This study systematically reviewed available evidence regarding associations between polymorphisms of the oxytocin receptor (OXTR) gene and socio-emotional and behavioral functioning in children and adolescents. The search yielded 69 articles, which were grouped into nine categories: depression, anxiety, and internalizing symptoms, alcohol abuse, borderline personality disorder, conduct disorder symptoms or diagnosis, autism spectrum disorder, attention deficit hyperactivity disorder, early childhood attachment and behavior, pro-social skills, and resilience. Direct and/or gene x environment interactions were identified in over half of the studies. ASD and conduct disorder (including callous unemotional traits) were the diagnoses that were most studied and for which there was the strongest evidence of direct links with OXTR polymorphisms. In most studies identifying gene x environment interactions, the candidate OXTR polymorphism was rs53576. Results suggest that OXTR polymorphisms are associated with social, emotional or behavioural functioning in children and adolescents. The mixed findings do, however, highlight the need for further research.

Williams Syndrome (WS) is a rare genetic multisystem disorder that occurs because of a deletion of approximately 25 genes in the 7q11.23 chromosome region. This causes dysmorphic facial appearances, multiple congenital cardiovascular defects, delayed motor skills, and abnormalities in connective tissues and the endocrine system. The patients are mostly diagnosed with mild to moderate mental retardation, however, they have a hyper sociable, socially dis-inhibited, and outgoing personality, empathetic behavior, and are highly talkative. Oxytocin (OT), a neuropeptide synthesized at the hypothalamus, plays an important role in cognition and behavior, and is thought to be affecting WS patients\' attitudes at its different amounts. Oxytocin receptor gene (OXTR), on chromosome 3p25.3, is considered regulating oxytocin receptors, via which OT exerts its effect. WS is a crucial disorder to understand gene, hormone, brain, and behavior associations in terms of sociality and neuropsychiatric conditions. Alterations to the WS gene region offer an opportunity to deepen our understandings of autism spectrum disorder, schizophrenia, anxiety, or depression. We aim to systematically present the data available of OT/OXTR regulation and expression, and the evidence for whether these mechanisms are dysregulated in WS. These results are important, as they predict strong epigenetic control over social behavior by methylation, single nucleotide polymorphisms, and other alterations. The comparison and collaboration of these studies may help to establish a better treatment or management approach for patients with WS if backed up with future research.

Evaluate effects of intranasal oxytocin (IN-OT) and OXTR genotype on resting state functional connectivity in the human brain.
We searched research databases for peer-reviewed empirical studies. Of 71 unique citations, 18 articles (13 IN-OT, five OXTR) met full inclusion criteria.
Two studies examined effects on large-scale networks; most examined acute effects on amygdala connectivity with other social and affective regions. OXTR studies identified three polymorphisms (rs2254298, rs2268498, rs53576) having allele- and sex-dependent effects on prefrontal functional connectivity, and additive effects of OXTR risk alleles on reward circuitry. Age, sex, early life stress, and psychopathology emerged as potential moderators of both IN-OT and OXTR effects.
IN-OT appears to modulate resting state functional connectivity in a manner similar to its effects on task fMRI, consistent with hypothesized models of IN-OT. However, conclusions are limited by the narrow range of neuroanatomical seed regions, and methodological and experimental design heterogeneity. Future studies should take into account individual differences. Findings may provide insight into mechanisms through which IN-OT impacts human behavior.

The neuropeptide Oxytocin (OXT) plays a central role in birthing, mother-infant bonding and a broad range of related social behaviours in mammals. More recently, interest has extended to epigenetic programming of genes involved in oxytocinergic neurotransmission. This review brings together early findings in a rapidly developing field of research, examining relationships between DNA methylation (DNAm) of the Oxytocin Receptor Gene (OXTR) and social and emotional behaviour in human populations.
A systematic search across Web of Knowledge/Science, Scopus, Medline and EMBASE captured all published studies prior to June 2017 examining the association between OXTR DNAm and human social and emotional outcomes. Search terms included \'oxytocin gene\' or \'oxytocin receptor gene\' and \'epigenetics\' or \'DNA methylation\'. Any article with a focus on social and emotional functioning was then identified from this set by manual review.
Nineteen studies met eligibility criteria. There was considerable heterogeneity of study populations, tissue samples, instrumentation, measurement, and OXTR site foci. Only three studies examined functional consequences of OXTR DNAm on gene expression and protein synthesis. Increases in OXTR DNAm were associated with callous-unemotional traits in youth, social cognitive deficits in Autistic Spectrum Disorder (ASD), rigid thinking in anorexia nervosa, affect regulation problems, and problems with facial and emotional recognition. In contrast, reductions in DNAm were associated with perinatal stress, postnatal depression, social anxiety and autism in children.
Consistent with an emerging field of inquiry, there is not yet sufficient evidence to draw conclusions about the role of OXTR DNAm in human social and emotional behaviour. However, taken together, findings point to increased OXTR DNAm in general impairments in social, cognitive and emotional functioning, and decreased OXTR DNAm in specific patterns of impairment related to mood and anxiety disorders (but not in all). Future progress in this field would be enhanced by adequately powered designs, greater phenotypic precision, and methodological improvements including longitudinal studies with multiple time-points to facilitate causal inference.

As discussed in the larger review in this special issue (MacDonald and Feifel), intranasal oxytocin (OT) is demonstrating a growing potential as a therapeutic agent in psychiatry. Importantly, research suggests that a variety of individual factors may influence a person\'s response to OT. In this mini-review, I provide a review of three: (1) sex and hormonal status; (2) genetic variation in aspects of the OT system (i.e., OT receptors); and (3) attachment history. Each of these factors will be important to monitor as we strive to develop a richer understanding of OT\'s role in human development, brain-based disease, and the potential for individualized, OT-targeted treatments.