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Published in: BMC Psychiatry 1/2018

Open Access 01-12-2018 | Research article

The role of oxytocin receptor gene (OXTR) DNA methylation (DNAm) in human social and emotional functioning: a systematic narrative review

Authors: Catherine Maud, Joanne Ryan, Jennifer E. McIntosh, Craig A. Olsson

Published in: BMC Psychiatry | Issue 1/2018

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Abstract

Background

The neuropeptide Oxytocin (OXT) plays a central role in birthing, mother-infant bonding and a broad range of related social behaviours in mammals. More recently, interest has extended to epigenetic programming of genes involved in oxytocinergic neurotransmission. This review brings together early findings in a rapidly developing field of research, examining relationships between DNA methylation (DNAm) of the Oxytocin Receptor Gene (OXTR) and social and emotional behaviour in human populations.

Method

A systematic search across Web of Knowledge/Science, Scopus, Medline and EMBASE captured all published studies prior to June 2017 examining the association between OXTR DNAm and human social and emotional outcomes. Search terms included ‘oxytocin gene’ or ‘oxytocin receptor gene’ and ‘epigenetics’ or ‘DNA methylation’. Any article with a focus on social and emotional functioning was then identified from this set by manual review.

Results

Nineteen studies met eligibility criteria. There was considerable heterogeneity of study populations, tissue samples, instrumentation, measurement, and OXTR site foci. Only three studies examined functional consequences of OXTR DNAm on gene expression and protein synthesis. Increases in OXTR DNAm were associated with callous-unemotional traits in youth, social cognitive deficits in Autistic Spectrum Disorder (ASD), rigid thinking in anorexia nervosa, affect regulation problems, and problems with facial and emotional recognition. In contrast, reductions in DNAm were associated with perinatal stress, postnatal depression, social anxiety and autism in children.

Conclusions

Consistent with an emerging field of inquiry, there is not yet sufficient evidence to draw conclusions about the role of OXTR DNAm in human social and emotional behaviour. However, taken together, findings point to increased OXTR DNAm in general impairments in social, cognitive and emotional functioning, and decreased OXTR DNAm in specific patterns of impairment related to mood and anxiety disorders (but not in all). Future progress in this field would be enhanced by adequately powered designs, greater phenotypic precision, and methodological improvements including longitudinal studies with multiple time-points to facilitate causal inference.
Literature
3.
go back to reference Swain JE, Tasgin E, Mayes LC, Feldman R, Constable RT, Leckman JF. Maternal brain response to own baby-cry is affected by cesarean section delivery. J Child Psychol Psychiatry. 2008;49(10):1042–52.CrossRefPubMedPubMedCentral Swain JE, Tasgin E, Mayes LC, Feldman R, Constable RT, Leckman JF. Maternal brain response to own baby-cry is affected by cesarean section delivery. J Child Psychol Psychiatry. 2008;49(10):1042–52.CrossRefPubMedPubMedCentral
5.
go back to reference Heinrichs M, Meinlschmidt G, Neumann I, Wagner S, Kirschbaum C, Ehlert U, Hellhammer DH. Effects of suckling on hypothalamic-pituitary-adrenal Axis responses to psychosocial stress in postpartum lactating women. J Clin Endocrinol Metab. 2001;86(10):4798–804.CrossRefPubMed Heinrichs M, Meinlschmidt G, Neumann I, Wagner S, Kirschbaum C, Ehlert U, Hellhammer DH. Effects of suckling on hypothalamic-pituitary-adrenal Axis responses to psychosocial stress in postpartum lactating women. J Clin Endocrinol Metab. 2001;86(10):4798–804.CrossRefPubMed
6.
go back to reference Hollander E, Bartz J, Chaplin W, Phillips A, Sumner J, Soorya L, Anagnostou E, Wasserman S. Oxytocin increases retention of social cognition in autism. Biol Psychiatry. 2007;61(4):498–503.CrossRefPubMed Hollander E, Bartz J, Chaplin W, Phillips A, Sumner J, Soorya L, Anagnostou E, Wasserman S. Oxytocin increases retention of social cognition in autism. Biol Psychiatry. 2007;61(4):498–503.CrossRefPubMed
7.
go back to reference Strathearn L, Fonagy P, Amico J, Montague PR. Adult attachment predicts maternal brain and oxytocin response to infant cues. Neuropsychopharmacol. 2009;34(13):2655–66.CrossRef Strathearn L, Fonagy P, Amico J, Montague PR. Adult attachment predicts maternal brain and oxytocin response to infant cues. Neuropsychopharmacol. 2009;34(13):2655–66.CrossRef
9.
go back to reference Buchheim A, Heinrichs M, George C, Pokorny D, Koops E, Henningsen P, O’Connor MF, Gundel H. Oxytocin enhances the experience of attachment security. Psychoneuroendocrinology. 2009;34(9):1417–22.CrossRefPubMedPubMedCentral Buchheim A, Heinrichs M, George C, Pokorny D, Koops E, Henningsen P, O’Connor MF, Gundel H. Oxytocin enhances the experience of attachment security. Psychoneuroendocrinology. 2009;34(9):1417–22.CrossRefPubMedPubMedCentral
10.
