A common oxytocin receptor gene (OXTR) polymorphism modulates intranasal oxytocin effects on the neural response to social cooperation in humans

Intranasal oxytocin (OT) can modulate social‐emotional functioning and related brain activity in humans. Consequently, OT has been discussed as a potential treatment for psychiatric disorders involving social behavioral deficits. However, OT effects are often heterogeneous across individuals. Here we explore individual differences in OT effects on the neural response to social cooperation as a function of the rs53576 polymorphism of the oxytocin receptor gene (OXTR). Previously, we conducted a double‐blind, placebo‐controlled study in which healthy men and women were randomized to treatment with intranasal OT or placebo. Afterwards, they were imaged with functional magnetic resonance imaging while playing an iterated Prisoner's Dilemma Game with same‐sex partners. Within the left ventral caudate nucleus, intranasal OT treatment increased activation to reciprocated cooperation in men, but tended to decrease activation in women. Here, we show that these sex differences in OT effects are specific to individuals with the rs53576 GG genotype, and are not found for other genotypes (rs53576 AA/AG). Thus, OT may increase the reward or salience of positive social interactions for male GG homozygotes, while decreasing those processes for female GG homozygotes. These results suggest that rs53576 genotype is an important variable to consider in future investigations of the clinical efficacy of intranasal OT treatment.     

Focus: Rare Disease: Oxytocin and Oxytocin Receptor Gene Regulation in Williams Syndrome: A Systematic Review

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.     

A functional MRI study on how oxytocin affects decision making in social dilemmas: Cooperate as long as it pays off,aggress only when you think you can win

We investigate if the neuropeptide oxytocin (OT), known to moderate social behaviour, influences strategic decision making in social dilemmas by facilitating the integration of incentives and social cues. Participants (N = 29) played two economic games with different incentive structures in the fMRI scanner after receiving OT or placebo (following a double blind, within-subject design). Pictures of angry or neutral faces (the social cues) were displayed alongside the game matrices. Consistent with a priori hypotheses based on the modulatory role of OT in mesolimbic dopaminergic brain regions, the results indicate that, compared to placebo, OT significantly increases the activation of the nucleus accumbens during an assurance (coordination) game that rewards mutual cooperation. This increases appetitive motivation so that cooperative behaviour is facilitated for risk averse individuals. OT also significantly attenuates the amygdala, thereby reducing the orienting response to social cues. The corresponding change in behaviour is only apparent in the chicken (or anti-coordination) game, where aggression is incentivized but fatal if the partner also aggresses. Because of this ambiguity, decision making can be improved by additional information, and OT steers decisions in the chicken game in accordance with the valence of the facial cue: aggress when face is neutral; retreat when it is angry. Through its combined influence on amygdala and nucleus accumbens, OT improves the selection of a cooperative or aggressive strategy in function of the best match between the incentives of the game and the social cues present in the decision environment.     

Association between the oxytocin receptor (OXTR) gene and children's social cognition at 18 months

At 18 months, children engage in a variety of social behaviors that reflect their nascent ability to understand the intentions of other people (e.g. joint attention, empathy, cooperation and self‐recognition). Although numerous contextual factors have been shown to predict social cognition in young children, the genetic underpinnings of social‐cognitive traits has been understudied in this age group. Owing to the known effects of oxytocin on adult social cognition and psychopathology, this study hypothesized that variability in the oxytocin receptor gene (OXTR) would be associated with social cognition in children at 18 months. Participants consisted of 350 children (182 males; 168 females) who were part of an ongoing longitudinal study that aimed to assess environmental and genetic contributions to children's cognitive and socio‐emotional functioning. At 18 months, social cognition was measured using previously validated and developmentally sensitive tasks assessing children's joint attention, empathy, cooperation and self‐recognition. Five potentially functional OXTR variants were genotyped: rs1042778, rs2254298, rs11131149, rs237897 and rs237899. A family‐based association design was used to control for population admixture and stratification, and additional non‐genomic covariates were controlled. Results showed that variability in rs11131149 was significantly associated with social cognition (P = 0.009), with more copies of the major allele related to higher social cognition, and more copies of the minor (risk) allele associated with lower social cognition. A haplotype consisting of rs11131149–rs2254298 was also associated with social cognition (P = 0.020). Implications for normative and pathological development are discussed, and key areas for future research are proposed.     

