Functional variation of the dopamine D2 receptor gene is associated with emotional control as well as brain activity and connectivity during emotion processing in humans

Abstract

Personality traits related to emotion processing are, at least in part, heritable and genetically determined. Dopamine D(2) receptor signaling is involved in modulation of emotional behavior and activity of associated brain regions such as the amygdala and the prefrontal cortex. An intronic single nucleotide polymorphism within the D(2) receptor gene (DRD2) (rs1076560, guanine > thymine or G > T) shifts splicing of the two protein isoforms (D(2) short, mainly presynaptic, and D(2) long) and has been associated with modulation of memory performance and brain activity. Here, our aim was to investigate the association of DRD2 rs1076560 genotype with personality traits of emotional stability and with brain physiology during processing of emotionally relevant stimuli. DRD2 genotype and Big Five Questionnaire scores were evaluated in 134 healthy subjects demonstrating that GG subjects have reduced "emotion control" compared with GT subjects. Functional magnetic resonance imaging in a sample of 24 individuals indicated greater amygdala activity during implicit processing and greater dorsolateral prefrontal cortex (DLPFC) response during explicit processing of facial emotional stimuli in GG subjects compared with GT. Other results also demonstrate an interaction between DRD2 genotype and facial emotional expression on functional connectivity of both amygdala and dorsolateral prefrontal regions with overlapping medial prefrontal areas. Moreover, rs1076560 genotype is associated with differential relationships between amygdala/DLPFC functional connectivity and emotion control scores. These results suggest that genetically determined D(2) signaling may explain part of personality traits related to emotion processing and individual variability in specific brain responses to emotionally relevant inputs.

Figure 1.

Plots showing the association of DRD2 rs1076560 with BFQ scores. Only the emotion control facet was significantly different between the two genotype groups. *p < 0.05. For statistics, see Results. Dy, Dynamism; DO, dominance; Co, cooperativeness; Po, politeness; Sc, scrupulousness; Pe, perseverance; Ec, emotion control; Ic, impulse control; Oc, openness to culture; Oe, openness to experience; Conscient, conscientiousness.

Figure 2.

A, Plot showing reaction time data during implicit and explicit processing of faces stimuli. For statistics, see Results. *p < 0.05. B, Coronal section and rendered image showing brain regions in which a DRD2 rs1076560 genotype × task interaction was present, i.e., left amygdala and left lateral prefrontal cortex. C, For illustrative purposes, parameter estimates extracted from clusters shown in A displaying BOLD response in left amygdala and left lateral prefrontal cortex during the implicit and the explicit part of the task as a function of DRD2 rs1076560 genotype.

Figure 3.

Rendered images of sagittal sections of the brain showing medial prefrontal clusters in which significant interaction between DRD2 rs1076560 and facial expressions was present on functional connectivity with left amygdala during implicit processing (left) and with left DLPFC during explicit processing (right). Mean ± SE. PPI values are shown in the plots.

Figure 4.

Scatter plots showing relationships between mean PPI values of emotionally charged faces (angry, fearful, and happy) extracted from clusters displayed in Figure 3 during implicit (x, y, z: −15, 38, 49) (left scatter plots) and explicit (x, y, z: −15, 41, 45) (right scatter plots) processing and emotion control scores as measured with the BFQ. In GT individuals, positive relationships are present during both implicit and explicit processing, whereas in GG subjects, no such relationships have been found. For statistics, see Results. mPFC, Medial prefrontal cortex.