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Objective: One proposed mechanism to subclassify depressive illness relates oxytocinergic dysregulation, via its effect on social behavior and Hypothalamic-pituitary-adrenal (HPA) axis inhibition. To further investigate the role of oxytocin in Major Depressive Disorder (MDD), we compared plasma oxytocin levels in patients with MDD to healthy controls. Methods: Plasma samples from 12 healthy controls and 33 MDD patients were collected at baseline, 8 weeks, and 12 weeks of treatment and oxytocin was measured by enzyme-immunoassay. Depression and anxiety scales were administered at screening, baseline, and at weeks 2, 4, 8, and 12 of treatment. Additionally, we investigated possible associations between blood concentrations of inflammatory biomarkers and oxytocin. Results: The average baseline oxytocin level was 429 pg/ml in MDD patients and 392 pg/ml in healthy control subjects. A significant negative correlation was found between baseline oxytocin and BMI. Treatment responders had significantly lower baseline oxytocin levels than non-responders. After stratifying patients into low and high oxytocin groups based on a median split, within the high oxytocin group, patients with no prior depressive episodes had significantly higher baseline oxytocin levels. A Chi-square distribution test revealed that African American patients were more likely to belong to the high baseline oxytocin group while Caucasian and Hispanic patients were more likely to belong to the low baseline oxytocin group. We found significant correlations between oxytocin and Von-Willebrand Factor (VWF) and Epidermal Growth Factor (EGF), only within the high oxytocin subgroup. There were no other significant correlations between baseline oxytocin and any other biomarkers. Conclusion: Within our limited patient cohort, our data adds to the mixed literature regarding the role of oxytocin in MDD. Oxytocinergic dysregulation and confounding factors may play a role for a subset of depressed patients.

ObjectiveEarly life trauma (ELT) and HIV are associated with social processing deficits. In people with HIV (PWH), we examined whether facial emotion identification accuracy differs by ELT and whether neuroendocrine factors including cortisol, oxytocin (OT), and arginine vasopressin, and/or immune system measures play a role in the ELT-performance association.MethodsWe used secondary data from the placebo condition of a pharmacologic challenge study in PWH. Presence of ELT was measured with the Childhood Trauma Questionnaire (at least moderate experiences of sexual, physical, and/or emotional abuse). Social processing was measured with the Facial Emotion Perception Test (FEPT). Salivary immune system measures and cortisol were sampled across a 5-hour study session. Blood was collected at study session start (12 pm ) to measure OT and arginine vasopressin. We examined the association of ELT with FEPT and five biological moderators (from principal components analysis of 12 biomarkers) of ELT-FEPT associations.ResultsOf 58 PWH (42 men; mean [standard deviation] age = 33.7 [8.9] years), 50% endorsed ELT. ELT-exposed PWH demonstrated lower identification accuracy across all emotional expressions (unstandardized β [ B ] = 0.13; standard error [SE] = 0.05; p = .021, d = 0.63) and had higher OT levels compared with ELT-unexposed PWH ( t(1,56) = 2.12, p = .039; d = 0.57). For total accuracy, an OT/C-reactive protein factor moderated the ELT-FEPT association ( B = 0.14; SE = 0.05; p = .014); accuracy was lower in ELT-exposed PWH versus ELT-unexposed PWH when the factor was low but not when high. Similar results were obtained for fearful, neutral, and happy faces ( p values < .05). Regardless of ELT, a myeloid migration (MCP-1/MMP-9) factor was associated with reduced accuracy ( p values < .05).ConclusionsOur pilot findings suggest that ELT may alter social processing in PWH, and OT and C-reactive protein may be a target for improving social processing in ELT-exposed PWH, and myeloid migration markers may be a target in PWH more generally.

Dozens of studies, most conducted in the last four decades, have implicated oxytocin, as well as vasopressin and their receptors, in processes that mediate selective sociality and the consequences of early experience. Oxytocin is critical for the capacity to experience emotional safety and healthy sexuality. Oxytocin also plays a central role in almost every aspect of physical and mental health, including the coordination of sociality and loving relationships with physiological reactions to challenges across the lifespan. Species, including prairie voles, that share with humans the capacity for selective social bonds have been a particularly rich source of insights into the behavioral importance of peptides. The purpose of this historical review is to describe the discovery of a central role for oxytocin in behavioral interactions associated with love, and in the capacity to use sociality to anticipate and cope with challenges across the lifespan - a process that here is called "sociostasis."

