■酒精使用障碍(AUD)是一种常见的精神障碍,其特征是反复的戒断发作。戒断期间的负面情绪是影响戒断成功的主要因素。催产素是情绪的关键调节剂。OXTR,催产素受体,也可能是治疗酒精戒断症状的有希望的候选人。先前的研究表明,据报道,具有不同OXTRrs2254298基因型的人在经历早期逆境时患有更明显的抑郁或高度焦虑症状。本研究旨在探讨OXTRrs2254298多态性对戒酒期间情绪障碍的调节作用,并帮助研究人员更好地理解和开发有效的预防酒精使用障碍的复发和干预措施。
■我们招募了265名AUD的成年汉族男性。使用焦虑自评量表和抑郁自评量表测量焦虑和抑郁症状。使用密歇根酒精中毒筛查测试测量酒精依赖水平。参与者外周血样本的基因组DNA提取和基因分型。
■首先,使用多元线性回归来设置酒精依赖水平,OXTR.rs2254298,交互项作为主要预测变量,和抑郁或焦虑作为结果;年龄和受教育年限是协变量。OXTRrs2254298与酒精依赖水平对焦虑有显著交互作用(B=0.23,95%置信区间[CI]:0.01-0.45),但对抑郁无交互作用(B=-0.06,95%CI:-0.30-0.18)。显著性区域检验显示,与具有A等位基因的受试者相比,GG纯合子的酒精依赖男性更可能出现焦虑症状(A等位基因:β=0.27,p<0.001;GG纯合子:β=0.50,p<0.001)。最后,重新参数化回归分析表明,OXTRrs2254298和酒精依赖对焦虑的这种基因-环境相互作用符合弱差异易感性模型(R2=0.17,F(5,259)=13.46,p<0.001)。
■这项研究揭示了OXTRrs2254298和酒精戒断对焦虑而不是抑郁之间的基因-环境交互作用。从基因-环境相互作用的角度来看,这种相互作用符合差异易感性模型;OXTRrs2254298GG纯合子携带者容易受到环境的影响,并且可能会出现酒精戒断的焦虑症状。
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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).
UNASSIGNED: 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.