Oxytocin selectively modulates brain response to stimuli probing social synchrony.

The capacity to act collectively within groups has led to the survival and thriving of Homo sapiens. A central group collaboration mechanism is "social synchrony," the coordination of behavior during joint action among affiliative members, which intensifies under threat. Here, we tested brain response to vignettes depicting social synchrony among combat veterans trained for coordinated action and following life-threatening group experience, versus controls, as modulated by oxytocin (OT), a neuropeptide supporting social synchrony. Using a randomized, double-blind, within-subject design, 40 combat-trained and control male veterans underwent magnetoencephalography (MEG) twice following OT/placebo administration while viewing two social vignettes rated as highly synchronous: pleasant male social gathering and coordinated unit during combat. Both vignettes activated a wide response across the social brain in the alpha band; the combat scene triggered stronger activations. Importantly, OT effects were modulated by prior experience. Among combat veterans, OT attenuated the increased response to combat stimuli in the posterior superior temporal sulcus (pSTS) - a hub of social perception, action observation, and mentalizing - and enhanced activation in the inferior parietal lobule (IPL) to the pleasant social scene. Among controls, OT enhanced inferior frontal gyrus (IFG) response to combat cues, demonstrating selective OT effects on mirror-neuron and mentalizing networks. OT-enhanced mirror network activity was dampened in veterans reporting higher posttraumatic symptoms. Results demonstrate that the social brain responds online, via modulation of alpha rhythms, to stimuli probing social synchrony, particularly those involving threat to survival, and OT's enhancing versus anxiolytic effects are sensitive to salient experiences within social groups.

Prior exposure to extreme pain alters neural response to pain in others.

In the extant literature examining the brain mechanisms implicated in pain perception, researchers have theorized that the overlapping responses to pain in the self and in others mark the human capacity for empathy. Here we investigated how prior exposure to extreme pain affects pain perception, by assessing the dynamics of pain processing in veterans who were previously exposed to severe injury. Forty-three participants (28 pain-exposed and 15 controls) underwent whole-head magnetoencephalography (MEG) while viewing photographs of limbs in painful and nonpainful (neutral) conditions. Among controls, an early (0-220 ms) "pain effect" in the posterior cingulate and sensorimotor cortices, and a later (760-900 ms) "pain effect" in the posterior cingulate cortex, superior temporal gyrus/insula, and fusiform gyrus were found, indicated by enhanced alpha suppression to the pain versus nonpain conditions. Importantly, pain-exposed participants exhibited an atypical pain response in the posterior cingulate cortex, indicated by a normative response to pain, but no pain-to-no-pain differentiation. This may suggest that individuals exposed to extreme pain may perceive neutral stimuli as potentially threatening. Our findings demonstrate alterations in pain perception following extreme pain exposure, chart the sequence from automatic to evaluative pain processing, and emphasize the importance of considering past experiences in studying the neural response to others' states.

Affiliation, reward, and immune biomarkers coalesce to support social synchrony during periods of bond formation in humans.

Social bonds are critical for survival and adaptation and periods of bond formation involve reorganization of neurobiological systems as mediated by social behavior. Theoretical accounts and animal studies suggest similarity between parent-infant and pair bonding, a hypothesis not yet directly tested in humans. In this study, we recruited three groups of human adults (N=189); parents who had their firstborn child in the last 4-6months, new lovers who began a romantic relationship within the past 4months, and non-attached singles. We measured plasma oxytocin (OT), beta endorphin (ß-End), and interlukin-6 (IL-6), biomarkers of the affiliation, reward, and stress-response systems, and micro-coded gaze and affect synchrony between parents and infants and among new lovers during social interaction. OT significantly increased during periods of parental and romantic bonding and was highest in new lovers. In contrast, IL-6 and ß-End were highest in new parents and lowest in singles. Biomarkers became more tightly coupled during periods of bond formation and inter-correlation among hormones was highest during romantic bonding. Structural equation modeling indicated that the effects of IL-6 and ß-End on behavioral synchrony were mediated by their impact on OT, highlighting the integrative role of the oxytocinergic system in supporting human social affiliation. Findings suggest that periods of bond formation are accompanied by increased activity, as well as tighter cross-talk among systems underpinning affiliation, reward, and stress management and that research on the multidimensional process of bonding may shed further light on the effects of attachment on health.

Oxytocin affects spontaneous neural oscillations in trauma-exposed war veterans.

