Severe PTSD is marked by reduced oxytocin and elevated vasopressin.

Neuroendocrine analyses of posttraumatic stress disorder (PTSD) have generally focused on hypothalamic-pituitary-adrenal (HPA) axis alterations. In the present analyses, we examine two additional neuroendocrine factors that have been previously implicated in biological stress responses: oxytocin (OT) and arginine vasopressin (AVP). Here we examined basal neuropeptide status in military veterans clinically diagnosed with PTSD (n = 29) and in two non-traumatized comparison groups with previous stress exposure (n = 11 SWAT trainees and n = 21 ultramarathon runners). PTSD patients showed low levels of plasma OT and high levels of AVP. The ratio of AVP/OT robustly related to PTSD status, and emerged as a statistically plausible mediator of relationships between the number of personal traumatic experiences and subsequent PTSD symptom burden. Over the course of behavioral therapy for PTSD, measures of OT showed a significant but modest normalization. Plasma cortisol levels were not statistically different among the three groups. This study suggests that AVP/OT ratios may represent a neuroendocrine predictor of severe PTSD, as well as a potential treatment response biomarker.

Maternal oxytocin treatment at birth increases epigenetic age in male offspring.

Exogenous oxytocin (OT) is widely used to induce or augment labor with little understanding of the impact on offspring development. In rodent models, including the prairie vole (Microtus ochrogaster), it has been shown that oxytocin administered to mothers can affect the nervous system of the offspring with long lasting behavioral effects especially on sociality. Here, we examined the hypothesis that perinatal oxytocin exposure could have epigenetic and transcriptomic consequences. Prairie voles were exposed to exogenous oxytocin, through injections given to the mother just prior to birth, and were studied at the time of weaning. The outcome of this study revealed increased epigenetic age in oxytocin-exposed animals compared to the saline-exposed group. Oxytocin exposure led to 900 differentially methylated CpG sites (annotated to 589 genes), and 2 CpG sites (2 genes) remained significantly different after correction for multiple comparisons. Differentially methylated CpG sites were enriched in genes known to be involved in regulation of gene expression and neurodevelopment. Using RNA-sequencing we also found 217 nominally differentially expressed genes (p<0.05) in nucleus accumbens, a brain region involved in reward circuitry and social behavior; after corrections for multiple comparisons 6 genes remained significantly differentially expressed. Finally, we found that maternal oxytocin administration led to widespread alternative splicing in the nucleus accumbens. These results indicate that oxytocin exposure during birth may have long lasting epigenetic consequences. A need for further investigation of how oxytocin administration impacts development and behavior throughout the lifespan is supported by these outcomes.

Neurophysin I is an analytically robust surrogate biomarker for oxytocin.

Oxytocin is a pleiotropic neuropeptide that plays roles in biological processes ranging from birth, lactation, and social bonding to immune function, cardiovascular repair, and regulation of appetite. Although measurements of endogenous oxytocin concentrations have been performed for more than 50 years, the ability to measure oxytocin accurately poses notable challenges. One potential solution for overcoming these challenges involves measurement of oxytocin's carrier molecule - neurophysin I (NP-1) - as a surrogate biomarker. NP-1 is secreted in equimolar concentrations with oxytocin but has a longer half-life, circulates in higher concentrations, and can be measured using a sandwich immunoassay. We report experiments that 1) analytically validate a commercially available NP-1 sandwich immunoassay for use with human plasma and urine samples, 2) confirm the specificity of this assay, based on detection of NP-1 in plasma from wild-type but not oxytocin knockout mice, 3) demonstrate that NP-1 concentrations are markedly elevated in late pregnancy, consistent with studies showing substantial increases in plasma oxytocin throughout gestation, and 4) establish strong correlation between NP-1 and plasma oxytocin concentrations when oxytocin is measured in extracted (but not non-extracted) plasma. The NP-1 assay used in this study has strong analytical properties, does not require time-intensive extraction protocols, and the assay itself can be completed in < 2 h (compared to 16-24 h for a competitive oxytocin immunoassay). Our findings suggest that much like copeptin has become a useful surrogate biomarker in studies of vasopressin, measurements of NP-1 have similar potential to advance oxytocin research.

