Partners matter: The psychosocial well-being of couples when dealing with endometriosis.

BACKGROUND: Endometriosis is often associated with severe dysmenorrhea, pelvic pain and dyspareunia and has a high impact on daily life as well as sexuality. Quality of partnership positively influences the course of various diseases and ability to cope with emotional and physical distress. However, studies focusing on the male partners of endometriosis patients are rare, and even less is known about the reciprocal relationship in these couples. Therefore, this study aims to explore the interrelations in couples with endometriosis in matters of psychological distress, sexual and partnership satisfaction and social support. METHODS: The cross-sectional study was conducted in two university-affiliated fertility centres in Germany and Austria with n = 104 female/male couples affected by endometriosis. Participants completed a questionnaire regarding endometriosis, partnership, sexuality, stress, anxiety, depression and social support. Both women and men were asked about the impact of women's endometriosis-related pain (IEP) on their everyday life (e.g. leisure time). Data were analysed using the Actor-Partner-Interdependence Model. RESULTS: Significant partner effects were evident: High depression, anxiety and stress scores in women were associated with a higher IEP in men (all p ≤ 0.01), reciprocally high stress and depression scores in men were correlated with a higher IEP in women (all p ≤ 0.05). Less sexual satisfaction in women was associated with a higher IEP in men (p = 0.040). There was a significant reciprocal association between the perceived lack of understanding from the social environment and a higher IEP, for both women (p = 0.022) and men (p = 0.027). CONCLUSIONS: The male partner should be taken into account when counselling or treating women with endometriosis. Our study shows a high interdependence and reciprocal influence from both partners-positively and negatively-concerning psychological distress and sexual satisfaction. Furthermore, there ought to be more awareness for the psychosocial impact of endometriosis, especially in regard to social support and understanding. Talking about and improving sexual satisfaction as well as enhancing stress reducing techniques may hold great benefits for dealing with endometriosis. Registration number The study is registered with the German Clinical Trials Register (DRKS), number DRKS00014362.

Still With Me? Assessing the Persisting Relationship to a Deceased Loved-One - Validation of the "Continuing Bonds Scale" in a German Population.

Continuing the bond (CB) to a deceased loved one plays a clinically significant role in grief. We validated the Continuing Bonds Scale (CBS) examining externalized CB (illusions and hallucinations) versus internalized CB (use of the deceased as a secure base) in relation to risk factors of complicated grief and bereavement-related adjustment. Data from 364 bereaved German participants on CBS, Inventory of Complicated Grief (ICG), and Posttraumatic Personal Growth Inventory (PPGI) entered an exploratory factor analysis. This yielded a two-factor-solution representing externalized and internalized CB (KMO = .89, χ2 = 2100.5, df = 120). Both factors demonstrated high internal consistency (Cronbach's α = .87). ICG and PPGI highly correlated with externalized and internalized CB. Cause of death and feelings of responsibility were associated with externalized CB. In the future, the use of the CBS could help predict problems in grief processing and consequently implement early interventions.

Impaired cognitive performance under psychosocial stress in cannabis-dependent men is associated with attenuated precuneus activity

Background: Deficient regulation of stress plays an important role in the escalation of substance use, addiction and relapse. Accumulating evidence suggests dysregulations in cognitive and reward-related processes and the underlying neural circuitry in cannabis dependence. However, despite the important regulatory role of the endocannabinoid system in the stress response, associations between chronic cannabis use and altered stress processing at the neural level have not been systematically examined. Methods: Against this background, the present functional MRI study examined psychosocial stress processing in cannabis-dependent men (n = 28) and matched controls (n = 23) using an established stress-induction paradigm (Montreal Imaging Stress Task) that combines computerized (adaptive) mental arithmetic challenges with social evaluative threat. Results: During psychosocial stress exposure, but not the no-stress condition, cannabis users demonstrated impaired performance relative to controls. In contrast, levels of experienced stress and cardiovascular stress responsivity did not differ from controls. Functional MRI data revealed that stress-induced performance deteriorations in cannabis users was accompanied by decreased precuneus activity and increased connectivity of this region with the superior frontal gyrus. Limitations: Only male cannabis-dependent users were examined; the generalizability in female users remains to be determined. Conclusion: Together, the present findings provide first evidence for exaggerated stress-induced cognitive performance deteriorations in cannabis users. The neural data suggest that deficient stress-related recruitment of the precuneus may be associated with the deterioration of performance at the behavioural level.

