Oxytocin gene polymorphisms interact with alcohol dependence in association with negative emotions in adult males during acute alcohol withdrawal

Abstract Objective The importance of multiple genes-environment interaction (G × E) has been highlighted in understanding the etiology of negative emotions. This study is the first to examine the impact of oxytocin polymorphisms (rs2740210, rs6133010, and rs2740209) in combination with alcohol dependence on anxiety and depression symptoms during acute alcohol withdrawal in different contextual cues. Additionally, the study aims to determine whether these G × E interactions align with the diathesis-stress model or the differential susceptibility hypothesis. Method A total of 414 Chinese Han adults participated in the study and provided blood samples, self-reported depression and anxiety symptoms, level of alcohol dependence, and information on different contextual cues. Results The results showed that the severity of alcohol dependence increased the risk of depression and anxiety symptoms, while oxytocin polymorphism did not have a direct effect on depressive and anxiety symptoms. However, a significant interaction was found between oxytocin polymorphism (rs2740210 and rs2740209) and alcohol dependence in relation to anxiety symptoms. This interaction was observed specifically among adults living with family or those who were married. Conclusions These findings provide evidence for distinct G × E interaction effects on anxiety and depression symptoms during acute alcohol withdrawal, supporting the diathesis-stress hypothesis. Furthermore, the study highlights the importance of considering contextual factors when investigating the role of oxytocin as a biological substrate underlying social bonding and the regulation of negative emotions.