Oxytocin (OT) and the OT receptor occupy essential roles in our current understanding of mammalian evolution, survival, sociality and reproduction. This narrative review examines the hypothesis that many functions attributed to OT can be traced back to conditions on early Earth, including challenges associated with managing life in the presence of oxygen and other basic elements, including sulfur. OT regulates oxidative stress and inflammation especially through effects on the mitochondria. A related nonapeptide, vasopressin, as well as molecules in the hypothalamic–pituitary–adrenal axis, including the corticotropin-releasing hormone family of molecules, have a broad set of functions that interact with OT. Interactions among these molecules have roles in the causes and consequence of social behaviour and the management of threat, fear and stress. Here, we discuss emerging evidence suggesting that unique properties of the OT system allowed vertebrates, and especially mammals, to manage over-reactivity to the ‘side effects’ of oxygen, including inflammation, oxidation and free radicals, while also supporting high levels of sociality and a perception of safety. This article is part of the theme issue ‘Interplays between oxytocin and other neuromodulators in shaping complex social behaviours’.

The roles of oxytocin (OT) and arginine-vasopressin (AVP) as crucial modulators of social cognition and related behaviours have been extensively addressed in the literature. The involvement of these neuropeptides in social cognition in ageing, however, and a potential mediating effect of basic cognitive capacities on this link, are not well understood. To fill these research gaps, this study assessed associations of plasma OT and AVP levels with dynamic emotion identification accuracy in generally healthy older men (aged 55–95 years) and probed the underlying roles of crystallized and fluid cognition in these associations. Higher plasma OT levels were associated with lower accuracy in dynamic emotion identification, with this negative relationship fully mediated by cognition. For plasma AVP levels, in contrast, there was no association with dynamic emotion identification accuracy. Integrated within existing theoretical accounts, results from this study advance understanding of the neuropeptide–social cognition link in ageing and support basic cognitive capacities as mediators in this association. This article is part of the theme issue ‘Interplays between oxytocin and other neuromodulators in shaping complex social behaviours’.

Cesarean delivery is associated with diminished plasma levels of several ‘birth-signaling’ hormones, such as oxytocin and vasopressin. These same hormones have been previously shown to exert organizational effects when acting in early life. For example, our previous work found a broadly gregarious phenotype in prairie voles exposed to oxytocin at birth. Meanwhile, cesarean delivery has been previously associated with changes in social behavior and metabolic processes related to oxytocin and vasopressin. In the present study, we investigated the long-term neurodevelopmental consequences of cesarean delivery in prairie voles. After cross-fostering, vole pups delivered either via cesarean or vaginal delivery were studied throughout development. Cesarean-delivered pups responded to isolation differently in terms of their vocalizations (albeit in opposite directions in the two experiments), huddled in less cohesive groups under warmed conditions, and shed less heat. As young adults, we observed no differences in anxiety-like or alloparental behavior. However, in adulthood, cesarean-delivered voles of both sexes failed to form partner preferences with opposite sex conspecifics. In a follow-up study, we replicated this deficit in partner-preference formation among cesarean-delivered voles and were able to normalize pair-bonding behavior by treating cesarean-delivered vole pups with oxytocin (0.25 mg/kg) at delivery. Finally, we detected minor differences in regional oxytocin receptor expression within the brains of cesarean-delivered voles, as well as microbial composition of the gut. Gene expression changes in the gut epithelium indicated that cesarean-delivered male voles have altered gut development. These results speak to the possibility of unintended developmental consequences of cesarean delivery, which currently accounts for 32.9% of deliveries in the U.S. and suggest that further research should be directed at whether hormone replacement at delivery influences behavioral outcomes in later life.

Birth is a critical period for the developing brain, a time when surging hormone levels help prepare the fetal brain for the tremendous physiological changes it must accomplish upon entry into the ‘extrauterine world’. A number of obstetrical conditions warrant manipulations of these hormones at the time of birth, but we know little of their possible consequences on the developing brain. One of the most notable birth signaling hormones is oxytocin, which is administered to roughly 50% of laboring women in the United States prior to / during delivery. Previously, we found evidence for behavioral, epigenetic, and neuroendocrine consequences in adult prairie vole offspring following maternal oxytocin treatment immediately prior to birth. Here, we examined the neurodevelopmental consequences in adult prairie vole offspring following maternal oxytocin treatment immediately. Control prairie voles and those exposed to 0.25 mg/kg oxytocin were scanned as adults using anatomical and functional MRI, with neuroanatomy and brain function analyzed as voxel-based morphometry and resting state functional connectivity, respectively. Overall, anatomical differences brought on by oxytocin treatment, while widespread, were generally small, while differences in functional connectivity, particularly among oxytocin-exposed males, were larger. Analyses of functional connectivity based in graph theory revealed that oxytocin-exposed males in particular showed markedly increased connectivity throughout the brain and across several parameters, including closeness and degree. These results are interpreted in the context of the organizational effects of oxytocin exposure in early life and these findings add to a growing literature on how the perinatal brain is sensitive to hormonal manipulations at birth.

