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The oxytocin receptor rs2254298 polymorphism and alcohol withdrawal symptoms: a gene–environment interaction in mood disorders

OBJECTIVE: Alcohol use disorder (AUD) is a common mental disorder characterized by repeated withdrawal episodes. Negative emotions during withdrawal are the primary factors affecting successful abstinence. Oxytocin is a critical modulator of emotions. OXTR, the oxytocin receptor, may also be a promi...

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Autores principales: Shen, Guanghui, Yang, Shizhuo, Wu, Liujun, Chen, Yingjie, Hu, Yueling, Zhou, Fan, Wang, Wei, Liu, Peining, Wu, Fenzan, Liu, Yanlong, Wang, Fan, Chen, Li
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10380931/
https://www.ncbi.nlm.nih.gov/pubmed/37520225
http://dx.doi.org/10.3389/fpsyt.2023.1085429
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author Shen, Guanghui
Yang, Shizhuo
Wu, Liujun
Chen, Yingjie
Hu, Yueling
Zhou, Fan
Wang, Wei
Liu, Peining
Wu, Fenzan
Liu, Yanlong
Wang, Fan
Chen, Li
author_facet Shen, Guanghui
Yang, Shizhuo
Wu, Liujun
Chen, Yingjie
Hu, Yueling
Zhou, Fan
Wang, Wei
Liu, Peining
Wu, Fenzan
Liu, Yanlong
Wang, Fan
Chen, Li
author_sort Shen, Guanghui
collection PubMed
description OBJECTIVE: Alcohol use disorder (AUD) is a common mental disorder characterized by repeated withdrawal episodes. Negative emotions during withdrawal are the primary factors affecting successful abstinence. Oxytocin is a critical modulator of emotions. OXTR, the oxytocin receptor, may also be a promising candidate for treating alcohol withdrawal symptoms. Previous studies indicated that people with different genotypes of OXTR rs2254298 were reported to suffer from more significant depressive or heightened anxiety symptoms when experiencing early adversity. The present study aims to explore the modulatory role of the polymorphism OXTR rs2254298 on mood disorders during alcohol withdrawal and to help researchers better understand and develop effective relapse prevention and interventions for alcohol use disorders. METHODS: We recruited 265 adult Chinese Han men with AUD. Anxiety and depressive symptoms were measured using the Self-Rating Anxiety Scale and Self-Rating Depression Scale. Alcohol dependence levels were measured using Michigan Alcoholism Screening Test. Genomic DNA extraction and genotyping from participants’ peripheral blood samples. RESULT: First, a multiple linear regression was used to set the alcohol dependence level, OXTR.rs2254298, interaction terms as the primary predictor variable, and depression or anxiety as an outcome; age and educational years were covariates. There was a significant interaction between OXTR rs2254298 and alcohol dependence level on anxiety (B = 0.23, 95% confidence interval [CI]: 0.01–0.45) but not on depression (B = −0.06, 95% CI: −0.30 – 0.18). The significance region test showed that alcohol-dependent men who are GG homozygous were more likely to experience anxiety symptoms than subjects with the A allele (A allele: β = 0.27, p < 0.001; GG homozygote: β = 0.50, p < 0.001). Finally, re-parameterized regression analysis demonstrated that this gene–environment interaction of OXTR rs2254298 and alcohol dependence on anxiety fits the weak differential susceptibility model (R(2) = 0.17, F (5,259) = 13.46, p < 0.001). CONCLUSION: This study reveals a gene–environment interactive effect between OXTR rs2254298 and alcohol withdrawal on anxiety but not depression. From the perspective of gene–environment interactions, this interaction fits the differential susceptibility model; OXTR rs2254298 GG homozygote carriers are susceptible to the environment and are likely to experience anxiety symptoms of alcohol withdrawal.
