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

Philipp Toepfer, Kieran J. O'Donnell, Sonja Entringer, Christine Marcelle Heim, David T.S. Lin, Julia L. MacIsaac, Michael S. Kobor, Michael J. Meaney, Nadine Provençal, Elisabeth B. Binder, Pathik D. Wadhwa, Claudia Buss

Research output: Contribution to journalArticle

Abstract

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.

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Oxytocin Receptors
Maternal Behavior
Quantitative Trait Loci
Mothers
Brain
Genes
Postpartum Depression
Genotype
Social Class
Alleles
Parenting
Homozygote
Principal Component Analysis
Postpartum Period
Single Nucleotide Polymorphism

All Science Journal Classification (ASJC) codes

  • Developmental and Educational Psychology
  • Psychiatry and Mental health

Cite this

Toepfer, Philipp ; O'Donnell, Kieran J. ; Entringer, Sonja ; Heim, Christine Marcelle ; Lin, David T.S. ; MacIsaac, Julia L. ; Kobor, Michael S. ; Meaney, Michael J. ; Provençal, Nadine ; Binder, Elisabeth B. ; Wadhwa, Pathik D. ; Buss, Claudia. / A Role of Oxytocin Receptor Gene Brain Tissue Expression Quantitative Trait Locus rs237895 in the Intergenerational Transmission of the Effects of Maternal Childhood Maltreatment. In: Journal of the American Academy of Child and Adolescent Psychiatry. 2019.
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title = "A Role of Oxytocin Receptor Gene Brain Tissue Expression Quantitative Trait Locus rs237895 in the Intergenerational Transmission of the Effects of Maternal Childhood Maltreatment",
abstract = "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.",
author = "Philipp Toepfer and O'Donnell, {Kieran J.} and Sonja Entringer and Heim, {Christine Marcelle} and Lin, {David T.S.} and MacIsaac, {Julia L.} and Kobor, {Michael S.} and Meaney, {Michael J.} and Nadine Proven{\cc}al and Binder, {Elisabeth B.} and Wadhwa, {Pathik D.} and Claudia Buss",
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A Role of Oxytocin Receptor Gene Brain Tissue Expression Quantitative Trait Locus rs237895 in the Intergenerational Transmission of the Effects of Maternal Childhood Maltreatment. / Toepfer, Philipp; O'Donnell, Kieran J.; Entringer, Sonja; Heim, Christine Marcelle; Lin, David T.S.; MacIsaac, Julia L.; Kobor, Michael S.; Meaney, Michael J.; Provençal, Nadine; Binder, Elisabeth B.; Wadhwa, Pathik D.; Buss, Claudia.

In: Journal of the American Academy of Child and Adolescent Psychiatry, 01.01.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A Role of Oxytocin Receptor Gene Brain Tissue Expression Quantitative Trait Locus rs237895 in the Intergenerational Transmission of the Effects of Maternal Childhood Maltreatment

AU - Toepfer, Philipp

AU - O'Donnell, Kieran J.

AU - Entringer, Sonja

AU - Heim, Christine Marcelle

AU - Lin, David T.S.

AU - MacIsaac, Julia L.

AU - Kobor, Michael S.

AU - Meaney, Michael J.

AU - Provençal, Nadine

AU - Binder, Elisabeth B.

AU - Wadhwa, Pathik D.

AU - Buss, Claudia

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

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