The peripartum period (pregnancy and postpartum) is a unique time filled with psychodynamic and biological changes that are critical in affecting the lives of mother and baby. Attachment, the biologically based emotional connection between a caregiver and infant, is critical to the development of the child. The early interactions in an infant's life shape their reward neuro-circuitry and the development of their internal working models and styles of attachment. Opioid use disorders in the mother affect the psychodynamics and neurobiology of attachment. There is significant overlap between the neurobiology of attachment and that of opioid use disorders. In this article, we hope to describe how opioid use disorders affect mother-infant attachment and how psychodynamic psychotherapy that is informed by attachment theory may be a potential treatment for mothers with opioid use disorders. Further, oxytocin plays a role in the attachment process and may function abnormally in mothers with opioid use disorders. As oxytocin affects attachment, administration of oxytocin during postpartum mother-infant interactions in the setting of psychotherapy may facilitate bonding and promote recovery from opioid use disorders in the peripartum population.

Oxytocin is a pleiotropic, peptide hormone with broad implications for general health, adaptation, development, reproduction, and social behavior. Endogenous oxytocin and stimulation of the oxytocin receptor support patterns of growth, resilience, and healing. Oxytocin can function as a stress-coping molecule, an anti-inflammatory, and an antioxidant, with protective effects especially in the face of adversity or trauma. Oxytocin influences the autonomic nervous system and the immune system. These properties of oxytocin may help explain the benefits of positive social experiences and have drawn attention to this molecule as a possible therapeutic in a host of disorders. However, as detailed here, the unique chemical properties of oxytocin, including active disulfide bonds, and its capacity to shift chemical forms and bind to other molecules make this molecule difficult to work with and to measure. The effects of oxytocin also are context-dependent, sexually dimorphic, and altered by experience. In part, this is because many of the actions of oxytocin rely on its capacity to interact with the more ancient peptide molecule, vasopressin, and the vasopressin receptors. In addition, oxytocin receptor(s) are epigenetically tuned by experience, especially in early life. Stimulation of G-protein-coupled receptors triggers subcellular cascades allowing these neuropeptides to have multiple functions. The adaptive properties of oxytocin make this ancient molecule of special importance to human evolution as well as modern medicine and health; these same characteristics also present challenges to the use of oxytocin-like molecules as drugs that are only now being recognized. SIGNIFICANCE STATEMENT: Oxytocin is an ancient molecule with a major role in mammalian behavior and health. Although oxytocin has the capacity to act as a "natural medicine" protecting against stress and illness, the unique characteristics of the oxytocin molecule and its receptors and its relationship to a related hormone, vasopressin, have created challenges for its use as a therapeutic drug.

To compare maternal psychological well-being, newborn behavior, and maternal and newborn salivary oxytocin (OT) and cortisol before and after two maternally administered multisensory behavioral interventions or an attention control group.Randomized prospective clinical trial.U.S. Midwest community hospital.Newborns and their mothers (n = 102 dyads) participated. Mothers gave birth vaginally at term gestation and had no physical or mental health diagnoses. Newborns with low Apgar scores, receipt of oxygen, suspected infection, or congenital anomalies were excluded.Dyads were randomly assigned to the auditory, tactile, visual, and vestibular (ATVV) intervention, the ATVV with odor from a baby lotion (ATVVO), or the attention control (AC) Group. Maternal psychological well-being, newborn behavior, and endocrine responses (salivary cortisol and OT) were measured before and after the intervention.Newborns in the ATVV and ATVVO groups exhibited increases in potent engagement behaviors (p .0001 and p = .001, respectively). Newborns in the AC group exhibited a decrease in potent engagement (p = .013) and an increase in potent disengagement (p = .029). Mothers in the ATVVO group exhibited an increase in OT (p = .01) and the largest change in OT (p = .02) compared to mothers in the ATVV and AC groups. We noted no change in maternal psychological well-being or newborn endocrine responses.Inclusion of an odor via lotion with a behavioral intervention (ATVV) influenced maternal OT more than the behavioral intervention alone. Newborns were behaviorally responsive to the interventions; however, endocrine measures were not associated with intervention changes.

