Human endogenous oxytocin and its neural correlates show adaptive responses to social touch based on recent social context.

Both oxytocin (OT) and touch are key mediators of social attachment. In rodents, tactile stimulation elicits the endogenous release of OT, potentially facilitating attachment and other forms of prosocial behavior, yet the relationship between endogenous OT and neural modulation remains unexplored in humans. Using a serial sampling of plasma hormone levels during functional neuroimaging across two successive social interactions, we show that contextual circumstances of social touch influence not only current hormonal and brain responses but also later responses. Namely, touch from a male to his female romantic partner enhanced her subsequent OT release for touch from an unfamiliar stranger, yet females' OT responses to partner touch were dampened following stranger touch. Hypothalamus and dorsal raphe activation reflected plasma OT changes during the initial social interaction. In the subsequent interaction, precuneus and parietal-temporal cortex pathways tracked time- and context-dependent variables in an OT-dependent manner. This OT-dependent cortical modulation included a region of the medial prefrontal cortex that also covaried with plasma cortisol, suggesting an influence on stress responses. These findings demonstrate that modulation between hormones and the brain during human social interactions can flexibly adapt to features of social context over time.

Neuroendocrine mechanisms involved in the physiological effects caused by skin-to-skin contact - With a particular focus on the oxytocinergic system.

The positive clinical effects caused by skin-to-skin contact immediately after birth or after repeated skin-to-skin contact of premature infants (kangaroo care) or fullterm infants are well documented in the literature. However, information regarding the physiological mechanisms mediating these effects are surprisingly scarce and incomplete. In this article the oxytocinergic system and the cutaneous sensory pathways by which the oxytocinergic system is activated in response to skin-to-skin contact are presented in more detail. In addition, we discuss how the effects of skin-to-skin treatment can be attributed to different aspects of the effect spectrum of the oxytocinergic or calm and connection system. The structure of the oxytocinergic system, comprising the peripheral (circulating, hormonal) and the central (neurotransmitter) components, as well as, the pathways and mechanisms by which these functions are coordinated are described. Also the various effects induced by the oxytocinergic system (the calm and connection system) are reviewed. The sensory pathways, which include visual, auditory, olfactory and tactile stimuli, given and received by both mother and newborn and which activate the oxytocinergic system in response to skin-to-skin contact, are reviewed. A special emphasis is placed on the role of cutaneous sensory nerves and their activation by touch, light pressure and in particular warmth. The important role of the rise and the pulsatility of maternal temperature in mediating the positive effects of skin-to-skin contact in the newborn is highlighted. The concept of maternal giving of warmth and its possible link to the experience of trust and safety in the newborn is discussed from an evolutionary perspective. The effects induced by skin-to-skin contact can be attributed to the different functions of the oxytocinergic system. Ameliorated social interaction (e.g., more tactile and auditory interaction, more sensitive and synchronous interaction between mother and baby, the baby's crawling behavior) are expressions of oxytocin's ability to stimulate social interaction. The decreased levels of fear and stress are expressions of oxytocin's ability to reduce the activity of the amygdala and of the stress system, e.g. the activity in the HPA-axis and the sympathetic nervous system. Increased HRV, increased activity in endocrine system of the gastrointestinal tract as well as stimulation of growth and maturation are examples of oxytocin's ability to stimulate the activity of the parasympathetic nervous system and other peripheral and central mechanisms related to restoration and growth. The propensity of different types of treatment with skin-to-skin contact to induce long-term effects is also highlighted. We propose that the sustained effects caused by skin-to-skin contact are induced by an enduring shift in the balance between the oxytocinergic system (the calm and connection system) and the stress system (fight flight reaction) in favor of the oxytocinergic system. This shift leads to a sustained decrease in the HPA-axis and the sympathetic nervous system probably involving alpha 2-adrenoceptors. It is of clinical importance to be aware of the mechanisms by which skin-to-skin contact induces short and longterm positive effects in parents and newborns. If ward routines are adapted to ascertain a maximal stimulation of these mechanisms, the function of the oxytocinergic system will be optimized, which will be linked to a better clinical outcome for parents and newborns.

Genetic risk-factors for anxiety in healthy individuals: polymorphisms in genes important for the HPA axis.

