oxytocin and Child-Behavior-Disorders

This literature review summarizes recent potential evidence, most of which is at the molecular/mechanistic level, in support of Hollander's hypothesis that excess oxytocin (OT), possibly through OT administration at birth, could contribute to the development of autistic spectrum disorders and related syndromes by proposed down regulation of the OT receptor (OTR). In this review, recent molecular evidence for OTR internalization by excess OT is related to OT's reported effects on animal social behavior, favoring social bondage, notably in sheep, voles, rats and especially mice. Adding indications for OT's capability of crossing the maternal placenta and OT's possibility of crossing an underdeveloped or stressed infantile blood brain barrier at birth, a causal connection between OT excess and behavioral disorders such as autism can be supported from a molecular perspective. Possible strategies such as a thorough statistical analysis of numerous birth records as well as molecular studies such as radiotracing using labeled OT are proposed to test this hypothesis.

Topics: Autistic Disorder; Brain; Child Behavior Disorders; Evidence-Based Medicine; Female; Humans; Infant, Newborn; Labor, Induced; Maternal-Fetal Exchange; Models, Biological; Oxytocin; Pregnancy; Receptors, Oxytocin

Previous studies have reported interaction effects of oxytocin receptor genotype (rs53576) and environmental factors on mental health in youth. However, the findings are mixed, especially regarding the type of allele (i.e., A vs. G), and it remains unanswered whether such an interaction presents at an early stage of development. Thus, using a unique longitudinal birth cohort sample in Japan (n = 568), we examined whether there was an effect of the interaction between the OXTR rs53576 genotype and maternal postpartum depression, as an environmental risk, on behavioural problems in children. Child behavioural problems (internalising and externalising problems) were ascertained using the Strengths and Difficulties Questionnaire when children were 6 years old. Maternal postpartum depression was measured using the Edinburgh Postnatal Depression Scale when children were at 2 months and 10 months of age. The results revealed a significant effect in the interaction between OXTR rs53576 genotype and maternal postpartum depression on externalising problems in children with AA genotype (β = 0.136, 95% CI 0.032 to 0.240), but not in those with GG/GA genotype. This indicates that an interaction of vulnerable genotypes (i.e., A allele of OXTR rs53576) with an environmental burden (i.e. maternal postpartum depression) may be one of the potential elements that predisposes the infant to developing behavioural problems early in life. Hence, special attention needs to be paid to children exposed to environmental risks such as maternal postpartum depression, to facilitate the provision of appropriate care.

Topics: Adult; Birth Weight; Child; Child Behavior Disorders; Child of Impaired Parents; Depression, Postpartum; Educational Status; Female; Follow-Up Studies; Gene-Environment Interaction; Genetic Predisposition to Disease; Genotype; Gestational Age; Humans; Income; Infant; Male; Mood Disorders; Oxytocin; Polymorphism, Single Nucleotide; Pregnancy; Problem Behavior; Receptors, Oxytocin

The neuropeptide and hormone oxytocin is known to have a significant impact on social cognition and behaviour in humans. There is growing concern regarding the influence of exogenous oxytocin (OT) administration in early life on later social and emotional development, including autism spectrum disorder (ASD). No study has examined offspring development in relation to the dose of exogenous oxytocin administered during labour.. Between 1989 and 1992, 2,900 mothers were recruited prior to the 18th week of pregnancy, delivering 2,868 live offspring. The Child Behaviour Checklist was used to measure offspring behavioural difficulties at ages 5, 8, 10, 14 and 17 years. Autism spectrum disorder was formally diagnosed by consensus of a team of specialists. At 20 years, offspring completed a measure of autistic-like traits, the Autism Spectrum Quotient (AQ). Oxytocin exposure prior to birth was analysed using categorical and continuous approaches (maternal oxytocin dose) with univariate and multivariate statistical techniques.. Categorical analyses of oxytocin exposure prior to birth demonstrated no group differences in any measures of child behaviour. A small in magnitude dose-response association was observed for clinically significant total behaviour symptoms (adjusted odds ratio 1.03; 95% CI: 1.01-1.06, p < .01). Exogenous oxytocin administration prior to birth was not associated with ASD (OR: 0.64; 95% CI: 0.15-2.12, p = .46) or high levels of autistic-like traits (p = .93), as assessed by the AQ.. This study is the first to investigate longitudinal mental health outcomes associated with the use of oxytocin-based medications during labour. The results do not provide evidence to support the theory that exogenous OT has a clinically significant negative impact on the long-term mental health of children.

