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French Scientists Link Mutation to Sensation Seeking in Alcoholic Men

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A team of French researchers has found that a mutation in the dopamine-receptor gene DRD1 in alcoholic men is linked to a moderately increased incidence of sensation-seeking behavior.

The findings, if validated, may lead to newer categories of drugs that can better target a particularly destructive form of alcoholism.

“Substances such as alcohol that share a potential for abuse by humans also share an ability to enhance dopaminergic activity in mesolimbic mesocortical circuits, which are thought to be important for reward and reinforcement behaviors,” according to Frédéric Limosin, a psychiatrist at the Albert Chenevier Hospital in Créteil, France and corresponding author for the study. “Among the different candidate genes, those acting in the dopaminergic pathway may be specifically involved.”

To be sure, previous studies had already shown a “significant degree” of sensation-seeking behavior in male alcoholics with Cloninger’s type I disease, which generally is gender based, has an earlier age of onset than other forms of alcoholism, and is usually more severe. Now, the French team has linked a SNP in the DRD1 gene, called DdeI, that drives this behavior in these individuals.

In fact, earlier research conducted with healthy as well as alcohol-dependent men had established links between “novelty seeking” and SNPs within dopaminergic genes like DRD2, DRD4, and DAT. However, SNPS in the DRD1 gene have been shown to be less-frequently examined than other dopamine receptor genes in alcohol-dependence.

In its work, which appears in the August issue of Alcoholism: Clinical & Experimental Research, the Albert Chenevier Hospital team studied 39 alcoholic men and 33 alcoholic women admitted to a psychiatric ward for alcohol withdrawal. All participants were genotyped and scored for sensation-seeking behavior according to a widely used psychological questionnaire.

Results of the group’s findings show a “limited association” between the DdeI polymorphism of the DRD1 gene and sensation seeking among alcoholic men, the researchers said. Limosin added that these findings have three main implications for alcohol research and treatment.

“First, in view of the heterogeneous results that are often found in association studies performed in alcohol-dependent patients, it may be relevant to restrict association studies with genetic polymorphisms to more homogeneous subgroups of patients,” Limosin said in the statement. The team’s results, for example, “contribute to a better understanding of a subgroup of alcohol-dependent men who are characterized by a higher level of sensation seeking that could be explained by a genetic factor of vulnerability — namely, the DRD1 gene DdeI polymorphism.”

Second, “by focusing on the D1 dopamine receptor to improve our knowledge of the biochemical mechanisms involved in the vulnerability to alcohol-dependence, we may one day be able to develop new, highly targeted drugs,” Limosin said. “Third, it may be well worth our while to examine the impact of specific treatments, such as cognitive behavioral techniques, on subgroups of alcohol-dependent patients who have particular personality traits.”

— KL

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