BACKGROUND: Two important aspects for the development of anxiety disorders are genetic predisposition and alterations in the hypothalamic-pituitary-adrenal (HPA) axis. In order to identify genetic risk-factors for anxiety, the aim of this exploratory study was to investigate possible relationships between genetic polymorphisms in genes important for the regulation and activity of the HPA axis and self-assessed anxiety in healthy individuals. METHODS: DNA from 72 healthy participants, 37 women and 35 men, were included in the analyses. Their DNA was extracted and analysed for the following Single Nucleotide Polymorphisms (SNP)s: rs41423247 in the NR3C1 gene, rs1360780 in the FKBP5 gene, rs53576 in the OXTR gene, 5-HTTLPR in SLC6A4 gene and rs6295 in the HTR1A gene. Self-assessed anxiety was measured by the State and Trait Anxiety Inventory (STAI) questionnaire. RESULTS: Self-assessed measure of both STAI-S and STAI-T were significantly higher in female than in male participants (p = 0.030 and p = 0.036, respectively). For SNP rs41423247 in the NR3C1 gene, there was a significant difference in females in the score for STAI-S, where carriers of the G allele had higher scores compared to the females that were homozygous for the C allele (p < 0.01). For the SNP rs53576 in the OXTR gene, there was a significant difference in males, where carriers of the A allele had higher scores in STAI-T compared to the males that were homozygous for the G allele (p < 0.01). CONCLUSION: This study shows that SNP rs41423247 in the NR3C1 gene and SNP rs53576 in the OXTR gene are associated with self-assessed anxiety in healthy individuals in a gender-specific manner. This suggests that these SNP candidates are possible genetic risk-factors for anxiety.

Interacting With a Visiting Dog Increases Fingertip Temperature in Elderly Residents of Nursing Homes.

The aim of this study was to investigate whether interacting with a visiting dog influences fingertip temperature and cortisol levels in residents living in nursing homes for the elderly. The study included two groups, the dog group (n = 13) and the control group (n = 11-15) and lasted for 8 weeks for the dog group and 6 weeks for the control group. All participants were residents living at nursing homes for the elderly. The researchers visited small groups of the participants twice weekly during the entire study in both the dog and the control group. The visiting dog and the dog handler accompanied the researchers during weeks 3-6. Fingertip temperature was measured and saliva samples for cortisol determination were collected at 0, 20 and 60 min for the dog group and at 0 and 20 min for the control group. For analysis the study was divided into periods; Period 1 (week 1-2), Period 2 (week 3-4), Period 3 (week 5-6) and Period 4 (week 7-8, only the dog group). Mean values based on all data obtained at 0 and 20 min during period 1-3 were compared between groups. A second, separate analysis for the dog group also included data from 60 min and for period 4. For the dog group fingertip temperature increased significantly between period 1 and 2, 1 and 3 and 1 and 4 (p < 0.05). In addition, fingertip temperature rose significantly between 0 and 20 min and between 0 and 60 min within all periods. For the control group a significant decrease in fingertip temperature was observed between period 1 and 3 (p < 0.05). Fingertip temperature did not differ between the two groups during period 1, but was significantly higher for the dog group than for the control group during periods 2 and 3 (p < 0.05 and p < 0.001, respectively). Cortisol results are only presented descriptively due to that many samples had too low volume of saliva to be analyzed. In the present study interaction between elderly residents and a visiting dog resulted in increased fingertip temperature, probably reflecting a decrease in the activity of the sympathetic nervous system and therefore a decrease in stress levels.

The Effect of Mechanical Massage and Mental Training on Heart Rate Variability and Cortisol in Swedish Employees-A Randomized Explorative Pilot Study.

Work-related stress is relatively common in modern society and is a major cause of sick-leave. Thus, effective stress reducing interventions are needed. This study examined the effects of mental training and mechanical massage, on employee's heart rate variability (HRV) and plasma cortisol at their workplaces. Moreover, it was investigated whether baseline systolic blood pressure (SBP) can explain differences in effectiveness of the intervention. Ninety-three participants from four workplaces were randomly assigned to one of the five programs: (I) Mechanical massage and mental training combined, II) Mechanical massage, III) Mental training, IV) Pause, or V) Control. HRV and plasma cortisol were measured at baseline and after 4 and 8 weeks. SBP was measured at baseline. On the reduction of cortisol levels, a small effect of the mechanical massage program was found, whereas no effect was found for the other programs. None of the programs showed any effect on HRV. Nonetheless, when the level of systolic blood pressure was taken into account, some small beneficial effects on HRV and cortisol of mental training and the mechanical massage were found. This exploratory pilot-study provides useful information for future studies that aim to reduce stress among employees.

Oxytocin is a principal hormone that exerts part of its effects by active fragments.

