Trained Memory of Human Uterine NK Cells Enhances Their Function in Subsequent Pregnancies.

Natural killer cells (NKs) are abundant in the human decidua, regulating trophoblast invasion and angiogenesis. Several diseases of poor placental development are associated with first pregnancies, so we thus looked to characterize differences in decidual NKs (dNKs) in first versus repeated pregnancies. We discovered a population found in repeated pregnancies, which has a unique transcriptome and epigenetic signature, and is characterized by high expression of the receptors NKG2C and LILRB1. We named these cells Pregnancy Trained decidual NK cells (PTdNKs). PTdNKs have open chromatin around the enhancers of IFNG and VEGFA. Activation of PTdNKs led to increased production and secretion of IFN-γ and VEGFα, with the latter supporting vascular sprouting and tumor growth. The precursors of PTdNKs seem to be found in the endometrium. Because repeated pregnancies are associated with improved placentation, we propose that PTdNKs, which are present primarily in repeated pregnancies, might be involved in proper placentation.

Mast cells contribute to the resolution of allergic inflammation by releasing resolvin D1.

BACKGROUND: Mast cells are initiators and main effectors of allergic inflammation, together with eosinophils, with whom they can interact in a physical and soluble cross-talk with marked pro-inflammatory features, the Allergic Effector Unit. The pro-resolution role of mast cells, alone or in co-culture with eosinophils, has not been characterized yet. OBJECTIVES: We aimed to investigate select pro-resolution pathways in mast cells in vitro and in vivo in allergic inflammation. METHODS: In vitro, we employed human and murine mast cells and analyzed release of resolvin D1 and expression of 15-lipoxygenase after IgE-mediated activation. We performed co-culture of IgE-activated mast cells with peripheral blood eosinophils and investigated 15-lipoxygenase expression and Resolvin D1 release. In vivo, we performed Ovalbumin/Alum and Ovalbumin/S. aureus enterotoxin B allergic peritonitis model in Wild Type mice following a MC "overshoot" protocol. RESULTS: We found that IgE-activated mast cells release significant amounts of resolvin D1 30 min after activation, while 15-lipoxygenase expression remained unchanged. Resolvin D1 release was found to be decreased in IgE-activated mast cells co-cultured with peripheral blood eosinophils for 30 min In vivo, mast cell-overshoot mice exhibited a trend of reduced inflammation, together with increased peritoneal resolvin D1 release. CONCLUSIONS: Mast cells can actively contribute to resolution of allergic inflammation by releasing resolvin D1.

Changing genetic architecture of body mass index from infancy to early adulthood: an individual based pooled analysis of 25 twin cohorts.

BACKGROUND: Body mass index (BMI) shows strong continuity over childhood and adolescence and high childhood BMI is the strongest predictor of adult obesity. Genetic factors strongly contribute to this continuity, but it is still poorly known how their contribution changes over childhood and adolescence. Thus, we used the genetic twin design to estimate the genetic correlations of BMI from infancy to adulthood and compared them to the genetic correlations of height. METHODS: We pooled individual level data from 25 longitudinal twin cohorts including 38,530 complete twin pairs and having 283,766 longitudinal height and weight measures. The data were analyzed using Cholesky decomposition offering genetic and environmental correlations of BMI and height between all age combinations from 1 to 19 years of age. RESULTS: The genetic correlations of BMI and height were stronger than the trait correlations. For BMI, we found that genetic correlations decreased as the age between the assessments increased, a trend that was especially visible from early to middle childhood. In contrast, for height, the genetic correlations were strong between all ages. Age-to-age correlations between environmental factors shared by co-twins were found for BMI in early childhood but disappeared altogether by middle childhood. For height, shared environmental correlations persisted from infancy to adulthood. CONCLUSIONS: Our results suggest that the genes affecting BMI change over childhood and adolescence leading to decreasing age-to-age genetic correlations. This change is especially visible from early to middle childhood indicating that new genetic factors start to affect BMI in middle childhood. Identifying mediating pathways of these genetic factors can open possibilities for interventions, especially for those children with high genetic predisposition to adult obesity.

Cromolyn Sodium differentially regulates human mast cell and mouse leukocyte responses to control allergic inflammation.

