Background Oxytocin is a potent uterotonic agent that is widely used for induction and augmentation of labor. Oxytocin has a narrow therapeutic index and the optimal dosing for any individual woman varies widely. Objective The objective of this study was to determine whether genetic variation in the oxytocin receptor ( OXTR ) or in the gene encoding G protein–coupled receptor kinase 6 ( GRK6 ), which regulates desensitization of the oxytocin receptor, could explain variation in oxytocin dosing and labor outcomes among women being induced near term. Study Design Pregnant women with a singleton gestation residing in Durham County, NC, were prospectively enrolled as part of the Healthy Pregnancy, Healthy Baby cohort study. Those women undergoing an induction of labor at 36 weeks or greater were genotyped for 18 haplotype-tagging single-nucleotide polymorphisms in OXTR and 7 haplotype-tagging single-nucleotide polymorphisms in GRK6 using TaqMan assays. Linear regression was used to examine the relationship between maternal genotype and maximal oxytocin infusion rate, total oxytocin dose received, and duration of labor. Logistic regression was used to test for the association of maternal genotype with mode of delivery. For each outcome, backward selection techniques were utilized to control for important confounding variables and additive genetic models were used. Race/ethnicity was included in all models because of differences in allele frequencies across populations, and Bonferroni correction for multiple testing was used. Results DNA was available from 482 women undergoing induction of labor at 36 weeks or greater. Eighteen haplotype-tagging single-nucleotide polymorphisms within OXTR and 7 haplotype-tagging single-nucleotide polymorphisms within GRK6 were examined. Five single-nucleotide polymorphisms in OXTR showed nominal significance with maximal infusion rate of oxytocin, and two single-nucleotide polymorphisms in OXTR were associated with total oxytocin dose received. One single-nucleotide polymorphism in OXTR and two single-nucleotide polymorphisms in GRK6 were associated with duration of labor, one of which met the multiple testing threshold ( P = .0014, rs2731664 [ GRK6 ], mean duration of labor, 17.7 hours vs 20.2 hours vs 23.5 hours for AA, AC, and CC genotypes, respectively). Three single-nucleotide polymorphisms, two in OXTR and one in GRK6 , showed nominal significance with mode of delivery. Conclusion Genetic variation in OXTR and GRK6 is associated with the amount of oxytocin required as well as the duration of labor and risk for cesarean delivery among women undergoing induction of labor near term. With further research, pharmacogenomic approaches may potentially be utilized to develop personalized treatment to improve safety and efficacy outcomes among women undergoing induction of labor.
Summary Brain oxytocin and dopamine systems interact to modulate social cognitive behavior. Whether the interactions are modulated by oxytocin receptor ( OXTR ) gene variations remains unclear. Considering the dopamine transporter (DAT) availability as an endophenotype and the degree of dopamine-mediated neuroticism as a phenotype of the OXTR genotypes, the current molecular imaging study used [99m Tc]TRODAT-1 single photon emission computed tomography (SPECT) to measure the striatal DAT availability and the 57-item Maudsley Personality Inventory to measure neuroticism personality traits in healthy individuals to investigate (A) the correlation between the rs53576 (G/A) of OXTR and the striatal DAT availability, (B) the correlation between the peripheral oxytocin level and striatal DAT availability among different OXTR rs53576 (G/A) genotypes, and (C) whether neuroticism traits could be modified by oxytocin in certain OXTR rs53576 genotypes. The results showed that the striatal DAT availability in the AG + GG group was significantly lower than that in the AA group (2.08 ± 0.47 vs. 1.90 ± 0.32, p = 0.04). Only individuals with one or two copies of the G allele of rs53576 showed a negative correlation between DAT availability and oxytocin level ( r = −0.41, p = 0.002). Furthermore, the oxytocin × DAT interaction was significantly correlated with the MPI neuroticism score in the AA group. Further analyses showed that the DAT availability was correlated with the neuroticism score only in the AA group with a low oxytocin level ( r = 0.74, p = 0.002). The results indicated that the OXTR rs53576 is connected with the striatal DAT availability in vivo and modulates the interactions between the oxytocinergic and dopaminergic systems. Carriers with a specific rs53576 OXTR genotype may present a greater biological sensitivity as well as stress reactivity in terms of environmental adaptation.
Interest in oxytocin has increased rapidly over the last decades. Consequently, quite a number of studies have addressed the influence of oxytocin on social stress, perception, cognition, and decision making in healthy adults as well as in clinical samples characterized by some form of social disturbance. Surprisingly little research on oxytocin has focused on ageing populations. This is particularly striking in two areas of study: the role of oxytocin in grandparents’ behavior toward and bonding with their grandchildren and the effects of oxytocin on the neurocognitive processing of socioemotional stimuli. The current mini-review offers an overview of the literature on the involvement of oxytocin in parental behavior and neurocognitive functioning, and discusses the relevance of these findings to ageing individuals. As the literature shows that oxytocin is profoundly involved in parenting and in bonding throughout life, it is highly likely that oxytocin plays a role in grandparenting and bonding between grandparents and grandchildren as well. However, results obtained with younger adults may not be directly applicable to older individuals in yet another type of relationship. The possibility that age-related changes occur in the oxytocin system (which is at present unclear) must be taken into account. In addition, ageing impairs neurocognitive processes that are profoundly affected by oxytocin (including some aspects of memory and emotion recognition) and is associated with alterations in both structure and function of the amygdala, which is prominently involved in mediating effects of oxytocin. Research investigating the ageing oxytonergic system and studies focusing on the involvement of oxytocin in socioemotional neurocognitive processes and social behavior in elderly individuals, including grandparents, are therefore urgently needed.