Topics: Adolescent; Autism Spectrum Disorder; Child; Child Behavior Disorders; Child Development; Child, Preschool; Female; Humans; Labor, Induced; Longitudinal Studies; Male; Oxytocin; Pregnancy; Prenatal Exposure Delayed Effects; Retrospective Studies; Young Adult

Externalizing problems are among the most common mental health problems of children. Research suggests that these problems are heritable, yet little is known about the specific genes involved in their pathophysiology. The current study examined a genotype-endophenotype-phenotype model of externalizing problems in 320 preschool-aged children. Markers of the oxytocin (OXT) and arginine vasopressin (AVP) hormone genes were selected as candidates owing to their known association with psychopathology in other domains. We tested whether OXT and AVP variants were related to children's externalizing problems, as well as two cognitive endophenotypes presumed to underlie these problems: theory of mind (ToM) and executive functioning (EF). Externalizing problems were assessed at age 4.5 using a previously-validated rating scale. ToM and EF were measured with age-appropriate tasks. Using a family-based association design and controlling for non-genomic confounds, support was found for an association between a two-marker OXT haplotype (rs2740210-rs2770378) and a two-marker AVP haplotype (rs1887854-rs3761249) and externalizing problems. Specific associations of these haplotypes with ToM and EF were also observed. Further, ToM and EF were shown to independently and jointly predict externalizing problems, and to partially mediate the effects of OXT and AVP on externalizing problems. This study provides the first evidence that genetic variation in OXT and AVP may contribute to individual differences in childhood externalizing problems, and that these effects may operate through emerging neurocognitive abilities in the preschool period.

Topics: Arginine Vasopressin; Attention Deficit and Disruptive Behavior Disorders; Child Behavior; Child Behavior Disorders; Child, Preschool; Cognition; Endophenotypes; Executive Function; Expressed Emotion; Female; Genome-Wide Association Study; Humans; Male; Oxytocin; Polymorphism, Single Nucleotide; Problem Behavior; Vasopressins

To determine the incidence of moderate to severe neonatal encephalopathy (NE) and neonatal seizures without encephalopathy, and the association with metabolic acidemia. Secondly, to investigate the occurrence of suboptimal intrapartum care and its impact on neonatal outcome.. Clinical audit.. Two university hospitals in Sweden.. Neonates ≥34 weeks with moderate or severe NE and neonatal seizures alone, i.e. without encephalopathy, from a population of 71 189 births, where umbilical blood gases were routinely analyzed.. Neonates were categorized depending on the presence of metabolic acidemia at birth by umbilical artery pH < 7.00, base deficit ≥12 mmol/L. Records were audited for suboptimal care and a decision was made on whether management was assessed to have impacted neonatal outcome.. Encephalopathy and seizures alone.. We identified 80 neonates with NE and 30 with seizures alone, of which 48 (60%) and none, respectively, had metabolic acidemia. Suboptimal care could be assessed in 77 and occurred in 28 (36%) NE cases and in one neonate with seizures alone (p < 0.001). In 47 NE cases with metabolic acidemia, suboptimal care occurred in 22 (47%) vs. 6/30 (20%) without metabolic acidemia (p = 0.02). Suboptimal care had an impact on outcome in 18/77 (23%) NE cases but in no cases with seizures alone.. Suboptimal care was commonly seen with NE, particularly in neonates with metabolic acidemia, and also affected neonatal outcome. No such associations were found in neonates with seizures alone.

Topics: Acidosis; Blood Gas Analysis; Cardiotocography; Cerebral Palsy; Child Behavior Disorders; Child, Preschool; Clinical Audit; Cognition Disorders; Fetal Blood; Humans; Incidence; Infant, Newborn; Intellectual Disability; Mental Disorders; Oxytocics; Oxytocin; Perinatal Care; Quality of Health Care; Retrospective Studies; Seizures; Speech Disorders; Sweden; Vacuum Extraction, Obstetrical

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-unemotionals cores 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.

Topics: Adolescent; Aggression; Alleles; Antisocial Personality Disorder; Anxiety; Canada; Case-Control Studies; Child; Child Behavior Disorders; Conduct Disorder; Emotions; Female; Genetic Markers; Genetic Predisposition to Disease; Genotype; Haplotypes; Humans; Male; Narcissism; Oxytocics; Oxytocin; Phenotype; Polymorphism, Genetic; Receptors, Oxytocin

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.

Topics: Adolescent; Adult; Aggression; Alleles; Case-Control Studies; Child; Child Behavior Disorders; Female; Gene Frequency; Genetic Predisposition to Disease; Genotype; Haplotypes; Humans; Male; Oxytocin; Polymorphism, Single Nucleotide; Receptors, Oxytocin; Sex Characteristics