Differential effect of the dopamine genotype on inflammatory cytokine responses during abstinence in amphetamine-dependent

Amphetamine exposure impacts innate and adaptive immunity, and DRD3 may modulate the effect of amphetamine on the immune response. We assessed the immune-cytokine markers in 72 female patients with amphetamine dependence (AD) at baseline and after 4 weeks of drug abstinence and in 51 healthy women. A multiplex magnetic bead assay was used to measure plasma cytokine expression levels in all participants simultaneously, and the DRD3 rs6280 polymorphism was genotyped in patients. We demonstrated an increase in the T helper 1 (Th1) cytokines (IL-2), Th2 cytokines (IL-4, IL-5, IL-6, and IL-10), and other cytokines (IL-1β) in the entire AD cohort. A similar cytokine pattern, along with significantly decreased IL-8 and IL-10 levels, was observed after 4 weeks of abstinence. Among AD patients with the DRD3 rs6280 TT genotype, the cytokine expression profile was consistent with that of the total AD cohort at baseline and revealed a significant down-regulation of plasma levels of Th1, Th2, and other cytokines, except for IL-6, after 4 weeks of abstinence. In the AD group with DRD3 rs6280 C allele carriers, we found that IL-2 levels were significantly higher than those of healthy controls at baseline and remained higher, accompanied by a borderline increase in IL-4, IL-6, and IL-1β levels after 4 weeks of abstinence. Our results suggest that chronic use of amphetamine increased both pro- and anti-inflammatory cytokines in AD patients, indicating the immune imbalance that may persist for 4 weeks or more. Besides, the DRD3 rs6280 TT genotype may be associated with favorable recovery in general inflammatory cytokines during the period of abstinence.

Dr. San-Yuan Huang graduated in medicine at the National Defense Medical Center, Taipei, Taiwan, ROC. He completed his psychiatry residency at Tri-Service General Hospital, Taipei, Taiwan. After completing his psychiatry resident training, Dr. Huang received his Ph.D. degree from the National Defense Medical Center. His academic research focuses on gene-gene and gene-behavior-environment interaction in substance use disorders such as alcohol dependence, depressive alcoholism, and other illegal drug abuse. After earning a Ph.D. degree, his main academic interests/ research are in gene, brain image with SPECT and PET, psycho-immunology in addiction and mental-related disorder.