European Child & Adolescent Psychiatry

, Volume 21, Issue 3, pp 125–132 | Cite as

Childhood aggression, callous-unemotional traits and oxytocin genes

  • Joseph H. BeitchmanEmail author
  • Clement C. Zai
  • Katherine Muir
  • Laura Berall
  • Behdin Nowrouzi
  • Esther Choi
  • James L. Kennedy
Original Contribution


Given the known behavior effects of oxytocin, and in particular its putative effect on trust, affiliation and anxiety, we hypothesized that oxytocin may be involved in the development and expression of callous-unemotional traits in children with aggressive antisocial behavior. We recruited 162 children between the ages of 6 and 16. The majority of subjects were Caucasian (84.0%) compared to African-Canadian (4.9%) and others (11.1%). The oxytocin and oxytocin receptor gene polymorphisms were genotyped and analyzed for possible association with child aggression in a case–control study design as well as with callous-unemotional traits in a within cases analysis. We did not have significant findings with our tested OXTR markers in the case–control analysis. We found the OXTR_rs237885 AA genotype carriers to score higher than AC or CC genotype carriers on the callous-unemotional traits. This result remained significant following correction for multiple testing. No other markers were found to be significant. However, the haplotype consisting of the OXTR_rs237885 A allele and OXTR_rs2268493 A allele was associated with significantly higher callous-unemotional scores than other haplotypes. This is the first known study to show a significant association between callous-unemotional traits in children and adolescents with extreme, persistent pervasive aggression and a polymorphism on the oxytocin receptor. Given the small sample size and the possibility of false positive effects, the need to replicate and verify these findings is required.


Childhood aggression Oxytocin Callous-unemotional trait Genetics Oxytocin receptor Aggression 



The authors acknowledge the support from the CAMH foundation, the Howitt/Dunbar Foundation and Youthdale Treatment Centres.

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Kadzin AE (1995) Conduct disorders in childhood and adolescence, 2nd edn. Sage, Thousand OaksGoogle Scholar
  2. 2.
    Steiner H (2000) Disruptive behavior disorders. In: Kaplan H, Sadock B (eds) Kaplan & Sadock’s comprehensive textbook of psychiatry, vol 2. Lippincott Williams & Wilkins Publishers, New York, pp 2693–2703Google Scholar
  3. 3.
    Moffitt TE (2003) Life-course-persistent and adolescence-limited antisocial behavior. In: Lahey BB, Moffitt TE, Caspi A (eds) Causes of conduct disorder and juvenile delinquency. Guilford Press, New YorkGoogle Scholar
  4. 4.
    Frick PJ, O’Brien BS, Wootton JM, McBurnett K (1994) Psychopathy and conduct problems in children. J Abnorm Psychol 103(4):700–707PubMedCrossRefGoogle Scholar
  5. 5.
    Blair RJR (2001) Neurocognitive models of aggression, the antisocial personality disorders, and psychopathy. J Neurol Neurosurg Psychiatry 71(6):727–731PubMedCrossRefGoogle Scholar
  6. 6.
    Frick PJ, Ellis M (1999) Callous-unemotional traits and subtypes of conduct disorder. Clin Child Family Psychol Rev 2(3):149–168CrossRefGoogle Scholar
  7. 7.
    Fisher L, Blair RJR (1998) Cognitive impairment and its relationship to psychopathic tendencies in children with emotional and behavioral difficulties. J Abnorm Child Psychol 26(6):511–519PubMedCrossRefGoogle Scholar
  8. 8.
    Mason DA, Frick PJ (1994) The heritability of antisocial behavior: a meta-analysis of twin and adoption studies. J Psychopathol Behav Assess 16(4):301–323CrossRefGoogle Scholar
  9. 9.
    Viding E, Blair RJR, Moffitt TE, Plomin R (2005) Strong genetic risk for psychopathic syndrome in children. J Child Psychol Psychiatry 46:592–597PubMedCrossRefGoogle Scholar
  10. 10.
