A Role of Oxytocin Receptor Gene Brain Tissue Expression Quantitative Trait Locus rs237895 in the Intergenerational Transmission of the Effects of Maternal Childhood Maltreatment

J Am Acad Child Adolesc Psychiatry. 2019 Dec;58(12):1207-1216. doi: 10.1016/j.jaac.2019.03.006. Epub 2019 Mar 9.


Objective: Women exposed to childhood maltreatment (CM) are more likely to exhibit insensitive parenting, which may have consequences for their offspring's development. Variation in the oxytocin-receptor gene (OXTR) moderates risk of CM-associated long-term sequelae associated with mother-child attachment, although functionality of previously investigated single nucleotide polymorphisms (SNPs) remained elusive. Here, we investigated the role of OXTR rs237895, a brain tissue expression quantitative trait locus (eQTL), as a moderator of the relationship between CM and maternal behavior (MB) and the association between MB and offspring attachment security.

Method: Of 110 women with information on rs237895 genotype (T-allele = 64, CC = 46), 107 had information on CM (CTQ) and 99 on standardized observer-based ratings of MB at 6 months postpartum (responsivity and detachment), which were used in principal component analysis to obtain a latent factor representing MB. Offspring (n = 86) attachment was evaluated at 12 months of age. Analyses predicting MB were adjusted for socioeconomic status, age, postpartum depression, and genotype-based ethnicity. Analyses predicting child attachment were adjusted for infant sex, socioeconomic status, and postpartum depression.

Results: rs237895 significantly moderated the relationship between CM and MB (F1;66 = 7.99, p < .01), indicating that CM was associated with maternal insensitivity only in high-OXTR-expressing T-allele carriers but not in low-OXTR-expressing CC homozygotes. Moreover, maternal insensitivity predicted offspring insecure attachment (B = -0.551; p < .05).

Conclusion: Women with a high OXTR expressing genotype are more susceptible to CM-related impairments in MB that, in turn, predict attachment security in their children, supporting the role of the OT system in the intergenerational transmission of risk associated with maternal CM.

Keywords: childhood maltreatment; cxytocin receptor gene; gene-environment interaction; intergenerational transmission; parenting.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Adult Survivors of Child Abuse / psychology*
  • Alleles
  • Depression, Postpartum / etiology
  • Depression, Postpartum / genetics
  • Female
  • Gene-Environment Interaction
  • Genotype
  • Humans
  • Infant
  • Mother-Child Relations / psychology*
  • Mothers / psychology*
  • Object Attachment*
  • Oxytocin / metabolism
  • Polymorphism, Single Nucleotide
  • Quantitative Trait Loci
  • Reactive Attachment Disorder / genetics
  • Reactive Attachment Disorder / psychology
  • Receptors, Oxytocin / genetics*
  • Regression Analysis
  • Stress, Psychological
  • Young Adult


  • OXTR protein, human
  • Receptors, Oxytocin
  • Oxytocin