Baseline Oxytocin Research Articles

Relationship of plasma oxytocin levels to baseline symptoms and symptom changes during three weeks of daily oxytocin administration in people with schizophrenia

Several clinical studies have found an inverse relationship between clinical symptoms and peripheral oxytocin (OT) levels in people with schizophrenia. As oxytocin is a putative treatment for schizophrenia, the effect of repeated dosing of OT on OT levels, clinical symptoms and the relationship between the two is of interest. In a, randomized, double blind, parallel group 3week study (N=28) with daily administration of intranasal OT (20IU twice daily) or placebo (PBO), we examined the effect of OT administration on the correlation between the change in peripheral OT levels and change in clinical symptoms in patients with schizophrenia. At baseline, there were no significant treatment group differences in OT levels. There were no significant associations between baseline OT levels and any symptom measures. After 3weeks of OT/PBO dosing, there was no significant difference in the magnitude of change in OT levels between the two treatment groups. Correlations between changes in peripheral OT levels and changes in the BPRS total and negative symptom scores were not different between treatment groups. Larger studies are needed to examine the effect of exogenous OT on peripheral OT levels and the relationship between the latter and clinical symptoms.Clinical Trials.gov=NCT00884897.

Oxytocin is associated with infant-care behavior and motivation in cooperatively breeding marmoset monkeys

The neurohormone oxytocin (OT) is positively involved in the regulation of parenting and social bonding in mammals, and may thus also be important for the mediation of alloparental care. In cooperatively breeding marmosets, infants are raised in teamwork by parents and adult and sub-adult non-reproductive helpers (usually older siblings). Despite high intrinsic motivation, which may be mediated by hormonal priming, not all individuals are always equally able to contribute to infant-care due to competition among care-takers. Among the various care-taking behaviors, proactive food sharing may reflect motivational levels best, since it can be performed ad libitum by several individuals even if competition among surplus care-takers constrains access to infants. Our aim was to study the link between urinary OT levels and care-taking behaviors in group-living marmosets, while taking affiliation with other adults and infant age into account. Over eight reproductive cycles, 26 individuals were monitored for urinary baseline OT, care-taking behaviors (baby-licking, -grooming, -carrying, and proactive food sharing), and adult-directed affiliation. Mean OT levels were generally highest in female breeders and OT increased significantly in all individuals after birth. During early infancy, high urinary OT levels were associated with increased infant-licking but low levels of adult-affiliation, and during late infancy, with increased proactive food sharing. Our results show that, in marmoset parents and alloparents, OT is positively involved in the regulation of care-taking, thereby reflecting the changing needs during infant development. This particularly included behaviors that are more likely to reflect intrinsic care motivation, suggesting a positive link between OT and motivational regulation of infant-care.

Relations between plasma oxytocin and cortisol: The stress buffering role of social support

Stress responses in humans can be attenuated by exogenous oxytocin administration, and these stress-buffering properties may be moderated by social factors. Yet, the influence of acute stressors on circulating endogenous oxytocin levels have been inconsistent, and limited information is available concerning the influence of social support in moderating this relationship. In the current investigation, undergraduate women (N = 67) were assessed in the Trier Social Stress Test (TSST) with either social support available from a close female friend or no social support being available. An additional set of women served as controls. The TSST elicited marked elevations of state anxiety and negative emotions, which were largely attenuated among women who received social support. Furthermore, baseline oxytocin levels were inversely related to women's general feelings of distrust, as well as basal plasma cortisol levels. Despite these associations, oxytocin levels were unaffected by the TSST, and this was the case irrespective of oral contraceptive use or estrogen levels. In contrast, plasma cortisol elevations were elicited by the psychosocial stressor, but only in women using oral contraceptives, an effect that was prevented when social support was available. Taken together, these data provisionally suggest that changes in plasma oxytocin might not accompany the stress attenuating effects of social support on cortisol levels. Moreover, as plasma oxytocin might not reliably reflect brain oxytocin levels, the linkage between oxytocin and prosocial behaviors remains tenuous.

