DRD1 gene is associated with craving changes during withdrawal among patients with alcohol use disorder

Alcohol use disorder (AUD) is a chronic relapsing condition in which craving is closely linked to relapse. Previous research has shown that the single nucleotide polymorphisms (SNPs) of the dopamine receptor D1 (DRD1) gene are not associated with craving severity when assessing cross-sectionally. Since craving severity may change after withdrawal, this study tracked craving dynamics over a two-week withdrawal period and examined the relationships with DRD1 SNPs.

We recruited 221 Taiwanese Han patients with severe AUD diagnosed based on DSM-5-TR and undergoing withdrawal treatment and 117 healthy controls. Alcohol craving was assessed at baseline and after one and two weeks of withdrawal using the Obsessive-Compulsive Drinking Scale (OCDS). DRD1 SNPs were imputed from the genome-wide database, including rs12518222, rs4867798, rs686, rs4532, rs5326, rs265981. Single SNP and haplotype-based analyses were used to evaluate the associations between DRD1 SNPs and craving.

DRD1 SNPs of rs12518222 (3'-UTR) and rs5326 (5'-UTR) of genotype and allele types were significantly associated with AUD (P = 0.008 and < 0.001, respectively). Carriers of the minor alleles at 3'-UTR of rs12518222 (T), rs4867798 (C), and rs5326 (A) and major alleles at 5'-UTR of rs686 (A), rs4532 (T), and rs265981 (G) were associated with higher post -withdrawal craving compared to the counterparts. The haplotype TCATTG, comprising the corresponding allele associated with higher craving was linked to more severe craving severity.

DRD1 gene influences post-withdrawal changes in cravings in AUD patients. These findings may guide personalized treatment strategies aimed at improving craving management and reducing relapse risk.