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Methylation of the oxytocin receptor gene and oxytocin blood levels in the development of psychopathy
Abstract
Child conduct problems (CPs) are a robust predictor of adult mental health; the concurrence of callous-unemotional (CU) traits confers specific risk for psychopathy. Psychopathy may be related to disturbances in the oxytocin (OXT) system. Evidence suggests that epigenetic changes in the OXT receptor gene (OXTR) are associated with lower circulating OXT and social-cognitive difficulties. We tested methylation levels of OXTR in 4- to 16-year-old males who met DSM criteria for a diagnosis of oppositional-defiant or conduct disorder and were stratified by CU traits and age. Measures were DNA methylation levels of six CpG sites in the promoter region of the OXTR gene (where a CpG site is a cytosine nucleotide occurs next to a guanine nucleotide in the linear sequence of bases along its lenth, linked together by phosphate binding), and OXT blood levels. High CU traits were associated with greater methylation of the OXTR gene for two cytosine nucleotide and guanine nucleotide phosphate linked sites and lower circulating OXT in older males. Higher methylation correlated with lower OXT levels. We conclude that greater methylation of OXTR characterizes adolescent males with high levels of CU and CPs, and this methylation is associated with lower circulating OXT and functional impairment in interpersonal empathy. The results add genetic evidence that high CU traits specify a distinct subgroup within CP children, and they suggest models of psychopathy may be informed by further identification of these epigenetic processes and their functional significance.
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“Our findings are in line with emerging evidence (Dadds et al., 2014; Haas et al., 2016) suggesting that epigenetic modification of genes regulating OT pathways and endogenous OT levels are associated with the way people form and maintain intimate social relationships with others.”
From Associations between oxytocin receptor gene (OXTR) methylation, plasma oxytocin, and attachment across adulthood (2019) · cites this paper as Dadds et al., 2014
In the citing paper
“When looking at only the older boys in their sample, however, they observed a negative relationship (i.e., higher OXTR methylation levels were associated with lower plasma OT levels in boys aged 9–16 years).”
From Associations between oxytocin receptor gene (OXTR) methylation, plasma oxytocin, and attachment across adulthood (2019) · cites this paper as Dadds et al. (2014)
In the citing paper
“Also, Dadds et al. (2014) found no associations between OXTR methylation and plasma OT in their total sample of young and older boys.”
From Associations between oxytocin receptor gene (OXTR) methylation, plasma oxytocin, and attachment across adulthood (2019) · cites this paper as Dadds et al. (2014)
Citations
Cites
The Strengths and Difficulties Questionnaire: A research note
Goodman, R. (1997) · Journal of Child Psychology and Psychiatry · doi:10.1111/j.1469-7610.1997.tb01545.x · Cited by 14,908
Adolescence-limited and life-course-persistent antisocial behavior: a developmental taxonomy
Moffitt, T. E. (1993) · Psychological Review · doi:10.1037/0033-295x.100.4.674 · Cited by 9,987
A self‐report measure of pubertal status: Reliability, validity and initial norms
Petersen, A. C., Crockett, L., Richards, M., & Boxer, A. (1988) · Journal of Youth and Adolescence · doi:10.1007/bf01537962 · Cited by 3,129
Kim-Cohen, J., Caspi, A., Moffitt, T. E., Harrington, H., Milne, B. J., & Poulton, R. (2003) · Archives of General Psychiatry · doi:10.1001/archpsyc.60.7.709 · Cited by 2,025
Oxytocin and vasopressin in the human brain: social neuropeptides for translational medicine
Meyer-Lindenberg, A., Domes, G., Kirsch, P., & Heinrichs, M. (2011) · Nature Reviews Neuroscience · doi:10.1038/nrn3044 · Cited by 1,688
Frick, P. J., & White, S. F. (2008) · Journal of Child Psychology and Psychiatry · doi:10.1111/j.1469-7610.2007.01862.x · Cited by 1,290
Dissociable neural responses to facial expressions of sadness and anger
Blair, R. J. R., Morris, J. S., Frith, C. D., Perrett, D. I., & Dolan, R. J. (1999) · Brain · doi:10.1093/brain/122.5.883 · Cited by 1,212
The neural basis of puberty and adolescence
Sisk, C. L., & Foster, D. L. (2004) · Nature Neuroscience · doi:10.1038/nn1326 · Cited by 1,085 · cited 1×
“In terms of the psychopathy phenotype, a wealth of evidence indicates that levels and the nature of aggression, antisocial behavior, and related traits, such as empathy and risk taking, undergo dramatic changes at puberty (Moffitt, 1993; Sisk & Foster, 2004).”
BackgroundMeaney, M. J., & Szyf, M. (2005) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2005.7.2/mmeaney · Cited by 958
Childhood and Adolescent Psychiatric Disorders as Predictors of Young Adult Disorders
Copeland, W. E., Shanahan, L., Costello, E. J., & Angold, A. (2009) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2009.85 · Cited by 844
Research works printed but not linked: 4
- Frick, 2010, A proposal to the DSM-V childhood disorders and ADHD and disruptive behavior disorders work groups to include a specifier to the diagnosis of conduct disorder based on the presence of callous–unemotional traits
- Mitchell I. J. , Smid W. , Troelstra J. , Wever E. , Ziegler T. E. , & Beech A. R. (2012). Psychopathy is related to high basal urinary oxytocin levels in male forensic patients. Paper presented at the 31st Annual Research Treatment Conference, Association for the Treatment of Sexual Abusers, Denver, CO.
