Interaction effect of oxytocin receptor (OXTR) rs53576 genotype and maternal postpartum depression on child behavioural problems

Abstract

Previous studies have reported interaction effects of oxytocin receptor genotype (rs53576) and environmental factors on mental health in youth. However, the findings are mixed, especially regarding the type of allele (i.e., A vs. G), and it remains unanswered whether such an interaction presents at an early stage of development. Thus, using a unique longitudinal birth cohort sample in Japan ( n = 568), we examined whether there was an effect of the interaction between the OXTR rs53576 genotype and maternal postpartum depression, as an environmental risk, on behavioural problems in children. Child behavioural problems (internalising and externalising problems) were ascertained using the Strengths and Difficulties Questionnaire when children were 6 years old. Maternal postpartum depression was measured using the Edinburgh Postnatal Depression Scale when children were at 2 months and 10 months of age. The results revealed a significant effect in the interaction between OXTR rs53576 genotype and maternal postpartum depression on externalising problems in children with AA genotype ( β = 0.136, 95% CI 0.032 to 0.240), but not in those with GG/GA genotype. This indicates that an interaction of vulnerable genotypes (i.e., A allele of OXTR rs53576) with an environmental burden (i.e. maternal postpartum depression) may be one of the potential elements that predisposes the infant to developing behavioural problems early in life. Hence, special attention needs to be paid to children exposed to environmental risks such as maternal postpartum depression, to facilitate the provision of appropriate care.

AVPR1A main effect and OXTR-by-environment interplay in individual differences in depression level

“…To date multiple efforts to unravel GxE interactions affecting depression-like behavior have been conducted, which demonstrated the interrelation of stress-related factors occurred at pre- and postnatal levels of development and OXTR gene polymorphisms. These studies reported a modulating effect of childhood adversity experienced by responders ( Park et al., 2019 ) or by their mother in childhood ( Elwood et al., 2019 ; Mileva-Seitz et al., 2013 ), maternal postnatal depression ( Choi et al., 2019 ), and even their child's OXTR genotype ( Asherin et al., 2019 ). Previously, an interaction between OXTR rs2254298 and the quality of the parental environment was reported to affect symptoms of depression and anxiety in female adolescents ( Thompson et al., 2011 ).…”

“…Since an interaction between childhood maltreatment and OXTR methylation at multiple CpG sites predicted depressive symptoms later in ontogenesis (Misra et al, 2019;Smearman et al, 2016), it was suggested that OXTR methylation might moderate, rather than mediate, the association between childhood abuse and depression (Park et al, 2019). According to previous research consistent with a diathesis-stress model (Augustine et al, 2018), rs53576 A-allele was frequently associated with psychopathologies correlated with an increased sensitivity to stress (Saphire-Bernstein et al, 2011;Choi et al, 2019). Despite the suggestion that individuals homozygous for the G-allele may exhibit greater sensitivity to social experiences (Asherin et al, 2019), the present findings oppositely demonstrated that A-allele carriers appeared to be more sensitive to parenting style (presumably, to the level of paternal interest in their lives) compared to those with GG genotypes.…”

“…Since oxytocin was shown to regulate different social behaviors including social recognition, affiliation and response to threat ( Meyer-Lindenberg et al., 2011 ; Skuse and Gallagher, 2009 ) via regulation of HPA axis and attenuate amygdala's response to stress ( Bernhard et al., 2016 ), the OXTR gene became explored with respect to depressive mood, stress reactivity, antisocial behavior, emotional loneliness ( Inoue et al., 2010 ; Kang et al., 2017 ; Kawamura et al., 2010 ; LoParo et al., 2016 ; Lucht et al., 2009 ; Thompson et al., 2011 ). Congruent with a suggestion that variations in the OXTR gene may differentially affect oxytocin regulation moderated by the effect of family environment, several studies clarified the effect of gene-by-environment interactions based on the OXTR gene variants in clinical samples ( Asherin et al., 2019 ; Choi et al., 2019 ; Elwood et al., 2019 ; Park et al., 2019 ; Parris et al., 2018 ). However, no findings of OXTR -by-environment effect on depressive-like behavior in non-clinical cohort were published to date.…”

Associations between maternal depression and mother and infant oxytocin receptor gene (OXTR_rs53576) polymorphisms

“…Maternal OXTR_rs53576 genotype was not assessed. Choi, Tsuchiya, and J., & Nori, T. () reported that behavioral difficulties in Japanese 6‐year‐olds whose mothers had experienced postpartum depression were significant only in children with the OXTR_rs53576 AA genotype. Kryski, Smith, Sheikh, Singh, and Hayden () showed that 3‐year‐olds with the OXTR_rs53576 AA genotype exhibited significantly more negative emotionality and behavior than those with at least one G allele, and further that negative infant behavior mediated the relation between infant genotype and lower parenting competence.…”

Oxytocin Pathway Genes (CD38, OXTR) and Psychosocial Characteristics Defined According to Strengths and Difficulties Questionnaire in Urban Siberian Adolescents: A School-based Study

“…These data correlate with the results of our study, which show relatively greater emotionality -in some cases, reaching problematic degree -in adolescents with genotypes corresponding to high production and reception of OT. Choi et al [48] showed that the carriage of the A allele of OXTR rs53576 in a homozygous state, in combination with the occurrence of postpartum depression in the mother, was associated with a high risk of conduct problems and hyperactivity in 6-year-old children. In our study, no association was found between the carriage of the OXTR rs53576 A allele and conduct problems in adolescents.…”