IntroductionPrevious studies have reported altered gamma-aminobutyric acid (GABA) and glutamate levels in borderline personality disorder (BPD), suggesting disruptions in excitatory-inhibitory neurotransmission. Electroencephalographic (EEG) research has indicated potential network hyperexcitability in BPD, evidenced by increased intermittent rhythmic delta and theta activity (IRDA/IRTA), which may reflect compensatory stabilization mechanisms. This study used multi-voxel magnetic resonance spectroscopic imaging (MRSI) to explore neurochemical abnormalities and their relationships with IRDA/IRTA, psychometric and neuropsychological measures.MethodsSixty-six female patients diagnosed with BPD (mean age: 30.2 ± 9.7 years) and 29 age-matched female healthy controls (mean age: 27.8 ± 8.0 years) received spirally encoded 3D MRSI scans. GABA, glutamate plus glutamine (Glx), total creatine (tCr) and total N-acetylaspartate (tNAA) were quantified and reported as ratios relative to tNAA and/or tCr. The resulting spectroscopic images were analyzed using LCModel and FreeSurfer software, and IRDA/IRTA detection in a clinical EEG session was performed using independent component analysis. Metabolite ratios were analyzed using hierarchical linear mixed-effects models (ROIs nested within participants), with fixed effects of group or, in separate models, continuous predictors (IRDA/IRTA and psychometric/neuropsychological measures), ROI, and their interaction, and a subject-level random intercept. ROI-specific effects were quantified using estimated marginal means and within-ROI contrasts (emmeans).ResultsNo metabolite ratio showed a significant BPD vs. control difference. In BPD, IRDA/IRTA-related measures were positively associated with Glx/tCr and Glx/tNAA in the accumbens, and with Glx/tCr in the right caudal anterior cingulate cortex (cACC). BSL-supplement scores showed ROI-dependent associations with tCr/tNAA, with positive ROI-specific effects in the bilateral caudate, right pallidum, and right putamen. Alertness measures were linked to GABA/tCr, Glx/tNAA, and tCr/tNAA (including caudate, pallidum/putamen, cACC, and thalamus), while divided attention omissions and working-memory errors were associated with higher Glx/tCr in the cACC, isthmus cingulate, and hippocampus. ROI-dependent associations were also observed for IQ and verbal learning/recognition with GABA/tCr and tNAA/tCr.DiscussionWhile no robust group differences emerged, mixed-models using continuous predictors linked higher Glx ratios in nucleus accumbens/cACC to IRDA/IRTA and higher striatal tCr/tNAA to BPD symptom severity and neurocognitive performance. These exploratory multimodal signatures point to cortico-striato-limbic mechanisms in BPD and should be confirmed in larger samples.

While social support from romantic partners is known to ameliorate stress responses, it remains unclear whether perceiving a partner’s body odor can elicit similar stress-buffering effects. In this study, 179 participants living in heterosexual romantic relationships underwent either the Trier Social Stress Test (TSST) or a non-stressful control condition while being exposed to their partner’s body odor (collected under standardized conditions over five consecutive nights) or a neutral, non-social control odor presented via an olfactometer. The partner’s odor had no effect on cortisol release. However, contrary to previous findings, subconsciously smelling one’s own partner increased subjective stress and heart rates. Potential underlying mechanisms include the causal misattribution of attraction-related, arousal-induced heart rate increases to the stressful experimental situation, or an evolutionarily adaptive mechanism that amplifies stress responses when a loved one is potentially involved in the threatening situation.

BACKGROUND:While psychological stress is increasing globally, the conditions under which stress facilitates or hinders prosocial behavior remain elusive. To resolve heterogeneous findings, it is essential to consider the modulatory effects of individuals' appraisals of stress as challenging versus threatening. Here, we tested the hypothesis that strengthening an individual's challenge appraisal under stress will enhance prosocial behavior. METHODS:121 individuals (62 women, 59 men) participated in the Trier Social Stress Test for Groups. Participants were instructed to either reappraise their upcoming arousal as adaptive (n = 61) or they performed a reading exercise without instructions on how to cope with the psychosocial stressor (n = 60). Participants then engaged in incentivised resource allocation games. The study's design and sample characteristics were preregistered as a clinical trial (DRKS00027518). RESULTS:We observed no general effect of arousal reappraisal on prosocial behavior. However, reappraising stress-related arousal as a functional resource did enhance prosocial behavior in individuals who had internalized the message and found this intervention to be effective. CONCLUSION:Our findings suggest that cognitive stress appraisals modulate behavioral stress effects, and appraisals can be leveraged to help improve stress-related response and outcomes.