- Holland, 1997, The Diagnostic Interview Schedule for Children, Adolescents, and Parents
- Dadds, 2006, Integrative Family Intervention for Child Conduct Disorders
Cited by
Sorted by citations
The oxytocin receptor: from intracellular signaling to behavior
Jurek, B., & Neumann, I. D. (2018) · Physiological Reviews · doi:10.1152/physrev.00031.2017 · Cited by 999
Hawes, D. J., Price, M. J., & Dadds, M. R. (2014) · Clinical Child and Family Psychology Review · doi:10.1007/s10567-014-0167-1 · Cited by 372
The Role of Epigenetic Change in Autism Spectrum Disorders
Loke, Y. J., Hannan, A. J., & Craig, J. M. (2015) · Frontiers in Neurology · doi:10.3389/fneur.2015.00107 · Cited by 266
Puglia, M. H., Lillard, T. S., Morris, J. P., & Connelly, J. J. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1422096112 · Cited by 216
“High levels of OXTR methylation at these same sites have been associated with autism (36), callous unemotional traits (39), and anorexia nervosa (40), suggesting the utility of OXTR methylation as a biomarker of phenotypic variability.”
BackgroundOxytocin receptor gene methylation: converging multilevel evidence for a role in social anxiety
Ziegler, C., Dannlowski, U., Bräuer, D., Stevens, S., Laeger, I., Wittmann, H., Kugel, H., Dobel, C., Hurlemann, R., Reif, A., et al. (2015) · Neuropsychopharmacology · doi:10.1038/npp.2015.2 · Cited by 193
Cecil, C. A. M., Lysenko, L., Jaffee, S. R., Pingault, J., Smith, R. G., Relton, C. L., Woodward, G., McArdle, W. L., Mill, J. S., & Barker, E. D. (2014) · Molecular Psychiatry · doi:10.1038/mp.2014.95 · Cited by 189
“Recently, Dadds et al (10) reported that elevated DNA methylation in the vicinity of the oxytocin receptor gene (OXTR) is associated with (i) lower levels of circulating oxytocin and (ii) higher levels of CU.”
BackgroundInfluentialUnternaehrer, E., Meyer, A. H., Burkhardt, S. C. A., Dempster, E., Staehli, S., Theill, N., Lieb, R., & Meinlschmidt, G. (2015) · Stress · doi:10.3109/10253890.2015.1038992 · Cited by 181
Developmental Perspectives on Oxytocin and Vasopressin
Hammock, E. A. D. (2014) · Neuropsychopharmacology · doi:10.1038/npp.2014.120 · Cited by 184
“The methylation status of the OXTR gene has also been explored in conduct disorder (Dadds et al, 2014), a developmental antecedent to psychopathic traits in adulthood.”
BackgroundSmearman, E. L., Almli, L. M., Conneely, K. N., Brody, G. H., Sales, J. M., Bradley, B., Ressler, K. J., & Smith, A. K. (2016) · Child Development · doi:10.1111/cdev.12493 · Cited by 173
Marsh, A. A. (2018) · Annual Review of Psychology · doi:10.1146/annurev-psych-010418-103010 · Cited by 171
“Together with evidence of atypical oxytocin-linked genetic expression in psychopathy (Cecil et al. 2014, Dadds et al. 2014), which could result in aberrant development of oxytocin circuits, these findings suggest that extreme deficits in care emerge early in life and may reflect developmental…”
BackgroundMaud, C., Ryan, J., McIntosh, J. E., & Olsson, C. A. (2018) · BMC Psychiatry · doi:10.1186/s12888-018-1740-9 · Cited by 151
“Two studies investigated a possible association between DNAm changes at the OXTR and subsequent oxytocin neuropeptide synthesis [47, 48].”
BackgroundInfluentialKong, X.-J., Liu, J., Liu, K., Koh, M., Sherman, H., Liu, S., Tian, R., Sukijthamapan, P., Wang, J., Fong, M., et al. (2021) · Nutrients · doi:10.3390/nu13051552 · Cited by 150
“These differences could be related to subsets of the ASD population with reduced biosynthesis or release of OXT [63,64], dysfunctional OXT processing dysfunction, or oxytocin receptor abnormalities [65].”
BackgroundOxytocin and the Neurobiology of Prosocial Behavior
Marsh, N., Marsh, A. A., Lee, M. R., & Hurlemann, R. (2020) · The Neuroscientist · doi:10.1177/1073858420960111 · Cited by 159
Waller, R. E., & Wagner, N. J. (2019) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2019.10.005 · Cited by 148
Barker, E. D., Walton, E., & Cecil, C. A. M. (2018) · Journal of Child Psychology and Psychiatry · doi:10.1111/jcpp.12782 · Cited by 134
“levels (Dadds et al., 2014), compared to boys with less severe CU traits.”