Exposure to combat-related trauma often leads to lifetime functional impairments. Previous research demonstrated the effects of oxytocin (OT) administration on brain regions implicated in post-traumatic stress disorder (PTSD); yet OT's effects on brain patterns in trauma-exposed veterans have not been studied. In the current study the effects of OT on spontaneous brain oscillatory activity were measured in 43 veterans using magnetoencephalography (MEG): 28 veterans who were exposed to a combat-related trauma and 15 trauma-unexposed controls. Participants participated in two experimental sessions and were administered OT or placebo (PBO) in a double-blind, placebo-control, within-subject design. Following OT/PBO administration, participants underwent a whole-head MEG scan. Plasma and salivary OT levels were assessed each session. Spontaneous brain activity measured during a 2-min resting period was subjected to source-localization analysis. Trauma-exposed veterans showed higher resting-state alpha (8-13 Hz) activity compared to controls in the left dorsolateral prefrontal cortex (dlPFC), specifically in the superior frontal gyrus (SFG) and the middle frontal gyrus (MFG), indicating decreased neural activity in these regions. The higher alpha activity was "normalized" following OT administration and under OT, group differences were no longer found. Increased resting-state alpha was associated with lower baseline plasma OT, reduced salivary OT reactivity, and more re-experiencing symptoms. These findings demonstrate effects of OT on resting-state brain functioning in prefrontal regions subserving working memory and cognitive control, which are disrupted in PTSD. Results raise the possibility that OT, traditionally studied in social contexts, may also enhance performance in cognitive tasks associated with working memory and cognitive control following trauma exposure.

Cumulative risk on the oxytocin receptor gene (OXTR) underpins empathic communication difficulties at the first stages of romantic love.

Empathic communication between couples plays an important role in relationship quality and individual well-being and research has pointed to the role of oxytocin in providing the neurobiological substrate for pair-bonding and empathy. Here, we examined links between genetic variability on the oxytocin receptor gene (OXTR) and empathic behaviour at the initiation of romantic love. Allelic variations on five OXTR single nucleotide polymorphisms (SNPs) previously associated with susceptibility to disorders of social functioning were genotyped in 120 new lovers: OXTRrs13316193, rs2254298, rs1042778, rs2268494 and rs2268490. Cumulative genetic risk was computed by summing risk alleles on each SNP. Couples were observed in support-giving interaction and behaviour was coded for empathic communication, including affective congruence, maintaining focus on partner, acknowledging partner's distress, reciprocal exchange and non-verbal empathy. Hierarchical linear modelling indicated that individuals with high OXTR risk exhibited difficulties in empathic communication. OXTR risk predicted empathic difficulties above and beyond the couple level, relationship duration, and anxiety and depressive symptoms. Findings underscore the involvement of oxytocin in empathic behaviour during the early stages of social affiliation, and suggest the utility of cumulative risk and plasticity indices on the OXTR as potential biomarkers for research on disorders of social dysfunction and the neurobiology of empathy.

Mutual influences between partners' hormones shape conflict dialog and relationship duration at the initiation of romantic love.

Early-stage romantic love involves reorganization of neurohormonal systems and behavioral patterns marked by mutual influences between the partners' physiology and behavior. Guided by the biobehavioral synchrony conceptual frame, we tested bidirectional influences between the partners' hormones and conflict behavior at the initiation of romantic love. Participants included 120 new lovers (60 couples) and 40 singles. Plasma levels of five affiliation and stress-related hormones were assessed: oxytocin (OT), prolactin (PRL), testosterone (T), cortisol (CT), and dehydroepiandrosterone sulfate (DHEAS). Couples were observed in conflict interaction coded for empathy and hostility. CT and DHEAS showed direct actor effects: higher CT and DHEAS predicted greater hostility. OT showed direct partner effects: individuals whose partners had higher OT showed greater empathy. T and CT showed combined actor-partner effects. High T predicted greater hostility only when partner also had high T, but lower hostility when partner had low T. Similarly, CT predicted low empathy only in the context of high partner's CT. Mediational analysis indicated that combined high CT in both partners was associated with relationship breakup as mediated by decrease in empathy. Findings demonstrate the mutual influences between hormones and behavior within an attachment bond and underscore the dynamic, co-regulated, and systemic nature of pair-bond formation in humans.

Salivary vasopressin increases following intranasal oxytocin administration.