    Beitchman JH, Mik HM, Ehtesham S, Douglas L, Kennedy JL (2004) MAOA and persistent, pervasive childhood aggression. Mol Psychiatry 9(6):546–547PubMedCrossRefGoogle Scholar
  11. 11.
    Caspi A, McClay J, Moffitt TE, Mill J, Martin J, Craig IW, Taylor A, Poulton R (2002) Role of genotype in the cycle of violence in maltreated children. Science 297(5582):851–854PubMedCrossRefGoogle Scholar
  12. 12.
    Beitchman JH, Baldassarra L, Mik H, De Luca V, King N, Bender D, Ehtesham S, Kennedy JL (2006) Serotonin transporter polymorphisms and persistent, pervasive childhood aggression. Am J Psychiatry 163(6):1103–1105PubMedCrossRefGoogle Scholar
  13. 13.
    Viding E, Hanscombe KB, Curtis CJC, Davis OSP, Meaburn EL, 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. J Child Psychol Psychiatry 51(7):780–788PubMedCrossRefGoogle Scholar
  14. 14.
    Frick PJ, Viding E (2009) Antisocial behavior from a developmental psychopathology perspective. Dev Psychopathol 21(Special Issue 04):1111–1131PubMedCrossRefGoogle Scholar
  15. 15.
    Barry TD, Barry CT, Deming AM, Lochman JE (2008) Stability of psychopathic characteristics in childhood. Crim Justice Behav 35(2):244–262CrossRefGoogle Scholar
  16. 16.
    Dadds M, Fraser J, Frost A, Hawes D (2008) Disentangling the underlying dimensions of psychopathy and conduct problems in childhood: A community study. J Consul Clin Psychol 73(3):400–410CrossRefGoogle Scholar
  17. 17.
    Rutherford M (1999) The 2-year Test-Retest Reliability of the Psychopathy Checklist-revised in methadone patients. Assessment 6(3):285–291PubMedCrossRefGoogle Scholar
  18. 18.
    Lynam DR, Charnigo R, Moffitt TE, Raine A, Loeber R, Stouthamer-Loeber M (2009) The stability of psychopathy across adolescence. Dev Psychopathol 21(04):1133–1153PubMedCrossRefGoogle Scholar
  19. 19.
    Muñoz LC, Frick PJ (2007) The reliability, stability, and predictive utility of the self report version of the antisocial process screening device. Scand J Psychol 48(4):299–312PubMedCrossRefGoogle Scholar
  20. 20.
    Forsman M, Lichtenstein P, Andershed H, Larsson H (2008) Genetic effects explain the stability of psychopathic personality from mid-to late adolescence. J Abnorm Psychol 117(3):606–617PubMedCrossRefGoogle Scholar
  21. 21.
    Campbell A (2010) Oxytocin and human social behavior. Pers Soc psychol Rev 14(3):281–295PubMedCrossRefGoogle Scholar
  22. 22.
    Engelmann M, Landgraf R, Wotjak CT (2004) The hypothalamic-neurohypophysial system regulates the hypothalamic-pituitary-adrenal axis under stress: an old concept revisited. Frontiers neuroendocrinol 25(3–4):132–149CrossRefGoogle Scholar
  23. 23.
    Viviani D, Stoop R (2008) Opposite effects of oxytocin and vasopressin on the emotional expression of the fear response. Prog Brain Res 170:207–218PubMedCrossRefGoogle Scholar
  24. 24.
    Hollander E, Bartz J, Chaplin W, Phillips A, Sumner J, Soorya L, Anagnostou E, Wasserman S (2007) Oxytocin increases retention of social cognition in autism. Biol Psychiatry 61(4):498–503Google Scholar
  25. 25.
    Lerer E, Levi S, Salomon S, Darvasi A, Yirmiya N, Ebstein RP (2008) Association between the oxytocin receptor (OXTR) gene and autism: relationship to Vineland Adaptive Behavior Scales and cognition. Mol Psychiatry 13(10):980–988PubMedCrossRefGoogle Scholar
  26. 26.