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spelling pubmed-103809312023-07-29 The oxytocin receptor rs2254298 polymorphism and alcohol withdrawal symptoms: a gene–environment interaction in mood disorders Shen, Guanghui Yang, Shizhuo Wu, Liujun Chen, Yingjie Hu, Yueling Zhou, Fan Wang, Wei Liu, Peining Wu, Fenzan Liu, Yanlong Wang, Fan Chen, Li Front Psychiatry Psychiatry OBJECTIVE: Alcohol use disorder (AUD) is a common mental disorder characterized by repeated withdrawal episodes. Negative emotions during withdrawal are the primary factors affecting successful abstinence. Oxytocin is a critical modulator of emotions. OXTR, the oxytocin receptor, may also be a promising candidate for treating alcohol withdrawal symptoms. Previous studies indicated that people with different genotypes of OXTR rs2254298 were reported to suffer from more significant depressive or heightened anxiety symptoms when experiencing early adversity. The present study aims to explore the modulatory role of the polymorphism OXTR rs2254298 on mood disorders during alcohol withdrawal and to help researchers better understand and develop effective relapse prevention and interventions for alcohol use disorders. METHODS: We recruited 265 adult Chinese Han men with AUD. Anxiety and depressive symptoms were measured using the Self-Rating Anxiety Scale and Self-Rating Depression Scale. Alcohol dependence levels were measured using Michigan Alcoholism Screening Test. Genomic DNA extraction and genotyping from participants’ peripheral blood samples. RESULT: First, a multiple linear regression was used to set the alcohol dependence level, OXTR.rs2254298, interaction terms as the primary predictor variable, and depression or anxiety as an outcome; age and educational years were covariates. There was a significant interaction between OXTR rs2254298 and alcohol dependence level on anxiety (B = 0.23, 95% confidence interval [CI]: 0.01–0.45) but not on depression (B = −0.06, 95% CI: −0.30 – 0.18). The significance region test showed that alcohol-dependent men who are GG homozygous were more likely to experience anxiety symptoms than subjects with the A allele (A allele: β = 0.27, p < 0.001; GG homozygote: β = 0.50, p < 0.001). Finally, re-parameterized regression analysis demonstrated that this gene–environment interaction of OXTR rs2254298 and alcohol dependence on anxiety fits the weak differential susceptibility model (R(2) = 0.17, F (5,259) = 13.46, p < 0.001). CONCLUSION: This study reveals a gene–environment interactive effect between OXTR rs2254298 and alcohol withdrawal on anxiety but not depression. From the perspective of gene–environment interactions, this interaction fits the differential susceptibility model; OXTR rs2254298 GG homozygote carriers are susceptible to the environment and are likely to experience anxiety symptoms of alcohol withdrawal. Frontiers Media S.A. 2023-07-14 /pmc/articles/PMC10380931/ /pubmed/37520225 http://dx.doi.org/10.3389/fpsyt.2023.1085429 Text en Copyright © 2023 Shen, Yang, Wu, Chen, Hu, Zhou, Wang, Liu, Wu, Liu, Wang and Chen. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Psychiatry
Shen, Guanghui
Yang, Shizhuo
Wu, Liujun
Chen, Yingjie
Hu, Yueling
Zhou, Fan
Wang, Wei
Liu, Peining
Wu, Fenzan
Liu, Yanlong
Wang, Fan
Chen, Li
The oxytocin receptor rs2254298 polymorphism and alcohol withdrawal symptoms: a gene–environment interaction in mood disorders
title The oxytocin receptor rs2254298 polymorphism and alcohol withdrawal symptoms: a gene–environment interaction in mood disorders
title_full The oxytocin receptor rs2254298 polymorphism and alcohol withdrawal symptoms: a gene–environment interaction in mood disorders
title_fullStr The oxytocin receptor rs2254298 polymorphism and alcohol withdrawal symptoms: a gene–environment interaction in mood disorders
title_full_unstemmed The oxytocin receptor rs2254298 polymorphism and alcohol withdrawal symptoms: a gene–environment interaction in mood disorders
title_short The oxytocin receptor rs2254298 polymorphism and alcohol withdrawal symptoms: a gene–environment interaction in mood disorders
title_sort oxytocin receptor rs2254298 polymorphism and alcohol withdrawal symptoms: a gene–environment interaction in mood disorders
topic Psychiatry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10380931/
https://www.ncbi.nlm.nih.gov/pubmed/37520225
http://dx.doi.org/10.3389/fpsyt.2023.1085429
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