Variation in the μ-opioid receptor gene ( OPRM1 ) is associated with dispositional and neural sensitivity to social rejection
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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 μ-opioid receptor, we examined whether variation in the μ-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 μ-opioid-related influence on social pain. Taken together, these data suggest that the A118G polymorphism specifically, and the μ-opioid receptor more generally, are involved in social pain in addition to physical pain.
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Individuals with the A118G MOR polymorphism show increased likelihood of affectionate relationships, increased sensitivity to social rejection, and increased brain activity in a rejection task, possibly indicating an altered attachment style.
“Individuals possessing the A118G polymorphism of the MOR gene show increased likelihood to engage in affectionate relationships, increased sensitivity to social rejection, and increased brain activity in a rejection task, possibly signaling an altered attachment style (Way et al 2009; Troisi et al 2011a).”
From The behavioral, anatomical and pharmacological parallels between social attachment, love and addiction (2012) · cites this paper as Way et al 2009
Much previous work on β-endorphin has focused on 'social pain' resulting from social rejection.
“much previous work on β -endorphin has focused on ' social pain ' resulting from social rejection (53, 54)”
From Variation in the β-endorphin, oxytocin, and dopamine receptor genes is associated with different dimensions of human sociality (2017) · cites this paper as [53]
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“, 2008) and humans (Way et al., 2009), suggest that OPRM1 variation may be involved in mediating senses of social-absence, since genotype appears to predict behavioral response to separation or rejection.”
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Lee, M. R., Gallen, C. L., Zhang, X., Hodgkinson, C. A., Goldman, D., Stein, E. A., & Barr, C. S. (2011) · PLoS ONE · doi:10.1371/journal.pone.0024203 · Cited by 27 · see citing works
Curley, J. P. (2011) · Behavioral Neuroscience · doi:10.1037/a0022939 · Cited by 19 · see citing works
Common neural responses to romantic rejection and acceptance in healthy adults
Hsu, D. T., Sankar, A., Malik, M. A., Langenecker, S. A., Mickey, B. J., & Love, T. M. (2020) · Social Neuroscience · doi:10.1080/17470919.2020.1801502 · Cited by 18 · see citing works
- Authors
- Way, B. M., Taylor, S. E., & Eisenberger, N. I.
- Affiliations
- University of California, Los Angeles (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2009-09
- Volume
- 106
- Issue
- 35
- Pages
- 15079-15084
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2736434
- OpenAlex
- W2123651254
- Cited by
- 264
- References
- 62
- Citations by year
- 2026: 4 · 2025: 10 · 2024: 12 · 2023: 8 · 2022: 10 · 2021: 7 · 2020: 18 · 2019: 19 · 2018: 20 · 2017: 14 · 2016: 17 · 2015: 19 · 2014: 21 · 2013: 13 · 2012: 25
- FWCI
- 9.95
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Harry Frank Guggenheim Foundation
- UCLA Health System
- National Institutes of Health
- National Institute on Aging (AG 030309, R01AG030309)
- National Institute of Mental Health (R21MH07152)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Social Sciences › Psychology › Social Psychology › Death Anxiety and Social Exclusion
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Keywords
- mu-opioid receptor, OPRM1, A118G polymorphism, social rejection, social pain, dorsal anterior cingulate cortex, anterior insula, individual differences, morphine, pain processing
- MeSH terms
- Alleles, Female, Humans, Interpersonal Relations, Magnetic Resonance Imaging, Male, Neurons, Pain, Polymorphism, Genetic, Rejection, Psychology, Receptors, Opioid, mu
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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