Oxytocin enhances the pain-relieving effects of social support in romantic couples.

Social support plays a vital role in physical and mental well-being. The neuropeptide hormone oxytocin (OXT) has been implicated in modulating pair-bonding and affiliative behaviors, but whether OXT contributes to the analgesic effects of a romantic partner's touch remains elusive. In the present randomized placebo-controlled, between-group, functional magnetic resonance imaging study involving 194 healthy volunteers (97 heterosexual couples), we tested the effects of intranasal OXT (24 IU) on handholding as a common mode of expressing emotional support in romantic couples. We scanned the subjects while brief electric shocks were administered. The subjects assumed that they received social support from either their romantic partner or an unfamiliar person. Unbeknown to the subject, in the partner and stranger support conditions, the same male experimenter always held the subject's left hand. Partner support was most effective in reducing the unpleasantness of electric shocks, and OXT further attenuated the unpleasantness across conditions. On the neural level, OXT significantly augmented the beneficial effects of partner support, as evidenced by a stronger decrease of neural responses to shocks in the anterior insula (AI), a stronger activity increase in the middle frontal gyrus (MFG), and a strengthened functional coupling between the AI and MFG. Our results support the notion that OXT specifically modulates the beneficial effects of social support in romantic couples by concomitantly reducing pain-associated activity and increasing activity linked to cognitive control and pain inhibition. We hypothesize that impaired OXT signaling may contribute to the experience of a lack of partner support.

Oxytocin differentially alters resting state functional connectivity between amygdala subregions and emotional control networks: Inverse correlation with depressive traits.

The hypothalamic neuropeptide oxytocin (OT) has received increasing attention for its role in modulating social-emotional processes across species. Previous studies on using intranasal-OT in humans point to a crucial engagement of the amygdala in the observed neuromodulatory effects of OT under task and rest conditions. However, the amygdala is not a single homogenous structure, but rather a set of structurally and functionally heterogeneous nuclei that show distinct patterns of connectivity with limbic and frontal emotion-processing regions. To determine potential differential effects of OT on functional connectivity of the amygdala subregions, 79 male participants underwent resting-state fMRI following randomized intranasal-OT or placebo administration. In line with previous studies OT increased the connectivity of the total amygdala with dorso-medial prefrontal regions engaged in emotion regulation. In addition, OT enhanced coupling of the total amygdala with cerebellar regions. Importantly, OT differentially altered the connectivity of amygdala subregions with distinct up-stream cortical nodes, particularly prefrontal/parietal, and cerebellar down-stream regions. OT-induced increased connectivity with cerebellar regions were largely driven by effects on the centromedial and basolateral subregions, whereas increased connectivity with prefrontal regions were largely mediated by right superficial and basolateral subregions. OT decreased connectivity of the centromedial subregions with core hubs of the emotional face processing network in temporal, occipital and parietal regions. Preliminary findings suggest that effects on the superficial amygdala-prefrontal pathway were inversely associated with levels of subclinical depression, possibly indicating that OT modulation may be blunted in the context of increased pathological load. Together, the present findings suggest a subregional-specific modulatory role of OT on amygdala-centered emotion processing networks in humans.

Oxytocin facilitates the sensation of social stress.