Oxytocin, vasopressin, and the motivational forces that drive social behaviors
Caldwell, H. K., & Albers, H. E. (2015) · Current Topics in Behavioral Neurosciences · doi:10.1007/7854_2015_390 · Cited by 129
Bell, A. F., Carter, C. S., Steer, C. D., Golding, J., Davis, J. M., Steffen, A. D., Rubin, L. H., Lillard, T. S., Gregory, S., Harris, J. C., et al. (2015) · Frontiers in Genetics · doi:10.3389/fgene.2015.00243 · Cited by 131
Overview of human oxytocin research
Kendrick, K. M., Guastella, A. J., & Becker, B. (2017) · Current Topics in Behavioral Neurosciences · doi:10.1007/7854_2017_19 · Cited by 121
Epigenetics in Personality Disorders: Today's Insights
Gescher, D. M., Kahl, K. G., Hillemacher, T., Frieling, H., Kuhn, J., & Frodl, T. (2018) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2018.00579 · Cited by 115
“Similarly, oxytocin serum levels significantly were negatively correlated with gene methylation level in the older boys (32).”
BackgroundInfluentialGouin, J.-P., Zhou, Q. Q., Booij, L., Boivin, M., Côté, S. M., Hébert, M., Ouellet‐Morin, I., Szyf, M., Tremblay, R. E., Turecki, G., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-07950-x · Cited by 106
Detection, processing and reinforcement of social cues: regulation by the oxytocin system
Menon, R., & Neumann, I. D. (2023) · Nature Reviews Neuroscience · doi:10.1038/s41583-023-00759-w · Cited by 100
“…was described, for example, in children that had suffered maltreatment and had insecure social attachment 157 , in neonates of mothers who had been subjected to intense stress during pregnancy 158 and in boys with conduct problems that were accompanied by lower plasma OXT concentrations 159 .”
BackgroundKim, Y.-R., Kim, J.-H., Kim, M. J., & Treasure, J. (2014) · PLoS ONE · doi:10.1371/journal.pone.0088673 · Cited by 97
“High levels of methylation of the OXTR gene are associated with callous unemotional traits in young males presenting with conduct problems [23].”
BackgroundAntisocial Personality as a Neurodevelopmental Disorder
Raine, A. (2018) · Annual Review of Clinical Psychology · doi:10.1146/annurev-clinpsy-050817-084819 · Cited by 105
Rijlaarsdam, J., van IJzendoorn, M. H., Verhulst, F. C., Jaddoe, V. W. V., Felix, J. F., Tiemeier, H. W., & Bakermans‐Kranenburg, M. J. (2016) · Autism Research · doi:10.1002/aur.1681 · Cited by 98
“, 2001] and levels of circulating oxytocin [Dadds et al., 2014].”
InfluentialConduct problems in youth and the RDoC approach: A developmental, evolutionary-based view
Fonagy, P., & Luyten, P. (2017) · Clinical Psychology Review · doi:10.1016/j.cpr.2017.08.010 · Cited by 94
“Journal of Child Psychology and Psychiatry, 55, 532-548. doi: 10.1111/jcpp.12152 Frick, P. J., Ray, J. V., Thornton, L. C., & Kahn, R. E. (2014).”
InfluentialOxytocin’s effect on resting-state functional connectivity varies by age and sex
Ebner, N. C., Chen, H., Porges, E., Lin, T., Fischer, H., Feifel, D., & Cohen, R. A. (2016) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2016.03.013 · Cited by 84
Genetic, epigenetic, and environmental factors controlling oxytocin receptor gene expression
Danoff, J. S., Wroblewski, K. L., Graves, A. J., Quinn, G. C., Perkeybile, A. M., Kenkel, W. M., Lillard, T. S., Parikh, H. I., Golino, H. F., Gregory, S. G., et al. (2021) · Clinical Epigenetics · doi:10.1186/s13148-021-01017-5 · Cited by 85
“For example, dysregulated DNA methylation in MT2 has been associated with autism [14], callous–unemotional traits [17, 18], anorexia nervosa [19, 20], schizoaffective disorders [21, 22], post-partum depression [23], attachment anxiety [24], obsessive compulsive disorder [25], and anxiety and depression [26].”
BackgroundEpigenetic evidence for involvement of the oxytocin receptor gene in obsessive–compulsive disorder
Cappi, C., Diniz, J. B., Requena, G. D. L., Lourenço, T., Lisbôa, B. C. G., Batistuzzo, M. C., Marques, A. H., Hoexter, M. Q., Pereira, C. A. D. B., Miguel, E. C., et al. (2016) · BMC Neuroscience · doi:10.1186/s12868-016-0313-4 · Cited by 84
“Methylation of oxytocin receptor gene (OXTR) has been associated with autism [15], psychopathy [16], acute psychosocial stress in the population experienced war adversities early in life [17] and anorexia [18].”
BackgroundBeery, A. K., McEwen, L. M., MacIsaac, J. L., Francis, D. D., & Kobor, M. S. (2016) · Hormones and Behavior · doi:10.1016/j.yhbeh.2015.05.022 · Cited by 81
“OXTR methylation has been associated with emotional traits and circulating oxytocin in humans (Dadds et al., 2014).”