Involvement of the oxytocin system in the bed nucleus of the stria terminalis in the sex-specific regulation of social recognition

Sex differences in the oxytocin (OT) system in the brain may explain why OT often regulates social behaviors in sex-specific ways. However, a link between sex differences in the OT system and sex-specific regulation of social behavior has not been tested. Here, we determined whether sex differences in the OT receptor (OTR) or in OT release in the posterior bed nucleus of the stria terminalis (pBNST) mediates sex-specific regulation of social recognition in rats. We recently showed that, compared to female rats, male rats have a three-fold higher OTR binding density in the pBNST, a sexually dimorphic area implicated in the regulation of social behaviors. We now demonstrate that OTR antagonist (5ng/0.5μl/side) administration into the pBNST impairs social recognition in both sexes, while OT (100pg/0.5μl/side) administration into the pBNST prolongs the duration of social recognition in males only. These effects seem specific to social recognition, as neither treatment altered total social investigation time in either sex. Moreover, baseline OT release in the pBNST, as measured with in vivo microdialysis, did not differ between the sexes. However, males showed higher OT release in the pBNST during social recognition compared to females. These findings suggest a sex-specific role of the OT system in the pBNST in the regulation of social recognition.

Strongly bonded family members in common marmosets show synchronized fluctuations in oxytocin

Oxytocin is a key regulator of social bonding and is positively linked to affiliation and prosocial behavior in several mammal species. In chimpanzees, this link is dyad-specific as affiliative interactions only elicit high oxytocin release if they involve strongly bonded individuals. These studies involved isolated dyads and sampling events. Little is known about the role of oxytocin in affiliation and social bonding, and about potential long-term patterns of bonding-related and dyad-specific oxytocin effects within highly affiliative and cooperative social groups. Our aim was to investigate whether bonding-related oxytocin signatures linked to dyadic affiliation are present in family groups of cooperatively breeding marmoset monkeys (Callithrix jacchus) that show high levels of cohesion and cooperation. In 30 dyads from four family groups and one pair, we measured urinary baseline oxytocin over six weeks and analyzed the link to bond strength (mean dyadic affiliation). Strongly bonded dyads showed synchronized longitudinal fluctuations of oxytocin, indicating that dyad-specific oxytocin effects can also be traced in the group context and in an interdependent species. We discuss these results in light of the potential function of differentiated relationships between marmoset dyads other than the breeding pair, and the role of oxytocin as a mediator for social bonding.

Changes in social functioning and circulating oxytocin and vasopressin following the migration to a new country

Prior studies have reported associations between plasma oxytocin and vasopressin and markers of social functioning. However, because most human studies have used cross-sectional designs, it is unclear whether plasma oxytocin and vasopressin influences social functioning or whether social functioning modulates the production and peripheral release of these peptides. In order to address this question, we followed individuals who experienced major changes in social functioning subsequent to the migration to a new country. In this study, 59 new international students were recruited shortly after arrival in the host country and reassessed 2 and 5months later. At each assessment participants provided information on their current social functioning and blood samples for oxytocin and vasopressin analysis. Results indicated that changes in social functioning were not related to changes in plasma oxytocin. Instead, baseline oxytocin predicted changes in social relationship satisfaction, social support, and loneliness over time. In contrast, plasma vasopressin changed as a function of social integration. Baseline vasopressin was not related to changes in social functioning over time. These results emphasize the different roles of plasma oxytocin and vasopressin in responses to changes in social functioning in humans.

Parent-child interaction and oxytocin production in pre-schoolers with autism spectrum disorder.

Autism spectrum disorder (ASD) is associated with genetic risk on the oxytocin system, suggesting oxytocin involvement in ASD; yet oxytocin functioning in young children with ASD is unknown. To assess baseline oxytocin in pre-schoolers with ASD and test whether oxytocin production may be enhanced by parent-child contact. Forty pre-schoolers with high-functioning ASD were matched with 40 typically developing controls. Two home visits included an identical 45-minute social battery once with the mother and once with the father. Four saliva oxytocin samples were collected from each parent and the child during each visit. Children with ASD had lower baseline oxytocin. Following 20 min of parent-child interactions, oxytocin normalised and remained high during social contact. Fifteen minutes after contact, oxytocin fell to baseline. Oxytocin correlated with parent-child social synchrony in both groups. Oxytocin dysfunction in ASD is observed in early childhood. The quick improvement in oxytocin production following parent-child contact underscores the malleability of the system and charts future directions for attachment-based behavioural and pharmacological interventions.

Does oxytocin modulate variation in maternal caregiving in healthy new mothers?

