Variation of the human mu-opioid receptor (OPRM1) gene predicts vulnerability to frustration

Alan M Daniel,Karla Y Tapia Menchaca,Brenda G Rushing

doi:10.1038/s41598-020-78783-4

Alan M Daniel, Karla Y Tapia Menchaca + Show 1 more

Open Access

https://doi.org/10.1038/s41598-020-78783-4

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Journal: Scientific Reports	Publication Date: Dec 1, 2020
Citations: 6	License type: open-access

Affiliation: Texas A&M University – San Antonio

Abstract

Understanding the emotional reaction to loss, or frustration, is a critical problem for the field of mental health. Animal models of loss have pointed to the opioid system as a nexus of frustration, physical pain, and substance abuse. However, few attempts have been made to connect the results of animal models of loss to human behavior. Allelic differences in the human mu opioid receptor gene, notably the A118G single nucleotide polymorphism, have been linked to individual differences in pain sensitivity, depressive symptoms, and reward processing. The present study explored the relationship between A118G and behavior in two frustrating tasks in humans. Results showed that carriers of the mutant G-allele were slower to recover behavior following a reward downshift and abandoned a frustrating task earlier than those without the mutation. Additionally, G-carriers were more sensitive to physical pain. These results highlight the overlap between frustration and pain, and suggest that genetic variation in opioid tone may contribute to individual differences in vulnerability and resilience following emotional disturbances.

Highlights

Understanding the emotional reaction to loss, or frustration, is a critical problem for the field of mental health
Genes code for both the precursors for neuropeptides and for their receptors, and it is reasonable to posit that allelic differences in the opioid system may contribute to individual differences in responses to reward downshifts
In humans there is a well-known variant of the mu opioid receptor gene (OPRM1) known as the A118G single nucleotide polymorphism (SNP) of the mu opioid receptor (MOR), in which the typically occurring adenine at position 118 is replaced with g uanine[15]

Summary

Introduction

Understanding the emotional reaction to loss, or frustration, is a critical problem for the field of mental health. Allelic differences in the human mu opioid receptor gene, notably the A118G single nucleotide polymorphism, have been linked to individual differences in pain sensitivity, depressive symptoms, and reward processing. G-carriers were more sensitive to physical pain These results highlight the overlap between frustration and pain, and suggest that genetic variation in opioid tone may contribute to individual differences in vulnerability and resilience following emotional disturbances. Artificial selection studies suggest that parental rates of recovery can have an impact on responses to reward downshifts in future g enerations[14] Genes code for both the precursors for neuropeptides and for their receptors, and it is reasonable to posit that allelic differences in the opioid system may contribute to individual differences in responses to reward downshifts. We hypothesized that G-carriers would be more vulnerable to the reward downshift, exhibiting slower recovery or reduced persistence compared to the resilience of AA homozygotes

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Conclusion