The genetic complexities of sensation-seeking behavior in alcoholic men

August 14, 2003

Previous research has found a significant degree of sensation-seeking behavior in male patients with a particular subtype of alcoholism called Cloninger's type I. A study in the August issue of Alcoholism: Clinical & Experimental Research has found for the first time an association between the DdeI polymorphism of the D1 dopamine receptor (DRD1) gene and sensation seeking among alcoholic men.

"Alcohol-dependence is a clinically heterogeneous disorder that arises from a combination of genetic and environmental biopsychological factors," said Frédéric Limosin, a psychiatrist at the Albert Chenevier Hospital in Créteil, France and corresponding author for the study. "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. Among the different candidate genes, those acting in the dopaminergic pathway may be specifically involved."

Environmental factors may include personality characteristics such as impulsiveness or sensation seeking. "Experimental studies on animals have demonstrated that behavioral characteristics such as impulsivity, excessive or deficient behavioral inhibition, and a larger tendency to explore, may predict genetically determined excessive alcohol consumption in animals," said Limosin.

Previous studies of both healthy subjects and alcohol-dependent patients have found associations between novelty seeking and polymorphisms of dopaminergic genes such as DRD2, DRD4, and DAT. Polymorphisms of the D1 receptor (DRD1) gene, however, have been much less examined in alcohol-dependence than other dopamine receptor genes.

For this study, participants comprised 72 alcoholic inpatients (39 men, 33 women) admitted to a psychiatric ward for alcohol withdrawal. All participants were assessed according to Diagnostic and Statistical Manual of Mental Disorders III - Revised criteria, genotyped using standard methods, and scored for sensation-seeking behavior according to the Zuckerman scale (a 34-item self-report questionnaire designed to assess sensation seeking by focussing on four components, disinhibition, thrill seeking, novelty seeking and boredom susceptibility). Patients completed the Zuckerman scale at least one week after beginning the alcohol-withdrawal process.

Results indicate a limited association between the DdeI polymorphism of the DRD1 gene and sensation seeking among alcoholic males. "An essential part of our results is that the association revealed is limited to male subjects," said Limosin. "This is in accordance with Cloninger's biopsychological typology which describes type I alcoholism as sex-specific, characterized by an earlier age at onset, a more severe course, with more social and somatic complications, more frequent paternal previous history of antisocial behaviors, and a personality profile with high levels of sensation seeking, and low levels of harm avoidance and reward dependence."

Limosin added that these findings have three main implications for alcohol research and treatment.

"First," he said, "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. Our 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, he added, "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. 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."

Limosin said he plans to continue searching for associations between genetic polymorphisms and personality traits, such as temperament dimensions, among alcoholics. "I think this is a particularly promising area of research," he said, "because we know that personality dimensions are highly involved in the vulnerability to alcoholism. We're just not sure to what degree they are involved."
Alcoholism: Clinical & Experimental Research (ACER) is the official journal of the Research Society on Alcoholism and the International Society for Biomedical Research on Alcoholism. Co-authors of the ACER paper included: Jean-Yves Loze and Frédéric Rouillon of the Department of Psychiatry at Albert Chenevier Hospital; and Jean Adès and Philip Gorwood of the Department of Psychiatry at Louis Mourier Hospital, and CNRS UMR, France. The study was funded by AP-HP.

Alcoholism: Clinical & Experimental Research

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