Does The Oxytocin System Modulate The Effect Of Childhood Trauma On Depression And Anxiety?

Childhood trauma（CT）generally refers to a series of adverse life events,experiences or treatment in early life,which lead to bad mental state,physical disease or social dysfunction after childhood or adulthood of those who experience it.CT is the main risk factor for a series of mental diseases,such as bipolar disorder,depression,anxiety,schizophrenia,addiction,post-traumatic stress disorder（PTSD）and so on.Epidemiological studies have shown that individuals with childhood trauma are at high risk of depression,anxiety,or both.Meanwhile,there are more and more researches on oxytocin and it’s receptor worldwide.Brain oxytocin system has been used as a potential system to treat anxiety,depression and fear related diseases,including social anxiety disorder,depression and PTSD.And nasal spray oxytocin has been used as a new potential treatment drug for schizophrenia,anxiety and depression patients.However,the mechanism of oxytocin system in individuals with CT influence on depression and anxiety is not clear.Therefore,the aim of this study is to explore whether oxytocin system can modulate the effect of childhood trauma on anxiety and depression from the oxytocin receptor gene（OXTR）and the level of oxytocin in blood.We performed two experiments:The first is mainly to explore whether the oxytocin receptor gene can modulate anxiety and depression in individuals experiencing childhood trauma.We recruited 242 healthy male and female subjects to participate in the experiment.buccal cells samples were collected for the determination of the single nucleotide polymorphism allele and genotype of the oxytocin receptor gene.And relevant questionnaires were completed,including Beck Depression Inventory（BDI）,State-Trait Anxiety Inventory（STAI）,Childhood Trauma Questionnaire（CTQ）.Based on previous studies,we explored five of the widely studied OXTR:rs2254298,rs2268498,rs2268498,rs237887 and rs53576.The moderate effects of different OXTR on depression and anxiety in individuals experiencing childhood trauma were mainly investigated using the moderate effect analysis（StudyⅠ）.The second study is mainly to explore whether blood oxytocin levels can moderate anxiety and depression in individuals experiencing childhood trauma.We recruited 130 healthy male subjects to participate in the experiment.We collected venous blood samples for plasma oxytocin level analysis.The subjects also completed same questionnaires as the first experiment.First,we did median-split group according to the questionnaire scores,and then two-way ANOVAs[2 CTQ group（high/low）×2 BDI group（high/low）or 2 CTQ group（high/low）×2 TAI group（high/low）]was conducted to investigate the differences in blood oxytocin level（Study II）.The results of studyⅠshowed that rs2254298 genotype significantly moderated the correlation between early childhood trauma and BDI scores.With post hoc tests indicating that higher childhood trauma（higher CTQ）was selectively correlated with higher BDI scores in GG carriers(t_（235）=3.97,P=0.0001).Similarly,rs2268498significantly moderated the association between childhood trauma and depression.With post hoc tests indicating that higher childhood trauma（higher CTQ）was selectively associated with higher BDI score(t_（231）=3.87,P=0.0001)in TT genotype.In addition,rs2254298 genotype significantly moderated the relationship between childhood trauma and anxiety.With post hoc tests showing that higher childhood trauma（higher CTQ）was selectively associated with higher anxiety score in GG carriers(t_（235）=3.78,P=0.0002).In StudyⅡ,we firstly conducted moderate effect analysis with oxytocin level as a moderate variable,childhood trauma level（CTQ score）as an independent variable,anxiety level（TAI score）and depression level（BDI score）as dependent variables,but nothing significant moderating effect was found（anxiety:P=0.112;depression:P=0.57）.Univariate ANOVA results suggested that we did not find any significant results[main effect of CTQ group,F_（1,126）=0.17,P=0.68;main effect of BDI group,F_（1,126）=0.11,P=0.74,interaction,F_（1,126）=1.34,P=0.25].On the other hand,nothing was significant using two-way CTQ group×TAI group ANOVA[main effect of CTQ group,F_（1,126）=0.06,P=0.80;main effect of TAI group,F_（1,126）=0.13,P=0.72;interaction,F_（1,126）=2.82,P=0.10].In conclusion,the results of studyⅠshowed that higher levels of childhood trauma were selectively associated with higher depression and anxiety scores in individuals with OXTR rs2254298 GG carriers,that is,with OXTR rs2254298 GG genotype,the more severe early childhood trauma,the higher depression and anxiety scores.In addition,for OXTR rs2268498 TT carriers,a higher score of childhood trauma was selectively associated with a higher anxiety score,that is,with OXTR the rs2268498 TT genotype,the more severe early childhood trauma,the higher the depression score.The results of studyⅡusing moderate effect analysis and ANOVA indicated that the oxytocin level in the blood of individuals suffering childhood trauma had no significant moderate effect on anxiety and depression.In summary,one of the oxytocin system-OXTR moderate the effect of childhood trauma on anxiety and depression and we should consider OXTR in the future studies.