We are presenting this document to medical providers as a systematic approach to improve outcomes of patients with COVID-19. The following variables are considered: Autonomic nervous system viewed from the perspective of the Polyvagal Theory; Timing of interventions in terms of phase of the body’s defense ( Fight, Flight, Freeze, Faint ); The nervous system considered the context of a “ One System ” perspective; Protein/Enzyme function; Immune system; Cytokine load - activity, inflammation and metabolic response; Viral load; Angiotensin 2 load. The ARDS and multi-system organ failure of the COVID-19 is a complex problem. This approach acknowledges the complexity and presents a structure where the variables are systematically addressed. 1. The common risk factors for death are associated with baseline elevations of pro-inflammatory cytokines. Measures can be taken to lower them before being exposed to the virus–Plan A. 2. Strategies to optimize the body’s defenses should be assessed and optimized. These include nutrition, vitamins, and trace elements, sleep, exercise, and minimizing threat. 3. The body’s own resources are utilized through recruiting the autonomic nervous system to counteract elevated pro-inflammatory cytokines. The interventions are implemented in the context of what stage of defense the body is in–fight, flight, freeze, or faint. 4. Progressive pharmacological interventions are considered with the early interventions being those with minimal risk. We are asking the following: This approach is viewed as the foundation for clinical interventions. They should be implemented in a systematic and stepwise manner. Most of the treatments are already medically proven with minimal or no risk. All basic treatments are in place before more aggressive interventions are implemented. That this process be considered a framework to test clinical protocols and novel therapies. Much work needs to be done regarding dosing and timing. We are particularly interested in the potential of the following interventions, which do need to be looked at in a protocol. o Allowing ketosis in the Mid and Late Phases of the illness. o Considering the use of ketone bodies instead of glucose for fuel in Mid and Late Phases of illness. o Eliminating glucocorticosteroids in the Early and Mid-Phases the use of steroids. o Utilizing the anti-inflammatory cholinergic nervous system (vagal stimulation, nicotine patches, etc.). o Closer monitoring of IL-6 to in real time deliver the most appropriate interventions. Doi: 10.28991/SciMedJ-2020-02-SI-2 Full Text: PDF

Researchers have endeavored to subclassify depressive illness based on pathophysiological mechanism. One model relates to hypothalamic-pituitary-adrenal (HPA) axis overactivation with a shift from corticotropin-releasing hormone (CRH) driven regulation to arginine vasopressin (AVP) driven regulation. Given the mixed literature, we compared plasma AVP levels in healthy controls to patients with major depressive disorder (MDD). Plasma samples from 33 patients and 12 controls were collected at baseline, 8 weeks, and 12 weeks of treatment and measured by immunochemical assay. Patients who were treatment responders trended toward lower AVP levels than non-responders. Patients were stratified into low and high AVP groups based on median split. Within the low AVP group, patients whose current episode lasted longer than a year had significantly higher baseline AVP levels than patients whose current episode was less than 6 months. Female patients in the low AVP group had significantly higher baseline AVP levels than male patients. Given the association between stress, HPA axis activation, immune dysregulation, and depression, we also measured concentrations of inflammatory biomarkers. We found a significant negative correlation between IL-10 and baseline AVP levels, within the low AVP subgroup. Given inconsistent data, HPA axis overactivation may be present within a subset of depressed patients.

Background The cesarean birth rate in the United States is 32%, and there is discussion about the cause of high surgical birth rates. Our purpose was to determine whether mode of birth is influenced by maternal, nurse, and system factors. Methods Secondary analysis of a data set of 163 women having postdates labor induction with oxytocin. Kaplan-Meier survival curves were calculated to compare the time for patients to reach an infusion rate of 6 mU/min, consistent with endogenous oxytocin levels in active labor. We used the log-rank test to evaluate survival curve differences. Multiple logistic regression and Cox proportional hazards models were conducted and included covariates that had statistically significant bivariate relationships with the time variable, or were clinically meaningful. Results The mean time to reach 6 mU/min was longer for women who birthed by cesarean (172.5 minutes) than for women who had vaginal birth (125.0 minutes, P = .024). The mean time to reach 6 mU/min was also longer for women admitted on night shift (147.0 minutes) than day shift (110.2 minutes, P = .018). No maternal characteristics were significantly related to the time to reach a rate of 6 mU/min. Conclusions Even during the initial hours of labor induction, it is important that the oxytocin infusion is titrated appropriately to aid women in achieving timely vaginal birth. Intrapartum nurses should receive education about the pharmacokinetics of intravenous oxytocin to understand proper administration of this high-alert medication.