go back to reference Nader F, van Ijzendoorn MH, Deschamps P, van Engeland H, Bakermans-Kraneburg MJ. Intranasal oxytocin increases fathers’ observed responsiveness during play with their children: a double-blind within-subject experiment. Psychoneuroendocrinology 2010:35(10);1583–1586. Nader F, van Ijzendoorn MH, Deschamps P, van Engeland H, Bakermans-Kraneburg MJ. Intranasal oxytocin increases fathers’ observed responsiveness during play with their children: a double-blind within-subject experiment. Psychoneuroendocrinology 2010:35(10);1583–1586.
11.
go back to reference Kosfeld M, Heinrichs M, Zak PJ, Fischbacher U, Fehr E. Oxytocin increases trust in humans. Nature. 2005;435(7042):673–6.CrossRefPubMed Kosfeld M, Heinrichs M, Zak PJ, Fischbacher U, Fehr E. Oxytocin increases trust in humans. Nature. 2005;435(7042):673–6.CrossRefPubMed
12.
go back to reference Heinrichs M, Baumgartner T, Kirschbaum C, Ehlert U. Social support and oxytocin interact to suppress cortisol and subjective responses to psychosocial stress. Biol Psychiatry. 2003;54(12):1389–98.CrossRefPubMed Heinrichs M, Baumgartner T, Kirschbaum C, Ehlert U. Social support and oxytocin interact to suppress cortisol and subjective responses to psychosocial stress. Biol Psychiatry. 2003;54(12):1389–98.CrossRefPubMed
13.
go back to reference Guastella A, Einfeld S, Gray K, Rinehart N, Tonge B, Lambert T, Hickie I. Intranasal oxytocin improves emotion recognition for youth with autism spectrum disorders. Biol Psychiatry. 2010;67(7):692–4.CrossRefPubMed Guastella A, Einfeld S, Gray K, Rinehart N, Tonge B, Lambert T, Hickie I. Intranasal oxytocin improves emotion recognition for youth with autism spectrum disorders. Biol Psychiatry. 2010;67(7):692–4.CrossRefPubMed
14.
go back to reference Domes G, Heinrichs M, Glascher J, Buchel C, Braus D, Herpertz S. Oxytocin attenuates amygdala responses to emotional faces regardless of valence. Biol Psychiatry. 2007;62(10):1187–90.CrossRefPubMed Domes G, Heinrichs M, Glascher J, Buchel C, Braus D, Herpertz S. Oxytocin attenuates amygdala responses to emotional faces regardless of valence. Biol Psychiatry. 2007;62(10):1187–90.CrossRefPubMed
15.
go back to reference Neumann I, Landgraf R. Balance of brain oxytocin and vasopression: implications of anxiety, depression and social behaviours. Trends Neurosci. 2012;35(11):649–59.CrossRefPubMed Neumann I, Landgraf R. Balance of brain oxytocin and vasopression: implications of anxiety, depression and social behaviours. Trends Neurosci. 2012;35(11):649–59.CrossRefPubMed
16.
go back to reference Uvnas-Moberg K, Petersson M. Oxytocin, a mediator of anti-stress, well-being, social interaction, growth and healing. Z Psychosom Med Psychother. 2005;51(1):57–80.PubMed Uvnas-Moberg K, Petersson M. Oxytocin, a mediator of anti-stress, well-being, social interaction, growth and healing. Z Psychosom Med Psychother. 2005;51(1):57–80.PubMed
17.
go back to reference Carson DS, Berquist SW, Trujillo TH, Garner JP, Hannah SL, Hyde SA, Sumiyoshi RD, Jackson LP, Moss JK, Strehlow MC, Cheshier SH, Partap S, Hardan AY, Parker KJ. Cerebrospinal fluid and plasma oxytocin concentrations are positively correlated and negatively predict anxiety in children. Mol Psychiatry. 2015;20:1085–90.CrossRefPubMed Carson DS, Berquist SW, Trujillo TH, Garner JP, Hannah SL, Hyde SA, Sumiyoshi RD, Jackson LP, Moss JK, Strehlow MC, Cheshier SH, Partap S, Hardan AY, Parker KJ. Cerebrospinal fluid and plasma oxytocin concentrations are positively correlated and negatively predict anxiety in children. Mol Psychiatry. 2015;20:1085–90.CrossRefPubMed
18.
go back to reference Tabak BA, McCullough ME, Szeto A, Mendez AJ, McCabe PM. Oxytocin indexes relational distress following interpersonal harms in women. Psychoneuroendocrinology. 2005;36(1):115–22.CrossRef Tabak BA, McCullough ME, Szeto A, Mendez AJ, McCabe PM. Oxytocin indexes relational distress following interpersonal harms in women. Psychoneuroendocrinology. 2005;36(1):115–22.CrossRef
19.
