Studies of the potential role of the dopamine D1 receptor gene in addictive behaviors.

Abnormalities in the dopaminergic reward pathways have frequently been implicated in substance abuse and addictive behaviors. Recent studies by Self and coworkers have suggested an important interaction between the dopamine D1 and D2 receptors in cocaine abuse. To test the hypothesis that the DRD1 gene might play a role in addictive behaviors we examined the alleles of the Dde I polymorphism in three independent groups of subjects with varying types of compulsive, addictive behaviors-Tourette syndrome probands, smokers and pathological gamblers. In all three groups there was a significant in the frequency of homozygosity for the DRD1 Dde I 1 or 2 alleles in subjects with addictive behaviors. The DRD1 11 or 22 genotype was present in 41.3% of 63 controls and 57.3% of 227 TS probands (P = 0.024). When 23 quantitative traits were examined by ANOVA those carrying the 11 genotype consistently had the highest scores. Based on these results, we examined the prevalence of the 11 genotype in controls, TS probands without a specific behavior, and TS probands with a specific behavior. There was a progressive, linear increase, significant at alpha < or = 0.005 for scores for gambling, alcohol use and compulsive shopping. Problems with three additional behaviors, drug use, compulsive eating and smoking were significant at alpha < or = 0.05. All six variables were related to addictive behaviors. In a totally separate group of controls and individuals attending a smoking cessation clinic, and smoking at least one pack per day, 39.3% of the controls versus 66.1% of the smokers carried the 11 or 22 genotype (P = 0.0002). In a third independent group of pathological gamblers, 55.8% carried the 11 or 22 genotype (P = 0.009 vs the combined controls). In the TS group and smokers there was a significant additive effect of the DRD1 and DRD2 genes. The results for both the DRD1 and DRD2 genes, which have opposing effects on cyclic AMP, were consistent with negative and positive heterosis, respectively. These results support a role for genetic variants of the DRD1 gene in some addictive behaviors, and an interaction of genetic variants at the DRD1 and DRD2 genes.

Pathological gambling among methadone patients.

This paper examines the correlates of problem gambling among a population of 220 methadone patients receiving treatment in the New York metropolitan area. Like most methadone patients, respondents were primarily adult males, ethnically mixed, of limited educational accomplishment and had long experiences with intravenous drug use. More than two-thirds of subjects had been convicted of one or more criminal offences. Analysis of the data showed seven percent of respondents to be probable pathological gamblers according to the South Oaks Gambling Screen (SOGS), indicating a high rate of gambling problems among this treatment population. Consistent with past studies, problem gamblers are more likely to be men, with histories of alcohol abuse, and with extensive criminal participation dating back to their teenage years. The data also suggested that problem gamblers who were also drug dependent were more likely to show greater evidence of social dysfunctionality compared to those who were exclusively substance abusers. More dually addicted respondents reported higher levels of recent heroin use, greater unemployment, and more reported hallucinations. Probable pathological gamblers who were substance abusers were also more likely to report being in conflict with their close friends. A multiple regression analysis suggested this to be the closest linked correlate to being a pathological gambler. Evidently, pathological gamblers create antipathy towards themselves as their compulsion to gamble is expressed; this in turn, may drive them toward further gambling, as they respond to this perceived opposition. These last preliminary findings will require further confirmation in future research.