Intranasal oxytocin,but not vasopressin,augments neural responses to toddlers in human fathers

This study investigates paternal brain function with the hope of better understanding the neural basis for variation in caregiving involvement among men. The neuropeptides oxytocin (OT) and vasopressin (AVP) are implicated in paternal caregiving in humans and other species. In a double-blind, placebo-controlled, within-subject pharmaco-functional MRI experiment, we randomized 30 fathers of 1–2 year old children to receive either 24 IU intranasal OT before one scan and placebo before the other scan (n = 15) or 20 IU intranasal AVP before one scan and placebo before the other scan (n = 15). Brain function was measured with fMRI as the fathers viewed pictures of their children, unknown children and unknown adults, and as they listened to unknown infant cry stimuli. Intranasal OT, but not AVP, significantly increased the BOLD fMRI response to viewing pictures of own children within the caudate nucleus, a target of midbrain dopamine projections, as well as the dorsal anterior cingulate (dACC) and visual cortex, suggesting that intranasal oxytocin augments activation in brain regions involved in reward, empathy and attention in human fathers. OT effects also varied as a function of order of administration such that when OT was given before placebo, it increased activation within several reward-related structures (substantia nigra, ventral tegmental area, putamen) more than when it was given after placebo. Neither OT nor AVP had significant main effects on the neural response to cries. Our findings suggest that the hormonal changes associated with the transition to fatherhood are likely to facilitate increased approach motivation and empathy for children, and call for future research that evaluates the potential of OT to normalize deficits in paternal motivation, as might be found among men suffering from post-partum depression.     

Intranasal oxytocin increases social grooming and food sharing in the common vampire bat Desmodus rotundus

Intranasal oxytocin (OT) delivery has been used to non-invasively manipulate mammalian cooperative behavior. Such manipulations can potentially provide insight into both shared and species-specific mechanisms underlying cooperation. Vampire bats are remarkable for their high rates of allogrooming and the presence of regurgitated food sharing among adults. We administered intranasal OT to highly familiar captive vampire bats of varying relatedness to test for an effect on allogrooming and food sharing. We found that intranasal OT did not have a detectable effect on food-sharing occurrence, but it did increase the size of regurgitated food donations when controlling for dyad and amount of allogrooming. Intranasal OT in females increased the amount of allogrooming per partner and across all partners per trial, but not the number of partners. We also found that the peak effect of OT treatments occurred 30–50 min after administration, which is consistent with the reported latency for intranasal OT to affect relevant brain areas in rats and mice. Our results suggest that intranasal OT is a potential tool for influencing dyadic cooperative investments, but measuring prior social relationships may be necessary to interpret the results of hormonal manipulations of cooperative behavior and it may be difficult to alter partner choice in vampire bats using intranasal OT alone.     

Thinking and doing: the effects of dopamine and oxytocin genes and executive function on mothering behaviours

Animal and human studies suggest that initial expression of maternal behaviour depends on oxytocin and dopamine systems. However, the mechanism by which these systems affect parenting behaviours and the timing of these effects are not well understood. This article explores the role of mothers' executive function in mediating the relation between oxytocin and dopamine gene variants and maternal responsiveness at 48 months post‐partum. Participants (n = 157) were mothers recruited in the Maternal Adversity, Vulnerability and Neurodevelopment Study, which assesses longitudinally two cohorts of mothers and children in Canada. We examined single nucleotide polymorphisms (SNPs) related to the dopamine and oxytocin systems (DRD1 rs686, DRD1 rs265976, OXTR rs237885 and OXTR rs2254298), assessed mothers' decision‐making at 48 months using the Cambridge Neurological Automated Testing Battery (CANTAB) and evaluated maternal responsiveness from videotaped interactions during the Etch‐A‐Sketch co‐operation task. Mediation analyses showed that OXTR rs2254298 A‐carriers had an indirect effect on positive parenting which was mediated by mothers' performance on decision‐making task (estimate = 0.115, P < 0.005), while OXTR rs2254298 A‐carriers had both direct and indirect effects on physically controlling parenting, also mediated through enhanced performance on decision‐making (estimate = ?0.059, P < 0.005). Dopamine SNPs were not associated with any measure of executive function or parenting (all P > 0.05). While oxytocin has previously been associated with only the early onset of maternal behaviour, we show that an OXTR polymorphism is involved in maternal behaviour at 48 months post‐partum through mothers' executive function. This research highlights the importance of the oxytocin system to maternal parenting beyond infancy.     