Positive social experiences may induce oxytocin release. However, previous studies of moral elevation have generally utilized cross-sectional and simple modeling approaches to establish the relationship between oxytocin and emotional stimuli. Utilizing a cohort of 30 non-lactating women (aged 23.6±5.7 years), we tested whether exposure to a video identified as capable of eliciting moral elevation could change plasma oxytocin levels. Uniquely, we utilized a high-frequency longitudinal sampling approach and multilevel growth curve modeling with landmark registration to test physiological responses. The moral elevation stimulus, versus a control video, elicited significantly greater reports of being "touched/inspired" and "happy/joyful". However, the measured plasma oxytocin response was found to be markedly heterogeneous. While the moral elevation stimulus elicited increased plasma oxytocin as expected, this increase was only modestly larger than that seen following the control video. This increase was also only present in some individuals. We found no relationship between plasma oxytocin and self-report responses to the stimulus. From these data, we argue that future studies of the relationship between oxytocin and emotion need to anticipate heterogeneous responses and thus incorporate comprehensive individual psychological data; these should include evidence-based variables known to be associated with oxytocin such as a history of trauma, and the individual's psychological and emotional state at the time of testing. Given the complexity of physiological oxytocin release, such studies also need to incorporate frequent biological sampling to properly examine the dynamics of hormonal release and response.

IntroductionHuman and nonhuman animal research suggests that greater oxytocin (OT) activity is protective against harmful substance use. Most research on this topic is preclinical, with few studies evaluating the association between substance use and individual differences in the human OT system. The present study sought to fill this gap by evaluating the relationship between alcohol use and multiple biological measures of OT activity in an overall low to moderate-drinking sample.MethodAs part of a larger study, generally healthy young (n=51) and older (n=53) adults self-reported whether they regularly used alcohol and how much alcohol they consumed per week. Participants also provided blood samples from which peripheral OT, and in an age-heterogeneous subset of participants (n=56) variation in the oxytocin receptor gene (the OXTR rs53576 polymorphism) and OXTR DNA methylation levels (at cytosine-guanine dinucleotide sites -860, -924, -934), were obtained.ResultsA-allele carriers of the OXTR rs53579 polymorphism were less likely to regularly consume alcohol. Among regular alcohol consumers, number of alcoholic drinks per week was positively associated with peripheral OT in regression models excluding observations of high influence (postdiagnostic models). Number of alcoholic drinks per week was consistently negatively associated with OXTR DNA methylation at site -860; and with OXTR DNA methylation at site -924 in postdiagnostic models.ConclusionsThe significant associations between alcohol use and individual differences in OT activity support the involvement of the OT system in alcohol use, which most likely reflect the role of OT when alcohol use is under control of its rewarding properties and/or the acute impacts of alcohol on the OT system. Additional research with markers of OT activity and alcohol use, particularly longitudinal, is needed to clarify the bidirectional effects of OT and alcohol use in moderate to harmful drinking and dependence.

Oxytocin has become a popular analyte in behavioral endocrinology in recent years, due in part to its roles in social behavior, stress physiology, and cognition. Urine samples have the advantage of being non-invasive and minimally disruptive to collect, allowing for oxytocin measurements even in some wild populations. However, methods for urinary oxytocin immunoassay have not been sufficiently optimized and rigorously assessed for their potential limitations. Using samples from oxytocin knockout (KO) and wildtype (WT) mice, we find evidence of considerable interference in unextracted urine samples, with similar distributions of measured oxytocin in both genotypes. Importantly, although this interference can be reduced by a reversed-phase solid-phase extraction (SPE), this common approach is not sufficient for eliminating false-positive signal on three immunoassay kits. To better understand the source of the observed interference, we conducted epitope mapping of the Arbor Assays antibody and assessed its cross-reactivity with known, biologically active fragments of oxytocin. We found considerable cross-reactivity (0.5-52% by-molarity) for three fragments of oxytocin that share the core epitope, with more cross-reactivity for longer fragments. Given the presence of some cross-reactivity for even the tripeptide MIF-1, it is likely that many small protein metabolites might be sufficiently similar to the epitope that at high concentrations they interfere with immunoassays. We present a new mixed-mode cation-exchange SPE method that minimizes interference-with knockout samples measuring below the assay's limit of detection-while effectively retaining oxytocin from the urine of wildtype mice. This method demonstrates good parallelism and spike recovery across multiple species (mice, dogs, sifakas, humans). Our results suggest that immunoassays of urine samples may be particularly susceptible to interference, even when using common extraction protocols, but that this interference can be successfully managed using a novel mixed-mode cation exchange extraction. These findings imply that previous conclusions based on urinary oxytocin measurements-especially those involving unextracted samples-may need to be reassessed.

