Cited by 128Neuroendocrine regulation and behaviorPsychopathy, Forensic Psychiatry, Sexual OffendingNeurotransmitter Receptor Influence on Behavior

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The role of oxytocin and oxytocin receptor gene variants in childhood‐onset aggression

Malik, A. I., Zai, C. C., Abu, Z., Nowrouzi, B., Beitchman, J. H.·2012·Genes, Brain and Behavior

DOI 10.1111/j.1601-183x.2012.00776.x

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Abstract

Aggressive antisocial behaviours are the most common reasons why adolescents are referred to mental health clinics. Antisocial behaviours are costly in social and financial terms. The aetiology of aggressive behaviours is unknown but growing evidence suggests it is heritable, and certain genetic variants have been implicated as contributing factors. The purpose of this study was to determine whether genes regulating the hormone oxytocin (OXT) were associated with aggressive antisocial behaviour. The case‐control study sample consisted of 160 cases of children displaying extreme, persistent and pervasive aggressive behaviour. This case sample was compared with 160 adult controls. We used polymerase chain reaction (PCR) to determine the genotype for three oxytocin gene (OXT) single nucleotide polymorphisms (SNPs): rs3761248, rs4813625 and rs877172; and five oxytocin receptor gene (OXTR) SNPs: rs6770632, rs11476, rs1042778, rs237902 and rs53576. Genotypic analyses were performed using stata, while differences in haplotypic and allelic frequencies were analysed using Unphased. We also performed within‐case analyses (n = 236 aggressive cases) examining genotypic and allelic associations with callous‐unemotional (CU) scores (as measured by the psychopathic screening device). OXTR SNPs rs6770632 and rs1042778 may be associated with extreme, persistent and pervasive aggressive behaviours in females and males, respectively. These and haplotype results suggest gender‐specific effects of SNPs. No significant differences were detected with respect to CU behaviours. These results may help to elucidate the biochemical pathways associated with aggressive behaviours, which may aid in the development of novel medications.