BACKGROUND: Cromolyn Sodium (CS) has been used in the past as an anti-allergy drug owing to its mast cell (MC) stabilizing properties that impair histamine release. However, additional mechanisms for its clinical actions are likely and might help to identify new roles for MCs and leukocytes in regulating inflammation. Here, using human cord blood-derived MCs (CBMCs), mouse bone marrow-derived MCs (BMMCs) and eosinophils (BMEos), and in vivo mouse models of allergic inflammation (AI), additional actions of CS on MCs were determined. METHODS: The in vitro effects of CS on IgE-activated human and mouse MCs were assessed by measuring the levels of pro-inflammatory (tryptase, LTC4, IL-8, CD48) and pro-resolution effectors (IL-10, CD300a, Annexin A1) before and after CS treatment. The in vivo effects of daily CS injections on parameters of inflammation were assessed using mouse models of allergic peritonitis (AP) (Ovalbumin/Alum- or Ovalbumin/S. aureus enterotoxin B) and allergic airways inflammation (AAI) (house dust mite (HDM)). RESULTS: In vitro, CS did not affect pro-inflammatory effectors but significantly increased the anti-inflammatory/pro-resolution CD300a levels and IL-10 release from IgE-activated CBMCs. BMMCs were not affected by CS. In vivo, CS injections decreased total cell and Eos numbers in the peritoneal cavity in the AP models and bronchoalveolar lavage and lungs in the AAI model. CS reduced EPX release from PAF-activated BMEos in vitro, possibly explaining the in vivo findings. CONCLUSION: Together, these results demonstrate immunomodulatory actions for CS in AI that are broader than only MC stabilization.

Caring babies: Concern for others in distress during infancy.

Concern for distressed others is a highly valued human capacity, but little is known about its early ontogeny. Theoretical accounts of empathy development have emphasized stages, but this has been called into question. This study sheds new light on four key issues: onset, consistency, development, and predictive power of early manifestations of concern for others. Three-month-old Israei infants (N = 165) were followed longitudinally at ages 6, 12, and 18 months, and their observed responses to others' distress were assessed. Concern for distressed others was seen early in the first year of life, long before previous theories assumed. Empathic concern was moderately consistent across both situation and age, from as early as 3 months. Concern for others grew only modestly with age, plateauing during the second year, whereas prosocial behavior increased rapidly during the second year. Early individual differences in concern for others predicted later prosocial behavior on behalf of distressed others. Findings underscore the early roots of caring, and appear to refute assumptions of prior stage theories of empathy development, by showing that concern for others develops much earlier and more gradually than previously assumed.

Beta-Carotene derivatives as novel therapy for the prevention and treatment of autistic symptoms.

Autistic Spectrum Disorders (ASD) are neurodevelopmental disorders characterized by impaired social interaction & communication as well as restricted and repetitive behavior. The currently reported incidence of ASD is 1-2%, and it increases dramatically to 10-20% in families predisposed to ASD. To date, there is no effective way to treat or prevent ASD, and only symptomatic treatment with limited efficacy is available. Oxytocin (Oxt) enhances affiliative behavior and improves social cognition. Social deficits characteristic of autism may be related to dysfunctional Oxt neurotransmission. Thus, administration of Oxt may relieve ASD, however it has a short plasma half-life and poor Blood Brain Barrier (BBB) permeability. CD38, a multifunctional ecto-enzyme expressed in brain and immune cells, was found to be critical for social behavior via regulation of Oxt secretion. All-trans retinoic acid (ATRA) is a potent inducer of CD38 and improves social behavior, but it is toxic and teratogenic. We have shown that beta-carotene has a similar therapeutic effect. The present study aimed to investigate the activity of novel beta-carotene derivatives in rescuing low sociability found in BTBR mice, providing an in vivo "proof of principle" that beta-carotene derivatives are potential agents to prevent/ameliorate the reappearance of ASD in high-risk populations for ASD. Beta-carotene and its synthetic analogs were administered orally to newborn BTBR mice with ASD associated like behavior. After 2 months, they were tested (at dosages of 0.1 and 1.0 mg/kg) by cognitive (T-maze spontaneous alteration and neurological score) and behavioral tests (reciprocal social interaction, repetitive grooming / bedding behavior), previously shown as indicators for autistic behavior. The following biochemical and molecular biology parameters were also examined: serum Oxt; gene expression in hippocampus and hypothalamus of CD 38, Oxt, Oxt receptor, BDNF, and retinoic acid receptor. The new compounds were significantly more effective than control. The most effective compounds, both in the behavioral tests and in their biochemical effects, were (3R,3'R)-astaxanthin bis(N-Cbz-l-alanine ester) (3B(and (3S,3'S)-astaxanthin bis(N,N-dimethylglycine ester (5). They did not exert any neurological symptoms. Thus, beta-carotene derivatives may have the potential to prevent and/or ameliorate autistic symptoms when administered orally after birth to newborns of families predisposed to autism.