    Israel S, Lerer E, Shalev I, Uzefovsky F, Reibold M, Bachner-Melman R, Granot R, Bornstein G, Knafo A (2008) Molecular genetics studies of the arginine vasopression 1a receptor (AVPR1a) and hte oxytocin receptor (OXTR) in human behaviour: from autism to altruism with some notes in between. In: Neumann I, Landgraf R (eds) Progress in Brain Research, vol 170. Elsevier, AmsterdamGoogle Scholar
  27. 27.
    Sala M, Braida D, Lentini D, Busnelli M, Bulgheroni E, Capurro V, Finardi A, Donzelli A, Pattini L, Rubino T, Parolaro D, Nishimori K, Parenti M, Chini B (2011) Pharmacologic rescue of impaired cognitive flexibility, social deficits, increased aggression, and seizure susceptibility in oxytocin receptor null mice: a neurobehavioral model of autism. Biol Psychiatry 69(9):875–882PubMedCrossRefGoogle Scholar
  28. 28.
    Campbell DB, Datta D, Jones ST, Batey Lee E, Sutcliffe JS, Hammock EA, Levitt P (2011) Association of oxytocin receptor (OXTR) gene variants with multiple phenotype domains of autism spectrum disorder. J Neurodev Disord 3(2):101–112. doi: 10.1007/s11689-010-9071-2 Google Scholar
  29. 29.
    Souza RP, de Luca V, Meltzer HY, Lieberman JA, Kennedy JL (2010) Schizophrenia severity and clozapine treatment outcome association with oxytocinergic genes. Int J Neuropsychopharmacol 13(06):793–798PubMedCrossRefGoogle Scholar
  30. 30.
    Fetissov SO, Hallman J, Nilsson I, Lefvert AK, Oreland L, Hökfelt T (2006) Aggressive behavior linked to corticotropin-reactive autoantibodies. Biol psychiatry 60(8):799–802PubMedCrossRefGoogle Scholar
  31. 31.
    Kirsch P, Esslinger C, Chen Q, Mier D, Lis S, Siddhanti S, Gruppe H, Mattay VS, Gallhofer B, Meyer-Lindenberg A (2005) Oxytocin modulates neural circuitry for social cognition and fear in humans. J Neurosci 25(49):11489–11493PubMedCrossRefGoogle Scholar
  32. 32.
    Bosch OJ, Meddle SL, Beiderbeck DI, Douglas AJ, Neumann ID (2005) Brain oxytocin correlates with maternal aggression: link to anxiety. J Neurosci 25(29):6807–6815PubMedCrossRefGoogle Scholar
  33. 33.
    Winslow JT, Hearn EF, Ferguson J, Young LJ, Matzuk MM, Insel TR (2000) Infant vocalization, adult aggression, and fear behavior of an oxytocin null mutant mouse. Horm Behav 37(2):145–155PubMedCrossRefGoogle Scholar
  34. 34.
    Bosch OJ, Sartori SB, Singewald N, Neumann ID (2007) Extracellular amino acid levels in the paraventricular nucleus and the central amygdala in high-and low-anxiety dams rats during maternal aggression: regulation by oxytocin. Stress: Int J Biol Stress 10(3):261–270CrossRefGoogle Scholar
  35. 35.
    Veenema AH, Beiderbeck DI, Lukas M, Neumann ID (2010) Distinct correlations of vasopressin release within the lateral septum and the bed nucleus of the stria terminalis with the display of intermale aggression. Hormones Behav 58(2):273–281CrossRefGoogle Scholar
  36. 36.
    Savaskan E, Ehrhardt R, Schulz A, Walter M, Schächinger H (2008) Post-learning intranasal oxytocin modulates human memory for facial identity. Psychoneuroendocrinology 33(3):368–374PubMedCrossRefGoogle Scholar
  37. 37.
    Ebstein RP, Israel S, Lerer E, Uzefovsky F, Shalev I, Gritsenko I, Riebold M, Salomon S, Yirmiya N (2009) Arginine vasopressin and oxytocin modulate human social behavior. Ann NY Acad Sci 1167(1):87–102PubMedCrossRefGoogle Scholar
  38. 38.