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The Association of Oxytocin Receptor Gene (OXTR) Polymorphisms Antisocial Behavior: A Meta-analysis
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Multi-centre analysis of networks and genes modulated by hypothalamic stimulation in patients with aggressive behaviours
Gouveia, F. V., Germann, J., Elias, G. J. B., Boutet, A., Loh, A., Ríos, A. L. L., Torres, C. V., López, W. O. C., Martinez, R. C. R., Fonoff, E. T., et al. (2023) · eLife · doi:10.7554/elife.84566 · Cited by 24
Oxytocin Receptor Gene (OXTR) and Deviant Peer Affiliation: A Gene–Environment Interaction in Adolescent Antisocial Behavior
Fragkaki, I., Cima, M., Verhagen, M., Maciejewski, D. F., Boks, M. P., van Lier, P. A. C., Koot, H. M., Branje, S., & Meeus, W. (2018) · Journal of Youth and Adolescence · doi:10.1007/s10964-018-0939-x · Cited by 24
Genetic variants in oxytocin receptor gene (OXTR) and childhood physical abuse collaborate to modify the risk of aggression in chinese adolescents
Zhang, Y., Wu, C., Chang, H., Yan, Q., Wu, L., Yuan, S., Xiang, J., Hao, W., & Yu, Y. (2017) · Journal of Affective Disorders · doi:10.1016/j.jad.2017.12.024 · Cited by 23
An interaction between early threat exposure and the oxytocin receptor in females: Disorder-specific versus general risk for psychopathology and social–emotional mediators
Byrd, A. L., Tung, I., Manuck, S. D., Vine, V., Horner, M. S., Hipwell, A. E., & Stepp, S. D. (2020) · Development and Psychopathology · doi:10.1017/s0954579420000462 · Cited by 22
Prolyl endopeptidase and dipeptidyl peptidase IV are associated with externalizing and aggressive behaviors in normal and autistic adolescents
Frenssen, F., Croonenberghs, J., den Steene, H. V., & Maes, M. H. J. (2015) · Life Sciences · doi:10.1016/j.lfs.2015.07.003 · Cited by 23
Association between oxytocin and receptor genetic polymorphisms and aggression in a northern Chinese Han population with alcohol dependence
Yang, L., Wang, F., Wang, M., Han, M., Hu, L., Zheng, M., Ma, J., Kang, Y., Wang, P., Sun, H., et al. (2017) · Neuroscience Letters · doi:10.1016/j.neulet.2016.10.066 · Cited by 19
The reliability, concurrent validity and association with salivary oxytocin of the self-report version of the Inventory of Callous-Unemotional Traits in adolescents with conduct disorder
Levy, 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
“…associated single nucleotide polymorphisms (SNPs) in the oxytocin receptor gene with persistent and pervasive childhood-onset aggressive behaviors (Malik et al., 2012) and with high levels of CU traits in youth with disruptive behavior disorder (Beitchman et al., 2012; Dadds et al., 2014b; Malik…”
Background
Rigorous tests of gene–environment interactions in a lab study of the oxytocin receptor gene (OXTR), alcohol exposure, and aggression
LoParo, D., Johansson, A., Walum, H., Westberg, L., Santtila, P. O., & Waldman, I. D. (2015) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.32359 · Cited by 21
“Further, variation inOXTR (i.e., the ‘C’ allele of rs4564970, ‘C’ allele of rs1488467, ‘T’ allele of rs6770632, and ‘G’ allele of rs1042778) has been shown to be associated with increased aggression in humans [Johansson et al., 2012a,b; Malik et al., 2012], particularly in interaction with alcohol.”
BackgroundMethodResultInfluential
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
Transactions Between Substance Use Intervention, the Oxytocin Receptor (OXTR) Gene, and Peer Substance Use Predicting Youth Alcohol Use
Cleveland, H. H., Griffin, A. M., Wolf, P. S. A., Wiebe, R. P., Schlomer, G. L., Feinberg, M. E., Greenberg, M. T., Spoth, R. L., Redmond, C. R., & Vandenbergh, D. J. (2017) · Prevention Science · doi:10.1007/s11121-017-0749-5 · Cited by 19
Oxytocin Response Following Playful Mother–Child Interaction in Survivors of the Great East Japan Earthquake
Nawa, N., Nakamura, K., & Fujiwara, T. (2020) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2020.00477 · Cited by 15
“org 10 with child behavior problems (54, 55).”
Background
Association between temperament related traits and single nucleotide polymorphisms in the serotonin and oxytocin systems in Merino sheep
Ding, L., Maloney, S. K., Wang, M., Rodger, J., Chen, L., & Blache, D. (2020) · Genes Brain & Behavior · doi:10.1111/gbb.12714 · Cited by 16
The Pan social brain: An evolutionary history of neurochemical receptor genes and their potential impact on sociocognitive differences
Staes, N., Guevara, E. E., Helsen, P., Eens, M., & Stevens, J. M. G. (2021) · Journal of Human Evolution · doi:10.1016/j.jhevol.2021.102949 · Cited by 16
