Dopamine Receptor DRD2 Gene rs1076560, Personality Traits and Anxiety in the Polysubstance Use Disorder

Abstract

Development of an addiction is conditioned by many factors. The dopaminergic system has been shown to be the key element in this process. In this paper, we analyzed the influence of dopamine receptor 2 polymorphism rs1076560 in two groups—polysubstance-dependent male patients (n = 299) and the controls matched for age (n = 301). In both groups, we applied the same questionnaires for testing—Mini-international neuropsychiatric interview, the NEO Five-Factor Inventory, and the State–Trait Anxiety Inventory. The real-time PCR method was used for genotyping. When we compared the controls with the case group subjects, we observed significantly higher scores in the second group on both the state and trait scales of anxiety, as well as on the Neuroticism and Openness scales of the NEO-FFI; and lower scores on the scales of Extraversion and Agreeability of the NEO-FFI. The model 2 × 3 factorial ANOVA of the addicted subjects and controls was performed, and the DRD2 rs1076560 variant interaction was found for the anxiety state and trait scales, and for the NEO-FFI Neuroticism scale. The observed associations allow noticing that analysis of psychological factors in combination with genetic data opens new possibilities in addiction research.

Expression of Dopamine-Related Genes in Four Human Brain Regions

“…Additionally, within this same block, the rs1076560 T allele has been associated with responsiveness to anti-psychotic medications [ 36 ] and reduction in symptomatology in pharmacologic treatment of Parkinson’s Disease [ 37 ], but was most recently demonstrated to be associated with the personality characteristics of neuroticism and anxiety in polysubstance dependent males [ 38 ]. However, other studies have not found an association for this variant and substance use disorder [ 39 , 40 ].…”

Emotional dysregulation, alexithymia and neuroticism: a systematic review on the genetic basis of a subset of psychological traits

“…One of the most interesting gene is DRD2; despite mixed results among candidate-gene association studies, with positive association ( Wacker et al ., 2005 ; Jutras-Aswad et al ., 2012 ; Grzywacz et al ., 2020 ; Suchanecka et al ., 2020 ) outweighing the null hypothesis ( Hibino et al ., 2006 ; Pełka-Wysiecka et al ., 2012 ), GWAS studies replicated several times the finding of its association with neuroticism ( Okbay et al ., 2016 ; Luciano et al ., 2018 ; Nagel et al ., 2018 , 2020 ; Turley et al ., 2018 ; Hill et al ., 2020 ). As mentioned previously, the DRD2 gene codes for a crucial dopamine receptor, currently regarded as being one of the main target of antipsychotics medications.…”

Association of Polymorphism within the Putative miRNA Target Site in the 3′UTR Region of the DRD2 Gene with Neuroticism in Patients with Substance Use Disorder

“…Other research studies showed that the combination of two highly prevalent DRD2 SNPs, rs6276 and rs6277, decreased the expression of DRD2 as a consequence of a diminished DRD2 mRNA, and moreover, a decreased D2R receptor availability and affinity [ 70 , 72 , 162 , 163 , 164 , 165 ]. Han et al found that these combined effects of DRD2 and SNPs also diminished the levels of phosphorylated β-catenin, presumably causing more β-catenin to be successfully degraded, and in this way, the transcription of the Wnt/β-catenin pathway of the target genes was stimulated.…”