不同DRD2TaqIA基因型美沙酮维持治疗的海洛因成瘾者岛叶功能连接差异的rs-fMRI研究

The differences of DRD2TaqIA genotype on functional connectivity of insula in heroin addicts undergoing methadone maintenance treatment: a resting-state fMRI study

目的运用功能连接(functional connectivity,FC)方法评价不同多巴胺D2受体(dopamineD2receptor,DRD2) TaqIA基因型美沙酮维持治疗(methadonemaintenance treatment,MMT)的海洛因成瘾者岛叶的全脑功能连接的差异特征及意义。材料与方法 27例接受美沙酮维持治疗的DRD2TaqIA A+型男性海洛因成瘾者和相匹配的20例A-型男性海洛因成瘾者,进行3.0 T核磁共振rs-fMRI扫描,并采集其后12个月内美沙酮维持治疗过程中的操守时间数据。影像学数据经dpabi软件分析,以双侧岛叶为感兴趣区(region of interest,ROI),获得两组被试全脑功能连接差异脑区,利用偏相关分析差异脑区功能连接强度与美沙酮维持治疗过程中操守时间的关系。结果与A-型相比,A+型组右侧岛叶与双侧背外侧前额叶及双侧尾状核功能连接强度显著减低(P<0.001,FDR校正,体素>5);右侧岛叶与右侧背外侧前额叶功能连接强度与美沙酮维持治疗操守时间呈正相关(r=0.378,P=0.011;Bonferroni校正P<0.05)。结论不同DRD2TaqIA基因型美沙酮维持治疗的海洛因成瘾者的岛叶功能连接特征存在显著差异,主要涉及脑岛调节的抑制控制及奖赏神经环路的脑区,这可能是DRD2TaqIA基因型影响美沙酮维持治疗的海洛因成瘾者复吸行为的重要途径之一。

Objective: This study aimed to explore the differences and significance of whole brain functional connectivity (FC) seeding as insula between heroin addicts undergoing methadone maintenance treatment (MMT) with different DRD2TaqIA genetic variants by a functional connectivity method. Materials and Methods: Twenty-seven male MMT carrier A1 allele (A+ group) and 20 age, education, smoking matched homozygous A2 allele males MMT (A- group) participated in this study. Rest-state functional MRI was performed with 3.0 T scanner. The abstinent time was defined by the monthly structure interview and urine test in the subsequent 12 nomths after the MRI scan. The MRI data analysis was conducted by the toolbox DPABI. The whole brain FC seeding as bilateral insula was obtained in group A+ and group A-. Next, intergroup differences of the insula FC was calculated with two-sample t test. Moreover, the partial correlation between abstinent time after the MRI scan and the intensity of FC which is intergroup significantly different was analyzed. Results: Compared with A- group, A+ group showed reduced FC between the right insula and the bilateral dorsolateral prefrontal cortex, and the bilateral caudate nucleus (cluster size >5, FDR correction, P<0.001). In addition, FC intensity between the right insula and the right dorsolateral prefrontal cortex had a positive correlation with abstinent time (r=0.378, P=0.011. Bonferroni correction P<0.05). Conclusions: There were significant differences in insular functional connectivity feature between heroin addicts undergoing methadone maintenance treatment (MMT) with different DRD2TaqIA genetic variants. It might one of the important pathway that the insula regulation of inhibitory control function and reward neural circuit, through which DRD2TaqIA genotype influence on relapse behavior in MMT.