Manipulation of the oxytocin system alters social behavior and attraction in pair-bonding primates, Callithrix penicillata

The establishment and maintenance of stable, long-term male-female relationships, or pair-bonds, are marked by high levels of mutual attraction, selective preference for the partner, and high rates of sociosexual behavior. Central oxytocin (OT) affects social preference and partner-directed social behavior in rodents, but the role of this neuropeptide has yet to be studied in heterosexual primate relationships. The present study evaluated whether the OT system plays a role in the dynamics of social behavior and partner preference during the first 3 weeks of cohabitation in male and female marmosets, Callithrix penicillata. OT activity was stimulated by intranasal administration of OT, and inhibited by oral administration of a non-peptide OT-receptor antagonist (L-368,899; Merck). Social behavior throughout the pairing varied as a function of OT treatment. Compared to controls, marmosets initiated huddling with their social partner more often after OT treatments but reduced proximity and huddling after OT antagonist treatments. OT antagonist treatment also eliminated food sharing between partners. During the 24-h preference test, all marmosets interacted more with an opposite-sex stranger than with the partner. By the third-week preference test, marmosets interacted with the partner and stranger equally with the exception that intranasal-OT treatments facilitated initial partner-seeking behavior over initial contact with the stranger. Our findings demonstrate that pharmacological manipulations of OT activity alter partner-directed social behavior during pair interactions, suggesting that central OT may facilitate the process of pair-bond formation and social relationships in marmoset monkeys.     

Association between temperament related traits and single nucleotide polymorphisms in the serotonin and oxytocin systems in Merino sheep

Animal temperament is defined as the consistent behavioral and physiological differences that are seen between individuals in response to the same stressor. Neurotransmitter systems, like serotonin and oxytocin in the central nervous system, underlie variation in behavioral traits in humans and other animals. Variations like single nucleotide polymorphisms (SNPs) in the genes for tryptophan 5-hydroxylase (TPH2), the serotonin transporter (SLC6A4), the serotonin receptor (HTR2A), and the oxytocin receptor (OXTR) are associated with behavioral phenotype in humans. Thus, the objective of this study was to identify SNPs in those genes and to test if those variations are associated with the temperament in Merino sheep. Using ewes from the University of Western Australia temperament flock, which has been selected on emotional reactivity for more than 20 generations, eight SNPs (rs107856757, rs107856818, rs107856856 and rs107857156 in TPH2, rs20917091 in SLC6A4, rs17196799 and rs17193181 in HTR2A, and rs17664565 in OXTR) were found to be distributed differently between calm and nervous sheep. These eight SNPs were then genotyped in 260 sheep from a flock that has never been selected on emotional reactivity, followed by the estimation of the behavioral traits of those 260 sheep using an arena test and an isolation box test. We found that several SNPs in TPH2 (rs107856757, rs107856818, rs107856856 and rs107857156) were in strong linkage disequilibrium, and all were associated with behavioral phenotype in the nonselected sheep. Similarly, rs17196799 in HTR2A was also associated with the behavioral phenotype.     

Genetic variants in oxytocin receptor and arginine-vasopressin receptor 1A are associated with the neural correlates of maternal and paternal affection towards their child

There is extensive evidence in animal studies, particularly in vole species (Microtus), that oxytocin (OT) receptor and arginine-vasopressin (AVP) receptor 1a is critical for the regulation of maternal and paternal behavior, respectively. Human studies have gained insight into the relationship between both hormone receptor gene variants and behavior, but not between the variants and the underlying brain activity. To study this, we investigated the association between neural activation of the anterior prefrontal cortex (APFC) in mothers and fathers in response to their child smiling video stimuli to induce the positive affect related to attachment with their child, and genetic variants of OT receptor (OXTR) and AVP receptor 1A (AVPR1A). Overall, 43 mothers and 41 fathers participated, and each parent's child smiling was video recorded. Participants were then genotyped and underwent near-infrared spectroscopy to measure neural activation of the APFC while observing their own child smiling compared with an unfamiliar child. We found that the right inferior APFC was activated in response to child video stimuli in mothers and differential hemispheric activation of the inferior APFC in OXTR rs2254298-G/G mothers compared with -A carrier mothers, but not in fathers. Furthermore, we found a difference in the left inferior APFC activation between AVPR1A RS3-non-334 and -334 carrier fathers, but not mothers. Our results indicate a sex-dependent association between the genetic variants and the inferior APFC activations of maternal and paternal positive affect, analogous to the results reported in voles.     

