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

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.

Integrative Approaches Utilizing Oxytocin to Enhance Prosocial Behavior: From Animal and Human Social Behavior to Autistic Social Dysfunction

“…A lower-than-normal plasma OT level in ASD subjects (Modahl et al, 1998;Andari et al, 2010; and an association of ASD with OXTR (Wu et al, 2005;Jacob et al, 2007;Lerer et al, 2008;Liu et al, 2010) further support a link between OT and ASD, although some inconsistency in association between ASD and OXTR was also recognized (Tansey et al, 2010;Campbell et al, 2011). Furthermore, several pioneering studies have suggested improvements in autistic behavioral and cognitive characteristics following administration of OT.…”

“…In addition, several studies have examined limbic brain structure in the context of rs2254298, a genetic polymorphism that has been repeatedly linked to ASD, although there has been heterogeneity regarding the risk-associated allele in populations of different ethnicity (Wu et al, 2005;Jacob et al, 2007;Liu et al, 2010). The first imaging genetics study in a large sample of healthy Japanese adults (Inoue et al, 2010) used manual tracing methods to derive amygdala volumes, and examined the relationship of these measures to seven SNPs and one haplotype block in OXTR linked to ASD.…”

“…The basis of this prevailing view has progressed from animal research documenting a pivotal role of OT in promoting social bonding and attachment (Insel, 1992;Young et al, 1998;Insel and Young, 2001;Kendrick, 2004;Insel, 2010) and controlling fear and stress responses (Neumann, 2002;Huber et al, 2005;Lukas et al, 2011;Viviani et al, 2011;Knobloch et al, 2012) to pharmacological challenge studies in healthy humans, which demonstrated beneficial effects of intranasal single-dose (24 -48 IU) administration of OT on behavioral responses in various social-economic and social-cognitive tasks. These tasks have addressed, for instance, interpersonal trust and cooperation (Kosfeld et al, 2005;De Dreu, 2011), generosity (Zak et al, 2007, social recognition memory (Guastella et al, 2008a;Savaskan et al, 2008;Rimmele et al, 2009), social reinforcement learning and emotional empathy (Hurlemann et al, 2010), assessments of facial attractiveness and trustworthiness (Theodoridou et al, 2009), and self-perception (Cardoso et al, 2012).…”

Oligomerization of GPCRs involved in endocrine regulation

“…The OTR and OT are involved in memory and learning, stress regulation and anxiety, and aggressive, sexual and maternal behaviors (e.g. Argiolas 1992, Malik et al 2012, Ebner et al 2013. Moreover, the OTR is involved in thermoregulation and brain development (Gimpl & Fahrenholz 2001, Kasahara et al 2013).…”

Relationship Between Oxytocin and Attention Deficit Hyperactivity Disorder

“…Özellikle, düşük oksitosin beyin omurilik sıvısı (28), oksitosin reseptör geninin (OXTR) işlevsel polimorfizmlerinde ortaya çıkan kayıp (29,30) ve oksitosin reseptör geni promoterinde (transkripsiyonu başlatan kısım) epigenetik susturma (metilasyon) genç erkeklerde dürtüsel ve saldırgan mizaçla, kişiler arası şiddet ve acımasız-duygusuz özelliklerle ilişkili bulunmuştur (31). Benzer şekilde hayvan çalışmaları alanındaki veriler, sosyal davranışsal yanıt düzenlenmesinde santral oksitosinerjik kontrolünün önemini güçlendirmiştir.…”