BackgroundThe genetic underpinnings of callous-unemotional traits: A systematic research review
Moore, A. A., Blair, J., Hettema, J. M., & Roberson‐Nay, R. (2019) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2019.02.018 · Cited by 91
King, L., Robins, S., Chen, G., Yerko, V., Zhou, Y., Nagy, C., Feeley, N., Gold, I., Hayton, B. C., Turecki, G., et al. (2017) · Hormones and Behavior · doi:10.1016/j.yhbeh.2017.09.006 · Cited by 85
Krol, K. M., Puglia, M. H., Morris, J. P., Connelly, J. J., & Grossmann, T. (2019) · Developmental Cognitive Neuroscience · doi:10.1016/j.dcn.2019.100648 · Cited by 86
“For example, increased OXTR m has been associated with callous unemotional traits, anorexia nervosa, postpartum depression, and autism spectrum disorder (ASD) (Gregory et al., 2009; Dadds et al., 2014; Bell et al., 2015; Kim et al., 2014).”
Ebner, N. C., Lin, T., Muradoglu, M., Weir, D. H., Plasencia, G. M., Lillard, T. S., Pournajafi-Nazarloo, H., Cohen, R. A., Sue Carter, C., & Connelly, J. J. (2019) · International Journal of Psychophysiology · doi:10.1016/j.ijpsycho.2018.01.008 · Cited by 79
Genetic influences on conduct disorder
Salvatore, J. E., & Dick, D. M. (2016) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.06.034 · Cited by 88
Maternal adversities during pregnancy and cord blood oxytocin receptor (OXTR) DNA methylation
Unternaehrer, E., Bolten, M., Nast, I., Staehli, S., Meyer, A. H., Dempster, E., Hellhammer, D. H., Lieb, R., & Meinlschmidt, G. (2016) · Social Cognitive and Affective Neuroscience · doi:10.1093/scan/nsw051 · Cited by 75
“, 2009), psychopathy (Dadds et al., 2014) and increased brain activity during a social task (Jack et al.”
BackgroundA, T. R. D. J., & Neumann, I. D. (2017) · Current topics in behavioral neurosciences · doi:10.1007/7854_2017_13 · Cited by 76
Genetic influences on antisocial behavior: recent advances and future directions
Gard, A. M., Dotterer, H. L., & Hyde, L. W. (2018) · Current Opinion in Psychology · doi:10.1016/j.copsyc.2018.07.013 · Cited by 84
Rubin, L. H., Connelly, J. J., Reilly, J. L., Carter, C. S., Drogos, L. L., Pournajafi‐Nazarloo, H., Ruocco, A. C., Keedy, S., Matthew, I., Tandon, N., et al. (2015) · Biological Psychiatry Cognitive Neuroscience and Neuroimaging · doi:10.1016/j.bpsc.2015.10.003 · Cited by 72
“Examination of OT levels may be important for understanding epigenetic effects because epigenetic changes in OXTR might represent a response to variations in OT levels (23).”
BackgroundFreitag, C. M., Konrad, K., Stadler, C., Brito, S. A. D., Popma, A., Herpertz, S. C., Herpertz‐Dahlmann, B., Neumann, I. D., Kieser, M., Chiocchetti, A. G., et al. (2018) · European Child & Adolescent Psychiatry · doi:10.1007/s00787-018-1172-6 · Cited by 75
The effects of DNA methylation on human psychology
Kader, F., Ghai, M., & Maharaj, L. (2017) · Behavioural Brain Research · doi:10.1016/j.bbr.2017.12.004 · Cited by 75
Cataldo, I., Azhari, A., Lepri, B., & Esposito, G. (2017) · Research in Developmental Disabilities · doi:10.1016/j.ridd.2017.10.007 · Cited by 72
“Higher methylation has been shown to be associated with lower oxytocin levels (Dadds et al., 2014), which has subsequently been correlated with low prosocial behaviors (Bethlehem et al.”
BackgroundOxytocin and Vasopressin Receptor Gene Polymorphisms: Role in Social and Psychiatric Traits
Aspé-Sánchez, M., Moreno, M., Rivera, M. I., Rossi, A., & Ewer, J. (2016) · Frontiers in Neuroscience · doi:10.3389/fnins.2015.00510 · Cited by 71
Mapping the developmental pathways of child conduct problems through the neurobiology of empathy
Moul, C., Hawes, D. J., & Dadds, M. R. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2017.03.016 · Cited by 72
“Encouragingly, novel approaches to treatment for children with conduct problems and high levels of CU traits have already begun to think about this evidence and some positive results have already been demonstrated (Hawes, Price, & Dadds, 2014).”