Oxytocin is a nonapeptide consisting of a cyclic six amino-acid structure and a tail of three amino acids. It was originally known for its ability to induce milk ejection and to stimulate uterine contractions. More recently, oxytocin has been shown to stimulate social behaviors, and exert pain-relieving, anti-stress/anti-inflammatory and restorative effects. We hypothesize that oxytocin is a principal hormone that, in part, exerts its effects after degradation to active fragments with more specific effect profiles. Experimental findings on rats show that administered oxytocin exerts biphasic effects. For example, after an initial increase in pain threshold, a second more long-lasting increase follows. Blood pressure and cortisol levels initially increase and then reverse into a long-lasting decrease in blood pressure and cortisol. Whereas the initial effects are, the second-phase effects are not blocked by an oxytocin antagonist, but by an opioid mu-antagonist and by an alpha 2-adrenoreceptor antagonist, respectively, suggesting that other receptors are involved. Repeated administration of oxytocin induces multiple anti-stress effects, which are mediated by alpha 2-adrenoreceptors. Repeated administration of linear oxytocin and linear oxytocin fragments with a retained C-terminal reduce spontaneous motor activity, a sedative or anti-stress effect, suggesting that alpha 2-adrenoreceptors have been activated. In contrast, linear mid-fragments stimulate motor activity. Low-intensity stimulation of cutaneous nerves in rats, as well as breastfeeding and skin-to-skin contact between mothers and babies, trigger immediate anti-stress effects. Some of these effects are likely caused by open ring/linear C-terminal fragments activating alpha 2-adrenoreceptors. Oxytocin fragments may be pre-formed and released in the brain or created by metabolic conversion of the principal hormone oxytocin in the central nervous system. Oxytocin and its fragments may also be released from peripheral sites, such as peripheral nerves, the gastrointestinal tract, and blood vessels in response to decreased sympathetic or increased parasympathetic nervous tone. Smaller fragments of oxytocin produced in the periphery may easily pass the blood-brain barrier to induce effects in the brain. In conclusion, oxytocin is linked to many different, sometimes opposite effects. The intact cyclic molecule may act to initiate social interaction and associated psychophysiological effects, whereas linear oxytocin and C-terminal fragments may induce relaxation and anti-stress effects following social interaction. In this way, the principal hormone oxytocin and its fragments may take part in a behavioral sequence, ranging from approach and interaction to calm and relaxation. Linear fragments, with an exposed cysteine-residue, may exert anti-inflammatory and antioxidant effects and thereby contribute to the health-promoting effects of oxytocin.

Oxytocin and Cortisol Levels in Dog Owners and Their Dogs Are Associated with Behavioral Patterns: An Exploratory Study.

We have previously shown that dog-owner interaction results in increasing oxytocin levels in owners and dogs, decreasing cortisol levels in owners but increasing cortisol levels in dogs. The present study aimed to further investigate whether oxytocin and cortisol levels in the previously tested owners and dogs were associated with their behaviors during the interaction experiment. Ten female volunteer dog-owners and their male Labrador dogs participated in a 60 min interaction experiment with interaction taking place during 0-3 min and blood samples for analysis of oxytocin and cortisol were collected at 0, 1, 3, 5, 15, 30, and 60 min. The entire experiment was videotaped and the following variables were noted; the different types (stroking, scratching, patting and activating touch, i.e., scratching and patting combined) as well as the frequency of touch applied by the owner, the number of times the owner touched her dog, the dog's positions and time spent in each position. Correlations were analyzed between the behavioral variables and basal oxytocin levels, maximum oxytocin levels, delta oxytocin levels, basal cortisol levels and cortisol levels at 15 min. Owners with low oxytocin levels before and during the interaction touched their dogs more frequently (0 min: Rs = -0.683, p = 0.042; oxytocin maximum: Rs = -0.783, p = 0.013). The lower the dogs' oxytocin levels during the interaction, the more stroking they received (Rs = -0.717, p = 0.041). The more frequently activating touch was applied by the owner, the higher the dogs' cortisol levels became (15 min: Rs = 0.661, p = 0.038). The higher the owners' maximum oxytocin level the fewer position changes the dogs made (Rs = -0.817, p = 0.007) and the shorter time they spent sitting (Rs = -0.786, p = 0.036), whereas the higher the owners' basal cortisol levels, the longer time the dogs spent standing (0 min: Rs = 0.683, p = 0.041). In conclusion, oxytocin and cortisol levels, both in dogs and in their owners, are associated with the way the owners interact with their dogs and also with behaviors caused by the interaction.

Mechanical massage and mental training programmes affect employees' anxiety, stress susceptibility and detachment-a randomised explorative pilot study.

