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Clinical and Research News
 DOI: 10.1176/appi.pn.2014.12a3
Genes Play a Large Role in Opioid Dependence
Psychiatric News
Volume 49 Number 3 page 1

Abstract

There is reason to think that opioid dependence is at least 60 percent inherited. Now a genomewide association study appears to have led to the identification of major genes contributing to this risk.

Abstract Teaser

Some major genes that contribute to the risk for opioid dependence appear to have been identified. The genes make proteins that influence calcium signaling or potassium signaling within neurons.

The lead scientist, Joel Gelernter, M.D., a professor of psychiatry, genetics, and neurobiology at Yale University, told Psychiatric Newsthat he was surprised by this finding. He had expected genes that code for opioid receptors to turn out to be major contributors, he said. But that was not the case.

Gelernter and his coworkers conducted a genomewide association study to see whether they could significantly link any gene variants with a risk for opioid dependence. They used a relatively large sample—some 5,700 subjects (over a third with opioid dependence and the rest controls). Afterward they conducted two more studies—one with some 4,000 subjects and the other with some 2,500 ones—to see whether they could replicate their initial findings.

They were able to link variants of a number of genes with a risk for opioid dependence. But the variants that were most strongly associated with opioid dependence risk were those from genes involved in calcium or potassium signaling within neurons.

“Thus, potassium and calcium transport and signaling mechanisms seem to play essential roles in opioid-dependence risk,” Gelernter and his colleagues concluded in their paper, which was published online October 21 in Biological Psychiatry.

If this is indeed the case, then manipulating calcium or potassium signaling in neurons might lead to some novel ways of treating opioid dependence or even preventing it, they believe.

For example, “So far medical treatment for opioid dependence relies on opioidergic pathways—for example, methadone,” Gelernter said. “It may be that some of the proteins coded by genes in the pathways we identified as significant may also be good therapeutic targets.”

Interestingly, variants of a gene that makes a subunit of calcium channels in the membranes of neurons—a gene called CACNA1C—have been strongly implicated in both bipolar disorder and schizophrenia by other researchers. One of the variants may contribute to bipolar disorder by reducing neuronal activity in an area of the brain involved in the processing of facial emotions (Psychiatric News,October 15). Therefore, variants of genes that cause calcium channels and calcium signaling within neurons to malfunction might pose a genetic vulnerability to not only opioid dependence, but also to some other psychiatric illnesses, Gelernter and his team proposed. ■

An abstract of “Genomewide Association Study of Opioid Dependence: Multiple Associations Mapped to Calcium and Potassium Pathways” is posted at www.biologicalpsychiatryjournal.com/article/S0006-3223(13)00826-3/abstract

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