go back to reference Meyer-Lindenberg A, Domes G, Kirsch P, Heinrichs M. Oxytocin and vasopressin in the human brain: social neuropeptides for translational medicine. Nat Rev Neurosci. 2011;12(9):524–38.CrossRefPubMed Meyer-Lindenberg A, Domes G, Kirsch P, Heinrichs M. Oxytocin and vasopressin in the human brain: social neuropeptides for translational medicine. Nat Rev Neurosci. 2011;12(9):524–38.CrossRefPubMed
20.
go back to reference Kimura T, Tanizawa O, Mori K, Brownstein MJ, Okayama H. Structure and expression of human oxytocin receptor. Nature. 1992;356(6369):526–9.CrossRefPubMed Kimura T, Tanizawa O, Mori K, Brownstein MJ, Okayama H. Structure and expression of human oxytocin receptor. Nature. 1992;356(6369):526–9.CrossRefPubMed
21.
go back to reference Mizumoto Y, Kimura T, Ivell R. A genomic element within the third intron of the human oxytocin receptor gene may be implicated in transcription suppression. Mol Cell Endocrinol. 1997;135(2):129–38.CrossRefPubMed Mizumoto Y, Kimura T, Ivell R. A genomic element within the third intron of the human oxytocin receptor gene may be implicated in transcription suppression. Mol Cell Endocrinol. 1997;135(2):129–38.CrossRefPubMed
22.
go back to reference Glimp G, Fahrenholz F. The oxytocin receptor system: structure, function and regulation. Physiol Rev. 2001;81(2):629–83.CrossRef Glimp G, Fahrenholz F. The oxytocin receptor system: structure, function and regulation. Physiol Rev. 2001;81(2):629–83.CrossRef
23.
go back to reference Feldman R, Monakhov M, Pratt M, Ebstein RP. Oxytocin pathway genes: evolutionary ancient system impacting on human affiliation, sociality and psychopathology. Biol Psychiatry. 2016;79(3):174–8.CrossRefPubMed Feldman R, Monakhov M, Pratt M, Ebstein RP. Oxytocin pathway genes: evolutionary ancient system impacting on human affiliation, sociality and psychopathology. Biol Psychiatry. 2016;79(3):174–8.CrossRefPubMed
24.
go back to reference Jacob S, Brunea CW, Carter CS, Leventhal BL, Lord C, Cook EH. Association of the oxytocin receptor gene (OXTR) in Caucasian children and adolescents with autism. Neurosci Lett. 2007;417(1):6–9.CrossRefPubMedPubMedCentral Jacob S, Brunea CW, Carter CS, Leventhal BL, Lord C, Cook EH. Association of the oxytocin receptor gene (OXTR) in Caucasian children and adolescents with autism. Neurosci Lett. 2007;417(1):6–9.CrossRefPubMedPubMedCentral
25.
go back to reference Apter-Levy MA, Feldman M, Vakart A, Ebstein RP, Feldman R. Impact of maternal depression across the first 6 years of life on the child's mental health, social engagement and empathy: the moderating role of oxytocin. Am J Psychiatry. 2013;170(10):1161–8.CrossRefPubMed Apter-Levy MA, Feldman M, Vakart A, Ebstein RP, Feldman R. Impact of maternal depression across the first 6 years of life on the child's mental health, social engagement and empathy: the moderating role of oxytocin. Am J Psychiatry. 2013;170(10):1161–8.CrossRefPubMed
26.
27.
go back to reference Skuse DH, Lori A, Cubells JF, Lee I, Conneely KN, Puura K, Lehtimaki T, Binder EB, Young L. Common polymorphism in the oxytocin receptor gene (OXTR) is associated with human social recognition skills. PNAS. 2014;111(5):1987–92.CrossRefPubMed Skuse DH, Lori A, Cubells JF, Lee I, Conneely KN, Puura K, Lehtimaki T, Binder EB, Young L. Common polymorphism in the oxytocin receptor gene (OXTR) is associated with human social recognition skills. PNAS. 2014;111(5):1987–92.CrossRefPubMed
28.
go back to reference Saphire-Bernstein S, Way BM, Kim HS, Sherman DK, Taylor SE. Oxytocin receptor gene (OXTR) is related to psychological resources. PNAS. 2011;108(37):15118–27.CrossRefPubMedPubMedCentral Saphire-Bernstein S, Way BM, Kim HS, Sherman DK, Taylor SE. Oxytocin receptor gene (OXTR) is related to psychological resources. PNAS. 2011;108(37):15118–27.CrossRefPubMedPubMedCentral
29.
go back to reference Rodrigues SM, Saslow LR, Garcia N, John OP, Keltner D. Oxytocin receptor genetic variation related to empathy and stress reactivity in humans. PNAS. 2009;106(50):21437–41.CrossRefPubMedPubMedCentral Rodrigues SM, Saslow LR, Garcia N, John OP, Keltner D. Oxytocin receptor genetic variation related to empathy and stress reactivity in humans. PNAS. 2009;106(50):21437–41.CrossRefPubMedPubMedCentral
30.
go back to reference Bakermans-Kranenburg MJ, van Ijzendoorn MH. Oxytocin receptor (OXTR) and serotonin transporter (5-HTT) genes associated with observed parenting. Soc Cog Affect Neurosci 2008;3(2):128–134. Bakermans-Kranenburg MJ, van Ijzendoorn MH. Oxytocin receptor (OXTR) and serotonin transporter (5-HTT) genes associated with observed parenting. Soc Cog Affect Neurosci 2008;3(2):128–134.
