With a strong tendency to socialise, the zebrafish is a useful model to study social behaviour, with implications for better treatments of social impairments, for instance in autism spectrum disorders. Although oxytocin is crucial for social behaviour in mammals, the importance of the fish orthologue-isotocin or zebrafish oxytocin (zOT)-for social behaviour in zebrafish is unclear. The aims of this study were firstly, to elucidate the receptor specificity of zOT and the related vasotocin or zebrafish vasopressin (zVP; the orthologue of mammalian vasopressin) and the nonpeptidergic oxytocin receptor antagonist L-368,899, and secondly to investigate if L-368,899 inhibits social preference in zebrafish. The potencies of ligands were evaluated for zOT/zVP family receptors in HEK293 cells. Adult and larval zebrafish were treated with L-368,899 or vehicle and subsequently assessed for social behaviour and anxiety (adults only). The antagonist L-368,899 specifically inhibited the two zOT receptors, but not the two zVP-1 receptors. The antagonist decreased social preference in adult and larval zebrafish. It did not affect anxiety in adults. These results indicate that endogenous zOT, and possibly zVP, is involved in social behaviour in zebrafish via either or both of the two zOT receptors, and show promise for future explorations of the anatomy and evolution of networks underlying social behaviour.

Oxytocin has repeatedly been shown to influence human behavior in social contexts; also, a relationship between oxytocin and the pathophysiology of Autism Spectrum Disorder (ASD) has been suggested. In the present study, we investigated SNPs in the oxytocin gene (OXT), and the genes for single-minded 1 (SIM1), aryl hydrocarbon receptor nuclear translocator 2 (ARNT2), and cluster of differentiation 38 (CD38), in a population of 1771 children from the Child and Adolescent Twin Study in Sweden. Statistical analyses were performed to investigate any association between SNPs and autistic-like traits (ALTs), measured through ASD scores in the Autism-Tics, ADHD and other Comorbidities inventory. Our main finding was a statistically significant association between the SIM1 SNP rs3734354 (Pro352Thr) and ASD scores for language impairment (p=0.0004). Furthermore, nominal associations were found between ASD scores and SNPs in OXT, ARNT2 and CD38. In summary, the present study lends support to the hypothesis that oxytocin and oxytocin neuron development may have an influence on the development of ALTs, and suggests a new candidate gene in the search for the pathophysiology of ASD.

The quantitative genetic contribution to antisocial behavior is well established, but few, if any, genetic variants are established as risk factors. Emerging evidence suggests that the neuropeptide oxytocin (OXT) may modulate interpersonal aggression. We here investigated whether single-nucleotide polymorphisms (SNPs) in the OXT receptor gene (OXTR) are associated with the expression of antisocial behavior. A discovery sample, including both sexes, was drawn from the Child and Adolescent Twin Study in Sweden (CATSS; n=2372), and a sample from the Twin Study of Child and Adolescent Development (TCHAD; n=1232) was used for replication. Eight SNPs in OXTR, selected on previous associations with social and antisocial behavior, were genotyped in the participants of CATSS. Significant polymorphisms were subsequently genotyped in TCHAD for replication. Participants completed self-assessment questionnaires-Life History of Aggression (LHA; available only in CATSS), and Self-Reported Delinquency (SRD; available in both samples)-designed to capture antisocial behavior as continuous traits. In the discovery sample, the rs7632287 AA genotype was associated with higher frequency of antisocial behavior in boys, and this was then replicated in the second sample. In particular, overt aggression (directly targeting another individual) was strongly associated with this genotype in boys (P=6.2 × 10(-7) in the discovery sample). Meta-analysis of the results for antisocial behavior from both samples yielded P=2.5 × 10(-5). Furthermore, an association between rs4564970 and LHA (P=0.00013) survived correction in the discovery sample, but there was no association with the SRD in the replication sample. We conclude that the rs7632287 and rs4564970 polymorphisms in OXTR may independently influence antisocial behavior in adolescent boys. Further replication of our results will be crucial to understanding how aberrant social behavior arises, and would support the OXT receptor as one potential target in the treatment of aggressive antisocial behavior.