Feasibility Study to Compare Oxytocin Function Between Body Mass Index Groups at Term Labor Induction.

OBJECTIVE: To determine the feasibility of a protocol to examine the association between oxytocin system function and birth outcomes in women with and without obesity before induction of labor. DESIGN: Prospective descriptive. SETTING: Academic medical center in the U.S. Midwest. PARTICIPANTS: Pregnant women scheduled for induction of labor at 40 weeks of gestation or greater (n = 15 normal weight; n = 15 obese). METHODS: We collected blood samples and abstracted data by chart review. We used percentages to examine adherence to protocol. We used t tests and chi-square tests to describe differences in sample characteristics, oxytocin system function variables, and birth outcomes between the body mass index groups. RESULTS: The recruitment rate was 85.7%, protocol adherence was 97.1%, and questionnaire completion was 80.0%. Mean plasma oxytocin concentration was higher in the obese group (M = 2774.4 pg/ml, SD = 797.4) than in the normal weight group (M = 2193.5 pg/ml, SD = 469.8). Oxytocin receptor DNA percentage methylation (CpG -934) was higher in the obese group than in the normal weight group. CONCLUSION: Our protocol was feasible and can serve as a foundation for estimating sample sizes in forthcoming studies investigating the diversity in oxytocin system measurements and childbirth outcomes among pregnant women in different body mass index categories.

Feasibility of Stress Research in Premature Infant-Maternal Dyads During and After Neonatal Intensive Care Unit Hospitalization.

BACKGROUND: Stress from preterm infant admission to the neonatal intensive care unit (NICU) is associated with infant and maternal physiologic changes, including endocrine and epigenetic alterations. Little is known about the mechanisms connecting NICU stress to biologic changes, and whether preterm infant and maternal stress are reciprocal. As a preliminary step, feasibility and acceptability of measuring indicators of stress are required. PURPOSE: This study evaluated the feasibility and acceptability of research examining perceptions and biologic markers of stress in premature infant-maternal dyads during and after NICU hospitalization. METHODS: We evaluated study feasibility using a longitudinal descriptive design. Acceptability was measured via a maternal questionnaire. Exploratory data regarding hospitalization, perceptions of stress, social support and social determinants of health, and biologic markers of stress were collected during the first week of life and again 3 months after NICU. RESULTS: Forty-eight mothers were eligible for the study, 36 mothers were approached, 20 mothers consented to participate, and 14 mothers completed data collection. Mothers reported high levels of study acceptability despite also voicing concern about the sharing of genetic data. Exploration of DNA methylation of SLC6A4 in preterm infants was significant for a strong correlation with perception of total chronic stress. IMPLICATIONS FOR PRACTICE AND RESEARCH: Clinical practice at the bedside in the NICU should include standardized screening for and early interventions to minimize stress. Complex research of stress is feasible and acceptable. Future research should focus on linking early life stress with epigenetic alterations and evaluation of the dyad for reciprocity.

Transcriptional diversity of the oxytocin receptor in prairie voles: mechanistic implications for behavioral neuroscience and maternal physiology.

The neurohormone oxytocin regulates many aspects of physiology primarily by binding to its receptor, the oxytocin receptor. The oxytocin receptor gene (Oxtr) has been shown to have alternative transcripts in the mouse brain which may each have different biological functions or be used in specific contexts. A popular animal model for studying oxytocin-dependent social behaviors is the prairie vole, a biparental and monogamous rodent. Alternative transcriptional capacity of Oxtr in prairie voles is unknown. We used 5' rapid amplification of cDNA ends to identify alternative Oxtr transcription start sites in prairie vole brain tissue and uterine tissue. We then validated expression of specific transcripts in fetal brains and assessed the impact of exogenous oxytocin administration in utero on offspring brain development. We identified seven distinct Oxtr transcripts, all of which are present in both brain and uterine tissue. We then demonstrated that maternal oxytocin administration alters expression of a specific subset of Oxtr transcripts and that these different transcripts are under unique epigenetic regulation, such that in the perinatal period only one of the alternative transcripts is associated with DNA methylation in the Oxtr promoter. These data establish the existence of multiple Oxtr transcripts in prairie vole brain and uterine tissue and implicate oxytocin in the regulation of alternative transcript expression. These data have significant implications for our understanding of null mutant models in both mice and voles and translation in human birth and behavior.

