The effects of DAT1 genotype on fMRI activation in an emotional go/no-go task

Abstract

Dopaminergic brain circuits participate in emotional processing and impulsivity. The dopamine transporter (DAT) modulates dopamine reuptake. A variable number tandem repeat (VNTR) in the dopamine transporter gene (DAT1) affects DAT expression. The influence of DAT1 genotype on neural activation during emotional processing and impulse inhibition has not been examined. Forty-two healthy subjects were classified as 9DAT (n = 17) or 10DAT (n = 25) based on DAT1 genotype (9DAT = 9R/9R and 9R/10R; 10DAT = 10R/10R). Subjects underwent fMRI during non-emotional and emotional go/no-go tasks. Subjects were instructed to inhibit responses to letters, happy faces, or sad faces in separate blocks. Accuracy and reaction time did not differ between groups. Within group results showed activation in regions previously implicated in emotional processing and response inhibition. Between groups results showed increased activation in 9DAT individuals during inhibition. During letter inhibition, 9DAT individuals exhibited greater activation in right inferior parietal regions. During sad inhibition, 9DAT Individuals exhibited greater activation in frontal, posterior cingulate, precuneus, right cerebellar, left paracentral, and right occipital brain regions. The interaction between DAT genotype and response type in sad versus letter stimuli showed increased activation in 9DAT individuals during sad no-go responses in the anterior cingulate cortex, extending into frontal-orbital regions. 9DAT individuals have greater activation than 10DAT individuals during neutral and sad inhibition, showing that genotypic variation influencing basal dopamine levels can alter the neural basis of emotional processing and response inhibition. This may indicate that 9R carriers exert more effort to overcome increased basal dopamine activation when inhibiting responses in emotional contexts.

Keywords: Dopamine transporter; Emotion; Response inhibition.

Figure 1. Difference between 10DAT and 9DAT Group Activation for the Letter No-go>Letter Go Condition

Figure 1 shows the differences between 10DAT (homozygous for 10-repeat allele, 10R/10R) and 9DAT (homozygous or heterozygous for 9-repeat allele, 9R/9R or 9R/10R) in the letter no-go > letter go condition. The statistical significance threshold for examining this effect was set at p=0.01 and a cluster size of 219 voxels corresponded to a corrected p=0.05. Here, the 9DAT group shows more activation in the right inferior parietal area than the 10DAT group.

Figure 2. Difference between 10DAT and 9DAT Group Activation for the Sad No-go>Sad Go Condition

Figure 2 shows the difference between 10DAT and 9DAT groups activation for sad no-go > sad go condition. The statistical significance threshold for examining this effect was set at p=0.01 and a cluster size of 219 voxels corresponded to a corrected p=0.05. (A) Left paracentral lobule, 9DAT>10DAT. (B) Right middle-inferior occipital, 9DAT>10DAT. (C) Left & Right PCC-precuneus, 9DAT>10DAT. (D) Left superior frontal and left & right superior medial frontal, 9DAT>10DAT.

Figure 3. Interaction between Groups (10DAT, 9DAT) and Conditions (Sad No-go > Sad Go, Letter No-Go > Letter Go)

Figure 3 shows the interaction between the sad emotion and non-emotional conditions between the 9DAT and 10DAT groups, the significance thershold for examining this this interaction was set at p=0.05 and a cluster size of 935 voxels corresponded to cluster-wise corrected p=0.05. The resultant area was the left ACC extending into the superior medial frontal and medial orbital areas.