Extant research has documented the effects of intranasal administration of oxytocin (OT), and to a lesser degree Arginine Vasopressin (AVP) - two structurally-related neuropeptides - on brain and behaviour, yet the effects of exogenous manipulation of one on circulating levels of the other remain unknown. Studies have shown that OT administration impacts the peripheral levels of numerous hormones; however, whether OT administration also increases AVP concentrations has not been explored. Utilizing a double-blind placebo-controlled within-subject design, ten male and female subjects provided ten saliva samples over four consecutive hours: at baseline and nine times following OT administration. Results indicate that salivary AVP increased in the first hour following OT manipulation (OT condition: mean AVP=2.17 pg/ml, SE=28, placebo condition: mean AVP=1.42 pg/ml, SE=.18) but returned to baseline levels at the next assessment (80 min) and remained low for the remaining period. Similar to OT, AVP showed high degree of individual stability and baseline levels of AVP correlated with AVP concentrations at the first and second post-administration hours regardless of drug condition (Pearson r=.85-.93). Validity of salivary AVP ELISA measurement was verified by demonstrating individual stability of salivary AVP over a six-month period (r=.70, p<.000) as well correlation with plasma levels over the same period (r=.32, p=.037) in a sample of 45 young adults who did not participate in the current study. Overall, findings suggest a potential crosstalk between OT and AVP and indicate that baseline levels of the two neuropeptides may shape the degree to which these systems respond to exogenous manipulation.

Plasma oxytocin distributions in a large cohort of women and men and their gender-specific associations with anxiety.

Research has consistently addressed the relations between plasma oxytocin (OT) - a nonapeptide implicated in mammalian social bonding - and psychological distress, but the direction of the association remains unclear. Utilizing the largest sample of plasma OT to date (N=473), the current study had two goals. First, we described the distributions of plasma OT in women and men, and second, we examined whether the relations between OT and two types of anxiety - trait and attachment anxiety - are moderated by gender. Results indicated that OT values (M=375.78 pg/ml, SD=264.03, range=51.40-2752.30) clustered around the mean with a long right tail, indicating trend toward high values. In most participants (N=323), OT was measured again six months after initial assessment and OT levels were highly stable within individuals. After removing outliers 2.5 SD above the mean (≥1098 pg/ml for men and ≥988 pg/ml for women), men showed significantly higher mean OT than women (women: 327.13 pg/ml, SD=164.43; men: 399.91, SD=183.65; t=2.57, p=.01). Gender was found to moderate the relations between OT and anxiety. Trait anxiety was lower among men with higher OT but no such links emerged for women, supporting the hypothesized anxiolytic effects of OT in males only. Furthermore, women with extreme values (≥988 pg/ml) had three times the probability of being classified as highly anxious (STAI-T≥45). Higher OT in women correlated with greater attachment anxiety, but no such relationships were found for men. Results are consistent with models on the differential associations between the neurobiology of attachment and the experience of anxiety in women and men.

Oxytocin during the initial stages of romantic attachment: relations to couples' interactive reciprocity.

Romantic relationships can have a profound effect on adults' health and well-being whereas the inability to maintain intimate bonds has been associated with physical and emotional distress. Studies in monogamous mammalian species underscore the central role of oxytocin (OT) in pair-bonding and human imaging studies implicate OT-rich brain areas in early romantic love. To assess the role of OT in romantic attachment, we examined plasma OT in 163 young adults: 120 new lovers (60 couples) three months after the initiation of their romantic relationship and 43 non-attached singles. Twenty-five of the 36 couples who stayed together were seen again six months later. Couples were observed in dyadic interactions and were each interviewed regarding relationship-related thoughts and behaviors. OT was significantly higher in new lovers compared to singles, F(1,152)=109.33, p<.001, which may suggest increased activity of the oxytocinergic system during the early stages of romantic attachment. These high levels of OT among new lovers did not decrease six months later and showed high individual stability. OT correlated with the couples' interactive reciprocity, including social focus, positive affect, affectionate touch, and synchronized dyadic states, and with anxieties and worries regarding the partner and the relationship, findings which parallel those described for parent-infant bonding. OT levels at the first assessment differentiated couples who stayed together six months later from those who separated during this period. Regression analysis showed that OT predicted interactive reciprocity independent of sex, relationship duration, and the partner's OT. Findings suggest that OT may play an important role at the first stages of romantic attachment and lend support to evolutionary models suggesting that parental and romantic attachment share underlying bio-behavioral mechanisms.

Sensitive parenting is associated with plasma oxytocin and polymorphisms in the OXTR and CD38 genes.

