Influence of the dopamine D2 receptor (DRD2) exon 8 genotype on efficacy of tiapride and clinical outcome of alcohol withdrawal

Abstract

We tested the hypothesis that allelic variants of the human dopamine D2 receptor E8 genotype are associated with (i) dopamine D2 antagonist tiapride dose in treatment of alcohol withdrawal (n = 50) and (ii) with anxiety and depression in patients during alcoholism detoxification therapy (admission n = 87; discharge n = 50). DRD2 E8 A/A genotype was associated with increased dose of tiapride during a 9-day detoxification therapy and with increased anxiety and depression scores on admission and 2 weeks later. The findings suggest a pharmacogenetic influence of DRD2 E8 genotype on tiapride efficacy in alcohol withdrawal. In an earlier report, DRD2 E8 A/A genotype was associated with reduced responsiveness to the dopamine D2 agonist apomorphine; however, it is not clear whether both findings share the same biological basis. Earlier findings concerning association of DRD2 E8 A/A with increased anxiety and depression are replicated for the first time.

Alcohol Consumption Is Associated with an Interaction between <i>DRD2</i> Exon 8 A/A Genotype and Self-Directedness in Males

“…Non-translated regions of mammalian genes are known for their influences in transcript half-life and preand posttranscriptional regulation. Furthermore, 2 pharmacogenetic results concerning an association of DRD2 (E8) A/A with alcohol-related phenotypes have been reported very similarly by Finckh et al [15] and our group [16] , so there is independent evidence to support the role of DRD2 (E8) with regard to our hypothesis.…”

“…Consumption in a typical week as dependent variable was tested in a 5-factorial analysis of variance (ANOVA) for between group differences with the following groups: (a) DRD2 (E8) genotypes A/A vs. A/G and G/G as described previously [16,36] ; (b) high vs. low SDD scores; (c) alcohol diagnosis versus no alcohol diagnosis, and (d) nicotine dependence. Alcohol dependence/ abuse diagnoses and smoking [12] are important factors for consumption levels.…”

“…The DRD2 (E8) A/A genotype has previously been shown to be associated with various alcoholism-related phenotypes which point to a reduced postsynaptic D 2 function or availability [15][16][17] , which in turn has been associated with higher alcohol consumption and consumption-related traits in both animal and human studies. Our results are also consistent with findings of higher consumption levels for the DRD2 (E8) A/A genotype in the male subgroup on a trend level [15] .…”

“…Finckh et al [15] reported an association between DRD2 (E8) A/A genotype and increased daily alcohol intake in male alcohol detoxification patients; however, the results only reflected a trend (p = 0.11), possibly due to lack of power (n = 75). The DRD2 (E8) A/A genotype has not only been found to be associated with reduced GH response to the D 2 receptor agonist apomorphine [15] ; the A/A genotype was associated with a higher D 2 antagonist tiapride dose demand in patients undergoing alcohol detoxification [16] . Thus, 2 similar studies indicate that DRD2 (E8) A/A might be associated with reduced D 2 function [17] .…”

The Use of a Symptom Checklist (SCL-90-R) as an Easy Method to Estimate the Relapse Risk after Alcoholism Detoxification

“…There is evidence that depression and anxiety symptoms in alcohol withdrawal reflect a mixture of various physiological states and traits involving at least partly the dopaminergic system. In two genetic studies by Finckh et al [12] and our own group [13] examining this subject, depression and anxiety scores during detoxification were associated with variants of the dopamine 2 receptor gene (DRD2 exon 8). In our study, the SCL-90-R was used.…”