Sex and hormonal status influence the anxiolytic-like effect of oxytocin in mice.

Anxiety and depression are highly prevalent psychiatric disorders, affecting approximately 18% of the United States population. Evidence indicates that central oxytocin mediates social cognition, social bonding, and social anxiety. Although it is well-established that oxytocin ameliorates social deficits, less is known about the therapeutic effects of oxytocin in non-social contexts. We hypothesized that positive effects of oxytocin in social contexts are attributable to intrinsic effects of oxytocin on neural systems that are related to emotion regulation. The present study investigated the effect of intracerebroventricular (ICV) oxytocin administration (i.e., central action) on anxiety- and depression-like behavior in C57Bl/6J mice using non-social tests. Male and female mice received an ICV infusion of vehicle or oxytocin (100, 200, or 500 ng), then were tested in the elevated zero maze (for anxiety-like behavior) and the tail suspension test (for depression-like behavior). Oxytocin dose-dependently increased open zone occupancy and entries in the elevated zero maze and reduced immobility duration in the tail suspension test in both sexes. Oxytocin decreased anxiety and depression-like behavior in male and female mice. The observed effect of oxytocin on anxiolytic-like behavior appeared to be driven by the males. Given the smaller anxiolytic-like effect of oxytocin in the female mice and the established interaction between oxytocin and reproductive hormones (estrogen and progesterone), we also explored whether oxytocin sensitivity in females varies across estrous cycle phases and in ovariectomized females that were or were not supplemented with estrogen or progesterone. Oxytocin reduced anxiety-like behavior in female mice in proestrus/estrus, ovariectomized females (supplemented or not with estrogen or progesterone), but not females in metestrus/diestrus. Additionally, oxytocin reduced depression-like behavior in all groups tested with slight differences across the various hormonal statuses. These results suggest that the effect of oxytocin in depression- and anxiety-like behavior in mice can be influenced by sex and hormonal status.

Close encounters with oxytocin.

The purpose of this narrative review is to use a personal perspective to describe unanticipated and pivotal findings that drew the author into the study oxytocin. Oxytocin was originally described as a "female reproductive hormone." However, supporting reproduction is only one of a myriad of functions now attributed to oxytocin. Oxytocin promotes survival and resilience in both sexes and across the lifespan, especially in the context of stress or trauma and helps to explain the health benefits of relationships. Oxytocin works in the context of individual histories and in conjunction with other molecules, as well as the autonomic nervous system and immune factors. The chemical properties of oxytocin make it biologically active, but difficult to measure. As a deeper understanding of the biology of oxytocin is emerging, we may use knowledge of the properties of oxytocin to uncover adaptive strategies that protect and heal in the face of stress and adversity in both males and females.

Father's care uniquely influences male neurodevelopment.

Mammalian infants depend on parental care for survival, with numerous consequences for their behavioral development. We investigated the epigenetic and neurodevelopmental mechanisms mediating the impact of early biparental care on development of alloparenting behavior, or caring for offspring that are not one's own. We find that receiving high parental care early in life leads to slower epigenetic aging of both sexes and widespread male-specific differential expression of genes related to synaptic transmission and autism in the nucleus accumbens. Examination of parental care composition indicates that high-care fathers promote a male-specific increase in excitatory synapses and increases in pup retrieval behavior as juveniles. Interestingly, females raised by high-care fathers have the opposite behavioral response and display fewer pup retrievals. These results support the concept that neurodevelopmental trajectories are programmed by different features of early-life parental care and reveal that male neurodevelopmental processes are uniquely sensitive to care by fathers.