Reduced salivary oxytocin after an empathic induction task in Intimate Partner Violence perpetrators: Importance of socio-affective functions and its impact on prosocial behavior
Comes‐Fayos, J., Blanco-Gandía, M. C., Moreno, I. R., Rodríguez‐Arias, M., Lila, M., Sarrate‐Costa, C., Romero‐Martínez, Á., & Moya‐Albiol, L. (2021) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2021.105644 · Cited by 16
“It has been hypothesized that reduced peripheral and central OXT levels (which may reflect a "hypooxytocinergic state") could be related to and even predict aggression due to difficulties in processing socio-affective information (Malik et al., 2012).”
Background
The effects of oxytocin on primates’ working memory depend on the emotional valence of contextual factors
Zarei, S. A., Sheibani, V., Tomaz, C. A. B., & Mansouri, F. A. (2018) · Behavioural Brain Research · doi:10.1016/j.bbr.2018.12.050 · Cited by 17
“Genetic differences in the oxytocin receptor gene (OXTR) have been linked to abnormal social behaviors such as aggressive behavior [7].”
Paradoxical Effects of Intranasal Oxytocin on Trust in Inpatient and Community Adolescents
Venta, A., Ha, C., Vanwoerden, S., Newlin, E., Strathearn, L., & Sharp, C. (2019) · Journal of Clinical Child & Adolescent Psychology · doi:10.1080/15374416.2017.1399401 · Cited by 15
Oxytocin and the role of “regulator of emotions”: Definition, neurobiochemical and clinical contexts, practical applications and contraindications
Giulio, P. (2020) · Archives of Depression and Anxiety · doi:10.17352/2455-5460.000043 · Cited by 15
“Other possible contraindications detected during an excessive presence of oxytocin in the organism concern: envious and rancorous behaviors, as shown by a research by the University of Haifa [51]; learning and memory defi cits [52]; immoral behavior and against social laws [53]; prejudicial conduct towards a subject o…”
Background
Review of eating disorders and oxytocin receptor polymorphisms
Burmester, V., Nicholls, D., Buckle, A., Stanojević, B., & Crous‐Bou, M. (2021) · Journal of Eating Disorders · doi:10.1186/s40337-021-00438-0 · Cited by 16
Antisocial and Callous Behaviour in Children
Viding, E. M., Seara‐Cardoso, A., & McCrory, E. J. P. (2013) · Current topics in behavioral neurosciences · doi:10.1007/7854_2013_266 · Cited by 15
“However, when the same group inspected different oxytocin and oxytocin receptor SNPs, no association with CU traits was found (Malik et al., 2012).”
Gene–environment interaction: Oxytocin receptor (OXTR) polymorphisms and parenting style as potential predictors for depressive symptoms
Keijser, R., Åslund, C., Nilsson, K. W., & Olofsdotter, S. (2021) · Psychiatry Research · doi:10.1016/j.psychres.2021.114057 · Cited by 13
“The OXTR SNPs rs6770632, rs1488467, and rs4564970 have individually been linked to aggressive behaviour (Ebstein et al., 2012; Hovey et al., 2016; Malik et al., 2012).”
Developmental risk for psychopathy
Viding, E. M., & McCrory, E. J. P. (2015) · Wiley eBooks · doi:10.1002/9781118381953.ch68 · Cited by 15
A meta-analytic review of the relationship between empathy and oxytocin: Implications for application in psychopathy research
Stark, N., Bobadilla, L., Michael, P., Saturn, S. R., & Portner, M. (2023) · Aggression and Violent Behavior · doi:10.1016/j.avb.2023.101828 · Cited by 11
Schizophrenia and alcohol dependence: Diverse clinical effects of oxytocin and their evolutionary origins
Pedersen, C. A. (2014) · Brain Research · doi:10.1016/j.brainres.2014.01.050 · Cited by 11
Relationship between Thyroid Hormone Levels and Crime Type: A Controlled Study in Prisoners
Acar, H., & Ülgen, A. (2020) · International Journal of Endocrinology · doi:10.1155/2020/9172134 · Cited by 13
“OXTR SNPs rs6770632 variants in girls and rs1042778 variants in boys were associated with excessive and persistent aggressive behaviour [2].”
Background
7q11.23 Microduplication Syndrome: Clinical and Neurobehavioral Profiling
Dentici, M. L., Bergonzini, P., Scibelli, F., Caciolo, C., Rose, P. D., Cumbo, F., Alesi, V., Capolino, R., Zanni, G., Sinibaldi, L., et al. (2020) · Brain Sciences · doi:10.3390/brainsci10110839 · Cited by 14
Identification of Candidate Genes and Pathways Linked to the Temperament Trait in Sheep
Romaniuk, E., Vera, B., Peraza, P., Ciappesoni, G., Damián, J. P., & van Lier, E. (2024) · Genes · doi:10.3390/genes15020229 · Cited by 11
Correction: Genetics of Callous-Unemotional Behavior in Children
Viding, E. M., Price, T. S., Jaffee, S. R., Trzaskowski, M., Davis, O. S. P., Meaburn, E. L., Haworth, C. M. A., & Plomin, R. J. (2013) · PLoS ONE · doi:10.1371/annotation/0b16418f-ceb5-41b2-be2a-a20f0c56f9a6 · Cited by 11