BackgroundTargeting the Oxytocin System: New Pharmacotherapeutic Approaches
Gulliver, D. W., Werry, E. L., Reekie, T. A., Katte, T. A., Jorgensen, W. T., & Kassiou, M. (2018) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2018.11.001 · Cited by 67
Puglia, M. H., Connelly, J. J., & Morris, J. P. (2018) · Translational Psychiatry · doi:10.1038/s41398-018-0159-x · Cited by 63
Genetic modulation of oxytocin sensitivity: A pharmacogenetic approach
Chen, F. S., Kumsta, R., Dvorak, F., Domes, G., Yim, O. S., Ebstein, R. P., & Heinrichs, M. (2015) · Translational Psychiatry · doi:10.1038/tp.2015.163 · Cited by 59
Self-citationOxytocin and anxiety disorders
Gottschalk, M. G., & Domschke, K. (2017) · Current Topics in Behavioral Neurosciences · doi:10.1007/7854_2017_25 · Cited by 61
Kraaijenvanger, E. J., He, Y., Spencer, H., Smith, A. K., Bos, P. A., & Boks, M. P. (2018) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2018.11.016 · Cited by 62
Milaniak, I., Cecil, C. A. M., Barker, E. D., Relton, C. L., Gaunt, T. R., McArdle, W. L., & Jaffee, S. R. (2017) · Development and Psychopathology · doi:10.1017/s0954579417001316 · Cited by 60
“Consistent with the possibility that OXTR methylation may be a mechanism by which prenatal exposures increase risk for psychopathology, Dadds et al. (2014) found that elevated methylation in OXTR in a sample of 4- to 16-year-olds was associated with lower levels of circulating oxytocin and higher…”
Dadds, M. R., English, T., Wimalaweera, S., Schollar‐Root, O., & Hawes, D. J. (2019) · Journal of Child Psychology and Psychiatry · doi:10.1111/jcpp.13023 · Cited by 54
Epigenetic perpetuation of the impact of early life stress on behavior
Janusek, L. W., Tell, D., & Mathews, H. L. (2019) · Current Opinion in Behavioral Sciences · doi:10.1016/j.cobeha.2019.01.004 · Cited by 54
Salivary oxytocin in adolescents with conduct problems and callous-unemotional traits
Levy, T., Bloch, Y., Bar-Maisels, M., Gat‐Yablonski, G., Djalovski, A., Borodkin, K., & Apter, A. S. (2015) · European Child & Adolescent Psychiatry · doi:10.1007/s00787-015-0765-6 · Cited by 57
“Moreover, the risk alleles of these SNPs were associated with lower circulating OT levels [37, 38].”
BackgroundMethodInfluentialSimons, R. L., Lei, M., Beach, S. R. H., Cutrona, C. E., & Philibert, R. A. (2016) · Development and Psychopathology · doi:10.1017/s0954579416000420 · Cited by 57
“…unemotional traits have found effects for sites located in our Factor 4 (Cecil et al., 2014) and in locations between our Factor 4 and our Factor 2 (Dadds et al., 2014); sites associated with autism have been located still further upstream from those included in our Factor 2 (Gregory et al.,…”
BackgroundMethodInfluentialZoratto, F., Sbriccoli, M., Martinelli, A., Glennon, J. C., Macrı̀, S., & Laviola, G. (2018) · Neuropharmacology · doi:10.1016/j.neuropharm.2018.09.010 · Cited by 53
DNA methylation analysis from saliva samples for epidemiological studies
Nishitani, S., Parets, S. E., Haas, B. W., & Smith, A. K. (2018) · Epigenetics · doi:10.1080/15592294.2018.1461295 · Cited by 50
“To evaluate PCR amplification and interrogation of BSC saliva DNA, we used a well-established assay for the oxytocin receptor (OXTR) (chr3: 8,792,095 to 8,811,300: GRCh37/hg19 build), which has used in studies of psychiatric disorders [52–54] and social behaviors [55,56].”
MethodAdolescent oxytocin response to stress and its behavioral and endocrine correlates
Bernhard, A., van der Merwe, C., Ackermann, K., Martinelli, A., Neumann, I. D., & Freitag, C. M. (2018) · Hormones and Behavior · doi:10.1016/j.yhbeh.2018.08.010 · Cited by 51
“Moreover, alterations of the OXT system have been found in mental disorders characterized by social dysfunctions, such as social anxiety, depression, autism spectrum disorder and conduct disorder (Cochran et al., 2013; Dadds et al., 2014; Netherton and Schatte, 2011; Neumann and Slattery, 2016).”
Apazoglou, K., Adouan, W., Aubry, J., Dayer, A. G., & Aybek, S. (2017) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp-2017-316469 · Cited by 47
Neonatal DNA methylation and early-onset conduct problems: A genome-wide, prospective study
Cecil, C. A. M., Walton, E., Jaffee, S. R., O'Connor, T., Maughan, B., Relton, C. L., Smith, R. G., McArdle, W., Gaunt, T. R., Ouellet-Morin, I., et al. (2018) · Development and Psychopathology · doi:10.1017/s095457941700092x · Cited by 46
“5 including lower DNAm of the Serotonin 1B Receptor gene (HTR1B; Moul, Dobson-Stone, Brennan, Hawes, & Dadds, 2015), and higher DNAm of the Oxytocin Receptor gene (OXTR; Dadds et al., 2014) – which in turn related to lower circulating oxytocin levels.”
