DAT by perceived MC interaction on human prefrontal activity and connectivity during emotion processing

Abstract

Background: Maternal care (MC) and dopamine modulate brain activity during emotion processing in inferior frontal gyrus (IFG), striatum and amygdala. Reuptake of dopamine from the synapse is performed by the dopamine transporter (DAT), whose abundance is predicted by variation in its gene (DAT 3'VNTR; 10 > 9-repeat alleles). Here, we investigated the interaction between perceived MC and DAT 3'VNTR genotype on brain activity during processing of aversive facial emotional stimuli.

Methods: Sixty-one healthy subjects were genotyped for DAT 3'VNTR and categorized in low and high MC individuals. They underwent functional magnetic resonance imaging while performing a task requiring gender discrimination of facial stimuli with angry, fearful or neutral expressions.

Results: An interaction between facial expression, DAT genotype and MC was found in left IFG, such that low MC and homozygosity for the 10-repeat allele are associated with greater activity during processing of fearful faces. This greater activity was also inversely correlated with a measure of emotion control as scored with the Big Five Questionnaire. Moreover, MC and DAT genotype described a double dissociation on functional connectivity between IFG and amygdala.

Conclusion: These findings suggest that perceived early parental bonding may interact with DAT 3'VNTR genotype in modulating brain activity during emotionally relevant inputs.

Keywords: amygdala; dopamine; emotion; fMRI; inferior frontal gyrus; maternal care.

Fig. 1

Means ± 0.95 confidence interval indicating the interaction between facial expression and MC on RTs. Although subjects with HMC have faster RTs during processing of fearful compared with angry faces, subjects with LMC do not present this difference. See text for statistics.

Fig. 2

Main effect of MC on BOLD fMRI responses averaged between angry-neutral and fearful neutral contrast in bilateral caudate and left putamen, where subjects with LMC have greater activity. (A) Axial section; (B) Coronal section; (C) Parameter estimates extracted from the cluster with Talairach coordinates, x = −19, y = 7; z = −7; (D) Parameter estimates extracted from the cluster with Talairach coordinates, x = 26, y = 4; z = −7.

Fig. 3

(A) Rendered image of the brain showing the cluster in left IFG with a three-way interaction between MC, DAT genotype and facial expression (BA 45; x = −56; y = 26; z = 6). See text for statistics. (B) BOLD response extracted from the IFG cluster depicted in (A). X-axis: DAT 3′ VNTR genotype for each emotional stimulus investigated (i.e. fearful and angry faces). The bars represent 0.95 confidence interval.

Fig. 4

Coronal (A) and axial (B) sections of the brain showing the cluster in left amygdala (x = −30, y = −4, z = −22) where an interaction between DAT 3′VNTR genotype and MC was found on PPI with the IFG. (C) PPI values extracted from the cluster in left amygdala shown in (A) and (B). The bars represent 0.95 confidence interval.

Fig. 5

Scatterplot showing a negative correlation between BOLD signal change in IFG and BFQ emotion control scores in LMC subjects. See text for statistics.