31.
go back to reference Feldman R, Zagoory-Sharon O, Weisman O, Schneiderman I, Gordon I, Maoz R, Shalev I, Ebstein RP. Sensitive parenting is associated with plasma oxytocin and ploymorphisms in the OXTR and CD 38 genes. Biol Psychiatry. 2012;72(3):175–81.CrossRefPubMed Feldman R, Zagoory-Sharon O, Weisman O, Schneiderman I, Gordon I, Maoz R, Shalev I, Ebstein RP. Sensitive parenting is associated with plasma oxytocin and ploymorphisms in the OXTR and CD 38 genes. Biol Psychiatry. 2012;72(3):175–81.CrossRefPubMed
32.
go back to reference Loth E, Poline J-B, Thyreau B, Jia T, Tao C, Lourdusamy A, Stacey D, Cattrell A, Desrivieres S, Ruggen B, Fritsch V, Banaschewski T, Barker GJ, ALW B, Buchel C, Carvalho FM, Conrod PJ, Fauth-Buehler M, Flor H, Gallinat J, Garavan H, Heinz A, Bruehl R, Lawrence C, Mann K, Martinot J-L, Nees F, Paus T, Pausova Z, Poustka L, Rietschel M, Smolka M, Struve M, Feng J, Schuman G, the IMAGEN Consortium. Oxytocin receptor genotype modulates ventral striatal activity to social cues and response to stressful life events. Biol Psychiatry. 2013;76(5):367–76.CrossRefPubMed Loth E, Poline J-B, Thyreau B, Jia T, Tao C, Lourdusamy A, Stacey D, Cattrell A, Desrivieres S, Ruggen B, Fritsch V, Banaschewski T, Barker GJ, ALW B, Buchel C, Carvalho FM, Conrod PJ, Fauth-Buehler M, Flor H, Gallinat J, Garavan H, Heinz A, Bruehl R, Lawrence C, Mann K, Martinot J-L, Nees F, Paus T, Pausova Z, Poustka L, Rietschel M, Smolka M, Struve M, Feng J, Schuman G, the IMAGEN Consortium. Oxytocin receptor genotype modulates ventral striatal activity to social cues and response to stressful life events. Biol Psychiatry. 2013;76(5):367–76.CrossRefPubMed
33.
go back to reference LoParo D, Waldman ID. The oxytocin receptor gene (OXTR) is associated with autism spectrum disorder: a meta-analysis. Mol Psychiatry. 2015;20(5):640–6.CrossRefPubMed LoParo D, Waldman ID. The oxytocin receptor gene (OXTR) is associated with autism spectrum disorder: a meta-analysis. Mol Psychiatry. 2015;20(5):640–6.CrossRefPubMed
35.
go back to reference Mamrut S, Harony H, Sood R, Shahar-Gold H, Gainer H, Shi YJ, Barki-Harrington L, Wagner S. DNA methylation of specific CpG sites in the promotor region regulates the transcription of the mouse oxytocin receptor. PLoS One. 2013;8(2):56869.CrossRef Mamrut S, Harony H, Sood R, Shahar-Gold H, Gainer H, Shi YJ, Barki-Harrington L, Wagner S. DNA methylation of specific CpG sites in the promotor region regulates the transcription of the mouse oxytocin receptor. PLoS One. 2013;8(2):56869.CrossRef
36.
go back to reference Harony Nicolas H, Mamrut S, Brodsky L, Shahar-Gold H, Barki-Harrington L, Wagner S. Brain region-specific methylation in the promoter of the murine oxytocin receptor gene is involved in its expression regulation. Psychoneuroendocrinology. 2014;39:121–31.CrossRefPubMed Harony Nicolas H, Mamrut S, Brodsky L, Shahar-Gold H, Barki-Harrington L, Wagner S. Brain region-specific methylation in the promoter of the murine oxytocin receptor gene is involved in its expression regulation. Psychoneuroendocrinology. 2014;39:121–31.CrossRefPubMed
37.
