Variation in the μ-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 -opioid receptor, we examined whether variation in the -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 -opioid-related influence on social pain. Taken together, these data suggest that the A118G polymorphism specifically, and the -opioid receptor more generally, are involved in social pain in addition to physical pain.anterior cingulate ͉ brain ͉ exclusion ͉ genetic ͉ social pain

Human Mu Opioid Receptor ( OPRM1 A118G) polymorphism is associated with brain mu-opioid receptor binding potential in smokers

“…Altered levels of G protein-coupled signaling molecules have also been observed in Neuro 2A cells transfected with the 118G hOPRM1 (31). Additional clinical evidence suggests that carriers of the OPRM1 118G polymorphism exhibit increased sensitivity to pain (32), as well as increased sensitivity to psychosocial stress at both the subjective and neural levels (33). Interestingly, during the stress challenge, increased neural activity in the G allele carriers was observed in the anterior cingulate cortex (33), a region significant for MOR BP ND and reward differences in the current study.…”

Mechanisms linking early life stress to adult health outcomes

“…Several laboratories that explore such epigenetic processes have productively focused on genes in the glucocorticoid system (19)(20)(21). Our laboratory has especially explored genes in the serotonin and the opioid systems (22,23). As an example, I describe a study from our laboratory that focused on the serotonin transporter gene (5-HTTLPR) (24).…”

The Strategies of the Genes: Genomic Conflicts, Attachment Theory, and Development of the Social Brain

“…Might oxytocin in autistics subserve, to some degree, positive reinforcement of non-social stimuli, or might epigenetically-based reduction of oxytocin receptor expression (Gregory et al 2009) follow from early social-19 interaction deficits? The µ-opioid system represents another important candidate mechanism, in addition to oxytocin, for neuroendocrine regulation of attachment, given links of allelic variants in the υ-opioid receptor gene OPRM1 with attachment patterns, sensitivity to social rejection, drug dependence, and risk of schizophrenia (Insel 2003;Barr et al 2008;Way et al 2009;Mague and Blendy 2010;Serý et al 2010) and evidence for parent of origin effects influencing phenotypic effects from this gene (Lemire 2005). …”