Importance:Close social relationships are linked to improved individual health and even longevity. These effects are hypothesized to be mediated through improved neuroendocrine and immune functioning, particularly in individuals who engage in positive and affectionate interactions. However, systematic data examining these factors in humans are currently lacking. Objective:To investigate the interacting effects of repeated intranasal oxytocin administration, a behavioral microintervention, and daily physical intimacy on neuroendocrine stress responses and dermatological wound healing. Design, Setting, and Participants:This randomized clinical trial was a double-blind, randomized, placebo-controlled study whereby participants completed 3 laboratory visits and a 5-day ecological momentary assessment (EMA). During the first laboratory visit, participants received 4 small suction-blister wounds applied to their forearms. Data were collected from November 20, 2011, to July 25, 2013; final analyses were conducted from December 2023 to February 2025. Interventions:Over the following 7 days, participants were instructed to self-administer either oxytocin or a placebo twice daily and to engage in structured positive interaction (Partner Appreciation Task [PAT]) up to 3 times in total or not. Main Outcomes and Measures:Wound healing was assessed at 24 hours and 7 days after wounding. Throughout the week, participants collected saliva samples for cortisol analyses and reported their stress levels and experiences of partner interaction 6 times per day (5760 measurement points in total). Results:The volunteer sample was 80 healthy, heterosexual couples (N = 160 participants, mean [SD] age, 27.6 [5.0] years). Couples in the PAT condition who received daily oxytocin showed improved wound healing (b = -0.125, t286 = -1.983; P = .048). However, these effects were not consistently robust in sensitivity analyses (b = -0.090, t282 = -1.643; P = .10). Notably, the administration of oxytocin combined with daily affectionate touch (b = -0.038, t137 = -2.091; P = .04) and sexual activity (b = -0.145, t137 = -2.122; P = .04) was linked to a reduction in wound severity. These associations remained largely consistent in sensitivity analyses (affectionate touch: b = -0.037, t135 = -2.057; P = .04; sexual activity: b = -0.131, t135 = -1.900; P = .06). Additionally, greater sexual activity was associated with reduced daily cortisol levels (b = -0.083, t488 = -2.813; P = .005). Conclusions and Relevance:This study found that intimate physical contact can reduce cortisol responses and, along with oxytocin administration, promote wound healing. These findings provide a foundation for future interventions that integrate relationship dynamics and neurohormonal modulation to improve health and recovery from illness. Trial Registration:ClinicalTrials.gov Identifier: NCT01594775.

With the increasing accessibility of large language models to the public, questions arise about whether, and under what conditions, social-emotional interactions with artificial intelligence (AI) can lead to human-like relationship building. Across two double-blind randomised controlled studies with pre-registered analyses, 492 participants engaged in dyadic online interactions using a modified, text-based version of the 'Fast Friends Procedure' (a method designed to enable rapid relationship building), with pre-generated responses by either human partners or a minimally prompted large language model. When labelled as human, the AI outperformed human partners in establishing feelings of closeness during emotionally engaging 'deep-talk' interactions. This striking effect appears to stem from the AI's higher levels of self-disclosure, which in turn enhanced participants' perceptions of closeness. Labelling the partner as an AI reduced, but did not eliminate, relationship building, likely due to participants' lower motivation to engage in interactions with an AI, reflected in both shorter responses and reduced feelings of closeness. These findings highlight AI's potential to relieve overburdened social fields while underscoring the urgent need for ethical safeguards to prevent its misuse in fostering deceptive social connections.

As stress levels rise globally, it is critical to understand whether stress promotes or inhibits prosocial behavior. The literature to date provides inconclusive evidence on this question. Here, we investigated whether the effects of stress on prosocial behavior depend on the interaction partner's social role. Specifically, 121 young adults (59 men, 62 women, age range = 18 - 34 years) performed the Trier Social Stress Test for Groups (TSST-G) before dividing resources among themselves and either another participant (i.e., a peer) or a TSST-G jury member (i.e., the stressor). We found that participants behaved less prosocially toward a stress-inducing TSST-G jury member compared to a peer across various behavioral measures (i.e., trust, trustworthiness, sharing, punishment). Overall, our results suggest that individuals adapt their behavior toward others depending on the social role of their interaction partner, behaving more prosocially toward potential allies than toward those who thwart social goals. More broadly, our study highlights the importance of considering situational variables when examining the effect of stress on prosocial behavior.