Essentially all social species experience social stress which can be a catalyst for detriments in mental and physical health. The neuropeptide oxytocin (OXT) has been shown to produce anxiolytic and antistress effects, thereby qualifying the OXT system as a promising drug target in the treatment of stress-related disorders. However, recently it has been shown that OXT can have anxiogenic effects as well. In the present study, we used functional magnetic resonance imaging to scan the brains of 60 healthy men while they were exposed to social stress after they received either intranasal OXT (24 IU) or placebo treatment. Although OXT administration did not alter salivary cortisol levels as a surrogate marker of stress axis activity, our participants initially reported an increment in perceived social stress. This behavioral effect was paralleled on the neural level by increased activity in the precuneus and cingulate cortex. Taken together, our results support the hypothesis that OXT can induce a self-referential processing bias which facilitates the sensation of social stress in the absence of altered endocrine responses.

Neural responses to instructed positive couple interaction: an fMRI study on compliment sharing.

Love is probably the most fascinating feeling that a person ever experiences. However, little is known about what is happening in the brains of a romantic couple-the central and most salient relationship during adult age-while they are particularly tender and exchanging loving words with one another. To gain insight into nearly natural couple interaction, we collected data from N = 84 individuals (including N = 43 heterosexual couples) simultaneously in two functional magnetic resonance imaging scanners, while they sent and received compliments, i.e. short messages about what they liked about each other and their relationship. Activation patterns during compliment sharing in the individuals revealed a broad pattern of activated brain areas known to be involved in empathy and reward processing. Notably, the ventral striatum, including parts of the putamen, was activated particularly when selecting messages for the partner. This provides initial evidence that giving a verbal treat to a romantic partner seems to involve neural reward circuitry in the basal ganglia. These results can have important implications for the neurobiological mechanisms protecting and stabilizing romantic relationships, which build a highly relevant aspect of human life and health.

Affectionate touch and diurnal oxytocin levels: An ecological momentary assessment study.

Background: Affectionate touch, which is vital for mental and physical health, was restricted during the Covid-19 pandemic. This study investigated the association between momentary affectionate touch and subjective well-being, as well as salivary oxytocin and cortisol in everyday life during the pandemic. Methods: In the first step, we measured anxiety and depression symptoms, loneliness and attitudes toward social touch in a large cross-sectional online survey (N = 1050). From this sample, N = 247 participants completed ecological momentary assessments over 2 days with six daily assessments by answering smartphone-based questions on affectionate touch and momentary mental state, and providing concomitant saliva samples for cortisol and oxytocin assessment. Results: Multilevel models showed that on a within-person level, affectionate touch was associated with decreased self-reported anxiety, general burden, stress, and increased oxytocin levels. On a between-person level, affectionate touch was associated with decreased cortisol levels and higher happiness. Moreover, individuals with a positive attitude toward social touch experiencing loneliness reported more mental health problems. Conclusions: Our results suggest that affectionate touch is linked to higher endogenous oxytocin in times of pandemic and lockdown and might buffer stress on a subjective and hormonal level. These findings might have implications for preventing mental burden during social contact restrictions. Funding: The study was funded by the German Research Foundation, the German Psychological Society, and German Academic Exchange Service.

Stress during the COVID-19 Pandemic Moderates Pain Perception and Momentary Oxytocin Levels.

