one of the great advantages of taking a genome-wide approach to discovery of risk variants for complex traits like cocaine-induced paranoia – you can learn about mechanisms that you would probably have never considered beforehand," he adds. "This will open a new line of inquiry into the physiology of cocaine-induced paranoia, and possibly into symptoms of paranoia more generally."

The lead author on the study was Lindsay A. Farrer of Boston University.

The work was funded by the National Institutes of Health.

(Source: Yale University: Archives of General Psychiatry: June 2009)