Neonatal subgaleal hemorrhage unrelated to assisted vaginal delivery: clinical course and outcomes.

PURPOSE: The purpose of the study was to evaluate the occurrence of subgaleal hemorrhage (SGH) following non-assisted vaginal delivery (normal vaginal delivery or cesarean delivery), and to characterize associated factors, clinical course, and outcomes, compared to attempted assisted vaginal delivery (AVD)-associated SGH METHODS: A retrospective cohort study was conducted. All cases of SGH encountered following delivery of a singleton neonate at Hadassah, Hebrew University Medical Center during 2011-2018 were included. Maternal, fetal, intrapartum, and neonatal characteristics and outcomes were compared between AVD-related and non-AVD-related SGH groups. RESULTS: The overall incidence of SGH was 4.5/1000 (369/82,256) singleton deliveries. The incidences of AVD- and non-AVD-related SGH were 44.6/1000 (350/7852) and 0.3/1000 (19/74,404) singleton deliveries, respectively. Ten (53%) of the 19 non-AVD-related SGH were diagnosed after vaginal delivery and 9 (47%) after an urgent cesarean section. SGH severity was mild, moderate, and severe in 68%, 16%, and 16% of the cases, respectively. SGH severity did not differ between the attempted AVD group and the non-AVD-related SGH group. A higher proportion of neonates with non-AVD SGH required phototherapy treatment than did those diagnosed with AVD-related SGH (56% vs. 24%, P = 0.003). Other neonatal outcomes, including Apgar scores, maximal bilirubin level, length of stay, and the rate of composite adverse outcomes, did not differ between the groups. CONCLUSIONS: SGH, although rare, may be diagnosed after unassisted vaginal or cesarean delivery in the absence of an AVD attempt. We advocate continuing education for all medical staff who participate in peripartum and neonatal care, regarding the possible occurrence of non-AVD-related SGH.

Risk factors associated with subgaleal hemorrhage in neonates exposed to vacuum extraction.

INTRODUCTION: Subgaleal hemorrhage (SGH) is a life-threatening neonatal condition that is strongly associated with vacuum assisted delivery (VAD). The factors associated with the development of SGH following VAD are not well-established. We aimed to evaluate the factors associated with the development of SGH following attempted VAD. MATERIAL AND METHODS: A retrospective case-control study of women who delivered at a tertiary university-affiliated medical center in Jerusalem, Israel, during 2009-2018. Cases comprised all parturients with singleton pregnancies for whom attempted VAD resulted in neonatal SGH. A control group of VAD attempts was established by matching one-to-one according to gestational age at delivery, parity and year of delivery. Fetal, intrapartum and vacuum procedure characteristics were compared between the groups. RESULTS: In all, 313 (89.5%) of the 350 attempted VAD were nulliparous. Baseline maternal and fetal characteristics were similar between the groups except for higher neonatal birthweight in the SGH group. In multivariate logistic regression analysis, only six independent risk factors were significantly associated with the development of SGH: second-stage duration (for each 30-minute increase, adjusted odds ratio [OR] 1.13; 95% confidence intervals [CI] 1.04-1.25; P = .006), presence of meconium-stained amniotic fluid (adjusted OR 2.61; 95% CI 1.52-4.48; P = .001), presence of caput succedaneum (adjusted OR 1.79; 95% CI 1.11-2.88; P = .01), duration of VAD (for each 3-minute increase, adjusted OR 2.04; 95% CI 1.72, 2.38; P < .001), number of dislodgments (adjusted OR 2.38; 95% CI 1.66-3.44; P < .001), and fetal head station (adjusted OR 3.57; 95% CI 1.42-8.33; P = .006). Receiver operating characteristic curves showed that VAD duration of ≥15 minutes had a 96.7% sensitivity and 75.0% specificity in predicting SGH formation, with an area under the curve equal to .849. CONCLUSIONS: Vacuum duration, the number of dislodgments, the duration of second stage of delivery, fetal head station, the presence of caput succedaneum and the presence of meconium were found to be independently associated with SGH formation.