Love and fear were forged by the same fundamental evolutionary processes that permitted life on Earth. Both love and fear are deeply interwoven with the adaptive management of stress and disease. Love and fear share common roots and both can play a role in reproduction, survival, perceived safety and wellbeing. This special issue of

Despite evidence supporting a role for oxytocin (OT) in regulating social behavior, surprisingly little is known about how this neuropeptide is calibrated during development. We systematically reviewed empirical studies in humans (k = 86 publications reporting on 66 independent samples; N = 7319) that examined associations between early-life stress and three OT system components: endogenous OT, methylation of the OT receptor gene (OXTRm), and biological and behavioral responses to intranasally administered OT. In a series of meta-analyses, we found some evidence that people who grew up under more adverse conditions tend to have lower endogenous OT (children: r =.12; adults: r =.09), that early adversity is associated with higher levels of OXTRm (r =.02), and that adults who report lower levels of childhood adversity tend to show more positive responses to intranasally administered OT (r =.12). These results were found in typical populations, and were in most cases absent in clinical samples. We discuss these findings in terms of both the prevailing medical model (focusing on the harmful effects of early-life stress) and the adaptive calibration model (focusing on developmental adaptation of biobehavioral systems to early conditions) and suggest that an adaptation-based approach could meaningfully advance research and intervention on the sequelae of early adversity.

Since its discovery more than a century ago, oxytocin has become one of the most intensively studied molecules in behavioral biology. In the last five years, Psychoneuroendocrinology has published more than 500 articles with oxytocin in the title, with many of these articles including measures of endogenous oxytocin concentrations. Despite longstanding interest, methods of measuring endogenous oxytocin are still in active development. The widely varying oxytocin concentrations detected by different approaches to measurement - and lack of correlation among these techniques - has led to controversy and confusion. We identify features of oxytocin that may help to explain why various approaches may be differentially sensitive to diverse conformational states of the oxytocin molecule. We propose that discrepancies in data generated by different methods of measurement are not necessarily an indicator that some methods are valid whereas others are not. Rather, we propose that current challenges in the measurement of oxytocin may be analogous to the parable of the blind men and the elephant, with different methods of sample preparation and measurement being sensitive to different states in which the oxytocin molecule can exist.

Background: Maternal milk production requires the neuropeptide oxytocin. Individual variation in oxytocin function is a compelling target for understanding low milk production, a leading cause of breastfeeding attrition. Complicating the understanding of oxytocin pathways is that vasopressin may interact with oxytocin receptors, yet little is known about the role of vasopressin in lactation. Research aims: The aims of this study were (1) to describe maternal plasma oxytocin, vasopressin, and prolactin patterns during breastfeeding following low-risk spontaneous labor and birth in healthy first-time mothers and (2) to relate hormone patterns to maternal characteristics and breastfeeding measures. Methods: Eligible women were recruited before hospital discharge. Forty-six participants enrolled and 35 attended the study visit. Participants kept a journal of breastfeeding frequency, symptoms of lactogenesis, and infant weight. Plasma samples were obtained at breastfeeding onset on Day 4–5 postpartum, and repeated after 20 min. Hormones were measured with immunoassays. Infant weight change, milk transfer, and onset of lactogenesis were also measured. Results: Baseline oxytocin and vasopressin were inversely related to one another. Oxytocin and prolactin increased significantly across the 20-min sampling period while vasopressin decreased. Higher oxytocin was associated with higher maternal age, lower BMI, shorter active labor, physiologic labor progression, and less weight loss in the newborn. Higher vasopressin correlated with younger maternal age, higher BMI, and greater newborn weight loss. Conclusions: Oxytocin and vasopressin have contrasting relationships with maternal clinical characteristics and newborn weight gain in early breastfeeding infants. Further study is needed to understand how oxytocin and vasopressin influence lactation outcomes.

BACKGROUND: Oxytocin (OT) and arginine vasopressin (AVP) exert sexually dimorphic effects on cognition and emotion processing. Abnormalities in these hormones are observed in schizophrenia and may contribute to multiple established sex differences associated with the disorder. Here we examined sex-dependent hormone associations with resting brain activity and their clinical associations in schizophrenia patients. METHODS: OT and AVP serum concentrations were assayed in 35 individuals with schizophrenia (23 men) and 60 controls (24 men) from the Chicago BSNIP study site. Regional cerebral function was assessed with resting state fMRI by measuring the amplitude of low-frequency fluctuations (ALFF) which are believed to reflect intrinsic spontaneous neuronal activity. RESULTS: In female patients, lower OT levels were associated with lower ALFF in frontal and cerebellar cortices (p’s