U-Shaped Relation between Plasma Oxytocin Levels and Behavior in the Trust Game

Trust underpins much of social and economic exchanges across human societies. In experimental economics, the Trust Game has served as the workhorse for the study of trust in a controlled incentivized setting. Recent evidence using intranasal drug administration, aka ‘sniffing’, suggests that oxytocin (OT) can function as a social hormone facilitating trust and other affiliative behaviors. Here we hypothesized that baseline plasma OT is a biomarker that partially predicts the degree of trust and trustworthiness observed in the trust game. Using a large sample of 1,158 participants, we observed a significant U-shaped relationship between plasma OT with the level of trust, and marginally with the level of trustworthiness, especially among males. Specifically, subjects with more extreme levels of plasma OT were more likely to be trusting as well as trustworthy than those with moderate levels of plasma OT. Our results contribute to a deeper understanding of the biological basis of human trust and underscore the usefulness of peripheral plasma OT measures in characterizing human social behavior. “You must trust and believe in people or life becomes impossible.” Anton Chekhov.     

Inhibitory effects of oxytocin and oxytocin receptor antagonist atosiban on the activities of carbonic anhydrase and acetylcholinesterase enzymes in the liver and kidney tissues of rats

The aim of this study was to investigate the effects of oxytocin (OT), atosiban, which is an OT receptor antagonist, and OT‐atosiban chemicals injected to rats on the activities of carbonic anhydrase (CA) and acetylcholinesterase (AChE) enzymes in liver and kidney tissues of rats. For this purpose, four different groups, each consisting of six rats (n = 6), were formed (control group, OT administered group, atosiban administered group, and both OT and atosiban administered group). The rats were necropsied 60 min after intraperitoneal injection of chemicals into the rats. Liver tissues of rats were extracted. CA and AChE enzyme activities were measured for each tissue by using hydratase, esterase, and acetylcholiniodide methods. Activity values for each enzyme obtained were statistically calculated.     

Combining oxytocin administration and positive emotion inductions: Examining social perception and analytical performance

Intranasal administration of the hypothalamic neuropeptide oxytocin (OT) has, in some studies, been associated with positive effects on social perception and cognition. Similarly, positive emotion inductions can improve a range of perceptual and performance-based behaviors. In this exploratory study, we examined how OT administration and positive emotion inductions interact in their associations with social and analytical performance. Participants (N = 124) were randomly assigned to receive an intranasal spray of OT (40 IU) or placebo and then viewed one of three videos designed to engender one of the following emotion states: social warmth, pride, or an affectively neutral state. Following the emotion induction, participants completed social perception and analytical tasks. There were no significant main effects of OT condition on social perception tasks, failing to replicate prior research, or on analytical performance. Further, OT condition and positive emotion inductions did not interact with each other in their associations with social perception performance. However, OT condition and positive emotion manipulations did significantly interact in their associations with analytical performance. Specifically, combining positive emotion inductions with OT administration was associated with worse analytical performance, with the pride induction no longer benefiting performance and the warmth induction resulting in worse performance. In sum, we found little evidence for main or interactive effects of OT on social perception but preliminary evidence that OT administration may impair analytical performance when paired with positive emotion inductions.     

Amelioration of rotenone-induced dopaminergic cell death in the striatum by oxytocin treatment

Oxytocin (OT) is essentially associated with uterine contraction during parturition and milk ejection reflex. Although several studies implicate the role of OT in anti-inflammatory, anti-oxidative and anti-apoptotic pathways, there is a lack of data with regard to the protective effects of oxytocin in neurodegenerative models such as Parkinson's disease (PD). The present study was undertaken to investigate the neuroprotective effects of oxytocin (OT) on rotenone-induced PD in rats. Twenty adult Sprague-Dawley rats were injected with rotenone (3 μg/μl in DMSO) or vehicle (1 μl DMSO) into the left substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) under stereotaxic surgery, and PD model was assessed by rotational test ten days after drug infusion. The valid PD rats were randomly divided into two groups; Group 1 (n = 7) and Group 2 (n = 7) were administered saline (1 ml/kg/day, i.p.) and oxytocin (160 μg/kg/day, i.p.) through 20 days, respectively. The effects of OT treatment were evaluated by behavioral, histological and immunohistochemical parameters. Apomorphine-induced stereotypic rotations in PD rats were significantly inhibited by OT treatment (p < 0.05). In addition, immunohistochemical studies clearly demonstrated the suppression of Bax, caspase-3, caspase-8 and elevation of Bcl-2 and tyrosine hydroxylase immunoexpression in OT-treated rats compared to saline group. Our findings suggest that oxytocin may have cytoprotective and restorative effects on dopaminergic neurons against rotenone-induced injury. The underlying mechanism may be associated with the inhibition of apoptotic pathways.     

