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Polymorphisms in the oxytocin receptor gene are associated with the development of psychopathy

  • Mark R. Dadds (a1), Caroline Moul (a1), Avril Cauchi (a1), Carol Dobson-Stone (a1) (a2), David J. Hawes (a3), John Brennan (a4), Ruth Urwin (a5) and Richard E. Ebstein (a6)...
Abstract

The co-occurrence of child conduct problems (CPs) and callous–unemotional (CU) traits confers risk for psychopathy. The oxytocin (OXT) system is a likely candidate for involvement in the development of psychopathy. We tested variations in the OXT receptor gene (OXTR) in CP children and adolescents with varying levels of CU traits. Two samples of Caucasian children, aged 4–16 years, who met DSM criteria for disruptive behavior problems and had no features of autism spectrum disorder, were stratified into low versus high CU traits. Measures were the frequencies of nine candidate OXTR polymorphisms (single nucleotide polymorphisms). In Sample 1, high CU traits were associated with single nucleotide polymorphism rs1042778 in the 3′ untranslated region of OXTR and the CGCT haplotype of rs2268490, rs2254298, rs237889, and rs13316193. The association of rs1042778 was replicated in the second rural sample and held across gender and child versus adolescent age groups. We conclude that polymorphic variation of the OXTR characterizes children with high levels of CU traits and CPs. The results are consistent with a hypothesized role of OXT in the developmental antecedents of psychopathy, particularly the differential amygdala activation model of psychopathic traits, and add genetic evidence that high CU traits specify a distinct subgroup within CP children.

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Corresponding author
Address correspondence and reprint requests to: Mark R. Dadds, School of Psychology, University of New South Wales, Sydney, NSW 2052, Australia; E-mail: m.dadds@unsw.edu.au.
References
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Apicella, C. L., Cesarini, D., Johannesson, M., Dawes, C. T., Lichtenstein, P., Wallace, B., et al. (2010). No association between oxytocin receptor (OXTR) gene polymorphisms and experimentally elicited social preferences. PLoS ONE, 5(6).
Bakermans-Kranenburg, M. J., & van IJzendoorn, M. H. (2008). Oxytocin receptor (OXTR) and serotonin transporter (5-HTT) genes associated with observed parenting. Social Cognitive and Affective Neuroscience, 3, 128134.
Bartz, J. A., & Hollander, E. (2008). Oxytocin and experimental therapeutics in autism spectrum disorders. Progress in Brain Research, 170, 451462.
Beitchman, J. H., Zai, C. C., Muir, K., Berall, L., Nowrouzi, B., Choi, E., et al. (2012). Childhood aggression, callous–unemotional traits and oxytocin genes. European Child and Adolescent Psychiatry, 21, 125132.
Blair, R. J. R. (2008). Fine cuts of empathy and the amygdala: Dissociable deficits in psychopathy and autism. Quarterly Journal of Experimental Psychology, 61, 157170.
Blair, R. J. R. (2011). Commentary: Are callous unemotional traits all in the eyes? Examining eye contact in youth with conduct problems and callous unemotional traits—Reflections on Dadds et al. (2011). Journal of Child Psychology and Psychiatry and Allied Disciplines, 52, 246247.
Blair, R. J. R., Morris, J. S., Frith, C. D., Perrett, D. I., & Dolan, R. J. (1999). Dissociable neural responses to facial expressions of sadness and anger. Brain, 122, 883893.
Bora, E., Yucel, M., & Allen, N. B. (2009). Neurobiology of human affiliative behaviour: Implications for psychiatric disorders. Current Opinion in Psychiatry, 22, 320325.
Brüne, M. (2012). Does the oxytocin receptor polymorphism (rs2254298) confer ‘vulnerability’ for psychopathology or ‘differential susceptibility’? Insights from evolution. BMC Medicine, 10. Advance online publication. doi:10.1186/1741-7015-10-38
Campbell, D. B., Datta, D., Jones, S. T., Lee, E. B., Sutcliffe, J. S., Hammock, E. A. D., et al. (2011). Association of oxytocin receptor (OXTR) gene variants with multiple phenotype domains of autism spectrum disorder. Journal of Neurodevelopmental Disorders, 3, 101112.
Chen, F. S., Barth, M., Johnson, S. L., Gotlib, I. H., & Johnson, S. C. (2011). Oxytocin receptor (intra-assay) polymorphisms and attachment in human infants. Frontiers in Psychology, 2. doi:10.3389/fpsyg.2011.00200
Chen, F. S., & Johnson, S. C. (2012). An oxytocin receptor gene variant predicts attachment anxiety in females and autism-spectrum traits in males. Social Psychological and Personality Science, 3, 9399.