go back to reference Kusui C, Kimura T, Ogita K, Nakamura H, Matsumura Y, Koyama M, Azuma C, Murata Y. DNA methylation of the human oxytocin receptor gene promotor regulates tissue-specific gene suppression. Biochem Biophys Res Commun. 2001;289(3):681–6.CrossRefPubMed Kusui C, Kimura T, Ogita K, Nakamura H, Matsumura Y, Koyama M, Azuma C, Murata Y. DNA methylation of the human oxytocin receptor gene promotor regulates tissue-specific gene suppression. Biochem Biophys Res Commun. 2001;289(3):681–6.CrossRefPubMed
38.
go back to reference Chagnon YC, Potvin O, Hudon C, Preville M. DNA methylation and single nucleotide variants in the brain derived neurotrophic factor (BDNF) and oxytocin receptor (OXTR) genes are associated with anxiety/depression in older women. Front Genet. 2015;6:230.CrossRefPubMedPubMedCentral Chagnon YC, Potvin O, Hudon C, Preville M. DNA methylation and single nucleotide variants in the brain derived neurotrophic factor (BDNF) and oxytocin receptor (OXTR) genes are associated with anxiety/depression in older women. Front Genet. 2015;6:230.CrossRefPubMedPubMedCentral
39.
go back to reference Bell AF, Carter CS, Steer CD, Golding J, Davis JM, Steffen AD, Rubin LH, Lillard TS, Gregory SP, Harris JC, Connelly JJ. Interaction between oxytocin receptor DNA methylation and genotype is associated with risk of postpartum depression in women without depression in pregnancy. Front Genet. 2015;6:243.CrossRefPubMedPubMedCentral Bell AF, Carter CS, Steer CD, Golding J, Davis JM, Steffen AD, Rubin LH, Lillard TS, Gregory SP, Harris JC, Connelly JJ. Interaction between oxytocin receptor DNA methylation and genotype is associated with risk of postpartum depression in women without depression in pregnancy. Front Genet. 2015;6:243.CrossRefPubMedPubMedCentral
40.
go back to reference Reiner I, Van Ijzendoorn MH, Bakermans-Kranenburg MJ, Bleich S, Beutel M, Frieling H. Methylation of the oxytocin receptor gene in clinically depressed patients compared to controls: the role of OXTR rs 53576 genotype. J Psychiatr Res 2015;65:9–15. Reiner I, Van Ijzendoorn MH, Bakermans-Kranenburg MJ, Bleich S, Beutel M, Frieling H. Methylation of the oxytocin receptor gene in clinically depressed patients compared to controls: the role of OXTR rs 53576 genotype. J Psychiatr Res 2015;65:9–15.
41.
go back to reference Smearman EL, Almli M, Conneely KN, Brody GH, Sales JM, Bradley B, Ressler KJ, Smith AK. Oxytocin receptor genetic and epigenetic variations: association with child abuse and adult psychiatric symptoms. Child Dev. 2016;87(1):122–34.CrossRefPubMedPubMedCentral Smearman EL, Almli M, Conneely KN, Brody GH, Sales JM, Bradley B, Ressler KJ, Smith AK. Oxytocin receptor genetic and epigenetic variations: association with child abuse and adult psychiatric symptoms. Child Dev. 2016;87(1):122–34.CrossRefPubMedPubMedCentral
42.
go back to reference Bell JT, Tsai P-C, Yang T-P, Pidsley R, Nisbet J, Glass D, Mangino M, Zhai G, Zhang F, Valdes A, Shin S-Y, Dempster EL, Murray RM, Grundberg E, Hedman AK, Nica A, Small KS, The MuTHER Consortium, Dermitzakis ET, MI MC, Mill J, Spector TD, Deloukas P. Epigenome-wide scans identify differentially methylated regions for age and age-related phenotypes in a healthy ageing population. PLoS Genet. 2012;8(4):1002629.CrossRef Bell JT, Tsai P-C, Yang T-P, Pidsley R, Nisbet J, Glass D, Mangino M, Zhai G, Zhang F, Valdes A, Shin S-Y, Dempster EL, Murray RM, Grundberg E, Hedman AK, Nica A, Small KS, The MuTHER Consortium, Dermitzakis ET, MI MC, Mill J, Spector TD, Deloukas P. Epigenome-wide scans identify differentially methylated regions for age and age-related phenotypes in a healthy ageing population. PLoS Genet. 2012;8(4):1002629.CrossRef
43.
go back to reference Smith AK, Kilaru V, Kocak M, Almli LM, Mercer KB, Ressler KJ, Tylavsky FA, Conneely KN. Methylation quantitative trait loci (meQTLs) are consistently detected across ancestry, developmental stage, and tissue type. BMC Genomics. 2014;15:145.CrossRefPubMedPubMedCentral Smith AK, Kilaru V, Kocak M, Almli LM, Mercer KB, Ressler KJ, Tylavsky FA, Conneely KN. Methylation quantitative trait loci (meQTLs) are consistently detected across ancestry, developmental stage, and tissue type. BMC Genomics. 2014;15:145.CrossRefPubMedPubMedCentral
44.