Human ethnocentrism—the tendency to view one's group as centrally important and superior to other groups—creates intergroup bias that fuels prejudice, xenophobia, and intergroup violence. Grounded in the idea that ethnocentrism also facilitates withingroup trust cooperation, and coordination, we conjecture that ethnocentrism may be modulated by brain oxytocin, a peptide shown to promote cooperation among in-group members. In double-blind, placebo-controlled designs, males self-administered oxytocin or placebo and privately performed computer-guided tasks to gauge different manifestations of ethnocentric in-group favoritism as well as out-group derogation. Experiments 1 and 2 used the Implicit Association Test to assess in-group favoritism and out-group derogation. Experiment 3 used the infrahumanization task to assess the extent to which humans ascribe secondary, uniquely human emotions to their in-group and to an out-group. Experiments 4 and 5 confronted participants with the option to save the life of a larger collective by sacrificing one individual, nominated as in-group or as out-group. Results show that oxytocin creates intergroup bias because oxytocin motivates in-group favoritism and, to a lesser extent, out-group derogation. These findings call into question the view of oxytocin as an indiscriminate "love drug" or "cuddle chemical" and suggest that oxytocin has a role in the emergence of intergroup conflict and violence.
Autism is a pervasive developmental disorder characterized by profound social and verbal communication deficits, stereotypical motor behaviors, restricted interests, and cognitive abnormalities. Autism affects approximately 1% of children in developing countries. Given this prevalence, identifying risk factors and therapeutic interventions are pressing objectives—objectives that rest on neurobiologically grounded and psychologically informed theories about the underlying pathophysiology. In this article, we review the evidence that autism could result from a dysfunctional oxytocin system early in life. As a mediator of successful procreation, not only in the reproductive system, but also in the brain, oxytocin plays a crucial role in sculpting socio-sexual behavior. Formulated within a (Bayesian) predictive coding framework, we propose that oxytocin encodes the saliency or precision of interoceptive signals and enables the neuronal plasticity necessary for acquiring a generative model of the emotional and social ‘self.’ An aberrant oxytocin system in infancy could therefore help explain the marked deficits in language and social communication – as well as the sensory, autonomic, motor, behavioral, and cognitive abnormalities – seen in autism.
The neuropeptide oxytocin (OT) has been implicated in a wide range of affiliative processes. OT exerts its functions via OT receptors, which are encoded by the oxytocin receptor gene ( ). Epigenetic modification of through the process of DNA methylation has been associated with individual differences in behavioral phenotypes. Specifically, lower levels of methylation have been linked to better social and affective functioning. However, research on epigenetic mechanisms of is scarce in non-clinical populations, and even less is known about epigenetic variability across adulthood. The present study assessed methylation levels at CpG site −934 and plasma OT levels in 22 young (20–31 years, = 23.6) and 34 older (63–80 years, = 71.4) participants. Lower levels of methylation and higher plasma OT levels were associated with less self-reported attachment anxiety in young but not older participants, with largely independent contributions of methylation and plasma OT levels. In contrast, in the overall sample, lower levels of methylation were associated with higher self-reported attachment avoidance. Age analysis suggested that these results were largely driven by young adults. Plasma OT levels were unrelated to attachment avoidance. Taken together, these findings support the emerging notion in the literature that epigenetic properties of , in addition to endogenous OT levels, are related to adult attachment. Further, the age effects observed in the associations between methylation, plasma OT, and adult attachment emphasize the importance of adopting a developmental perspective when studying properties of the OT system and their relation to affiliative processes. Findings contribute to growing evidence suggesting that epigenetic modification of genes regulating OT pathways and endogenous OT levels are associated with the way people form and maintain intimate social relationships.
Abstract Despite widespread reports that intranasal application of oxytocin has a variety of behavioral effects, very little of the huge amounts applied intranasally appears to reach the cerebrospinal fluid. However, peripheral concentrations are increased to supraphysiologic levels, with likely effects on diverse targets including the gastrointestinal tract, heart, and reproductive tract. The wish to believe in the effectiveness of intranasal oxytocin appears to be widespread and needs to be guarded against with scepticism and rigor. Preregistering trials, declaring primary and secondary outcomes in advance, specifying the statistical methods to be applied, and making all data openly available should minimize problems of publication bias and questionable post hoc analyses. Effects of intranasal oxytocin also need proper dose-response studies, and such studies need to include control subjects for peripheral effects, by administering oxytocin peripherally and by blocking peripheral actions with antagonists. Reports in the literature of oxytocin measurements include many that have been made with discredited methodology. Claims that peripheral measurements of oxytocin reflect central release are questionable at best.