BACKGROUND: Working people's reduced ability to recover has been proposed as a key factor behind the increase in stress-related health problems. One not yet evidence-based preventive method designed to help employees keep healthy and be less stressed is an armchair with built-in mechanical massage and mental training programmes, This study aimed to evaluate possible effects on employees' experience of levels of "Anxiety", "Stress Susceptibility", "Detachment" and "Social Desirability" when using mechanical massage and mental training programmes, both separately and in combination, during working hours. METHODS: Employees from four different workplaces were randomly assigned to one of the following groups: i) Massage and mental training (sitting in the armchair and receiving mechanical massage while listening to the mental training programmes, n=19), ii) Massage (sitting in the armchair and receiving mechanical massage only, n=19), iii) Mental training (sitting in the armchair and listening to the mental training programmes only, n=19), iv) Pause (sitting in the armchair but not receiving mechanical massage or listening to the mental training programmes, n=19), v) Control (not sitting in the armchair at all, n=17). In order to discover how the employees felt about their own health they were asked to respond to statements from the "Swedish Scale of Personality" (SSP), immediately before the randomisation, after four weeks and after eight weeks (end-of-study). RESULTS: There were no significant differences between the five study groups for any of the traits studied ("Somatic Trait Anxiety", "Psychic Trait Anxiety", "Stress Susceptibility", "Detachment" and "Social Desirability") at any of the occasions. However, the massage group showed a significant decrease in the subscale "Somatic Trait Anxiety" (p=0.032), during the entire study period. Significant decreases in the same subscale were also observed in the pause group between start and week eight (p=0.040) as well as between week four and week eight (p=0.049) and also in the control group between the second and third data collection (p=0.014). The massage and mental training group showed a significant decrease in "Stress Susceptibility" between week four and week eight (p=0.022). The pause group showed a significant increase in the subscale "Detachment" (p=0.044). CONCLUSIONS: There were no significant differences between the five study groups for any of the traits studied. However, when looking at each individual group separately, positive effects in their levels of "Anxiety", "Stress Susceptibility" and "Detachment" could be seen. Although the results from this pilot study indicate some positive effects, mechanical chair massage and mental training programmes used in order to increase employee's ability to recover, needs to be evaluated further as tools to increase the employees ability to recover. AUSTRALIAN NEW ZEALAND CLINICAL TRIALS REGISTRY: ACTRN12615000020583 , Date of registration: 15/01/2015.

Dogs' endocrine and behavioural responses at reunion are affected by how the human initiates contact.

For dogs, humans are likely to be the most important feature in their environment influencing their welfare. To investigate a commonly occurring human­dog interaction, behavioural and endocrine responses of 12 female beagle dogs were measured before, upon and after the return of a familiar person. Each dog was left by the person in a test arena to which it had been habituated prior to the experiment. Three different treatments were applied when the person returned and each dog experienced all these in a balanced design; the familiar person entered the test arena and 1) initiated physical and verbal contact in a calm and friendly way (PV), 2) there was verbal contact only (V) or, as a 'control', 3) the person ignored the dog (C). Interaction continued for 4 min during which the person behaved in a standardized way according to the treatment. Blood samples were collected to investigate oxytocin and cortisol levels. Upon return, oxytocin increased initially, probably because of the dog seeing the person entering the room and walking towards the area where the dog was housed. In treatment PV, where physical contact was applied, elevated levels of oxytocin were observed even after the interaction had ended. Cortisol levels showed a decreasing curve throughout the test, however this decrease was most pronounced in treatment PV, possibly as a consequence of the oxytocin release. Also, dogs in this treatment initiated more physical contact with the familiar person and expressed more lip licking upon reunion. The initial responses to reunion in treatment V were tail wagging and vocalisations. When dogs were ignored upon reunion in treatment C, they could have redirected their approach-behaviour towards an assistant (who was always situated in the room). To conclude, the type of interaction evidently affected the endocrine and behavioural responses of dogs in different ways. The mere return of the familiar person had a positive effect on oxytocin levels and induced contact-seeking behaviour, whereas physical contact was necessary in order to induce a sustained increase in oxytocin levels and to decrease cortisol levels in the period following reunion.

Self-soothing behaviors with particular reference to oxytocin release induced by non-noxious sensory stimulation.