go back to reference Lemerise AWF. An integrated model of emotion processes and cognition in social information processing. Child Dev. 2000;71(1):107–18.CrossRefPubMed Lemerise AWF. An integrated model of emotion processes and cognition in social information processing. Child Dev. 2000;71(1):107–18.CrossRefPubMed
45.
go back to reference Rijlaarsdam J, van IJzendoorn MH, Verhulst FC, Jaddoe VWV, Felix JF, Tiemeier H, Bakermans-Kranenburg MJ. Prenatal stress exposure, oxytocin receptor gene (OXTR) methylation and child autistic traits: the moderating role of OXTR rs53576 genotype. Autism Res. 2017;10:430–8.CrossRefPubMed Rijlaarsdam J, van IJzendoorn MH, Verhulst FC, Jaddoe VWV, Felix JF, Tiemeier H, Bakermans-Kranenburg MJ. Prenatal stress exposure, oxytocin receptor gene (OXTR) methylation and child autistic traits: the moderating role of OXTR rs53576 genotype. Autism Res. 2017;10:430–8.CrossRefPubMed
46.
go back to reference Gregory SG, Connelly JJ, Towers AJ, Johnson J, Biscocho D, Markunas CA, Lintas C, Abramson RK, Wright HH, Ellis P, Langford CF, Worley G, Delong GR, Murphy SK, Cuccaro M, Persico A, Pericak-Vance MA. Genomic and epigenetic evidence for oxytocin receptor deficiency in autism. BMC Med. 2009;7(62):1–13. Gregory SG, Connelly JJ, Towers AJ, Johnson J, Biscocho D, Markunas CA, Lintas C, Abramson RK, Wright HH, Ellis P, Langford CF, Worley G, Delong GR, Murphy SK, Cuccaro M, Persico A, Pericak-Vance MA. Genomic and epigenetic evidence for oxytocin receptor deficiency in autism. BMC Med. 2009;7(62):1–13.
47.
go back to reference Dadds MR, Moul C, Cauchi A, Dobson-Stone C, Hawes DJ, Brennan J, Ebstein RE. Methylation of the oxytocin receptor gene and oxytocin blood levels in the development of psychopathy. Dev Psychopathol. 2014;26(1):33–40.CrossRefPubMed Dadds MR, Moul C, Cauchi A, Dobson-Stone C, Hawes DJ, Brennan J, Ebstein RE. Methylation of the oxytocin receptor gene and oxytocin blood levels in the development of psychopathy. Dev Psychopathol. 2014;26(1):33–40.CrossRefPubMed
48.
go back to reference Rubin LH, Connelly JJ, Reilly JL, Carter CS, Drogos LL, Pournajafi-Nazarloo H, Ruocco AC, Keedy SK, Matthew I, Tandon N, Pearlson GD, Clementz BA, Tamminga CA, Gershon ES, Keshavan MS, Bishop JR, Sweeney JA. Sex and diagnosis-specific associations between DNA methylation of the oxytocin receptor gene with emotion processing and temporal-limbic and prefrontal brain volumes in psychotic disorders. Biol Psychiatry Cogn Neurosci Neuroimaging. 2016;1:141–51.CrossRefPubMed Rubin LH, Connelly JJ, Reilly JL, Carter CS, Drogos LL, Pournajafi-Nazarloo H, Ruocco AC, Keedy SK, Matthew I, Tandon N, Pearlson GD, Clementz BA, Tamminga CA, Gershon ES, Keshavan MS, Bishop JR, Sweeney JA. Sex and diagnosis-specific associations between DNA methylation of the oxytocin receptor gene with emotion processing and temporal-limbic and prefrontal brain volumes in psychotic disorders. Biol Psychiatry Cogn Neurosci Neuroimaging. 2016;1:141–51.CrossRefPubMed
49.
go back to reference Kim Y-R, Kim J-H, Kim MJ, Treasure J. Differential methylation of the oxytocin receptor gene in patients with anorexia nervosa: a pilot study. PLoS One. 2014;9(2):88673.CrossRef Kim Y-R, Kim J-H, Kim MJ, Treasure J. Differential methylation of the oxytocin receptor gene in patients with anorexia nervosa: a pilot study. PLoS One. 2014;9(2):88673.CrossRef
50.
go back to reference Jack A, Connelly JJ, Morris JP. DNA methylation of the oxytocin receptor gene predicts neural response to ambiguous social stimuli. Front Hum Neurosci. 2012;6(280):1–7. Jack A, Connelly JJ, Morris JP. DNA methylation of the oxytocin receptor gene predicts neural response to ambiguous social stimuli. Front Hum Neurosci. 2012;6(280):1–7.