Long-acting reversible contraception: A route to reproductive justice or injustice.

This article presents information on unintended pregnancies and the ongoing efforts of policy makers to promote long-acting reversible contraception (LARC) to reduce the numbers of such pregnancies. Also discussed is the tension between the encouragement of LARC to promote the public's interests in achieving that goal versus the need to assure that all women can decide about their bodies and reproductive needs. Our discussion includes information, primarily from the United States, on (a) risks associated with unintended pregnancies, (b) LARC devices approved in the United States (copper intrauterine devices (IUDs), hormone IUDs, and implants), (c) public and social benefits of increasing the use of LARC, (d) disadvantages and barriers to using LARC, (e) dangers of promoting LARC in unjust ways, and (f) the meaning of reproductive justice and its connection to social justice. By sharing the information with the audience of this journal, we hope that it will be integrated into clinical work and research on mental health and development. We also hope that experts in those fields will become discussants in the conversation regarding women's reproductive health and social justice that is taking place in the United States and elsewhere.

Este artículo presenta información sobre embarazos no intencionales y el continuo esfuerzo de las autoridades para promover LARC (Contracepción Reversible de Larga Actuación) con el fin de reducir el número de tales embarazos. También se discute la tensión entre el aconsejar LARC para promover los intereses públicos de alcanzar esa meta vs. la necesidad de asegurar que todas las mujeres puedan ellas mismas decidir sobre sus cuerpos y necesidades reproductivas. Nuestra discusión incluye información, primariamente de los Estados Unidos (EUA), sobre: (1) riesgos asociados con embarazos no intencionales, (2) objetos de LARC aprobados en EUA (objetos intrauterinos de cobre -IUD-, IUD de hormonas, e implantes), (3) los beneficios públicos y sociales de aumentar el uso de LARC, (4) desventajas y barreras que presenta el uso de LARC, (5) peligros de promover LARC de maneras injustas, y (6) el significado de la justicia reproductiva y su conexión con la justicia social. Al compartir la información con el público de esta revista especializada, esperamos que la misma sea integrada dentro del trabajo clínico y la investigación sobre salud y desarrollo mental. También esperamos que los expertos en esos campos de estudio participarán activamente en la conversación acerca de la salud reproductiva de las mujeres y la justicia social que se lleva a cabo en EUA y otros lugares.

Cet article porte sur les grossesses involontaires et les efforts continus que font les responsables politiques pour promouvoir la contraception à long terme et réversible LARC (en anglais Long Acting Reversible Contraception) de façon à réduire le nombre de ces grossesses. Nous discutons aussi la tension entre l'encouragement de la LARC à promouvoir les intérêts publics pour arriver ce but et le besoin qui existe de s'assurer que toutes les femmes puissent décider d'elles-mêmes ce qu'elles veulent faire avec leur propre corps et leurs besoins sexuels. Notre discussion inclut des renseignements, principalement des Etats-Unis d'Amériques, sur: (1) les risques liés aux grossesses involontaires; (2) les dispositifs de contraception à long terme réversible approuvés aux Etats-Unis d'Amérique (dispositifs intra-utérins au cuivre (DIU), hormones DIU, et implants), (3) les avantages publics et sociaux qu'il y a à augmenter l'utilisation de la LARC, (4) les désavantages et les barrières à l'utilisation de la LARC, (5) les dangers de la promotion de la LARC de manières injustes, et (6) la signification de la justice reproductive et son lien à la justice sociale. En partageant ces informations avec les lecteurs de cette revue, nous espérons qu'elles seront intégrées dans le travail clinique et les recherches sur la santé mentale et le développement. Nous espérons aussi que les experts dans ces domaines pourront ainsi intervenir dans la conversation qui concerne la santé reproductive des femmes et la justice sociale qui se tient aux Etats-Unis et ailleurs.

Predicting the use of corporal punishment: Child aggression, parent religiosity, and the BDNF gene.