Background The neuropeptide oxytocin regulates mammalian social behavior. Disruptions in oxytocin signaling are a feature of many psychopathologies. One commonly studied biomarker for oxytocin involvement in psychiatric diseases is DNA methylation at the oxytocin receptor gene (OXTR). Such studies focus on DNA methylation in two regions of OXTR, exon 3 and a region termed MT2 which overlaps exon 1 and intron 1. However, the relative contribution of exon 3 and MT2 in regulating OXTR gene expression in the brain is currently unknown. Results Here, we use the prairie vole as a translational animal model to investigate genetic, epigenetic, and environmental factors affecting Oxtr gene expression in a region of the brain that has been shown to drive Oxtr related behavior in the vole, the nucleus accumbens. We show that the genetic structure of Oxtr in prairie voles resembles human OXTR. We then studied the effects of early life experience on DNA methylation in two regions of a CpG island surrounding the Oxtr promoter: MT2 and exon 3. We show that early nurture in the form of parental care results in DNA hypomethylation of Oxtr in both MT2 and exon 3, but only DNA methylation in MT2 is associated with Oxtr gene expression. Network analyses indicate that CpG sites in the 3′ portion of MT2 are most highly associated with Oxtr gene expression. We also identify two novel SNPs in exon 3 of Oxtr in prairie voles and a novel alternative transcript originating from the third intron of the gene. Expression of the novel alternative transcript is associated with genotype at SNP KLW2. Conclusions These results identify putative regulatory features of Oxtr in prairie voles which inform future studies examining OXTR in human social behaviors and disorders. These studies indicate that in prairie voles, DNA methylation in MT2, particularly in the 3′ portion, is more predictive of Oxtr gene expression than DNA methylation in exon 3. Similarly, in human temporal cortex, we find that DNA methylation in the 3′ portion of MT2 is associated with OXTR expression. Together, these results suggest that among the CpG sites studied, DNA methylation of MT2 may be the most reliable indicator of OXTR gene expression. We also identify novel features of prairie vole Oxtr, including SNPs and an alternative transcript, which further develop the prairie vole as a translational model for studies of OXTR.

Background Oxytocin is a neuropeptide associated with maternal behavior. However the mechanisms underlying this link remain unclear. In a previous study we observed an indirect effect of increased plasma oxytocin during late pregnancy on early postpartum maternal interactive behavior via theory of mind, as assessed by the Reading the Mind in the Eyes Test (RMET). The current study aimed to extend these findings by testing whether this indirect effect would hold longitudinally for maternal behavior at 2–3 years postpartum, as well as for an additional observational measure of maternal mind-mindedness. Method The original sample of 316 pregnant women (Mage = 31.92 years) was assessed at 12–14 weeks gestation (T1), 32–34 weeks gestation (T2), and 7–9 weeks postpartum (T3). Follow-up measures were taken at 2–3 years postpartum (T4). Results Mothers’ RMET performance (T3) was associated with more structuring and less intrusive maternal behavior at 2–3 years (T4), while their tendency to use mind-related comments (T3) was associated with greater sensitivity (T4). Bootstrap estimates also revealed a significant indirect effect of plasma oxytocin levels during late pregnancy (T2) on maternal structuring and non-intrusive behavior at 2–3 years postpartum (T4) through RMET performance (T3). Conclusions Results: of the current study confirm and extend the previous findings, demonstrating that theory of mind may represent a social cognitive mechanism linking endogenous oxytocin and maternal behavior. Important changes in the oxytocinergic system during late pregnancy may help prepare for motherhood by promoting the awareness of social cues, which in turn promote maternal behavior from the early postpartum to the early childhood years.

Purpose of review PWS is a severe developmental disability for which there is no known treatment. The oxytocin system is currently a primary target for intervention. The aim of this article is to review the evidence for the efficacy of intranasal oxytocin in PWS. Recent findings To date, there have been five clinical trials of oxytocin in PWS. Four of these studies reported that oxytocin improved behaviors. However, each of these studies suffered important limitations that likely influenced the findings. For example, one study did not include a control group. Another study did not statistically analyze the effects of oxytocin on behavior. The final two studies used study-specific measures for which psychometric properties have not been assessed. Summary Because of these limitations, the most appropriate conclusion to draw from the existing studies is that there is currently no convincing evidence that intranasal oxytocin improves symptoms of PWS. However, this does not mean that oxytocin is not involved in PWS. Rather, it suggests that further work is needed to understand the nature of the PWS oxytocin abnormality.