BackgroundHovey, D., Lindstedt, M., Zettergren, A., Jönsson, L., Johansson, A., Melke, J., Kerekes, N., Anckarsäter, H. S., Lichtenstein, P., Lundström, S., et al. (2015) · Molecular Psychiatry · doi:10.1038/mp.2015.144 · Cited by 47
Baribeau, D. A., Dupuis, A., Paton, T., Scherer, S. W., Schachar, R. J., Arnold, P. D., Szatmári, P., Nicolson, R., Georgiades, S., Crosbie, J., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-10821-0 · Cited by 51
Dadds, M. R., & Frick, P. J. (2019) · Behaviour Research and Therapy · doi:10.1016/j.brat.2019.103410 · Cited by 47
Wiederhofer, J. (2024) · Springer eBooks · doi:10.1007/978-3-658-46275-8_2 · Cited by 42
Bey, K., Campos-Martín, R., Klawohn, J., Reuter, B., Grützmann, R., Riesel, A., Wagner, M., Ramı́rez, A., & Kathmann, N. (2021) · Epigenetics · doi:10.1080/15592294.2021.1943864 · Cited by 40
“One study reported that increased OXTR methylation at chr3:8,810,833 was negatively associated with circulating oxytocin levels [46], while another study found no significant association between methylation at site −934 upstream of the OXTR start codon (located in exon II) and plasma oxytocin [47].”
BackgroundOxytocin receptor gene methylation in male and female PTSD patients and trauma-exposed controls
Nawijn, L., Krzyzewska, I. M., van Zuiden, M., Henneman, P., Koch, S. B. J., Mul, A. N. P. M., Frijling, J. L., Veltman, D. J., Mannens, M. M. A. M., & Olff, M. (2018) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2018.10.006 · Cited by 41
Chen, X., Nishitani, S., Haroon, E., Smith, A. K., & Rilling, J. K. (2019) · Genes Brain & Behavior · doi:10.1111/gbb.12555 · Cited by 39
Frazier, A., Ferreira, P. A., & Gonzales, J. E. (2019) · Personality Neuroscience · doi:10.1017/pen.2019.7 · Cited by 38
“Dadds et al. (2014) observed maturation-related differences in genetic activity, with the lowCU group showing lower methylation of the OXT gene in older children, while the opposite trend was observed in the high-CU group.”
BackgroundResultThagard, P. R. (2019) · doi:10.1093/oso/9780190678739.001.0001 · Cited by 38
Reuter, M., Montag, C., Altmann, S., Bendlow, F., Elger, C. E., Kirsch, P., Becker, A. J., Schoch, S., Simon, M., Weber, B., et al. (2016) · Social Neuroscience · doi:10.1080/17470919.2016.1214174 · Cited by 38
“Moreover, further gene regulatory mechanisms like DNA hyper- as well as hypomethylation of the OXTR will fine-tune the activity of the oxytocinergic system leading to behavioral variability and psychiatric disorders (Dadds et al., 2014; Ziegler et al., 2015).”
BackgroundDanoff, J. S., Connelly, J. J., Morris, J. P., & Perkeybile, A. M. (2021) · Comprehensive Psychoneuroendocrinology · doi:10.1016/j.cpnec.2021.100098 · Cited by 37
“[55] Whole blood MT2 EpiTYPER Callous-unemotional traits Callous unemotional traits were associated with higher”
BackgroundSocial Behavior of Pet Dogs Is Associated with Peripheral OXTR Methylation
Cimarelli, G., Virányi, Z., Turcsán, B., Rónai, Z., Sasvári‐Székely, M., & Bánlaki, Z. (2017) · Frontiers in Psychology · doi:10.3389/fpsyg.2017.00549 · Cited by 36
Methylation of the OXTR gene in women with anorexia nervosa: Relationship to social behavior
Thaler, L., Brassard, S. L., Booij, L., Kahan, E., McGregor, K., Labbe, A., Israël, M., & Steiger, H. (2019) · European Eating Disorders Review · doi:10.1002/erv.2703 · Cited by 39
Towers, A. J., Tremblay, M. W., Chung, L., Li, X.-L., Bey, A. L., Zhang, W., Cao, X., Wang, X., Wang, P., Duffney, L. J., et al. (2018) · JCI Insight · doi:10.1172/jci.insight.120592 · Cited by 31
Moul, C., Dobson‐Stone, C., Brennan, J., Hawes, D. J., & Dadds, M. R. (2015) · PLoS ONE · doi:10.1371/journal.pone.0126903 · Cited by 40
“Indeed, childhood adversity has been associated with hypermethylation and the reduced expression of HTR1B [26, 27] and recent research has identified methylation of the promoter region of the oxytocin receptor gene as being associated with the development of CU traits in children [28, 29].”
BackgroundOxytocin and Facial Emotion Recognition
Ellenbogen, M. A. (2017) · Current topics in behavioral neurosciences · doi:10.1007/7854_2017_20 · Cited by 34
Işık, Ü., Bi̇lgi̇ç, A., Toker, A., & Kılınç, İ. (2018) · Psychiatry Research · doi:10.1016/j.psychres.2017.12.076 · Cited by 32
“Similar to ADHD, recent studies have suggested that neuroendocrine hormones might be related to the etiopathogenesis of conduct disorder (Alink et al., 2008; Dorn et al., 2009; Freitag et al., 2009; Golubchik et al., 2009; Dadds et al., 2014; Levy et al., 2015; Northover et al., 2016).”