    Israel S, Lerer E, Shalev I, Uzefovsky F, Riebold M, Laiba E, Bachner-Melman R, Maril A, Bornstein G, Knafo A (2009) The oxytocin receptor (OXTR) contributes to prosocial fund allocations in the dictator game and the social value orientations task. PLoS One 4(5):5535CrossRefGoogle Scholar
  39. 39.
    Kosfeld M, Heinrichs M, Zak PJ, Fischbacher U, Fehr E (2005) Oxytocin increases trust in humans. Nature 435(7042):673–676PubMedCrossRefGoogle Scholar
  40. 40.
    Lee H-J, Macbeth AH, Pagani JH, Young WS (2009) Oxytocin: the great facilitator of life. Prog Neurobiol 88(2):127–151PubMedGoogle Scholar
  41. 41.
    Stanley B, Siever LJ (2010) The interpersonal dimension of borderline personality disorder: toward a neuropeptide model. Am J Psychiatry 167(1):24–39PubMedCrossRefGoogle Scholar
  42. 42.
    Gordon I, Zagoory Sharon O, Schneiderman I, Leckman JF, Weller A, Feldman R (2008) Oxytocin and cortisol in romantically unattached young adults: associations with bonding and psychological distress. Psychophysiology 45(3):349–352PubMedCrossRefGoogle Scholar
  43. 43.
    Grewen KM, Girdler SS, Amico J, Light KC (2005) Effects of partner support on resting oxytocin, cortisol, norepinephrine, and blood pressure before and after warm partner contact. Psychosom Med 67(4):531PubMedCrossRefGoogle Scholar
  44. 44.
    Bakermans-Kranenburg MJ, van Ijzendoorn MH (2008) Oxytocin receptor (OXTR) and serotonin transporter (5-HTT) genes associated with observed parenting. Soc Cogn Affect Neurosci 3(2):128–134PubMedCrossRefGoogle Scholar
  45. 45.
    Thompson RJ, Parker KJ, Hallmayer JF, Waugh CE, Gotlib IH (2011) Oxytocin receptor gene polymorphism (rs2254298) interacts with familial risk for psychopathology to predict symptoms of depression and anxiety in adolescent girls. Psychoneuroendocrinology 36(1):144–147PubMedCrossRefGoogle Scholar
  46. 46.
    Montag C, Fiebach CJ, Kirsch P, Reuter M (2011) Interaction of 5-HTTLPR and a variation on the oxytocin receptor gene influences negative emotionality. Biol Psychiatry 69:601–603PubMedCrossRefGoogle Scholar
  47. 47.
    Inoue H, Yamasue H, Tochigi M, Abe O, Liu X, Kawamura Y, Takei K, Suga M, Yamada H, Rogers MA (2010) Association between the oxytocin receptor gene and amygdalar volume in healthy adults. Biol Psychiatry 68(11):1066–1072PubMedCrossRefGoogle Scholar
  48. 48.
    Furman DJ, Chen MC, Gotlib IH (2011) Variant in oxytocin receptor gene is associated with amygdala volume. Psychoneuroendocrinology 36(6):891–897PubMedCrossRefGoogle Scholar
  49. 49.
    Reuter M, Weber B, Fiebach CJ, Elger C, Montag C (2009) The biological basis of anger: associations with the gene coding for DARPP-32 (PPP1R1B) and with amygdala volume. Behav Brain Res 202(2):179–183PubMedCrossRefGoogle Scholar
  50. 50.
    Achenbach TM, Rescorla LA (2001) Manual for the ASEBA School-Age Forms and Profiles. University of Vermont, Research Center for Children, Youth and Families, BurlingtonGoogle Scholar
  51. 51.
    Weschsler D (1991) Manual for the Wechsler Intellgience Scale for Children. The Psychological Corporation, San AntonioGoogle Scholar
  52. 52.
    First MB, Spitzer RL, Gibbon M, Williams JBW (1997) Structured clinical interview for DSM IV-TR Axis I Disorders, research version, non-patient edition (SCID-I/NP). Biometrics Research, New York State Psychiatric Institute, New YorkGoogle Scholar
  53. 53.