Self-reported pain levels have been associated with increased stress levels during the COVID-19 pandemic. Less is known about the long-term effects of stress on individuals' physical and emotional pain levels and their associations with the neuropeptide hormone oxytocin. We aimed to predict momentary pain through individual stress levels and momentary oxytocin levels at genuinely high-stress phases, namely during COVID-related lockdowns. In a cross-sectional (n = 254) and a longitudinal (n = 196) assessment during lockdowns in Germany, participants completed a 2-day ecological momentary assessment (EMA) protocol (collecting six saliva samples on two consecutive days each and simultaneously reporting on stress, physical, and emotional pain levels) in 2020, as well as one year later, in 2021. Hierarchical linear modeling revealed significant positive associations between individuals' stress levels and physical pain, both cross-sectionally (b = 0.017; t(103) = 3.345; p = 0.001) and longitudinally (b = 0.009; t(110) = 2.025; p = 0.045). Similarly, subjective stress ratings showed significant positive associations with emotional pain on a within-person (b = 0.014; t(63) = 3.594; p < 0.001) as well as on a between-person (b = 0.026; t(122) = 5.191; p < 0.001) level. Participants further displayed significantly lower salivary oxytocin when experiencing higher levels of emotional pain (b = -0.120; t(163) = -2.493; p = 0.014). In addition, high-stress levels significantly moderated the association between physical pain and salivary oxytocin (b = -0.012; t(32) = -2.150; p = 0.039). Based on mechanistic and experimental research, oxytocinergic mechanisms have long been suggested to modulate pain experiences, however, this has not yet been investigated in everyday life. Our data, which was collected from a large sample experiencing continued stress, in this case, during the COVID-19 pandemic, suggests that individuals experience more intense physical pain and elevated stress levels, as shown by particularly low salivary oxytocin concentrations.

Loneliness and diurnal cortisol levels during COVID-19 lockdown: the roles of living situation, relationship status and relationship quality.

Loneliness and social isolation have become increasing concerns during COVID-19 lockdown through neuroendocrine stress-reactions, physical and mental health problems. We investigated living situation, relationship status and quality as potential moderators for trait and state loneliness and salivary cortisol levels (hormonal stress-responses) in healthy adults during the first lockdown in Germany. N = 1242 participants (mean age = 36.32, 78% female) filled out an online questionnaire on demographics, trait loneliness and relationship quality. Next, N = 247 (mean age = 32.6, 70% female) completed ecological momentary assessment (EMA), collecting twelve saliva samples on 2 days and simultaneously reporting their momentary loneliness levels. Divorced/widowed showed highest trait loneliness, followed by singles and partnerships. The latter displayed lower momentary loneliness and cortisol levels compared to singles. Relationship satisfaction significantly reduced loneliness levels in participants with a partner and those who were living apart from their partner reported loneliness levels similar to singles living alone. Living alone was associated with higher loneliness levels. Hierarchical linear models revealed a significant cross-level interaction between relationship status and momentary loneliness in predicting cortisol. The results imply that widowhood, being single, living alone and low relationship quality represent risk factors for loneliness and having a partner buffers neuroendocrine stress responses during lockdown.

Calming Effects of Touch in Human, Animal, and Robotic Interaction-Scientific State-of-the-Art and Technical Advances.

Small everyday gestures such as a tap on the shoulder can affect the way humans feel and act. Touch can have a calming effect and alter the way stress is handled, thereby promoting mental and physical health. Due to current technical advances and the growing role of intelligent robots in households and healthcare, recent research also addressed the potential of robotic touch for stress reduction. In addition, touch by non-human agents such as animals or inanimate objects may have a calming effect. This conceptual article will review a selection of the most relevant studies reporting the physiological, hormonal, neural, and subjective effects of touch on stress, arousal, and negative affect. Robotic systems capable of non-social touch will be assessed together with control strategies and sensor technologies. Parallels and differences of human-to-human touch and human-to-non-human touch will be discussed. We propose that, under appropriate conditions, touch can act as (social) signal for safety, even when the interaction partner is an animal or a machine. We will also outline potential directions for future research and clinical relevance. Thereby, this review can provide a foundation for further investigations into the beneficial contribution of touch by different agents to regulate negative affect and arousal in humans.

Neuroendocrine mechanisms of grief and bereavement: A systematic review and implications for future interventions.