Corporal punishment (CP) has been associated with deleterious child outcomes, highlighting the importance of understanding its underpinnings. Although several factors have been linked with parents' CP use, genetic influences on CP have rarely been studied, and an integrative view examining the interplay between different predictors of CP is missing. We focused on the separate and joint effects of religiosity, child aggression, parent's gender, and a valine (Val) to methionine (Met) substitution in the brain-derived neurotrophic factor (BDNF) gene. Data came from a twin sample (51% male, aged 6.5 years). We used mothers' and fathers' self-reports of CP and religiosity, and the other parent's report on child aggression. Complete data were available for 244 mothers and their 466 children, and for 217 fathers and their 409 children. The random split method was employed to examine replicability. For mothers, only the effect of religiosity appeared to replicate. For fathers, several effects predicting CP use replicated in both samples: child aggression, child sex, religiosity, and a three-way (GxExE) interaction implicating fathers' BDNF genotype, child aggression and religiosity. Religious fathers who carried the Met allele and had an aggressive child used CP more frequently; in contrast, secular fathers' CP use was not affected by their BDNF genotype or child aggression. Results were also repeated longitudinally in a subsample with age 8-9 data. Findings highlight the utility of a bio-ecological approach for studying CP use by shedding light on pertinent gene-environment interaction processes. Possible implications for intervention and public policy are discussed.

Spontaneous first trimester miscarriage rates per woman among parous women with 1 or more pregnancies of 24 weeks or more.

BACKGROUND: The purpose of this study was to quantify spontaneous first trimester miscarriage rates per woman among parous women. A vast amount of data has accumulated regarding miscarriage rates per recognized pregnancy as well as about recurrent miscarriage. This is the second study of miscarriage rates per woman in a parous population and the first study of recurrent and non-recurrent, spontaneous first trimester miscarriage rates per woman in a large parous population. METHODS: Extraction of the following variables from all delivery room admissions from both Hadassah Medical Centers in Jerusalem Israel, 2004-2014: # of first trimester spontaneous miscarriages, # live births; # living children; age on admission, pre-pregnancy height and weight, any smoking this pregnancy, any alcohol or drug abuse this pregnancy, blood type, history of ectopic pregnancy, history of cesarean surgery (CS) and use of any fertility treatment(s). RESULTS: Among 53,479 different women admitted to labor and delivery ward, 43% of women reported having had 1 or more first trimester spontaneous miscarriages; 27% reported having had one, 10% two, 4% three, 1.3% four, 0.6% five and 0.05% reported having 6-16 spontaneous first trimester miscarriages. 18.5% had one or more first trimester miscarriages before their first live birth. Eighty-one percent of women with 11 or more living children experienced one or more first trimester miscarriages. First trimester miscarriage rates rose with increasing age, increasing parity, after previous ectopic pregnancy, after previous cesarean surgery, with any smoking during pregnancy and pre-pregnancy BMI ≥30. CONCLUSIONS: Miscarriages are common among parous women; 43% of parous women report having experienced one or more first trimester spontaneous miscarriages, rising to 81% among women with 11 or more living children. One in every 17 parous women have three or more miscarriages. Depending on her health, nutrition and lifestyle choices, even a 39 year old parous woman with a history of 3 or more miscarriages has a good chance of carrying a future pregnancy to term but she should act expediently.

Maternal resolution of preterm birth from 1 to 18 months.

Preterm birth can be traumatic for some mothers, involving feelings of grief over the hoped-for full-term pregnancy. In this longitudinal study, we interviewed 50 mothers of preterm infants, using the reaction to diagnosis interview when their child was 1 month and 18 months old. We examined change and stability in resolution status over time. Additionally, we explored possible predictors of resolution trajectories between 1 and 18 months. Findings indicated that resolution at 1 month was not yet common. The rate of resolution at 18 months was 62.6%, compared with 38.2% at 1 month. Prenatal precursors of preterm birth, lower medical neonatal risk, and lower maternal stress at 1 month significantly differentiated mothers who attained resolution as early as at 1 month from those who were unresolved at 1 and 18 months. Lower maternal stress at 1 month was the only predictor that significantly differentiated initially unresolved mothers who later attained resolution from those who remained unresolved at 18 months. Discussion focuses on maternal stress, which may mark a subgroup of mothers of preterm infants who are at risk of being unresolved through the first 18 months, and who may benefit from resolution-focused intervention.

Twin's Birth-Order Differences in Height and Body Mass Index From Birth to Old Age: A Pooled Study of 26 Twin Cohorts Participating in the CODATwins Project.