51.
go back to reference Puglia MH, Lillard TS, Morris JP, Connelly JJ. Epigenetic modification of the oxytocin receptor gene influences the perception of anger and fear in the human brain. PNAS. 2015;112(11):3308–13.CrossRefPubMedPubMedCentral Puglia MH, Lillard TS, Morris JP, Connelly JJ. Epigenetic modification of the oxytocin receptor gene influences the perception of anger and fear in the human brain. PNAS. 2015;112(11):3308–13.CrossRefPubMedPubMedCentral
52.
go back to reference Unternaehrer E, Luers P, Mill J, Dempster E, Meyer AH, Staehli S, Lieb R, Hellhammer DH, Meinischmidt G. Dynamic changes in DNA methylation of stress-associated genes (OXTR, BDNF) after acute psychosocial stress. Transl Psychiatry. 2012;2(8):150.CrossRef Unternaehrer E, Luers P, Mill J, Dempster E, Meyer AH, Staehli S, Lieb R, Hellhammer DH, Meinischmidt G. Dynamic changes in DNA methylation of stress-associated genes (OXTR, BDNF) after acute psychosocial stress. Transl Psychiatry. 2012;2(8):150.CrossRef
53.
go back to reference Ziegler C, Dannlowski U, Brauer D, Stevens S, Laeger I, Wittmann H, Kugel H, Dobel C, Hurlemann R, Reif A, Lesch K-P, Heindel W, Kirschbaum C, Arolt V, Gerlach AL, Hoyer J, Deckert J, Zwanzger P, Domschke K. Oxytocin receptor gene methylation: converging multilevel evidence for a role in social anxiety. Neuropsychopharmacol. 2015;40:1528–38.CrossRef Ziegler C, Dannlowski U, Brauer D, Stevens S, Laeger I, Wittmann H, Kugel H, Dobel C, Hurlemann R, Reif A, Lesch K-P, Heindel W, Kirschbaum C, Arolt V, Gerlach AL, Hoyer J, Deckert J, Zwanzger P, Domschke K. Oxytocin receptor gene methylation: converging multilevel evidence for a role in social anxiety. Neuropsychopharmacol. 2015;40:1528–38.CrossRef
54.
go back to reference Cappi C, Diniz JB, Requena GL, Lourenço T, Lisboa BCG, Batistuzzo MC, Marques AH, Hoexter MQ, Pereira CA, Miguel EC, Brentani H. Epigenetic evidence for involvement of the oxytocin receptor gene in obsessive– compulsive disorder. BMC Neurosci. 2016;17(1):79.CrossRefPubMedPubMedCentral Cappi C, Diniz JB, Requena GL, Lourenço T, Lisboa BCG, Batistuzzo MC, Marques AH, Hoexter MQ, Pereira CA, Miguel EC, Brentani H. Epigenetic evidence for involvement of the oxytocin receptor gene in obsessive– compulsive disorder. BMC Neurosci. 2016;17(1):79.CrossRefPubMedPubMedCentral
55.
go back to reference Unternaehrer E, Bolten M, Nast I, Staehli S, Meyer AH, Dempster E, Hellhammer DH, Lieb R, Meinlschmidt G. Maternal adversities during pregnancy and cord blood oxytocin receptor (OXTR) DNA methylation. Soc Cogn Affect Neurosci. 2016;11(9):1460–70.CrossRefPubMedPubMedCentral Unternaehrer E, Bolten M, Nast I, Staehli S, Meyer AH, Dempster E, Hellhammer DH, Lieb R, Meinlschmidt G. Maternal adversities during pregnancy and cord blood oxytocin receptor (OXTR) DNA methylation. Soc Cogn Affect Neurosci. 2016;11(9):1460–70.CrossRefPubMedPubMedCentral
56.
go back to reference Kimmel M, Clive M, Gispen F, Guintivano J, Brown T, Cox O, Beckmann MW, Kornhuber J, Fasching PA, Osborne LM, Binder E, Payne JL, Kaminsky Z. Oxytocin receptor DNA methylation in postpartum depression. Psychoneuroendocrinology. 2016;69:150–60.CrossRefPubMed Kimmel M, Clive M, Gispen F, Guintivano J, Brown T, Cox O, Beckmann MW, Kornhuber J, Fasching PA, Osborne LM, Binder E, Payne JL, Kaminsky Z. Oxytocin receptor DNA methylation in postpartum depression. Psychoneuroendocrinology. 2016;69:150–60.CrossRefPubMed
57.
go back to reference Unternaehrer E, Meyer AH, Burkhardt SCA, Dempster E, Staehli S, Theill N, Lieb R, Meinischmidt G. Childhood maternal care is associated with DNA methylation of the genes for brain-derived neurotrophic factor (BDNF) and oxytocin receptor (OXTR) in peripheral cells adult men and women. Stress. 2015;18(4):451–61.CrossRefPubMed Unternaehrer E, Meyer AH, Burkhardt SCA, Dempster E, Staehli S, Theill N, Lieb R, Meinischmidt G. Childhood maternal care is associated with DNA methylation of the genes for brain-derived neurotrophic factor (BDNF) and oxytocin receptor (OXTR) in peripheral cells adult men and women. Stress. 2015;18(4):451–61.CrossRefPubMed
58.