Bereavement is associated with many negative behavioural, psychological and physiological consequences and leads to an increased risk of mortality and morbidity. However, studies specifically examining neuroendocrine mechanisms of grief and bereavement have yet to be reviewed. This systematic review is a synthesis of the latest evidence in this field and aims to draw conclusions about the implications of neurobiological findings on the development of new interventions. PRISMA guidelines for systematic reviews were used to search for articles assessing neuroendocrine correlates of grief. Findings were qualitatively summarised. The National Heart, Lung, and Blood Institute Study Assessment Tool was used to assess the quality of the included studies. Out of 460 papers, 20 met the inclusion criteria. However, most were of fair quality only. As a neuroendocrine marker, the majority of the studies reported cortisol as the outcome measure and found elevated mean cortisol levels, flattened diurnal cortisol slopes and higher morning cortisol in bereaved subjects. Cortisol alterations were moderated by individual differences such as emotional reaction to grief, depressive symptoms, grief severity, closeness to the deceased and age or gender. Research on neuroendocrine mechanisms of grief is still in its early stages regarding grief measures and the use and timing of neuroendocrine assessments. Most of the studies focus on cortisol as outcome, and only limited data exist on other biomarkers such as oxytocin. Future research might consider assessing a broader range of neuroendocrine markers and use longitudinal designs with a focus on the psychobiological reactions to loss. Based on this, individually tailored psychosocial interventions, possibly in the palliative care context, might be developed to prevent prolonged grief disorder.

Menstrual Cycle Changes in Vagally-Mediated Heart Rate Variability are Associated with Progesterone: Evidence from Two Within-Person Studies.

A recent meta-analysis revealed that cardiac vagal activity (mostly indicated by vagally-mediated heart rate variability; HRV) decreases significantly from the follicular to luteal menstrual cycle phase in naturally-cycling participants. However, the question remains as to whether cyclical changes in estradiol (E2), progesterone (P4), or both are responsible for HRV fluctuations. We present the first studies to use repeated measures of E2, P4, and HRV across the cycle to model both the unique and interactive effects of person-centered E2 and P4 on HRV in multilevel models. In study one, 40 naturally-cycling participants were assessed weekly across four weeks, and were blind to the cycle focus of the study. In study two, 50 naturally-cycling participants were examined in three precisely defined cycle phases via ovulation testing. Both studies revealed that only P4 was correlated with HRV, such that higher-than-usual P4 significantly predicted lower-than-usual HRV within a given participant. In line with this, cycle phase comparisons revealed lower HRV in the mid-luteal phase (characterized by elevated P4) than in other phases. No significant main or interactive effects of E2 on HRV were found. Future female health studies should investigate individual differences in these effects and potential consequences of cyclical HRV changes on daily functioning.

Oxytocin Modulates the Cognitive Appraisal of the Own and Others Close Intimate Relationships.

Close and intimate relationships are important promoters of health. Oxytocin and its association with social cognition have been investigated in a large number of studies, especially highlighting the neuropeptide's involvement in attachment behavior and intimate relationships. However, mixed findings on exogenous oxytocin application have led to the focus on moderators and mediators, suggesting that the effects are depended on specific factors - namely context and salience. The objective of the current study was to assess the effect of intranasal oxytocin on social appraisal of own and others' close intimate relationship characteristics. Different characteristics of relationships, including trust or closeness, between romantic couples (unknown and own) were assessed using the Couple Appraisal Task. In a randomized controlled double-blind cross-over within subject design, N = 71 healthy men and women were investigated after receiving first intranasal oxytocin and 2 weeks later placebo, or vice versa. We found an oxytocin-induced increase in the positive appraisal of one's own overall relationship characteristics but not in the evaluation of the relationship of others. The present study - one of the first of its kind administrating oxytocin in a repeated measures cross-over design - adds further evidence to the mediating role of oxytocin in social cognition, specifically with regard to romantic relationship characteristics.

Oxytocin increases eye-gaze towards novel social and non-social stimuli.