InfluentialJones‐Mason, K., Allen, I. E., Bush, N. R., & Hamilton, S. (2016) · Brain and Behavior · doi:10.1002/brb3.480 · Cited by 30
“For example, greater methylation levels of the oxytocin gene has been linked to conduct disorder (Dadds et al. 2014), and it may be that the decrease in environmental sensitivity associated with high methylation levels found here potentially explain some of the resistance to intervention associated…”
BackgroundD’Addario, C., Pucci, M., Bellia, F., Girella, A., Sabatucci, A., Fanti, F., Vismara, M. E. M., Benatti, B., Ferrara, L., Fasciana, F., et al. (2022) · Clinical Epigenetics · doi:10.1186/s13148-022-01264-0 · Cited by 31
“Moreover, besides OCD, OXTR DNA methylation at exon 3 has been associated with other central nervous system disorders such as anxiety disorder [66], autism spectrum disorder [67], depression [68] and psychopathy [69].”
BackgroundPatin, A., & Hurlemann, R. (2015) · Handbook of experimental pharmacology · doi:10.1007/978-3-319-16522-6_10 · Cited by 37
Lønfeldt, N. N., Verhulst, F. C., Strandberg-Larsen, K., Plessen, K. J., & Lebowitz, E. R. (2019) · Psychological Medicine · doi:10.1017/s0033291718003021 · Cited by 29
“Hypermethylation is associated with decreased peripheral levels of oxytocin (Dadds et al., 2014).”
BackgroundThe association between attachment and psychopathic traits
van der Zouwen, M., Hoeve, M., Hendriks, A. M., Asscher, J. J., & Stams, G. J. J. M. (2018) · Aggression and Violent Behavior · doi:10.1016/j.avb.2018.09.002 · Cited by 32
Evenepoel, M., Moerkerke, M., Daniëls, N., Chubar, V., Claes, S. J., Turner, J. D., Vanaudenaerde, B. M., Willems, L., Verhaeghe, J., Prinsen, J., et al. (2023) · Translational Psychiatry · doi:10.1038/s41398-023-02524-0 · Cited by 27
“One study by Dadds et al. (2014) demonstrated that increased OXTR DNAm in peripheral blood was associated with lower plasma oxytocin levels in children/ adolescents with oppositional-defiant/conduct disorder (4-to-16 year old) [33].”
BackgroundGalbally, M., Ryan, J. L., van IJzendoorn, M. H., Watson, S., Spigset, O., Lappas, M., Saffery, R., de Kloet, E. R., & Lewis, A. J. (2018) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2018.01.004 · Cited by 29
Oxytocin receptor gene methylation and substance use problems among young African American men
Kogan, S. M., Cho, J., Beach, S. R. H., Smith, A. K., & Nishitani, S. (2018) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2018.08.022 · Cited by 29
“Consistent with prior research (Dadds et al., 2014), the present study used an index summing 13 consecutive CpG sites across chr3: 8810890 (CpG14) to chr3: 8810682/8810680 (CpG25,26).”
ResultDNA Methylation and Hydroxymethylation and Behavior
Rustad, S. R., Papale, L. A., & Alisch, R. S. (2019) · Current topics in behavioral neurosciences · doi:10.1007/7854_2019_104 · Cited by 26
Kogan, S. M., Bae, D., Cho, J., Smith, A. K., & Nishitani, S. (2019) · Psychological Science · doi:10.1177/0956797619854735 · Cited by 27
“Previous research has focused on methylation at individual CpG sites as well as mean methylation levels across sites in this region (Dadds et al., 2014).”
BackgroundResultHuang, M., Liu, K., Wei, Z., Feng, Z., Chen, J., Yang, J., Zhong, Q., Wan, G., & Kong, X. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.721884 · Cited by 28
Epigenetic and Neural Circuitry Landscape of Psychotherapeutic Interventions
Miller, C. W. T. (2017) · Psychiatry Journal · doi:10.1155/2017/5491812 · Cited by 26
“, autistic traits and elements of psychopathy) [55, 56], they”
BackgroundThøgersen, D. M., Elmose, M., Viding, E. M., McCrory, E. J. P., & Bjørnebekk, G. (2022) · Journal of Child and Family Studies · doi:10.1007/s10826-022-02435-6 · Cited by 24
“Primary CU traits are assumed to be caused by biological constraints or dysfunctions in the emotional systems, and one possible mechanism might be the increased DNA methylation of areas close to the oxytocin receptor gene (Cecil et al., 2014; Dadds et al., 2013).”