BackgroundAutistic-like traits (ALTs) are continuously distributed in the general population, with the autism spectrum disorder (ASD) at the upper extreme end. A genetic overlap has been shown between ALTs and ASD, indicating that common variation in ASD candidate genes may also influence ALTs. In our study, we have investigated the SNP rs4307059 that has been associated with both ALTs and ASD. In addition, we genotyped polymorphisms in a selection of genes involved in synaptic functioning, that is, SHANK3, RELN, and CNTNAP2, which repeatedly have been associated with ASD. The possible associations of these polymorphisms with ALTs, as well as genetic factors for neurodevelopmental problems (NDPs), were investigated in a large cohort from the general population: The Child and Adolescent Twin Study in Sweden. For analyses of ALTs and NDPs, 12,319 subjects (including 2,268 monozygotic (MZ) and 3,805 dizygotic (DZ) twin pairs) and 8,671 subjects (including 2,243 MZ and 2,044 DZ twin pairs), respectively, were included in the analyses.FindingsWe could not replicate the previous association between rs4307059 and social communication impairment. Moreover, common variations in CNTNAP2 (rs7794745 and rs2710102), RELN (rs362691), and SHANK3 (rs9616915) were not significantly associated with ALTs in our study.ConclusionsOur results do not suggest that the investigated genes, which previously has been found associated with ASD diagnosis, have any major influence on ALTs in children from the general population.Electronic supplementary materialThe online version of this article (doi:10.1186/2040-2392-5-55) contains supplementary material, which is available to authorized users.

The ability to recognize the identity of faces and voices is essential for social relationships. Although the heritability of social memory is high, knowledge about the contributing genes is sparse. Since sex differences and rodent studies support an influence of estrogens and androgens on social memory, polymorphisms in the estrogen and androgen receptor genes (ESR1, ESR2, AR) are candidates for this trait. Recognition of faces and vocal sounds, separately and combined, was investigated in 490 subjects, genotyped for 10 single nucleotide polymorphisms (SNPs) in ESR1, four in ESR2 and one in the AR Four of the associations survived correction for multiple testing: women carrying rare alleles of the three ESR2 SNPs, rs928554, rs1271572 and rs1256030, in linkage disequilibrium with each other, displayed superior face recognition compared with non-carriers. Furthermore, the uncommon genotype of the ESR1 SNP rs2504063 was associated with better recognition of identity through vocal sounds, also specifically in women. This study demonstrates evidence for associations in women between face recognition and variation in ESR2, and recognition of identity through vocal sounds and variation in ESR1. These results suggest that estrogen receptors may regulate social memory function in humans, in line with what has previously been established in mice.

Atypical patterns of face-scanning in individuals with autism spectrum disorder (ASD) may contribute to difficulties in social interactions, but there is little agreement regarding what exactly characterizes face-viewing in ASD. In addition, little research has examined how face-viewing is modulated by the emotional expression of the stimuli, in individuals with or without ASD. We used eye-tracking to explore viewing patterns during perception of dynamic emotional facial expressions in relatively large groups of individuals with (n = 57) and without ASD (n = 58) and examined diagnostic- and age-related effects, after subgrouping children and adolescents (≤18 years), on the one hand, and adults (>18 years), on the other. Results showed that children/adolescents with ASD fixated the mouth of happy and angry faces less than their typically developing (TD) peers, and conversely looked more to the eyes of happy faces. Moreover, while all groups fixated the mouth in happy faces more than in other expressions, children/adolescents with ASD did relatively less so. Correlation analysis showed a similar lack of relative orientation towards the mouth of smiling faces in TD children/adolescents with high autistic traits, as measured by the Autism-Spectrum Quotient (AQ). Among adults, participants with ASD only attended less to the eyes for neutral faces. Our study shows that the emotional content of a face influences gaze behaviour, and that this effect is not fully developed in children/adolescents with ASD. Interestingly, this lack of differentiation observed in the younger ASD group was also seen in younger TD individuals with higher AQ scores. Autism Res 2017, 10: 901-910. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

No abstract

The mechanisms underlying the role of oxytocin (OT) as a regulator of social behavior in mammals are only partly understood. Recently, it has been proposed that OT increases the salience of social stimuli. We carried out a randomized, double-blind, cross-over study of the effects of OT on binocular rivalry, a visual phenomenon underpinned by the interplay of excitation and inhibition in the cortex. A final sample of 45 participants viewed images of social stimuli (faces with different emotional expressions) and non-social stimuli (houses and Gabor patches). We demonstrate a robust effect that intranasal OT increases the salience of human faces in binocular rivalry, such that dominance durations of faces are longer—this effect is not modulated by the facial expression. We tentatively show that OT treatment increases dominance durations for non-social stimuli. Our results lend support to the social salience hypothesis of OT, and in addition offer provisional support for the role of OT in influencing excitation-inhibition balance in the brain.