Research on oxytocin (OT) has revealed a substantial involvement of this neuropeptide in social cognition processes and attachment behavior. The rationale of the present project was to decipher the differential role of OT in basic social cognition processes towards non-erotic attachment stimuli vs. reproduction-related stimuli in human subjects. In a randomized double-blind repeated-measures cross-over design, N = 82 participants were investigated twice and received either intranasal OT or placebo at the first assessment followed by placebo or OT at second assessment. Participants were presented with standardized pictures of parent-child dyads, romantic couples engaging in non-erotic or explicit sexual activities, and non-social pictures while we assessed pupil dilation and eye focus on specific pre-defined areas of interest. Multilevel analyses suggest that during the initial presentation, OT increased pupil dilation towards all categories of stimuli and led the eye focus towards the eyes and body regions, followed by a strong decrease in pupil dilation and fixations at the second session. These carry-over effects indicate that hormonal treatment at an initial contact to social stimuli can determine how these stimuli are processed later. These results might have implications for OT as a treatment in interventions with repeated exposure to social material.

Oxytocin for learning calm and safety.

The appropriate discrimination between safe and dangerous situations and the subsequent decrease of fear expression in the presence of safety signals are crucial for survival and mental health. Learning of safety associations is often studied in terms of fear extinction, that is re-learning of a previously conditioned stimulus which is now no longer positively associated with danger. Numerous studies investigated neurobiological processes of fear extinction and provide a valid picture of the underlying neural structures and endocrine processes involved. However, a formerly neutral conditioned stimulus (CS) can also predict the non-occurrence of an aversive, potentially dangerous, unconditioned stimulus (US) from the very beginning and thus can serve as a safety stimulus. This process has been termed safety learning. Although safety learning has been known for almost a century, there has been little research on its underlying neurobiological mechanisms, in contrast to the more prominent Pavlovian fear conditioning and fear extinction. In this review, we propose that the well-known action of the hypothalamic neuropeptide oxytocin (OXT) in the regulation of fear and stress responses is complementary to safety learning. We summarize the literature focused on OXT signaling and safety learning in animals and humans, from the first studies of fear extinction and conditioned inhibition of fear to the most recent findings in molecular and behavioral research on initial social safety stimuli. At the end, we discuss the application of OXT as a therapeutic agent to psychopathologies related to deficits in safety learning.

The NeMo real-time fMRI neurofeedback study: protocol of a randomised controlled clinical intervention trial in the neural foundations of mother-infant bonding.

INTRODUCTION: Most mothers feel an immediate, strong emotional bond with their newborn. On a neurobiological level, this is accompanied with the activation of the brain reward systems, including the striatum. However, approximately 10% of all mothers report difficulties to bond emotionally with their infant and display impaired reward responses to the interaction with their infant which might have long-term negative effects for the child's development. As previous studies suggest that activation of the striatal reward system can be regulated through functional MRI (fMRI)-based neurofeedback (NFB), we have designed and investigate fMRI-NFB training to treat maternal bonding difficulties. METHODS AND ANALYSIS: In the planned trial, mothers will be presented pictures of their infant and real-time fMRI (rtfMRI), peripheral measures, neural, endocrine, psychophysiological and behavioural measures will be assessed. Mothers with bonding difficulties (n=68) will be randomised to one of two double-blind intervention groups at 4-6 months postpartum. They will participate in three repeated NFB training sessions with rtfMRI-NFB training to increase activation of (a) the ventral striatum or (b) the anterior cingulate. Interview data and real-time mother-infant interaction behaviour pre-intervention, post-intervention and at follow-up will serve as clinical outcome measures. ETHICS AND DISSEMINATION: Study procedures are in line with the recommendations of the World Medical Association (revised Declaration of Helsinki) and were approved by the Ethics Committee of the Medical Faculty, s-450/2017, Heidelberg University. All participants will provide written informed consent after receiving a detailed oral and written explanation of all procedures and can withdraw their consent at any time without negative consequence. Results will be internationally published and disseminated, to further the discussion on non-pharmacological treatment options in complex mental disorders. TRIAL REGISTRATION NUMBER: DRKS00014570; Pre-results.