Cohen, J. (1992). A power primer. Psychological Bulletin, 112, 155159.
Copeland, W., Shanahan, L., Costello, E., & Angold, A. (2009). Childhood and adolescent psychiatric disorders as predictors of young adult disorders. Archives of General Psychiatry, 66, 764772. doi:10.1001/archgenpsychiatry.2009.85
Costa, B., Pini, S., Gabelloni, P., Abelli, M., Lari, L., Cardini, A., et al. (2009). Oxytocin receptor polymorphisms and adult attachment style in patients with depression. Psychoneuroendocrinology, 34, 15061514.
Crow, T. J. (2011). The missing genes: What happened to the heritability of psychiatric disorders? Molecular Psychiatry, 16, 362364.
Dadds, M. R., Cauchi, A. J., Wimalaweera, S., Hawes, D. J., & Brennan, J. (2012). Outcomes, moderators, and mediators of empathic-emotion recognition training for complex conduct problems in childhood. Psychiatry Research.
Dadds, M. R., Frost, A., Fraser, J., & Hawes, D. J. (2005). Disentangling the underlying dimensions of psychopathy and conduct problems in childhood: A community study. Journal of Consulting and Clinical Psychology, 73, 400410.
Dadds, M. R., & Hawes, D. J. (2006). Integrative Family Intervention for Child Conduct Disorders. Brisbane: Australian Academic Press.
Dadds, M. R., Perry, Y., Hawes, D. J., Merz, S., Riddell, A. C., Haines, D. J., et al. (2006). Attention to the eyes and fear-recognition deficits in child psychopathy. British Journal of Psychiatry, 189, 280281.
Dadds, M. R., & Rhodes, T. (2008). Aggression in young children with concurrent callous–unemotional traits: Can the neurosciences inform progress and innovation in treatment approaches? Philosophical Transactions of the Royal Society, 363B, 25672576.
De Brito, S. A., McCrory, E. J., Mechelli, A., Wilke, M., Jones, A. P., Hodgins, S., et al. (2011). Small, but not perfectly formed: Decreased white matter concentration in boys with psychopathic tendencies. Molecular Psychiatry, 16, 476477.
Deeley, Q., Daly, E., Surguladze, S., Tunstall, N., Mezey, G., Beer, D., et al. (2006). Facial emotion processing in criminal psychopathy: Preliminary functional magnetic resonance imaging study. British Journal of Psychiatry, 189, 533539.
Ebstein, R. P., Knafo, A., Mankuta, D., Chew, S. H., & Lai, P. S. (2012). The contributions of oxytocin and vasopressin pathway genes to human behavior. Hormones and Behavior, 61, 359379.
Feldman, R., Zagoory-Sharon, O., Weisman, O., Schneiderman, I., Gordon, I., Maoz, R., et al. (2012). Sensitive parenting is associated with plasma oxytocin and polymorphisms in the OXTR and CD38 genes. Biological Psychiatry, 72, 175181.
Frick, P. J., & Hare, R. D. (2001). Antisocial Process Screening Device: APSD. Toronto: Multi-Health Systems.
Frick, P. J., Lilienfeld, S. O., Ellis, M., Loney, B., & Silverthorn, P. (1999). The association between anxiety and psychopathy dimensions in children. Journal of Abnormal Child Psychology, 27, 383392.
Frick, P. J., & Moffitt, T. E. (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. Washington, DC: American Psychiatric Association.
Frick, P. J., & White, S. F. (2008). The importance of callous–unemotional traits for developmental models of aggressive and antisocial behavior. Journal of Child Psychology and Psychiatry and Allied Disciplines, 49, 359375.
Furman, D. J., Chen, M. C., & Gotlib, I. H. (2011). Variant in oxytocin receptor gene is associated with amygdala volume. Psychoneuroendocrinology, 36, 891897.
Gimpl, G., & Fahrenholz, F. (2001). The oxytocin receptor system: Structure, function, and regulation. Physiological Reviews, 81, 629683.
Goodman, R. (1997). The Strengths and Difficulties Questionnaire: A research note. Journal of Child Psychology and Psychiatry and Allied Disciplines, 38, 581586.
Gopal Rao, V. V. N., Loffler, C., Battey, J., & Hansmann, I. (1992). The human gene for oxytocin-neurophysin I (OXT) is physically mapped to chromosome 20p13 by in situ hybridization. Cytogenetics and Cell Genetics, 61, 271273.
