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

Guanghui Shen; Shizhuo Yang; Liujun Wu; Yingjie Chen; Yueling Hu; Fan Zhou; Wei Wang; Peining Liu; Fenzan Wu; Yanlong Liu; Fan Wang; Li Chen

doi:10.3389/fpsyt.2023.1085429

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

Front Psychiatry. 2023 Jul 14:14:1085429. doi: 10.3389/fpsyt.2023.1085429. eCollection 2023.

Authors

Guanghui Shen^{1

2}, Shizhuo Yang³, Liujun Wu^{2

4

5}, Yingjie Chen^{3

5}, Yueling Hu², Fan Zhou⁶, Wei Wang², Peining Liu⁶, Fenzan Wu^{3

7}, Yanlong Liu², Fan Wang^{8

9}, Li Chen^{2

10}

Affiliations

¹ Wenzhou Seventh People's Hospital, Wenzhou, China.
² School of Mental Health, Wenzhou Medical University, Wenzhou, China.
³ School of Pharmacy, Wenzhou Medical University, Wenzhou, China.
⁴ Applied Psychology (Ningbo) Research Center, Wenzhou Medical University, Ningbo, China.
⁵ Cixi Biomedical Research Institute, Wenzhou Medical University, Ningbo, China.
⁶ Department of Pediatrics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
⁷ Laboratory of Translational Medicine, Affiliated Cixi Hospital, Wenzhou Medical University, Ningbo, China.
⁸ Beijing Hui-Long-Guan Hospital, Peking University, Beijing, China.
⁹ Key Laboratory of Psychosomatic Medicine, Inner Mongolia Medical University, Hohhot, Inner Mongolia, China.
¹⁰ Zhejiang Provincial Clinical Research Center for Mental Disorders, The Affiliated Wenzhou Kangning Hospital, Wenzhou Medical University, Wenzhou, China.

Abstract

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 (R² = 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.

Keywords: OXTR; alcohol use disorder; alcohol withdrawal; mood disorders; single-nucleotide polymorphism.