Oxytocin Receptor Gene Variation and Differential Susceptibility to Family Environment in Predicting Youth Borderline Symptoms

Abstract

Oxytocin appears to be centrally involved in socioemotional functioning, and is hypothesized to be relevant to the severe disruption in close relationships characteristic of borderline personality pathology. We examined whether a polymorphism of the oxytocin receptor gene (OXTR rs53576) interacts with quality of family functioning to predict borderline personality disorder (BPD) symptomatology in a sample of youth at age 20. A total of 385 youth from a longitudinal study of offspring of depressed or nondepressed mothers who were well characterized with respect to their family conditions and BPD symptomatology provided DNA for genotyping. Analyses revealed a significant moderation of the link between early family quality and later BPD symptoms by OXTR rs53576, and the pattern was consistent with differential susceptibility (plasticity). Whereas A-allele carriers had high levels of BPD symptoms under negative family conditions and low levels under positive conditions, GG homozygotes had average levels of BPD symptoms regardless of their family quality.

On the role of oxytocin in borderline personality disorder

“…As regards (epi‐)genetics of the oxytocinergic system, there is some evidence in support of the view that variation of the OXTR gene follows a pattern consistent with differential susceptibility to environmental conditions (Amad et al ., ; Cicchetti et al ., ; Ellis, Shirtcliff, Boyce, Deardorff, & Essex, ; Hammen et al ., ) and that methylation of the OXTR through stressful early experiences may act as a proxy for the intergenerational transmission of insecure attachment patterns (van Ijzendoorn et al ., ). This perspective may have implications for the prevention of non‐genetic transmission of BPD over successive generations (Newman, Stevenson, Bergman, & Boyce, ; Stepp, Whalen, Pilkonis, Hipwell, & Levine, ).…”

“…Conversely, a recent study reported a diametrically opposite finding, whereby A‐allele carriers of the same SNP had high levels of BPD symptoms when raised by depressed mothers and low levels when grown up in families with non‐depressed mothers. GG homozygotes were unresponsive to early rearing conditions, suggesting that the SNP rs53576 of the OXTR gene could confer ‘differential susceptibility’ to environmental contingencies (Hammen, Bower, & Cole, ). The concept of differential susceptibility suggests that a particular allele can be associated with opposite outcomes concerning psychological traits, depending on the quality of early environmental experiences (Belsky et al ., ; Boyce & Ellis, ).…”

Oxytocin pathways in the intergenerational transmission of maternal early life stress

“…It must be acknowledged however that not all findings support the notion of OXTR rs53576 G allele carriers being more sensitive to the social environment (Hammen et al, 2015; McInnis et al, 2015; Thompson et al, 2014). For instance, OXTR rs53576 moderated the relationship between exposure to maternal depression in childhood and depressive symptoms at age 15 years (Thompson et al, 2014).…”

“…Presence of at least one A allele conferred higher risk to depressive symptoms in individuals whose mothers reported at least one episode of MDD during the child’s lifetime. There is also evidence for a differential susceptibility to develop symptoms of Borderline personality disorder (BPD) at age 20 in response to family quality in adolescence (Hammen et al, 2015). Under conditions of low familial constraint, presence of at least one A allele was associated with lower BPD symptoms compared to G allele homozygous participants, whereas under high family discord A allele carriers were more likely to develop more severe BPD symptoms than G allele homozygotes.…”

“…Under conditions of low familial constraint, presence of at least one A allele was associated with lower BPD symptoms compared to G allele homozygous participants, whereas under high family discord A allele carriers were more likely to develop more severe BPD symptoms than G allele homozygotes. These two studies (Hammen et al, 2015; Thompson et al, 2014) that found A allele carriers of the rs53576 SNP to be more susceptible to environmental variation do not discuss inconsistencies with studies in support of G allele carriers being more susceptible, which impedes the formulation of general conclusions. Together, the majority of findings clearly supports the G allele being associated with higher environmental sensitivity and consequently the G allele of the rs53576 SNP may be more accurately described as a plasticity allele.…”