    Maxwell E (1992) The Family Interview for Genetic Studies: Manual. Clinical Neurogenetics Branch, Intramural Research Program, National Institute of Mental Health, WashingtonGoogle Scholar
  54. 54.
    American Psychiatric Association (1994) Diagnostic and statistical manual of mental health disorders, 4th edn. American Psychiatric Association, WashingtonGoogle Scholar
  55. 55.
    Shaffer D, Fisher P, Lucas CP, Dulcan MK, Schwab-Stone ME (2000) NIMH diagnostic interview schedule for children version IV (NIMH DISC-IV): description, differences from previous versions, and reliability of some common diagnoses. J Am Acad Child Adolesc Psychiatry 39(1):28–38PubMedCrossRefGoogle Scholar
  56. 56.
    Kovacs M (1985) The Children’s Depression Inventory (CDI). Psychopharmacol Bull 21(4):995–998PubMedGoogle Scholar
  57. 57.
    Frick PJ, Hare RD (2001) Psychopathy screening device. Multi-Health Systems, TorontoGoogle Scholar
  58. 58.
    Lahiri DK, Nurnberger JI Jr (1991) A rapid non-enzymatic method for the preparation of HMW DNA from blood for RFLP studies. Nucleic Acids Res 19(19):5444PubMedCrossRefGoogle Scholar
  59. 59.
    SPSS (2007) SPSS Version 15 for Windows. SPSS Inc., ChicagoGoogle Scholar
  60. 60.
    Barrett JC, Fry B, Maller J, Daly MJ (2005) Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21(2):263–265PubMedCrossRefGoogle Scholar
  61. 61.
    Dudbridge F (2003) Pedigree disequilibrium tests for multilocus haplotypes. Genet Epidemiol 25(2):115–121PubMedCrossRefGoogle Scholar
  62. 62.
    Gauderman WJ, Morrison JM (2006) QUANTO 1.1: a computer program for power and sample size calculations for genetic-epidemiology studies.
  63. 63.
    Nyholt DR (2004) A simple correction for multiple testing for single-nucleotide polymorphisms in linkage disequilibrium with each other. AmJ Human Genet 74(4):765–769CrossRefGoogle Scholar
  64. 64.
    Rutherford M, Cacciola JS, Alterman AI, McKay JR, Cook TG (1999) The 2-year test-retest reliability of the Psychopathy Checklist-revised in methadone patients. Assessment 6(3):285PubMedCrossRefGoogle Scholar
  65. 65.
    Dadds MR, Fraser J, Frost A, Hawes DJ (2005) Disentangling the underlying dimensions of psychopathy and conduct problems in childhood: a community study. J Consult Clin Psychol 73(3):400PubMedCrossRefGoogle Scholar
  66. 66.
    Frick PJ, Kimonis ER, Dandreaux DM, Farell JM (2003) The 4 year stability of psychopathic traits in non-referred youth. Behav Sci Law 21(6):713–736PubMedCrossRefGoogle Scholar
  67. 67.
    Fontaine NMG, Rijsdijk FV, McCrory EJP, Viding E (2010) Etiology of different developmental trajectories of callous-unemotional traits. J Am Acad Child Adoles Psychiatry 49(7):656–664Google Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Joseph H. Beitchman
    • 1
    • 3
    Email author
  • Clement C. Zai
    • 2
    • 3
  • Katherine Muir
    • 4
  • Laura Berall
    • 5
  • Behdin Nowrouzi
    • 1
  • Esther Choi
    • 1
  • James L. Kennedy
    • 2
    • 3
  1. 1.Child, Youth and Family Program, Centre for Addiction and Mental HealthTorontoCanada
  2. 2.Neurogenetics SectionCentre for Addiction and Mental HealthTorontoCanada
  3. 3.Department of PsychiatryUniversity of TorontoTorontoCanada
  4. 4.University of TorontoTorontoCanada
  5. 5.University of Western OntarioLondonCanada

Personalised recommendations