Oxytocin has garnered much interest due to its role in affective states, social behaviors, and diverse physiological functions. However, approaches for measuring endogenous oxytocin concentrations have generated considerable controversy and debate. Common procedures for measuring oxytocin often produce uncorrelated results, and the detected concentrations frequently vary across two orders of magnitude. These findings have led some researchers to argue that immunoassays of plasma oxytocin may be unreliable and nonspecific, particularly when samples are not first processed using an extraction procedure. Here, we assess the specificity of oxytocin immunoassays using plasma samples from wildtype (WT) and oxytocin knockout (KO) mice. Plasma samples from both genotypes were measured using immunoassay and were measured with or without a solid-phase extraction. Using a commercially available kit from Arbor Assays, we demonstrate that both techniques generate a clear contrast between genotypes, with wildtype samples containing high concentrations of oxytocin (unextracted mean = 468pg/ml; extracted mean = 381pg/ml), while knockout samples measured below the lower limit of detection. Analytical validations demonstrated good parallelism and spike recovery for both methods. Furthermore, the same wildtype samples measured with both procedures were highly correlated (r=0.95), although unextracted samples measured at significantly higher concentrations (p=2.0×10-7, Cohen's d = 2.65). To test the generalizability of these results across immunoassay kits, we performed additional assays with kits from Cayman Chemical and Enzo Life Sciences. The Cayman Chemical kit produced results similar to Arbor Assays with a clean signal differentiating WT and KO plasma, both with and without an extraction step. The Enzo kit also differentiated the genotypes, with correlation between extracted and unextracted samples, but was considerably more susceptible to interference without the extraction, as evidenced by false positive signal in KO plasma samples. The extent to which these results generalize to other species remains unknown and challenging to assess.

A series of vasopressin receptor V 1a ligands have been synthesized for positron emission tomography (PET) imaging. The lead compound (1 S, 5 R )- 1 ( (4-(1H-indol-3-yl)-3-methoxyphenyl) ((1 S ,5R)-1,3,3-trimethyl-6-azabicyclo[3.2.1]octan-6-yl)methanone ) and its F-ethyl analog 6c exhibited the best combination of high binding affinity and optimal lipophilicity within the series. (1 S, 5 R )- 1 was radiolabeled with 11 C for PET studies. [ 11 CH 3 ](1 S, 5 R )- 1 readily entered the mouse (4.7% ID/g tissue) and prairie vole brains (∼2% ID/g tissue) and specifically (30–34%) labeled V 1a receptor. The common animal anesthetic Propofol significantly blocked the brain uptake of [ 11 CH 3 ](1 S, 5 R )- 1 in the mouse brain, whereas anesthetics Ketamine and Saffan increased the uptake variability. Future PET imaging studies with V 1a radiotracers in non-human primates should be performed in awake animals or using anesthetics that do not affect the V 1a receptor.

The role of oxytocin (OT) in close relationships is complex, as both positive and negative associations have been found between OT and relationship processes. Also, with most research focusing on the effects of exogenous OT administration on communication and couple behaviors, our knowledge about the association between endogenous OT and couple dynamics remains limited. This study is the first to assess the link between peripheral OT levels and observed communication behaviors during sexual and nonsexual conflict discussions in romantic relationships. A sample of 126 young, heterosexual couples (Mean age=23.3, SD=2.4; average relationship duration=1.9 years, SD=0.9) participated in videotaped sexual and nonsexual couple conflict discussions of 7min each. Communication behaviors were coded using an adaptation of the Specific Affect Coding System (SPAFF) and the System for Coding Interactions and Family Functioning (SCIFF). Blood samples were collected prior to the couple discussions, during a separate lab visit, and OT plasma levels were determined using enzyme-linked immunosorbent assays (ELISA). Plasma OT levels were positively associated with validating behaviors during sexual discussions in both women (r=+.24, p=.008) and men (r=+.18, p=.052). No significant associations were found between OT levels and validating behaviors during nonsexual discussions and between OT and affectionate and negative behaviors during either sexual or nonsexual discussions. Analyses revealed significant associations between OT levels and one's own validating behaviors during sexual discussions (b =47.82, t(201.16)=3.81, p&nbsp

Alloparenting, defined as care provided by individuals other than parents, is a universal behavior among humans that has shaped our evolutionary history and remains important in contemporary society. Dysfunctions in alloparenting can have serious and sometimes fatal consequences for vulnerable infants and children. In spite of the importance of alloparenting, they still have much to learn regarding the underlying neurobiological systems governing its expression. Here, they review how a lack of alloparental behavior among traditional laboratory species has led to a blind spot in our understanding of this critical facet of human social behavior and the relevant neurobiology. Based on what is known, they draw from model systems ranging from voles to meerkats to primates to describe a conserved set of neuroendocrine mechanisms supporting the expression of alloparental care. In this review we describe the neurobiological and behavioral prerequisites, ontogeny, and consequences of alloparental care. Lastly, they identified several outstanding topics in the area of alloparental care that deserve further research efforts to better advance human health and wellbeing. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 214-232, 2017.