OXTR polymorphism in depression and completed suicide—A study on a large population sample
Wasilewska, K., Pawlak, A., Kostrzewa, G., Sobczyk‐Kopcioł, A., Kaczorowska, A., Badowski, J., Brzozowska, M., Drygas, W., Piwoński, J., Bielecki, W., et al. (2016) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2016.12.003 · Cited by 10
The Vindication of Lamarck? Epigenetics at the Intersection of Law and Mental Health
DeLisi, M., & Vaughn, M. G. (2015) · Behavioral Sciences & the Law · doi:10.1002/bsl.2206 · Cited by 11
Association of OXTR rs53576 with the Developmental Trajectories of Callous-Unemotional Traits and Stressful Life Events in 3- to 9-Year-Old Community Children
Ezpeleta, L., Penelo, E., de la Osa, N., Navarro, J. B., Fañanás, L., & Fatjó‐Vilas, M. (2019) · Research on Child and Adolescent Psychopathology · doi:10.1007/s10802-019-00548-z · Cited by 12
The Neurobiology of Adolescent-Onset Borderline Personality Disorder
Goodman, M. S., Pérez-Rodríguez, M. M., & Siever, L. J. (2014) · Springer eBooks · doi:10.1007/978-1-4939-0591-1_9 · Cited by 8
The Role of Oxytocin in Polycystic Ovary Syndrome: A Systematic Review
Cera, N., Pinto, J., & Pignatelli, D. (2024) · Current Issues in Molecular Biology · doi:10.3390/cimb46060313 · Cited by 6
“Specifically, a significant association between rs237902 and negative symptoms, such as blunted affect, alogia, avolition asociality, and anhedonia, in schizophrenic patients and an overrepresentation in male aggressive children were observed [99–101].”
Background
Aggression and empathy as genetic differentiation factors of urban population
Атраментова, Л. А., & Luchko, E. (2016) · Russian Journal of Genetics · doi:10.1134/s1022795416050021 · Cited by 7
The relationship between different types of genetically defined aggressive behavior
Ilchibaeva, T. V., Tsybko, A. S., Kozhemyakina, R. V., Konoshenko, M. Y., Popova, N. K., & Naumenko, V. S. (2016) · Journal of Ethology · doi:10.1007/s10164-016-0493-5 · Cited by 7
“Infanticide and intermale aggression are closely related to antisocial and criminal violence in humans and, hence, are the subject of intensive investigation (Blanchard et al. 1999; Foster and Jones 2006; Kazdin et al. 2006; Malik et al. 2012).”
Background
Genomic Signatures of Positive Selection in Human Populations of the OXT, OXTR, AVP, AVPR1A and AVR1B Gene Variants Related to the Regulation of Psychoemotional Response
Bakoev, S., Korobeinikova, A. V., Mishina, A. I., Kabieva, S. S., Игоревич, М. С., Ивашечкин, А. А., Akinshina, A. I., Snigir, E. A., Yudin, S. M., Yudin, V. S., et al. (2023) · Genes · doi:10.3390/genes14112053 · Cited by 7
“According to the results of our analysis, other positively selected variants of the OXTR gene are associated with aggressive behavior and depressive states [22,23,63], alcohol abuse and associated aggressive behavior [24,64], severe schizophrenia, and autism spectrum disorders [23,24,65].”
Result
Oxytocin system polymorphisms rs237887 and rs2740210 variants increase the risk of depression in pregnant women with early abuse
Olazábal, D. E., Bertoni, B., Grandi, G., Musetti, D., Rey, G., Sandberg, N. Y., Fernández, L., Laporte, G., Medici, F., & Nicolaisen‐Sobesky, E. (2023) · Developmental Psychobiology · doi:10.1002/dev.22400 · Cited by 5
Associations Between Vocal Symptoms and Genetic Variants in the Oxytocin Receptor and Arginine Vasopressin 1A Receptor Gene
Holmqvist-Jämsén, S., Johansson, A., Westberg, L., Santtila, P. O., von der Pahlen, B., & Simberg, S. (2017) · Journal of Speech Language and Hearing Research · doi:10.1044/2016_jslhr-s-16-0059 · Cited by 6
Genetic Contributions to the Development of Psychopathic Traits and Antisocial Behavior in Youths
Fontaine, N. M. G., McCrory, E. J. P., & Viding, E. M. (2018) · doi:10.1002/9781118650868.ch18 · Cited by 5
The Neurobiological Underpinnings of Psychopathy
Brito, S. A. D., & Mitchell, I. (2018) · Wiley eBooks · doi:10.1002/9781118650868.ch9 · Cited by 5
The Role of Oxytocin and Vasopressin in People with Borderline Personality Disorder: A Closer Look at Adolescents
Uzar, M., Dmitrzak‐Węglarz, M., & Słopień, A. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252212046 · Cited by 5
“There was also some evidence for associations between severe, persistent, and pervasive aggressive behaviors in a group of 6–16 year-olds and single nucleotide polymorphisms in OXTR rs1042778 and rs6770632 [106].”
Causal Factors in Aggression and Violence: Examining Social and Biological Theories
Frieze, I. H., Newhill, C. E., & Fusco, R. A. (2020) · Springer eBooks · doi:10.1007/978-3-030-42608-8_2 · Cited by 4