Rhythmic activities of hypothalamic magnocellular neurons: Autocontrol mechanisms

Electrophysiological recordings in lactating rats show that oxytocin (OT) and vasopressin (AVP) neurons exhibit specific patterns of activities in relation to peripheral stimuli: periodic bursting firing for OT neurons during suckling, phasic firing for AVP neurons during hyperosmolarity (systemic injection of hypertonic saline). These activities are autocontrolled by OT and AVP released somato-dentritically within the hypothalamic magnocellular nuclei. In vivo, OT enhances the amplitude and frequency of bursts, an effect accompanied with an increase in basal firing rate. However, the characteristics of firing change as facilitation proceeds: the spike patterns become very irregular with clusters of spikes spaced by long silences; the firing rate is highly variable and clearly oscillates before facilitated bursts. This unstable behaviour dramatically decreases during intense tonic activation which temporarily interrupts bursting, and could therefore be a prerequisite for bursting. In vivo, the effects of AVP depend on the initial firing pattern of AVP neurons: AVP excites weakly active neurons (increasing duration of active periods and decreasing silences), inhibits highly active neurons, and does not affect neurons with intermediate phasic activity. AVP brings the entire population of AVP neurons to discharge with a medium phasic activity characterised by periods of firing and silence lasting 20–40 s, a pattern shown to optimise the release of AVP from the neurohypophysis. Each of the peptides (OT or AVP) induces an increase in intracellular Ca²⁺ concentration, specifically in the neurons containing either OT or AVP respectively. OT evokes the release of Ca²⁺ from IP3-sensitive intracellular stores. AVP induces an influx of Ca²⁺ through voltage-dependent Ca²⁺ channels of T-, L- and N-types. We postulate that the facilitatory autocontrol of OT and AVP neurons could be mediated by Ca²⁺ known to play a key role in the control of the patterns of phasic neurons.     

CSF and Blood Oxytocin Concentration Changes following Intranasal Delivery in Macaque

Oxytocin (OT) in the central nervous system (CNS) influences social cognition and behavior, making it a candidate for treating clinical disorders such as schizophrenia and autism. Intranasal administration has been proposed as a possible route of delivery to the CNS for molecules like OT. While intranasal administration of OT influences social cognition and behavior, it is not well established whether this is an effective means for delivering OT to CNS targets. We administered OT or its vehicle (saline) to 15 primates (Macaca mulatta), using either intranasal spray or a nebulizer, and measured OT concentration changes in the cerebral spinal fluid (CSF) and in blood. All subjects received both delivery methods and both drug conditions. Baseline samples of blood and CSF were taken immediately before drug administration. Blood was collected every 10 minutes after administration for 40 minutes and CSF was collected once post-delivery, at the 40 minutes time point. We found that intranasal administration of exogenous OT increased concentrations in both CSF and plasma compared to saline. Both delivery methods resulted in similar elevations of OT concentration in CSF, while the changes in plasma OT concentration were greater after nasal spray compared to nebulizer. In conclusion our study provides evidence that both nebulizer and nasal spray OT administration can elevate CSF OT levels.     

Salivary Oxytocin Concentrations in Males following Intranasal Administration of Oxytocin: A Double-Blind,Cross-Over Study

The use of intranasal oxytocin (OT) in research has become increasingly important over the past decade. Although researchers have acknowledged a need for further investigation of the physiological effects of intranasal administration, few studies have actually done so. In the present double-blind cross-over study we investigated the longevity of a single 24 IU dose of intranasal OT measured in saliva in 40 healthy adult males. Salivary OT concentrations were significantly higher in the OT condition, compared to placebo. This significant difference lasted until the end of testing, approximately 108 minutes after administration, and peaked at 30 minutes. Results showed significant individual differences in response to intranasal OT administration. To our knowledge this is the largest and first all-male within-subjects design study to demonstrate the impact of intranasal OT on salivary OT concentrations. The results are consistent with previous research in suggesting that salivary OT is a valid matrix for OT measurement. The results also suggest that the post-administration ‘wait-time’ prior to starting experimental tasks could be reduced to 30 minutes, from the 45 minutes typically used, thereby enabling testing during peak OT concentrations. Further research is needed to ascertain whether OT concentrations after intranasal administration follow similar patterns in females, and different age groups.     

