DRD2 TaqIA polymorphism-related functional connectivity between anterior insula and dorsolateral prefrontal cortex predicts the retention time in heroin-dependent individuals under methadone maintenance treatment

Background Dopamine receptor D2 (DRD2) TaqIA polymorphism has an influence on addiction treatment response and prognosis by mediating brain dopaminergic system efficacy. Insula is crucial for conscious urges to take drugs and maintain drug use. However, it remains unclear about the contribution of DRD2 TaqIA polymorphism to the regulation of insular on addiction behavioral and its relation with the therapeutic effect of methadone maintenance treatment (MMT). Methods 57 male former heroin dependents receiving stable MMT and 49 matched male healthy controls (HC) were enrolled. Salivary genotyping for DRD2 TaqA1 and A2 alleles, brain resting-state functional MRI scan and a 24-month follow-up for collecting illegal-drug-use information was conducted and followed by clustering of functional connectivity (FC) patterns of HC insula, insula subregion parcellation of MMT patients, comparing the whole brain FC maps between the A1 carriers and non-carriers and analyzing the correlation between the genotype-related FC of insula sub-regions with the retention time in MMT patients by Cox regression. Results Two insula subregions were identified: the anterior insula (AI) and the posterior insula (PI) subregion. The A1 carriers had a reduced FC between the left AI and the right dorsolateral prefrontal cortex (dlPFC) relative to no carriers. And this reduced FC was a poor prognostic factor for the retention time in MMT patients. Conclusion DRD2 TaqIA polymorphism affects the retention time in heroin-dependent individuals under MMT by mediating the functional connectivity strength between left AI and right dlPFC, and the two brain regions are promising therapeutic targets for individualized treatment.