Authors: Malik, A. I., Zai, C. C., Abu, Z., Nowrouzi, B., & Beitchman, J. H.
Affiliations: Centre for Addiction and Mental Health (CA)
Corresponding author: Beitchman, J. H.
ORCID: Zai, C. C.
Venue: Genes, Brain and Behavior
Publisher: Wiley
Published: 2012-03-23
Volume: 11
Issue: 5
Pages: 545-551
ISSN: 1601-183X (ISSN-L)
1601-1848
DOI: 10.1111/j.1601-183x.2012.00776.x
OpenAlex: W1964979302
Cited by: 128
References: 45
Citations by year: 2025: 2 · 2024: 6 · 2023: 7 · 2022: 3 · 2021: 5 · 2020: 14 · 2019: 5 · 2018: 12 · 2017: 15 · 2016: 10 · 2015: 12 · 2014: 17 · 2013: 17 · 2012: 3
FWCI: 23.67
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Genes Brain & Behavior (publishedVersion)
PubMed (publishedVersion)
Funders: Natural Sciences and Engineering Research Council of Canada
Topics: Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroendocrine regulation and behavior
Social Sciences › Psychology › Clinical Psychology › Psychopathy, Forensic Psychiatry, Sexual Offending
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords: oxytocin, oxytocin receptor, antisocial behavior, callous-unemotional traits, single nucleotide polymorphisms, haplotypes, sex differences, genetic susceptibility
MeSH terms: Adolescent, Adult, Aggression, Alleles, Child, Child Behavior Disorders, Female, Gene Frequency, Genotype, Haplotypes, Humans, Male, Oxytocin, Sex Characteristics, Case-Control Studies, Receptors, Oxytocin, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide

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The role of oxytocin and oxytocin receptor gene variants in childhood‐onset aggression

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