We analyzed birth order differences in means and variances of height and body mass index (BMI) in monozygotic (MZ) and dizygotic (DZ) twins from infancy to old age. The data were derived from the international CODATwins database. The total number of height and BMI measures from 0.5 to 79.5 years of age was 397,466. As expected, first-born twins had greater birth weight than second-born twins. With respect to height, first-born twins were slightly taller than second-born twins in childhood. After adjusting the results for birth weight, the birth order differences decreased and were no longer statistically significant. First-born twins had greater BMI than the second-born twins over childhood and adolescence. After adjusting the results for birth weight, birth order was still associated with BMI until 12 years of age. No interaction effect between birth order and zygosity was found. Only limited evidence was found that birth order influenced variances of height or BMI. The results were similar among boys and girls and also in MZ and DZ twins. Overall, the differences in height and BMI between first- and second-born twins were modest even in early childhood, while adjustment for birth weight reduced the birth order differences but did not remove them for BMI.

Dopamine receptor polymorphism modulates the relation between antenatal maternal anxiety and fetal movement.

We determined whether the combination of fetal genotype (dopamine D4 receptor; DRD4) and mothers' anxiety during pregnancy is associated with fetal behavior. Two hundred and six pregnant women underwent an ultrasound exam. Fetal movement measures (Movement Frequency, Total Activity, Movement Duration, and Longest Quiet Time) were derived from off-line coding. A moderating role of the DRD4-III polymorphism was found: Results indicate that higher levels of antenatal maternal anxiety symptoms were associated with more frequent fetal movements among fetuses carrying a 7R allele, but not among fetuses carrying shorter alleles. Total Activity did not show full moderation by DRD4, though the measure was correlated with maternal anxiety among fetuses in the Anxious Group with a 7R allele; not among fetuses without both factors. The findings provide the first evidence of a GXE interaction in association with fetal behavior. Results also demonstrate that some individuals are inherently more susceptible to uterine environmental influences than are others.

Exposure to childhood traumas ups the odds of giving birth to daughters.

This study examined the likelihood of giving birth to a daughter as a function of women's exposure to four categories of stressors: childhood trauma, adult trauma, chronic stressors, and recent (adverse) life events. Hypothesis 1 stated that exposure to recent life events (near conception) and to childhood traumas would increase women's chances of having a girl baby. Hypothesis 2 stated that the relationship between stress and gender outcome is mediated by persistent posttraumatic stress disorder (PTSD) symptoms. The final sample was comprised of 225 women. The design was prospective observational. At first contact, women were retained if they were <27 weeks pregnant and met initial inclusion criteria. In interview 2, at 27-30 weeks, women were excluded for positive diagnoses of anxiety disorders besides PTSD with or without depression (Structured Clinical Interview for DSM-IV Disorders). In interview 3 (30-34 weeks), reports on stress categories (Social Stress Indicator Questionnaire) and PTSD symptoms (Post-Traumatic Checklist) were obtained. Infant gender was obtained from medical records. The relationship between stress categories and the distribution of girl/boy infants was examined with Chi Squares and logistic regression analyses. Mediation was tested with the macro PROCESS (Hayes 2012). Childhood trauma was the only stress category that increased the odds of having a girl, with an odds ratio of >3.0 for women who had been exposed to more than two such events. PTSD symptoms (partially) mediated the relationship between childhood trauma and infant gender. Findings suggest that women's exposure to childhood trauma contributes to the determination of the sex ratio at birth and that PTSD symptoms are part of the cause.

The contributions of oxytocin and vasopressin pathway genes to human behavior.

Arginine vasopressin (AVP) and oxytocin (OXT) are social hormones and mediate affiliative behaviors in mammals and as recently demonstrated, also in humans. There is intense interest in how these simple nonapeptides mediate normal and abnormal behavior, especially regarding disorders of the social brain such as autism that are characterized by deficits in social communication and social skills. The current review examines in detail the behavioral genetics of the first level of human AVP-OXT pathway genes including arginine vasopressin 1a receptor (AVPR1a), oxytocin receptor (OXTR), AVP (AVP-neurophysin II [NPII]) and OXT (OXT neurophysin I [NPI]), oxytocinase/vasopressinase (LNPEP), ADP-ribosyl cyclase (CD38) and arginine vasopressin 1b receptor (AVPR1b). Wherever possible we discuss evidence from a variety of research tracks including molecular genetics, imaging genomics, pharmacology and endocrinology that support the conclusions drawn from association studies of social phenotypes and detail how common polymorphisms in AVP-OXT pathway genes contribute to the behavioral hard wiring that enables individual Homo sapiens to interact successfully with conspecifics. This article is part of a Special Issue entitled Oxytocin, Vasopressin, and Social Behavior.