Peripheral expression of dopamine genes as a biomarker for cocaine addiction in humans.

Introduction: Objective measures for severity of addiction are needed to identify and appropriately stratify patients into effective treatment groups for intervention and recovery. Our aim was to determine if blood-derived, dopamine-related biomarkers hold predictive validity in patients with cocaine use disorder. Methods: 349 participants [163 patients with moderate-to-severe cocaine use disorder (CUD), 186 healthy control participants without a history of substance use disorder] were recruited for a cross-sectional case-control study in the East of England, UK. Data on individual differences in cocaine use disorder-related traits, e.g., impulsivity, sensation-seeking, were collected. Measurements included mRNA transcription of dopamine-related genes (DRD2, DRD3, DRD4, and COMT) and risk alleles (rs6277, rs1800497, rs12364283, rs6280, and rs4680). Results: CUD patients showed elevated DRD2 mRNA in peripheral blood (B0=0.43, 95% CI [0.13, 0.73], pFDR=0.020) and the DRD2-related rs6277 risk allele was associated with CUD diagnosis (Odds ratio [OR]= 2.16, 95% CI [1.15, 4.17], p=0.02). DRD2 mRNA levels related to self-reported impulsivity (B0=−0.17, 95% CI [−0.32, −0.03], p=0.013). Conclusions: Blood-based expression of DRD2 may be a useful biomarker related to CUD diagnosis and related traits.