The physiological component of alcoholism is defined by tolerance and/or withdrawal: the more severe the dependency on alcohol, the more severe the clinical complications, such as greater intensity and/or complications of alcohol withdrawal. A new study of polymorphisms – two or more mutually exclusive forms or alleles – within the dopamine transporter (DAT1) gene has shown that four of them are associated with withdrawal seizures.
Results are published in the January issue of Alcoholism: Clinical & Experimental Research.
“People with alcoholism continue to die because of complications related to withdrawal symptoms, mainly delirium tremens – delirium associated with visual hallucinations – and /or seizures,” said Philip Gorwood, professor of psychiatry at INSERM and corresponding author for the study. “Benzodiazepine has helped to prevent such severe complications, but there are still some patients – approximately three percent – for whom prevention is difficult because we have few cues to detect which ones are highly vulnerable. One approach is to look at the genetic vulnerability of the patient as part of a gene/environment interaction, which helps to distinguish patients who may or may not develop the phenotype, in this case the ‘storm' triggered by an acute interruption of alcohol consumption.”
Frédéric Limosin, professor of psychiatry at the University of Reims, France agrees that alcoholism must be regarded as a complex disorder arising from a combination of genetic and environmental factors.
“Alcohol can enhance dopaminergic activity in mesolimbic mesocortical circuits, thought to be important for reward and reinforcement behaviors,” he said. “Thus, among the different candidate genes, those acting in the dopaminergic pathway may be more specifically involved. Several previous studies have found an association between some polymorphisms of the DAT gene and the occurrence of withdrawal seizures in alcohol-dependent patients. Results from this study could help identify patients at high risk of developing this complication, and/or to prevent the seizures more efficiently.”
“If a marker is going to be used for clinical purpose, it is important that we use the marker that is really involved, not a neighbour which is only partially involved,” explained Gorwood. “This is why we decided to look at a large sample of patients experiencing withdrawal seizures, also seven other makers in the DAT1 gene, as well as potentially confounding factors like gender, severity of dependence, and the presence of other complications.”