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

Abstract

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 D 1 and D 2 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 increase 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 ␣ Յ 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 ␣ Յ 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.

5′ UTR-region SNP in the NTRK3 gene is associated with panic disorder

“…1 Although others have reported similar associations, [6][7][8] in other cases our data have not been replicated and different genes have been associated with PG. 8,9 These results could be in agreement with the existence of different models for this polygenic disorder in such a way that different sets of genes are altered in different sets of pathological gamblers.…”

Association of the DRD2 gene Taq1A polymorphism and smoking behavior: A meta-analysis and new data

“…A total of 28 studies published between 1994 and 2007, comprising k = 34 independent samples, were identifi ed by the search strategy, met the inclusion criteria, and contributed to the metaanalysis ( Bierut et al, 2000 ;Comings et al, 1996Comings et al, , 1997Connor et al, 2007 ;Costa-Mallen et al, 2000 ;David et al, 2007 ;Erblich, Lerman, Self, Diaz, & Bovbjerg, 2004Freire, Marques, Hutz, & Bau, 2006 ;Hamajima et al, 2002 ;Johnstone, Yudkin, Griffi ths, et al, 2004 ;Lee, 2003 ;Lerman et al, 1999Lerman et al, , 2003Morton et al, 2006 ;Noble et al, 1994 ;Preuss, Zill, Koller, Bondy, & Sokya, 2007 ;Qi, Tan, Xing, Miao, & Lin, 2002 ;Robinson et al, 2006 ;Sabol et al, 1999 ;Singleton et al, 1998 ;Spitz et al, 1998 ;Swan et al, 2005 ;Timberlake et al, 2007 ;Ton et al, 2007 ;Wu, Hudmon, Detry, Chamberlain, & Spitz, 2000 ;Yoshida et al, 2001 ). Data from the present study also were included in the meta-analysis.…”

“…When studies that recruited samples of predominantly East Asian ancestry were analyzed separately ( k = 5), we found no strong evidence of association in either the fi xed-effects ( OR = 0.89, p = .23) or the random-effects ( OR = 0.86, p = .49) model. Metaregression, excluding two studies ( Comings et al, 1997 ;Wu et al, 2000 ) comprising three samples in which data were not available, indicated a positive association between effect size and proportion of male participants (Z = 3.71, p < .001), suggesting increasing effect size with increasing proportion of male participants (<50% male: k = 7, OR = 0.93, 95% CI = 0.84 -1.03, Z = 1.38, p = .17; >50% male: k = 11, OR = 1.32, 95% CI = 1.17 -1.48, Z = 4.60, p < .001; Figure 3 ). Excluding the data from the present study did not alter these results substantially.…”

The DRD2 TaqI polymorphism and symptoms of attention deficit hyperactivity disorder

“…In another study of the DRD1 and DRD2 genes, the Comings' group used a questionnaire-based measure of DSM-IV ADHD symptoms, as we do in this study. 11 Thus, they treated ADHD symptoms as a continuous trait rather than as a diagnostic category. They found that ADHD symptoms correlated positively with the A1 allele of DRD2.…”