go back to reference Cecil CAM, Lysenko LJ, Jaffee SR, Pingault J-B, Smith RG, Relton CL, Woodward G, McArdle W, Mill J, Barker ED. Environmental risk, oxytocin receptor gene (OXTR) methylation and youth callous-unemotional traits: a 13-year longitudinal study. Mol Psychiatry. 2014;19(10):1071–7.CrossRefPubMedPubMedCentral Cecil CAM, Lysenko LJ, Jaffee SR, Pingault J-B, Smith RG, Relton CL, Woodward G, McArdle W, Mill J, Barker ED. Environmental risk, oxytocin receptor gene (OXTR) methylation and youth callous-unemotional traits: a 13-year longitudinal study. Mol Psychiatry. 2014;19(10):1071–7.CrossRefPubMedPubMedCentral
59.
go back to reference Dadds MR, Moul C, Cauchi A, Dobston-Stone C, Hawes DJ, Brennan J, Urwin R, Ebstein RE. Polymorphisms in the oxytocin receptor gene are associated with the development of psychopathy. Dev Psychopathol. 2014;26(1):21–31.CrossRefPubMed Dadds MR, Moul C, Cauchi A, Dobston-Stone C, Hawes DJ, Brennan J, Urwin R, Ebstein RE. Polymorphisms in the oxytocin receptor gene are associated with the development of psychopathy. Dev Psychopathol. 2014;26(1):21–31.CrossRefPubMed
60.
go back to reference Elagoz Yuksel M, Yuceturk B, Karatas OF, Ozen M, Dogangun B. The altered promoter methylation of oxytocin receptor gene in autism. J Neurogenet. 2016;30(3–4):280–4.CrossRefPubMed Elagoz Yuksel M, Yuceturk B, Karatas OF, Ozen M, Dogangun B. The altered promoter methylation of oxytocin receptor gene in autism. J Neurogenet. 2016;30(3–4):280–4.CrossRefPubMed
61.
go back to reference Lowe R, Gemma C, Beyan H, Hawa MI, Bazeos A, Leslie RD, Monpetit A, Rakyan VK, Ramagopalan SV. Buccals are likely to be a more informative surrogate tissue than blood for epigenome-wide association studies. Epigenetics. 2013;8(4):1–10.CrossRef Lowe R, Gemma C, Beyan H, Hawa MI, Bazeos A, Leslie RD, Monpetit A, Rakyan VK, Ramagopalan SV. Buccals are likely to be a more informative surrogate tissue than blood for epigenome-wide association studies. Epigenetics. 2013;8(4):1–10.CrossRef
62.
go back to reference Ng JWY, Barrett LM, Wong A, Kuh A, Smith GD, Relton CL. The role of longitudinal cohort studies in epigenetic epidemiology: challenges and opportunities. Genome Biol. 2012;13:246.CrossRefPubMedPubMedCentral Ng JWY, Barrett LM, Wong A, Kuh A, Smith GD, Relton CL. The role of longitudinal cohort studies in epigenetic epidemiology: challenges and opportunities. Genome Biol. 2012;13:246.CrossRefPubMedPubMedCentral
63.
go back to reference Boyd A, Golding J, Macleod J, Lawlor DA, Fraser A, Henderson J, Molloy L, Ness A, Ring S, Davey SG. Cohort profile: the "children of the 90s" - the index offspring of the Avon longitudinal study of parents and children. Int J Epidemiol. 2013;42(1):111–27.CrossRefPubMed Boyd A, Golding J, Macleod J, Lawlor DA, Fraser A, Henderson J, Molloy L, Ness A, Ring S, Davey SG. Cohort profile: the "children of the 90s" - the index offspring of the Avon longitudinal study of parents and children. Int J Epidemiol. 2013;42(1):111–27.CrossRefPubMed
64.
65.
go back to reference Ainsworth MDS, Bell S. Attachment, exploration and separation: illustrated by the behaviour of one-year-olds in a strange situation. Child Dev. 1970;41(1):49–67.CrossRefPubMed Ainsworth MDS, Bell S. Attachment, exploration and separation: illustrated by the behaviour of one-year-olds in a strange situation. Child Dev. 1970;41(1):49–67.CrossRefPubMed
66.
go back to reference Gluckman PD, Hanson MA. Developmental origin of disease paradigm: a mechanistic and evolutionary perspective. Pediatr Res. 2004;56(3):311–7.CrossRefPubMed Gluckman PD, Hanson MA. Developmental origin of disease paradigm: a mechanistic and evolutionary perspective. Pediatr Res. 2004;56(3):311–7.CrossRefPubMed
Metadata
Title
The role of oxytocin receptor gene (OXTR) DNA methylation (DNAm) in human social and emotional functioning: a systematic narrative review
Authors
Catherine Maud
Joanne Ryan
Jennifer E. McIntosh
Craig A. Olsson
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Psychiatry / Issue 1/2018
Electronic ISSN: 1471-244X
DOI
https://doi.org/10.1186/s12888-018-1740-9

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