BackgroundMaternal sensitivity to infant cues and developmental needs may be pivotal for social and cognitive development. Animal and recent human studies emphasise a major role for Oxytocin (OT) in mediating sensitive caregiving but no study has examined the relationship between OT and extreme variation in human maternal sensitivity. Methods: From 105 expectant mothers, 80 underwent blind-rating of maternal sensitivity at 4–6 months postpartum through free-play interaction with their infants. At 7–9 months postpartum, 30 mothers at extremes of maternal sensitivity: 15 ‘sensitive mothers’ (high sensitivity mothers – HSMs, mean=4.47; SD=0.74) and 15 ‘less sensitive mothers’ (low sensitivity mothers – LSMs, mean=2.13; SD=0.52) underwent plasma OT measurements before and after 10min infant play. Results: Baseline and post-interaction plasma OT was higher in LSMs than HSMs [F(1, 26)=8.42; p=0.01]. HSMs showed a trend towards significant reduction in plasma OT [t(14)=2.01; p=0.06] following play-interaction; no change was shown by LSMs [t(13)=−0.14; p=0.89]. Conclusion Higher baseline OT levels in healthy LSMs may imply greater stress responses to the demands of caring for an infant, or past deficiencies in own parenting relationship and act as a biomarker for poor parental sensitivity. OT may be acting to reduce stress and anxiety in LSMs consistent with studies of plasma OT and stress in women. By contrast, in HSMs, play interaction with their infants maybe relaxing as indicated by significant reduction in plasma OT from baseline. Ascertainment of mothers in well-defined sensitivity groups might facilitate examination of distinct coping strategies in parents and better understanding of variation in parental caregiving behaviour and its potential for modulation by OT.This article is part of a Special Issue entitled Oxytocin and Social Behav.

Plasma oxytocin changes and anti-obsessive response during serotonin reuptake inhibitor treatment: a placebo controlled study

BackgroundThe drug treatments of choice for obsessive-compulsive disorder (OCD) are serotonin reuptake inhibitors (SRIs). However, a correlation between the neuropeptide oxytocin in cerebrospinal fluid and the severity of OCD has previously been shown, and oxytocin and serotonin are interconnected within the brain. Few studies have investigated whether SRIs have any effect on oxytocin; thus, our aim was to explore the possibility that oxytocinergic mechanisms contribute to the anti-obsessive effect of SRIs.MethodIn a randomized, double-blind trial, comparing SRIs (clomipramine and paroxetine) with placebo in 36 adults with OCD (characterized for subtypes), plasma oxytocin was measured with radioimmunoassay after plasma extraction, at baseline, after 1 week, and after 4 weeks of treatment, and related to baseline severity and clinical response after 12 weeks, as measured by the Yale-Brown Obsessive Compulsive Scale (Y-BOCS).ResultsBaseline oxytocin levels correlated positively with baseline Y-BOCS ratings, but only among the future SRI responders. Patients with early onset of OCD had higher baseline oxytocin. During treatment, plasma oxytocin did not differ between SRI and placebo treatment. In SRI responders, plasma oxytocin first decreased and then increased; in non-responders (to SRI as well as to placebo), the reverse was the case. After 4 weeks, treatment responders had attained higher oxytocin levels compared to non-responders. The intra-individual range (i.e. the variability) of plasma oxytocin between measurements was the measure that best differentiated responders from non-responders. This range was higher in responders than non-responders, and lower in patients with autistic traits.ConclusionsSRIs have highly variable effects on plasma oxytocin between individuals. The associations between baseline oxytocin and OCD severity and between oxytocin changes and treatment response support the notions that oxytocin is involved in OCD pathophysiology, and that the anti-obsessive effects of SRIs are partly exerted through oxytocinergic mechanisms.

Oxytocin and Vasopressin Are Dysregulated in Williams Syndrome, a Genetic Disorder Affecting Social Behavior