Gregory, S. G., Connelly, J. J., Towers, A. J., Johnson, J., Biscocho, D., Markunas, C. A., et al. (2009). Genomic and epigenetic evidence for oxytocin receptor deficiency in autism. BMC Medicine, 7, 62.
Herpers, P. C., Rommelse, N. N., Bons, D. M., Buitelaar, J. K., & Scheepers, F. E. (2012). Callous–unemotional traits as a cross-disorders construct. Social Psychiatry and Psychiatric Epidemiology, 47, 20452064. doi:10.1007/s00127-012-0513-x
Holland, D., & Dadds, M. R. (1997). The Diagnostic Interview Schedule for Children, Adolescents, and Parents. Unpublished manuscript, Griffith University, Brisbane.
Inoue, H., Yamasue, H., Tochigi, M., Abe, O., Liu, X., Kawamura, Y., et al. (2010). Association between the oxytocin receptor gene and amygdalar volume in healthy adults. Biological Psychiatry, 68, 10661072.
Insel, T. R., Young, L., Witt, D. M., & Crews, D. (1993). Gonadal steroids have paradoxical effects on brain oxytocin receptors. Journal of Neuroendocrinology, 5, 619628.
Israel, S., Lerer, E., Shalev, I., Uzefovsky, F., Riebold, M., Laiba, E., et al. (2009). The oxytocin receptor (OXTR) contributes to prosocial fund allocations in the Dictator Game and the social value orientations task. PLoS ONE, 4(5).
Jacob, S., Brune, C. W., Carter, C. S., Leventhal, B. L., Lord, C., & Cook, E. H. Jr. (2007). Association of the oxytocin receptor gene (OXTR) in Caucasian children and adolescents with autism. Neuroscience Letters, 417, 69.
Johansson, A., Westberg, L., Sandnabba, K., Jern, P., Salo, B., & Santtila, P. (2012). Associations between oxytocin receptor gene (OXTR) polymorphisms and self-reported aggressive behavior and anger: Interactions with alcohol consumption. Psychoneuroendocrinology, 37, 15461556.
Jones, A. P., Laurens, K. R., Herba, C. M., Barker, G. J., & Viding, E. (2009). Amygdala hypoactivity to fearful faces in boys with conduct problems and callous–unemotional traits. American Journal of Psychiatry, 166, 95102.
Kawamura, Y., Liu, X., Akiyama, T., Shimada, T., Otowa, T., Sakai, Y., et al. (2010). The association between oxytocin receptor gene (OXTR) polymorphisms and affective temperaments, as measured by TEMPS-A. Journal of Affective Disorders, 127, 3137.
Kawamura, Y., Liu, X., Shimada, T., Otowa, T., Kakiuchi, C., Akiyama, T., et al. (2011). Association between oxytocin receptor gene polymorphisms and autistic traits as measured by the Autism-Spectrum Quotient in a non-clinical Japanese population. Asia-Pacific Psychiatry, 3, 128136.
Kim, H. S., Sherman, D. K., Sasaki, J. Y., Xu, J., Chu, T. Q., Ryu, C., et al. (2010). Culture, distress, and oxytocin receptor polymorphism (OXTR) interact to influence emotional support seeking. Proceedings of the National Academy of Sciences, 107, 1571715721.
Kim-Cohen, J., Caspi, A., Moffitt, T. E., Harrington, H., Milne, B. J., & Poulton, R. (2003). Prior juvenile diagnoses in adults with mental disorder: Developmental follow-back of a prospective-longitudinal cohort. Archives of General Psychiatry, 60, 709717. doi:10.1001/archpsyc.60.7.709
Kogan, A., Saslow, L. R., Impett, E. A., Oveis, C., Keltner, D., & Saturn, S. R. (2012). Thin-slicing study of the oxytocin receptor (OXTR) gene and the evaluation and expression of the prosocial disposition. Proceedings of the National Academy of Sciences, 109, 1808.
Kroneman, L. M., Hipwell, A. E., Loeber, R., Koot, H. M., & Pardini, D. A. (2011). Contextual risk factors as predictors of disruptive behavior disorder trajectories in girls: The moderating effect of callous–unemotional features. Journal of Child Psychology and Psychiatry and Allied Disciplines, 52, 167175.