Erickson, E. N., Myatt, L., Danoff, J. S., Krol, K. M., & Connelly, J. J. (2023) · Communications Medicine · doi:10.1038/s43856-023-00244-6 · Cited by 24
Lancaster, K., Goldbeck, L., Puglia, M. H., Morris, J. P., & Connelly, J. J. (2018) · Social Cognitive and Affective Neuroscience · doi:10.1093/scan/nsy086 · Cited by 25
Engel, S., Klusmann, H., Laufer, S., Pfeifer, A.-C., Ditzen, B., van Zuiden, M., Knaevelsrud, C., & Schumacher, S. (2019) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2019.08.003 · Cited by 26
Tamatea, A. J. (2015) · Behavioral Sciences & the Law · doi:10.1002/bsl.2201 · Cited by 22
The role of oxytocin signaling in depression and suicidality in returning war veterans
Warrener, C., Valentin, E. M., Gallin, C., Richey, L., Ross, D. B., Hood, C. J., Lori, A., Cubells, J. F., Rauch, S. A. M., & Rilling, J. K. (2020) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2020.105085 · Cited by 19
“, 2015), and evidence is accumulating that peripheral OXTR methylation has functional correlates in humans (Andari et al., 2020; Dadds et al., 2014; Gregory et al., 2009; Jack et al., 2012; Puglia et al., 2015).”
BackgroundLevy, T., Apter, A., Djalovski, A., Peskin, M., Fennig, S., Gat‐Yablonski, G., Bar-Maisels, M., Borodkin, K., & Bloch, Y. (2017) · Psychiatry Research · doi:10.1016/j.psychres.2017.06.028 · Cited by 20
“Moreover, serum oxytocin levels in youth were correlated with CU trait severity (Dadds et al., 2014a).”
BackgroundWhy Do They Do It? The Psychology Behind Antisocial Behavior in Children and Adolescents
Mazza, M., Lisci, F. M., Marzo, E. M., Masi, V. D., Abate, F., & Marano, G. (2025) · Pediatric Reports · doi:10.3390/pediatric17020026 · Cited by 25
“Unfortunately, this study did not include the female population [33].”
Daily oxytocin patterns in relation to psychopathy and childhood trauma in residential youth
Fragkaki, I., Verhagen, M., van Herwaarden, A. E., & Cima, M. (2018) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2018.11.040 · Cited by 27
Nance, M. G., Sullivan, K. M., & Puglia, M. H. (2024) · Pediatric Research · doi:10.1038/s41390-024-03563-z · Cited by 18
“54 Similarly, in a 13-year longitudinal study, Cecil et al. examined cord blood OXTR m at birth and peripheral blood in childhood in patients with CU traits.”
Dalkner, N., Reininghaus, E., Riedrich, K., Rieger, A., Birner, A., Fellendorf, F., Bengesser, S., Queissner, R., Platzer, M., Mayr-Mauhart, M., et al. (2018) · Psychiatry Research · doi:10.1016/j.psychres.2018.09.018 · Cited by 11
Kogan, S. M., Bae, D., Cho, J., Smith, A. K., & Nishitani, S. (2020) · Development and Psychopathology · doi:10.1017/s0954579420000632 · Cited by 22
“OXTR DNA methylation index Previous researchers have evaluated methylation at individual CpG sites as well as mean methylation levels across sites in this region (Dadds et al., 2014; Szyf & Bick, 2013).”
BackgroundInfluentialLong-term epigenetic effects of parental caregiving
Unternäehrer, E., Meier, M., Bouvette–Turcot, A., & Dass, S. A. H. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-819262-7.00006-4 · Cited by 16
Metadata
- Authors
- Dadds, M. R., Moul, C., Cauchi, A., Dobson-Stone, C., Hawes, D. J., Brennan, J., & Ebstein, R. E.
- Affiliations
- UNSW Sydney (AU)
- The University of Sydney (AU)
- Sydney Children's Hospital (AU)
- Corresponding author
- Dadds, Mark R.
- Venue
- Development and Psychopathology
- Publisher
- Cambridge University Press (CUP)
- Published
- 2013-09-23
- Volume
- 26
- Issue
- 1
- Pages
- 33-40
- ISSN
- 0954-5794 (ISSN-L)
- 1469-2198
- OpenAlex
- W2075192390
- Cited by
- 230
- References
- 58
- Citations by year
- 2026: 8 · 2025: 12 · 2024: 11 · 2023: 7 · 2022: 11 · 2021: 22 · 2020: 14 · 2019: 34 · 2018: 42 · 2017: 26 · 2016: 19 · 2015: 16 · 2014: 7 · 2013: 1
- FWCI
- 15.93
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Development and Psychopathology (publishedVersion)
- PubMed (publishedVersion)
- National University of Singapore (submittedVersion)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Psychopathy, Forensic Psychiatry, Sexual Offending
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroendocrine regulation and behavior
- Social Sciences › Psychology › Clinical Psychology › Child and Adolescent Psychosocial and Emotional Development
- Keywords
- oxytocin receptor gene, oxytocin receptor, DNA methylation, psychopathy, callous-unemotional traits, child conduct problems, oppositional defiant disorder, conduct disorder, epigenetics, promoter CpG sites, adolescent boys, interpersonal empathy, social cognition
- MeSH terms
- Adolescent, Age Factors, Antisocial Personality Disorder, Child, Empathy, Family, Humans, Male, Oxytocin, Social Environment, Receptors, Oxytocin, DNA Methylation, Conduct Disorder, Epigenesis, Genetic
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