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

Abstract

Polymorphisms in the oxytocin receptor gene, OXTR_rs53576, have been linked to differences in maternal sensitivity and depressive symptoms. Although some studies suggest the A allele confers risk for mood disorders, individuals homozygous for the G allele may exhibit greater sensitivity to both positive and negative social experiences, including in the mother-infant dyad. Given the bi-directional nature of mother-infant influences on maternal mood, we tested the association between both mothers' and infants' OXTR_rs53576 genotype and maternal depression, as assessed through a self-report inventory. Although Beck Depression Inventory (BDI-II) scores were significantly higher for GG in comparison to AG/AA mothers, and for mothers of GG in comparison to AG/AA infants, an ANCOVA revealed that after sociodemographic risk factors had been controlled, infants', but not mothers', OXTR genotype predicted maternal depression scores, with no significant interaction between the two. The effect of infant OXTR on maternal depression was not explained by maternal reports of difficult infant temperament. We propose that GG infants have an enhanced capacity for processing both positive and negative socially meaningful contextual information, first amplifying and then differentially perpetuating negative affectivity in mothers who exhibit depressive characteristics. K E Y W O R D Sinfant temperament, mood disorders, oxytocin receptor gene, postpartum depression | 497 ASHERIN Et Al.

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

“…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. Therefore, together with the “plasticity genes model” the data obtained allow to hypothesize that A-allele is a plasticity marker, contributing to a greater sensitivity to both positive and negative environmental influences.…”

“…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 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.…”

Oxytocin and postpartum depression - a possible treatment for depressed mothers

“…Similar patterns of methylation density in oxytocin receptor gene were observed in women with perinatal depression and with insecure attachment style, which indicates association between those two characteristics [43]. Moreover, it was proposed that infants' oxytocin receptor genotype might also alter the behaviour of mothers who exhibit depressive characteristics [44]. Oxytocin seems to interact also with serotonergic system.…”

Roles of the Oxytocin Receptor (OXTR) in Human Diseases

“…As evidenced above, the published conclusions on the role of OXTR polymorphism and methylation in depression are contradictory, making the question unanswered. There were further studies showing the influence of the rs53576 polymorphism on different aspects of depression, such as negative social interactions [ 74 ], prepulse inhibition of the startle reflex and startle reactivity [ 75 ], interpersonal risk factors [ 76 ], suicide attempts [ 77 ], hippocampal volume [ 78 ], effects of social environment on postpartum depression [ 79 , 80 ], negative affectivity [ 81 ], trauma-related psychopathology [ 82 ], and work stress [ 83 ]. However, other reports presented results showing no correlations between depression and the rs53576 polymorphism in the OXTR gene [ 84 , 85 , 86 , 87 , 88 ].…”