The molecular and neural mechanisms regulating human social-emotional behaviors are fundamentally important but largely unknown; unraveling these requires a genetic systems neuroscience analysis of human models. Williams Syndrome (WS), a condition caused by deletion of ∼28 genes, is associated with a gregarious personality, strong drive to approach strangers, difficult peer interactions, and attraction to music. WS provides a unique opportunity to identify endogenous human gene-behavior mechanisms. Social neuropeptides including oxytocin (OT) and arginine vasopressin (AVP) regulate reproductive and social behaviors in mammals, and we reasoned that these might mediate the features of WS. Here we established blood levels of OT and AVP in WS and controls at baseline, and at multiple timepoints following a positive emotional intervention (music), and a negative physical stressor (cold). We also related these levels to standardized indices of social behavior. Results revealed significantly higher median levels of OT in WS versus controls at baseline, with a less marked increase in AVP. Further, in WS, OT and AVP increased in response to music and to cold, with greater variability and an amplified peak release compared to controls. In WS, baseline OT but not AVP, was correlated positively with approach, but negatively with adaptive social behaviors. These results indicate that WS deleted genes perturb hypothalamic-pituitary release not only of OT but also of AVP, implicating more complex neuropeptide circuitry for WS features and providing evidence for their roles in endogenous regulation of human social behavior. The data suggest a possible biological basis for amygdalar involvement, for increased anxiety, and for the paradox of increased approach but poor social relationships in WS. They also offer insight for translating genetic and neuroendocrine knowledge into treatments for disorders of social behavior.

Molecular, Immunohistochemical, and Pharmacological Evidence of Oxytocin’s Role as Inhibitor of Carbohydrate But Not Fat Intake

Oxytocin (OT) facilitates feeding termination stemming from high osmolality, stomach distention, and malaise. Recent knockout (KO) studies suggested a crucial function for OT in carbohydrate intake: OT-/- mice had increased preference for carbohydrates, including sucrose, but not fat (Intralipid). In striking contrast, sugar appetite was unaffected in the OT receptor KO mouse; data from wild-type animals have been insufficient. Therefore, we examined the involvement of OT in the regulation of sucrose vs. fat intake in C57BL/6 mice that served as a background KO strain. We exposed mice to a meal of sucrose or Intralipid and determined that the percentage of c-Fos-immunoreactive paraventricular hypothalamic OT neurons was elevated at termination of intake of either of the tastants, but this increase was 2-fold higher in sucrose-fed mice. A 48-h exposure to sucrose compared with Intralipid caused up-regulation of OT mRNA, whereas inherent individual preferences for sucrose vs. fat were not associated with differences in baseline OT expression as established with quantitative PCR. We found that L-368,899, an OT receptor antagonist, increased sugar intake when sucrose was presented alone or concurrently with Intralipid; it had no effect on Intralipid or total calorie consumption. L-368,899 affected Fos immunoreactivity in the paraventricular hypothalamus, arcuate nucleus, amygdala, and nucleus of the solitary tract, areas involved in aversion, satiety, and reward. This pattern serves as neuroanatomical basis of OT's complex role in food intake, including sucrose intake. The current findings expand our knowledge on OT and suggest that it acts as a carbohydrate-specific inhibitor of feeding.

More frequent partner hugs and higher oxytocin levels are linked to lower blood pressure and heart rate in premenopausal women

In animals, ventral stroking for >5 days increases oxytocin (OT) activity and decreases blood pressure (BP), but related human studies are few. Thus, relationships between self-reported frequency of partner hugs, plasma OT and BP levels were examined in 59 premenopausal women before and after warm contact with their husbands/partners ending with hugs. Higher baseline OT before partner contact was associated with lower BP and heart rate, and met criteria to be a partial mediator of the lower resting BP shown by women reporting more frequent hugs ( P < 0.05). OT levels during post-contact stress were unrelated to hugs or BP. Menstrual cycle phase did not influence any OT measure. Thus, frequent hugs between spouses/partners are associated with lower BP and higher OT levels in premenopausal women; OT-mediated reduction in central adrenergic activity and peripheral effects of OT on the heart and vasculature are pathways to examine in future research.

Effects of Cleaning Duration and Water Temperature on Oxytocin Release and Milk Removal in an Automatic Milking System

Four different methods of teat preparation during milking in an automatic milking system were studied in 2 experiments on Red Holstein/German Fleckvieh cross-breed cows. Milking routines used were milking: 1) without premilking teat preparation; 2) with one cleaning cycle (58 to 60s) with cold (13 to 15°C) water; 3) with one cleaning cycle with warm water (30 to 32°C); or 4) with 2 cleaning cycles (122s) with warm water. In experiment 1, milking characteristics were evaluated and milking routines were randomly assigned to 62 cows during 3 measuring periods of 24h each. In experiment 2, 10 randomly selected cows were assigned to the same milking routines during 4 d and blood samples for oxytocin (OT) determination were taken during milking in addition to milk flow recording. Milk production, peak flow rate, total, and quarter milk yields showed no differences among treatments. Premilking preparation with cold water compared with warm water showed no differences in OT release, milk yield, peak flow rate, main milking time, average flow rate, or time until main milk flow. Baseline OT concentrations were consistently low. At the start of teat cup attachment without premilking teat preparation OT concentrations remained on the basal level but were elevated in all other treatments. By 30s from the start of milking, OT concentrations were markedly increased in all treatments and were no longer different between treatments. In conclusion, the teat cleaning device used in the automatic milking system, either with warm or cold water, was suitable to induce milk ejection in cows before the start of milking.