Evolution of Conformity in Social Dilemmas

People often deviate from their individual Nash equilibrium strategy in game experiments based on the prisoner’s dilemma (PD) game and the public goods game (PGG), whereas conditional cooperation, or conformity, is supported by the data from these experiments. In a complicated environment with no obvious “dominant” strategy, conformists who choose the average strategy of the other players in their group could be able to avoid risk by guaranteeing their income will be close to the group average. In this paper, we study the repeated PD game and the repeated m-person PGG, where individuals’ strategies are restricted to the set of conforming strategies. We define a conforming strategy by two parameters, initial action in the game and the influence of the other players’ choices in the previous round. We are particularly interested in the tit-for-tat (TFT) strategy, which is the well-known conforming strategy in theoretical and empirical studies. In both the PD game and the PGG, TFT can prevent the invasion of non-cooperative strategy if the expected number of rounds exceeds a critical value. The stability analysis of adaptive dynamics shows that conformity in general promotes the evolution of cooperation, and that a regime of cooperation can be established in an AllD population through TFT-like strategies. These results provide insight into the emergence of cooperation in social dilemma games.     

No evidence of association of oxytocin polymorphisms with breastfeeding in 2 independent samples

Oxytocin has an important function in breastfeeding via its role in the milk ejection reflex and in attachment and bonding processes. Genetic factors account for a significant part of the individual differences in breastfeeding behavior. OXT and OXTR have been proposed as gene candidates for breastfeeding. Previous studies have focused on certain single‐nucleotide polymorphisms (SNPs) within these genes, finding null or inconsistent results. The present study analyses the associations between a wide coverage of polymorphisms in OXT and OXTR and breastfeeding duration from 2 large and independent unselected samples comprising a total of 580 and 2112 female twin mothers from the Murcia Twin Registry (Spain) and QIMR Berghofer Medical Research Institute (Australia), respectively. A total of 19 SNPs in OXT and 137 in OXTR SNPs were covered in both samples. Effects of the OXT and OXTR polymorphisms on breastfeeding duration were calculated by means of linear regression controlling for age at survey time, educational level, interaction between age and educational level and principal components of genetic ancestry. The analyses were conducted independently in the 2 samples and also meta‐analyzed. Although some SNPs were associated at an alpha level of .05 with breastfeeding, they did not survive multiple testing correction. We conclude that SNPs within or nearby OXT and OXTR are unlikely to have large effects on breastfeeding behavior.     

On the genetic basis of face cognition and its relation to fluid cognitive abilities

The oxytocin and the dopaminergic systems have turned out to be highly relevant for social abilities and cognition. Therefore, we examined the association between two functional gene polymorphisms and face cognition (FC) in a multivariate study (N = 250) by applying structural equation modeling. The catechol‐O‐methyltransferase (COMT) val158met polymorphism influences the enzyme activity of COMT, which affects the prefrontal dopamine concentration. The rs226849 is a single‐nucleotide polymorphism located in the promoter region of the oxytocin receptor (OXTR) gene, modulating the mRNA expression. By modeling a general fluid ability factor (defined by working memory and reasoning) and nested FC factors, we tested genetic contributions to FC, after controlling for variance in FC that was also associated with fluid abilities. In line with several previous studies, we found a significant association between the COMT genotype and fluid abilities (Gf) but not with FC. The association between the oxytocin polymorphism and Gf was opposite in direction for men and women. Women with the C⁺ genotype performed better on Gf tasks than those with the C^? genotype. Conversely, men with the C^? genotype performed better than those with the C⁺ genotype. There was no significant association between OXTR and the nested FC factor. Therefore, the relationship between the oxytocin polymorphism and FC can be fully accounted for by Gf. The sex specificity of this relationship is a novel finding and warrants a mechanistic explanation.