The relationship between endogenous oxytocin and vasopressin levels and the Prader-Willi syndrome behaviour phenotype.

Background: Oxytocin and vasopressin systems are altered in Prader Willi syndrome (PWS). However, investigations into endogenous oxytocin and vasopressin levels as well as clinical trials evaluating the effect of exogenous oxytocin on PWS symptoms have had mixed results. It is also unknown whether endogenous oxytocin and vasopressin levels are associated with certain PWS behaviours. Method: We compared plasma oxytocin and vasopressin and saliva oxytocin levels in 30 adolescents and adults with PWS to 30 typically developing age-matched controls. We also compared neuropeptide levels between gender and genetic subtypes within the PWS cohort and examined the relationship between neuropeptide levels and PWS behaviours. Results: While we did not measure a group difference in plasma or saliva oxytocin levels, plasma vasopressin was significantly lower in individuals with PWS compared to controls. Within the PWS cohort, saliva oxytocin levels were higher in females compared to males and individuals with the mUPD compared to the deletion genetic subtype. We also found the neuropeptides correlated with different PWS behaviours for males and females and for genetic subtypes. For the deletion group, higher plasma and saliva oxytocin levels were related to fewer behaviour problems. For the mUPD group, higher plasma vasopressin levels were related to more behaviour problems. Conclusion: These findings support existing evidence of a vasopressin system defect in PWS and for the first time identify potential differences in the oxytocin and vasopressin systems across PWS genetic subtypes.

Lasting consequences on physiology and social behavior following cesarean delivery in prairie voles.

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.

Neuroanatomical and functional consequences of oxytocin treatment at birth in prairie voles.

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 prior to birth. 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.

Sex matters: The impact of oxytocin on healthy conditions and psychiatric disorders.

Oxytocin (OT) is involved in the regulation of physiological processes and emotional states, with increasing evidence for its beneficial actions being mediated by the autonomic and immune systems. Growing evidence suggests that OT plays a role in the pathophysiology of different psychiatric disorders. Given the limited information in humans the aim of this study was to retrospectively explore plasma OT levels in psychiatric patients, particularly focusing on sex-related differences, as compared with healthy controls. The patients studied here were divided into three groups diagnosed with obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD) or major depressive disorder (MDD). Plasma OT levels were significantly different between healthy men and women, with the latter showing higher values, while none of the three psychiatric groups showed sex-related differences in the parameters measured here. The intergroup analyses showed that the OT levels were significantly higher in OCD, lower in PTSD and even more reduced in MDD patients than in healthy subjects. These differences were also confirmed when gender was considered, with the exception of PTSD men, in whom OT levels were similar to those of healthy men. The present results indicated that OT levels were higher amongst healthy women than men, while a sex difference was less apparent or reversed in psychiatric patients. Reductions in sex differences in psychopathologies may be related to differential vulnerabilities in processes associated with basic adaptive and social functions.

Sex, love and oxytocin: Two metaphors and a molecule.

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."

Love and fear: A special issue.

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 Comprehensive Psychoneuroendocrinology focuses specifically on the causes and consequences of love from the interactive perspectives of evolution, neurobiology and culture.

Early Life Trauma and Social Processing in HIV: The Role of Neuroendocrine Factors and Inflammation.

OBJECTIVE: Early 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. METHODS: We 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. RESULTS: Of 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 ß [ 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). CONCLUSIONS: Our 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.

Oxytocin and oxygen: the evolution of a solution to the 'stress of life'.

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'.

Evaluating the neuropeptide-social cognition link in ageing: the mediating role of basic cognitive skills.

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'.

What are oxytocin assays measuring? Epitope mapping, metabolites, and comparisons of wildtype & knockout mouse urine.

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.

Longitudinal tracking of human plasma oxytocin suggests complex responses to moral elevation.

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.