Lerer, E., Levi, S., Salomon, S., Darvasi, A., Yirmiya, N., & Ebstein, R. P. (2008). Association between the oxytocin receptor (OXTR) gene and autism: Relationship to Vineland Adaptive Behavior Scales and cognition. Molecular Psychiatry, 13, 980988.
Liu, X., Kawamura, Y., Shimada, T., Otowa, T., Koishi, S., Sugiyama, T., et al. (2010). Association of the oxytocin receptor (OXTR) gene polymorphisms with autism spectrum disorder (ASD) in the Japanese population. Journal of Human Genetics, 55, 137141.
Lucht, M. J., Barnow, S., Sonnenfeld, C., Rosenberger, A., Grabe, H. J., Schroeder, W., et al. (2009). Associations between the oxytocin receptor gene (OXTR) and affect, loneliness and intelligence in normal subjects. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 33, 860866.
Malik, A. I., Zai, C. C., Abu, Z., Nowrouzi, B., & Beitchman, J. H. (2012). The role of oxytocin and oxytocin receptor gene variants in childhood-onset aggression. Genes, Brain and Behavior, 11, 545551.
McCarthy, M. I., Abecasis, G. R., Cardon, L. R., Goldstein, D. B., Little, J., Ioannidis, J. P. A., et al. (2008). Genome-wide association studies for complex traits: Consensus, uncertainty and challenges. Nature Reviews Genetics, 9, 356369.
Mendlewicz, J., Crisafulli, C., Calati, R., Kocabas, N. A., Massat, I., Linotte, S., et al. (2012). Influence of COX-2 and OXTR polymorphisms on treatment outcome in treatment resistant depression. Neuroscience Letters, 516, 8588.
Meyer-Lindenberg, A., Domes, G., Kirsch, P., & Heinrichs, M. (2011). Oxytocin and vasopressin in the human brain: Social neuropeptides for translational medicine. Nature Reviews Neuroscience, 12, 524538.
Meyer-Lindenberg, A., Polin, J. B., Kohn, P. D., Holt, J. L., Egan, M. F., Weinberger, D. R., et al. (2001). Evidence for abnormal cortical functional connectivity during working memory in schizophrenia. American Journal of Psychiatry, 158, 18091817.
Modahl, C., Green, L., Fein, D., Morris, M., Waterhouse, L., Feinstein, C. et al. (1998). Plasma oxytocin levels in autistic children. Biological Psychiatry, 43, 270277.
Montag, C., Brockman, E. M., Bayerl, M., Rujescu, D., Müller, D. J., & Gallinat, J. (2012). Oxytocin and oxytocin receptor gene polymorphisms and risk for schizophrenia: A case-control study. World Journal of Biological Psychiatry. Advance online publication. doi:10.3109/15622975.2012.677547
Moul, C., Killcross, S., & Dadds, M. R. (2012). A model of differential amygdala activation in psychopathy. Psychological Review, 119, 789806. doi:10.1037/a0029342
Norman, G. J., Hawkley, L., Luhmann, M., Ball, A. B., Cole, S. W., Berntson, G. G., et al. (2012). Variation in the oxytocin receptor gene influences neurocardiac reactivity to social stress and HPA function: A population based study. Hormones and Behavior, 61, 134139.
Oxford, M., Cavell, T. A., & Hughes, J. N. (2003). Callous/unemotional traits moderate the relation between ineffective parenting and child externalizing problems: A partial replication and extension. Journal of Clinical Child and Adolescent Psychology, 32, 577585.
Park, J., Willmott, M., Vetuz, G., Toye, C., Kirley, A., Hawi, Z., et al. (2010). Evidence that genetic variation in the oxytocin receptor (OXTR) gene influences social cognition in ADHD. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 34, 697702.
Pasalich, D. S., Dadds, M. R., Hawes, D. J., & Brennan, J. (2011). Do callous–unemotional traits moderate the relative importance of parental coercion versus warmth in child conduct problems? An observational study. Journal of Child Psychology and Psychiatry and Allied Disciplines, 52, 13081315.
Patterson, G. R., DeBaryshe, B. D., & Ramsey, E. (1989). A developmental perspective on antisocial behavior. American Psychologist, 44, 329335.
Petersen, A. C., Crockett, L., Richards, M., & Boxer, A. (1988). A self-report measure of pubertal status: Reliability, validity, and initial norms. Journal of Youth and Adolescence, 17, 117133.
Poulin, M. J., Holman, E. A., & Buffone, A. (2012). The neurogenetics of nice: Receptor genes for oxytocin and vasopressin interact with threat to predict prosocial behavior. Psychological Science, 23, 446452.
