Altogether, the present findings suggested that the ADORA2A gene and the interaction of ADORA2A and DRD2 genes may play a role in anxiety disorders in children and adolescents with ADHD.
We previously reported that dopamine D2 receptor knockout (D2R<sup>-/-</sup>) mice display increased anxiety and depression-like behaviors upon chronic stress.
After adjusting for age, occupation, education, marital status, self-rating anxiety score, and disease status, we observed significant negative associations of catechol-O-methyltransferase (COMT), dopamine receptor D2 (DRD2) gene score and smoking cessation, as well as significant positive associations between ankyrin repeat and kinase domain containing 1 (ANKK1), dopamine transporter (SLC6A3), dopamine receptor D4 (DRD4) gene score and smoking cessation.
It is hypothesized that dopaminergic genes-dopamine type-2 receptor (DRD2), aldehyde dehydrogenase 2 (ALDH2), and catechol-O-methyltransferase (COMT)-are associated with bipolar disorder (BP) and anxiety disorder (AD).
Although no DRD2 polymorphisms were associated with the risk of alcoholism, +32806C>T and Block2-ht1 showed associations (in dominant models) with both the state anxiety level scale (STAI-S) and the trait anxiety level scale (STAI-T) (P=0.004 and P=0.003, and P=0.01 and P=0.005, respectively).
The paper focuses on such candidate gene polymorphisms that alter alcoholism-related intermediate phenotypes including: dopaminergic system polymorphic variants (DRD2 -141C Ins/Del in promoter region, exon 8 and DRD2 TaqI A and DAT 40bp VNTR genes polymorphisms) that cause predisposition to severe alcoholism (haplotype Ins/G/A2); COMT Val158Met gene polymorphism related to differences in executive cognitive function and 5-HTT gene promoter polymorphism, which alters stress response and affects anxiety and dysphoria.
Subjects with the DRD2 Al allele compared to those without this allele had significantly higher scores on GHQ 2 (anxiety/insomnia), GHQ 3 (social dysfunction) and GHQ 4 (depression).
However, for men, but not for women, we observed a strong and specific association between low neuroticism-anxiety and the A1+ allele of the DRD2 TaqI A polymorphism across two independent samples and across two alternative personality scales.
Within the bupropion group, subgroup analyses with stratification by genotype demonstrated that craving, irritability, and anxiety were significantly attenuated only among subjects with DRD2-Taq1 A2/A2 genotypes.