BACKGROUND: Research in mammals has demonstrated the involvement of oxytocin (OT) in social bond formation; yet, its role in human bonding remains unclear. Plasma OT has been used as a proxy for central activity and studies indicate its association with human affiliative behaviors. Molecular genetic studies also reveal a role for OT neuropathways in shaping the social brain. However, the links between peripheral OT, genetic markers, and their combined contribution to human parenting are unknown. METHODS: Participants included 352 individuals: 272 mothers and fathers and their 4- to 6-month-old-infants and 80 nonparents. Plasma OT was assayed from adults who were genotyped for oxytocin receptor (OXTR) and CD38 risk alleles associated with social dysfunctions. CD38 is an ectoenzyme that mediates the release of brain OT. Parent-infant interactions were microcoded for parental touch and gaze synchrony and participants reported on parental care in childhood. RESULTS: OXTR (rs2254298 and rs1042778) and CD38 (rs3796863) risk alleles were each associated with lower plasma OT. Reduced plasma OT and both OXTR and CD38 risk alleles were related to less parental touch. The interaction of high plasma OT and low-risk CD38 alleles predicted longer durations of parent-infant gaze synchrony. Parents reporting greater parental care showed higher plasma OT, low-risk CD38 alleles, and more touch toward their infants. CONCLUSIONS: Results indicate that peripheral and genetic markers of the extended OT pathway are interrelated and underpin core behaviors associated with human parenting and social engagement. These findings may have important implications for understanding neuropsychiatric disorders marked by early social dysfunctions.

Love alters autonomic reactivity to emotions.

Periods of bond formation are accompanied by physiological and emotional changes, yet, little is known about the effects of falling in love on the individual's physiological response to emotions. We examined autonomic reactivity to the presentation of negative and positive films in 112 young adults, including 57 singles and 55 new lovers who began a romantic relationship 2.5 months prior to the experiment Autonomic reactivity was measured by Respiratory Sinus Arrhythmia (RSA) to two baseline emotionally neutral films, two negative films, and two positive films. Results demonstrated that RSA in singles decreased during the presentation of negative emotions, indicating physiological stress response. However, no such decrease was found among new lovers, pointing to more optimal vagal regulation during the period of falling in love. Autonomic reactivity, indexed by RSA decrease from the positive to the negative films, was greater among singles as compared to lovers, suggesting that love buffers against autonomic stress and facilitates emotion regulation. Findings suggest that vagal regulation may be one mechanism through which love and attachment reduce stress and promote well-being and health.

Natural variations in maternal and paternal care are associated with systematic changes in oxytocin following parent-infant contact.

Animal studies have demonstrated that the neuropeptide oxytocin (OT) plays a critical role in processes of parent-infant bonding through mechanisms of early parental care, particularly maternal grooming and contact. Yet, the involvement of OT in human parenting remains poorly understood, no data are available on the role of OT in the development of human fathering, and the links between patterns of parental care and the OT response have not been explored in humans. One hundred and twelve mothers and fathers engaged in a 15-min play-and-contact interaction with their 4-6-month-old infants and interactions were micro-coded for patterns of parental touch. Results showed that baseline levels of plasma and salivary OT in mothers and fathers were similar, OT levels in plasma and saliva were inter-related, and OT was associated with the parent-specific mode of tactile contact. Human mothers who provided high levels of affectionate contact showed an OT increase following mother-infant interaction but such increase was not observed among mothers displaying low levels of affectionate contact. Among fathers, only those exhibiting high levels of stimulatory contact showed an OT increase. These results demonstrate consistency in the neuroendocrine basis of human parental interactions with those seen in other mammals. The findings underscore the need to provide opportunities for paternal care to trigger the biological basis of fatherhood and suggest that interventions that permit social engagement may be recommended in conditions of diminished maternal-infant contact, such as prematurity or postpartum depression.

Oxytocin and cortisol in romantically unattached young adults: associations with bonding and psychological distress.

Despite extensive research on the involvement of oxytocin (OT) in mammalian bonding, less is known about its role in human social affiliation across the life cycle. Forty-five romantically unattached young adults participated. Plasma oxytocin and salivary cortisol were assessed using enzyme immuno-assay, and self-report measures of bonding, attachment, anxiety, and depression were collected. Oxytocin was associated with bonding to own parents and inversely related to psychological distress, particularly depressive symptoms. Cortisol was related to attachment anxiety. Regression analysis indicated that the adult's representations of bonding to parents predicted OT levels above and beyond cortisol, psychological distress, and attachment. Findings are consistent with antistress models of oxytocin and suggest that oxytocin may play a role in bonding-related cognitions across the life span.