Rey, J. M., Singh, M., Hung, S. F., Dossetor, D. R., Newman, L., Plapp, J. M., et al. (1997). A global scale to measure the quality of the family environment. Archives of General Psychiatry, 54, 817822.
Rodrigues, S. M., Saslow, L. R., Garcia, N., John, O. P., & Keltner, D. (2009). Oxytocin receptor genetic variation relates to empathy and stress reactivity in humans. Proceedings of the National Academy of Sciences, 106, 2143721441.
Sakai, J. T., Crowley, T. J., Stallings, M. C., McQueen, M., Hewitt, J. K., Hopfer, C., et al. (2012). Test of association between 10 single nucleotide polymorphisms in the oxytocin receptor gene and conduct disorder. Psychiatric Genetics, 22, 99102.
Saphire-Bernstein, S., Way, B. M., Kim, H. S., Sherman, D. K., & Taylor, S. E. (2011). Oxytocin receptor gene (OXTR) is related to psychological resources. Proceedings of the National Academy of Sciences, 108, 1511815122.
Sturge-Apple, M. L., Cicchetti, D., Davies, P., Davies, P. T., & Suor, J. H. (2012). Differential susceptibility in spillover between interparental conflict and maternal parenting practices: Evidence for OXTR and 5-HTT genes. Journal of Family Psychology, 26, 431442. doi:10.1037/a0028302
Tansey, K. E., Brookes, K. J., Hill, M. J., Cochrane, L. E., Gill, M., Skuse, D., et al. (2010). Oxytocin receptor (OXTR) does not play a major role in the aetiology of autism: Genetic and molecular studies. Neuroscience Letters, 474, 163167.
Thompson, R. J., Parker, K. J., Hallmayer, J. F., Waugh, C. E., & Gotlib, I. H. (2011). Oxytocin receptor gene polymorphism (rs2254298) interacts with familial risk for psychopathology to predict symptoms of depression and anxiety in adolescent girls. Psychoneuroendocrinology, 36, 144147.
Tost, H., Kolachana, B., Hakimi, S., Lemaitre, H., Verchinski, B. A., Mattay, V. S., et al. (2010). A common allele in the oxytocin receptor gene (OXTR) impacts prosocial temperament and human hypothalamic-limbic structure and function. Proceedings of the National Academy of Sciences, 107, 1393613941.
Viding, E., Blair, R. J. R., Moffitt, T. E., & Plomin, R. (2005). Evidence for substantial genetic risk for psychopathy in 7-year-olds. Journal of Child Psychology and Psychiatry and Allied Disciplines, 46, 592597.
Viding, E., Frick, P. J., & Plomin, R. (2007). Aetiology of the relationship between callous–unemotional traits and conduct problems in childhood. British Journal of Psychiatry, 190(Suppl. 49), s33s38.
Viding, E., Hanscombe, K. B., Curtis, C. J. C., Davis, O. S. P., Meaburn, E. L., & Plomin, R. (2010). In search of genes associated with risk for psychopathic tendencies in children: A two-stage genome-wide association study of pooled DNA. Journal of Child Psychology and Psychiatry and Allied Disciplines, 51, 780788.
Viding, E., Sebastian, C. L., Dadds, M. R., Lockwood, P. L., Cecil, C. A. M., De Brito, S. A., et al. (in press). Fast and fearless: Amygdala response to pre-attentive masked fear is associated with callous–unemotional traits in children with conduct problems. American Journal of Psychiatry.
Wermter, A. K., Kamp-Becker, I., Hesse, P., Schulte-Körne, G., Strauch, K., & Remschmidt, H. (2010). Evidence for the involvement of genetic variation in the oxytocin receptor gene (OXTR) in the etiology of autistic disorders on high-functioning level. American Journal of Medical Genetics, 153B, 629639.
Wootton, J. M., Frick, P. J., Shelton, K. K., & Silverthorn, P. (1997). Ineffective parenting and childhood conduct problems: The moderating role of callous–unemotional traits. Journal of Consulting and Clinical Psychology, 65, 301308.
Wu, N., Li, Z., & Su, Y. (2012). The association between oxytocin receptor gene polymorphism (OXTR) and trait empathy. Journal of Affective Disorders, 138, 468472.
Wu, S., Jia, M., Ruan, Y., Liu, J., Guo, Y., Shuang, M., et al. (2005). Positive association of the oxytocin receptor gene (OXTR) with autism in the Chinese Han population. Biological Psychiatry, 58, 7477.
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