Oxytocin release and milk ejection parameters during milking of dairy ewes in and out of natural season of lactation

Two groups of 40 milking Lacaune ewes were monitored during their natural (spring) and off-season (autumn) lactation. Serial samples collected before, during and after milkings were used to study oxytocin release in relation to milk flow patterns recorded during milking. Overall, oxytocin release was significant in 92.5% of the ewes but only 56% of them exhibited clear alveolar milk ejection. Oxytocin is essential for milk ejection but no correlation between oxytocin ejection and milk fraction volumes of milking was detected. Baseline oxytocin and progesterone concentrations and the proportion of cisternal milk were significantly higher in autumn than in spring. It was concluded that clear alveolar emission of milk during milk flow recordings are not reliable indicators of milk ejection efficiency in high producing animals with large cisternal volumes. Likewise, the amount of oxytocin released during milking cannot be used to select the animals best adapted to machine milking or the best producers. Nevertheless, this study suggests that luteal oxytocin has a major role in milk transfer between milkings.

Estrogenic activity of RU 486 (mifepristone) in rat uterus and cultured uterine myocytes

OBJECTIVE: Our purpose was to determine whether RU 486 (mifepristone) has direct estrogenic activity in uterine myocytes. STUDY DESIGN: Ovariectomized adult rats were treated with RU 486, and its effect on uterine oxytocin receptor concentration, as a marker of estrogenic activity, was measured. Results were compared with th induction by RU 486 of an estrogen-responsive reporter gene in a cultured Syrian hamster uterine myocyte cell line. RESULTS: Baseline oxytocin receptor concentration was 58.8 ± 7.2 fmol/mg protein (mean ± SEM) and increased to 227 ± 49 fmol/mg with 17β-estradiol (2.5 μg/kg) and to 145 ± 18 fmol/mg afte RU 486 (5 mg/kg) treatment, an effect that was inhibited by the antiestrogen ICI 182,780 (1.5 mg/kg). In the cultured Syrian hamster uterine myocyte cell line cells RU 486 (10 −6 mol/L) caused a 2.17 ± 0.17-fold increase in the expression of the reporter gene versus 113.0 ± 7.4-fold with 17β-estradiol (10 −8 mol/L). The estrogenic activity of RU 486 was dependent on the presence of both estrogen receptor and the promoter's estrogen response element. CONCLUSION: RU 486 has a weak estrogen-like activity in uterine myocytes. This activity may partly explain the therapeutic effects of RU 488 on this target organ.

Teat stimulation-induced oxytocin and catecholamine release in pregnant and lactating holstein heifers

The effect of manual teat stimulation (milking paradigm) on release of oxytocin, epinephrine and norepinephrine was studied in (1) 15 heifers at 100, 150, 200 and 250 d of gestation and at 30 and 90 d of lactation (during machine milking) and (2) simultaneously in six heifers at <100 d and in six heifers at >200 d of gestation. Oxytocin responses to teat stimulation, including peak heights and area under the response curves, at 150, 200 and 250 d or at >200 d of gestation were similar and were significantly greater than responses at 100 d or at <100 d. Responses to milking were lower at 90 d compared to responses at 30 d. Catecholamines were measured only during gestation and were generally not affected by teat stimulation. Epinephrine levels were significantly higher at 200 and 250 d compared to levels at 100 and 150 d. Baseline oxytocin concentrations and responses to teat stimulation were greatest at 150 d of gestation when epinephrine levels were still low, suggesting that stimulatory mechanisms responsible for the release of oxytocin develop and/or are expressed prior to the development of inhibitory sympathetic mechanisms. For norepinephrine, linear analyses did not show significant responses to teat stimulation overall. However, elevated norepinephrine responses (>.2 pmol/ml) following teat stimulation were seen in 28 of 51 trials, and large oxytocin responses (>75 pg/ml/min) were seen predominantly only when norepinephrine responses were low (<=.2 pmol/ml).