Oxytocin, a hypothalamic nonapeptide, is linked to increased levels of social interaction, well-being and anti-stress effects. The effects of oxytocin that is released by sensory stimulation during different kinds of interactive behaviors are often underestimated or even forgotten. In fact, many of the positive effects caused during interaction, such a wellbeing, stress reduction and even health promotion, are indeed linked to oxytocin released in response to activation of various types of sensory nerves. Oxytocin is released in response to activation of sensory nerves during labor, breastfeeding and sexual activity. In addition oxytocin is released in response to low intensity stimulation of the skin, e.g., in response to touch, stroking, warm temperature, etc. Consequently oxytocin is not only released during interaction between mothers and infants, but also during positive interaction between adults or between humans and animals. Finally oxytocin is also released in response to suckling and food intake. Oxytocin released in the brain in response to sensory stimulation as a consequence of these types of interactive behaviors, contributes to every day wellbeing and ability to handle stress. Food intake or sex may be used or even abused to achieve oxytocin-linked wellbeing and stress relief to compensate for lack of good relationships or when the levels of anxiety are high. The present review article will summarize the role played by oxytocin released by sensory (in particular somatosensory) stimulation, during various kinds of interactive behaviors. Also the fact that the anti-stress effects of oxytocin are particularly strong when oxytocin is released in response to "low intensity" stimulation of the skin will be highlighted.

Influence of common birth interventions on maternal blood pressure patterns during breastfeeding 2 days after birth.

OBJECTIVE: This study investigated possible influences of medical interventions during labor on maternal blood pressure during a breastfeed 2 days postpartum. SUBJECTS AND METHODS: Sixty-six primiparae with normal deliveries were consecutively recruited. Blood pressure was measured at -5, 10, 30, and 60 minutes during a morning breastfeed 2 days postpartum. Five treatment groups were formed based on the medical interventions received during labor: Non-medicated mothers (Control group, n=21); mothers receiving epidural analgesia (EDA) with oxytocin (OT) stimulation (EDA(OT) group, n=14); mothers receiving EDA without OT stimulation (EDA(non-OT) group, n=7); mothers receiving OT stimulation only (OT intravenously [iv] group, n=9); and mothers receiving 10 IU of OT intramuscularly (im) only (OT im group, n=15). RESULTS: Baseline diastolic, but not systolic, blood pressure differed between the groups as displayed by significantly lower diastolic blood pressure in the EDA(non-OT) group compared with the Control group, the OT iv group, and the EDA(OT) group (p=0.045, p=0.041, and p=0.024, respectively). Both systolic and diastolic blood pressure fell significantly during the breastfeeding session in the Control group (p=0.001 and p=0.004, respectively), the OT im group (p=0.006 and p=0.001, respectively), and the EDA(OT) group (p=0.028 and p=0.002, respectively), and the fall in diastolic blood pressure tended to be significant in the OT iv group (p=0.050). The duration of skin-to-skin contact before breastfeeding correlated positively with the decrease in systolic blood pressure in the OT im group (R(s)=0.540, p=0.046). CONCLUSION: Administration of EDA during labor lowers baseline diastolic blood pressure and abolishes the fall in blood pressure in response to a breastfeed 2 days after birth.

Effects of sucking and skin-to-skin contact on maternal ACTH and cortisol levels during the second day postpartum-influence of epidural analgesia and oxytocin in the perinatal period.

BACKGROUND AND AIMS: In this study we made a detailed analysis of the mothers' release pattern of adrenocorticotropic hormone (ACTH) and cortisol during a breastfeeding session during the second day postpartum and related these patterns to maternal oxytocin levels as well to the duration of sucking and the duration of skin-to-skin contact before sucking the breast. Furthermore, we investigated if epidural analgesia and oxytocin administration during and after labor influenced the release pattern of ACTH and cortisol. METHODS: Sixty-three primiparae were included in the study. Fourteen received oxytocin intramuscularly postpartum, nine received oxytocin infusion, 14 received epidural analgesia combined with oxytocin infusion, and six received epidural analgesia alone. Twenty mothers did not receive any of these medical interventions. Blood samples were analyzed for ACTH and cortisol by enzyme-linked immunoassay. RESULTS: Both ACTH and cortisol levels fell significantly during the breastfeeding session. A significant negative relationship was found between oxytocin and ACTH levels, but not between oxytocin and cortisol levels. A positive and significant relationship was found between ACTH and cortisol levels. The duration of skin-to-skin contact before onset of sucking was significantly and negatively associated with lower cortisol levels, but not with ACTH levels. Cortisol levels differed significantly between mothers having received epidural analgesia with and without oxytocin. CONCLUSIONS: Breastfeeding is associated with a decrease of ACTH and cortisol levels. Skin-to-skin contact contributes to this effect. ACTH correlated negatively with the duration of sucking and with median oxytocin levels, whereas cortisol levels correlated inversely with the duration of skin-to-skin contact preceding sucking, suggesting a partial dissociation between the mechanisms regulating ACTH and cortisol release. In addition, medical interventions in connection with birth influence the activity of the hypothalamic-pituitary-adrenal axis 2 days after birth.