Interactive effects of dopamine transporter genotype and aging on resting-state functional networks

Aging and dopamine modulation have both been independently shown to influence the functional connectivity of brain networks during rest. Dopamine modulation is known to decline during the course of aging. Previous evidence also shows that the dopamine transporter gene (DAT1) influences the re-uptake of dopamine and the anyA9 genotype of this gene is associated with higher striatal dopamine signaling. Expanding these two lines of prior research, we investigated potential interactive effects between aging and individual variations in the DAT1 gene on the modular organization of brain acvitiy during rest. The graph-theoretic metrics of modularity, betweenness centrality and participation coefficient were assessed in 41 younger (age 20–30 years) and 37 older (age 60–75 years) adults. Age differences were only observed in the participation coefficient in carriers of the anyA9 genotype of the DAT1 gene and this effect was most prominently observed in the default mode network. Furthermore, we found that individual differences in the values of the participation coefficient correlated with individual differences in fluid intelligence and a measure of executive control in the anyA9 carriers. The correlation between participation coefficient and fluid intelligence was mainly shared with age-related differences, whereas the correlation with executive control was independent of age. These findings suggest that DAT1 genotype moderates age differences in the functional integration of brain networks as well as the relation between network characteristics and cognitive abilities.

已有研究独立证实，衰老与多巴胺调节均可影响静息态下脑网络的功能连接。已知在衰老进程中，多巴胺调节功能会逐渐减退。既往研究还表明，多巴胺转运体基因（dopamine transporter gene, DAT1）可调控多巴胺的再摄取，且该基因的anyA9基因型与更高水平的纹状体多巴胺信号传导相关。本研究拓展此前这两个研究方向，探讨了衰老与多巴胺转运体基因（DAT1）的个体差异之间的潜在交互效应，及其对静息态下脑活动模块化组织的影响。研究纳入41名年轻成年人（年龄20~30岁）与37名年长成年人（年龄60~75岁），对脑活动的图论指标——模块化指数、介数中心性与参与系数——进行了评估。仅在携带DAT1基因anyA9基因型的受试者中，观察到年龄差异体现在参与系数上，且该效应在默认模式网络中最为显著。此外，本研究发现，在携带anyA9基因型的受试者中，参与系数的个体差异与流体智力的个体差异，以及一项执行控制测评的得分均存在相关性。参与系数与流体智力之间的相关性，主要与年龄相关差异共享变异；而其与执行控制的相关性则与年龄无关。上述研究结果表明，DAT1基因型可调节脑网络功能整合的年龄差异，以及脑网络特征与认知能力之间的关联。