Variation in the mu-opioid receptor gene (OPRM1) is associated with dispositional and neural sensitivity to social rejection

Abstract

Scientific understanding of social pain--the hurt feelings resulting from social rejection, separation, or loss--has been facilitated by the hypothesis that such feelings arise, in part, from some of the same neural and neurochemical systems that generate the unpleasant feelings resulting from physical pain. Accordingly, in animals, the painkiller morphine not only alleviates the distress of physical pain, but also the distress of social separation. Because morphine acts on the mu-opioid receptor, we examined whether variation in the mu-opioid receptor gene (OPRM1), as measured by the functional A118G polymorphism, was associated with individual differences in rejection sensitivity. Participants (n = 122) completed a self-report inventory of dispositional sensitivity to social rejection and a subsample (n = 31) completed a functional MRI session in which they were rejected from an online ball-tossing game played with two supposed others. The A118G polymorphism was associated with dispositional sensitivity to rejection in the entire sample and in the fMRI subsample. Consistent with these results, G allele carriers showed greater reactivity to social rejection in neural regions previously shown to be involved in processing social pain as well as the unpleasantness of physical pain, particularly the dorsal anterior cingulate cortex (dACC) and anterior insula. Furthermore, dACC activity mediated the relationship between the A118G polymorphism and dispositional sensitivity to rejection, suggesting that this is a critical site for mu-opioid-related influence on social pain. Taken together, these data suggest that the A118G polymorphism specifically, and the mu-opioid receptor more generally, are involved in social pain in addition to physical pain.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1.

Bar graph of the relationship between the A118G polymorphism and dispositional sensitivity to rejection (Total n = 122; A/A = 73; A/G = 44; G/G = 5).

Fig. 2.

Mean parameter estimates for the affective pain matrix ROI according to A118G genotype (F (1, 24) = 4.71, P < 0.05). (Inset) Shaded regions denote ROI location.

Fig. 3.

Sagittal (A; dACC) and axial (B; anterior insula, denoted by arrow) sections of neural activations during social exclusion vs. inclusion that showed significantly greater activity (P < 0.001, 20 voxel extent) for G allele carriers than A allele homozygotes. (C) Parameter estimates from the dACC (8,12,44; t (24) = 4.06, P < 0.001); (D) Parameter estimates from the left anterior insula (−22,24,–8; t (24) = 5.07, P < 0.001). x denotes G allele homozygote.

Fig. 4.

Correlation of the dACC ROI with dispositional sensitivity to rejection (r = 0.34, P < 0.05); + denotes G allele carriers; • denotes A allele homozygotes. (Inset) Sagittal section of ROI.