OBJECTIVE:This study aimed at evaluating the effects of a minimal couple intervention focusing on positive aspects within the relationship (instructed partnership appreciation task; PAT) in daily life. We hypothesized a stress-buffering effect of this intervention on perceived stress, salivary cortisol and alpha-amylase. METHODS:N = 40 couples were randomly assigned to either PAT or a no PAT (nPAT) condition. Self-reports and saliva samples were assessed six times per day on five consecutive days. To account for couple interdependencies, multilevel modelling (MLM) approaches were used to test the effects of (a) group assignment (PAT vs. nPAT) and (b) practicing the PAT in everyday life (PAT group only). RESULTS:Overall perceived stress was lower for women in the PAT group as compared with women in the nPAT group (b = -.380, p = .0098). Within the PAT group, daily positive interaction (PAT) significantly reduced cortisol (b = -.127, p = .02) and alpha amylase (b = -.122, p = .037). Sex-specific analyses of within-participants effects in daily life indicate that these results were driven by the men in the sample: Practicing the PAT led to a decrease in perceived stress (b = -.271, p = 001) and sCort (b = -.226, p = .006) in men, but not in women (all p > .05). CONCLUSIONS:The findings suggest that a minimal couple intervention can improve individual health-related outcomes in a sex-specific manner, and that effects depend on actually practicing the positive exchange in daily life. TRIAL REGISTRATION:The analysis of the present study is based on a sub-sample (placebo group) of a larger neuropharmacological intervention and longitudinal trial 'Oxytocin, Couple Interaction and Wound Healing' (clinicaltrials.gov, identifier NCT01594775).

OBJECTIVE:Binge eating disorder (BED) is maintained by increased food-related incentive salience, which is reflected by an attentional bias for food. Oxytocin acutely attenuates this bias in patients with anorexia nervosa and reduces food intake in males with normal or increased body weight. However, results in individuals with BED have been inconclusive. We assessed the acute effect of oxytocin on food stimulus processing and reward-driven eating behavior in females with or without BED in a double-blind, placebo-controlled cross-over study. METHOD:Females with BED (n = 48) and female control participants with overweight (n = 46) or normal weight (n = 40) received intranasal oxytocin (24 IU) and, respectively, placebo, after an overnight fast and a standardized breakfast. In participants with a natural menstrual cycle, sessions were scheduled during consecutive luteal phases. Participants completed a food-related dot-probe task with concurrent eye tracking and a bogus taste test measuring snack intake. RESULTS:Oxytocin compared to placebo increased dwell time bias on food stimuli in the BED relative to the overweight control group, in which this effect was reversed. Contrary to our hypothesis, oxytocin increased calorie intake across groups. Exploratory analyses indicated that the latter effect focused on females taking hormonal contraception. DISCUSSION:These results indicate disorder- and, respectively, sex-specific effects of oxytocin on food-related incentive salience and food intake and point to a role of oxytocin in binge eating pathology. They moreover suggest that sex hormones determine the acute effect of oxytocin on eating behavior in females.

Introduction: Previous neuroimaging studies have reported structural brain alterations and local network hyperexcitability in terms of increased slow-wave electroencephalography (EEG) activity in patients with borderline personality disorder (BPD). In particular, intermittent rhythmic delta and theta activity (IRDA/IRTA) has drawn attention in mental health contexts due to its links with metabolic imbalances, neuronal stress, and emotional dysregulation—processes that are highly pertinent to BPD. These functional disturbances may be reflected in corresponding structural brain changes. The current study investigated cortical thickness and subcortical volumes in BPD and examined their associations with IRDA/IRTA events per minute, symptom severity, and neuropsychological measures. Methods: Seventy female BPD patients and 36 age-matched female healthy controls (HC) were included (for clinical EEG comparisons even 72 patients were available). IRDA/IRTA rates were assessed using an automatic independent component analyses (ICA) approach. T1-weighted MRI data were obtained using a MAGNETOM Prisma 3T system and analyzed with FreeSurfer (version 7.2) for subcortical structures and CAT12 for cortical thickness and global volume measurements. Psychometric assessments included questionnaires such as Borderline Symptom List (BSL-23) and Inventory of Personality Organization (IPO). Neuropsychological performance was evaluated with the Test for Attentional Performance (TAP), Culture Fair Intelligence Test (CFT-20-R), and Verbal Learning and Memory Test (VLMT). Results: Between-group comparisons exhibited no significant increase in IRDA/IRTA rates or structural abnormalities between the BPD and HC group. However, within the BPD group, cortical thickness of the right isthmus of the cingulate gyrus negatively correlated with the IRDA/IRTA difference (after minus before hyperventilation, HV; p < 0.001). Furthermore, BPD symptom severity (BSL-23) and IPO scores positively correlated with the thickness of the right rostral anterior cingulate cortex (p < 0.001), and IPO scores were associated with the thickness of the right temporal pole (p < 0.001). Intrinsic alertness (TAP) significantly correlated with relative cerebellar volume (p = 0.01). Discussion: While no group-level structural abnormalities were observed, correlations between EEG slowing, BPD symptom severity, and alertness with cortical thickness and/or subcortical volumes suggest a potential role of the anterior cingulate cortex, temporal pole, and cerebellum in emotion regulation and cognitive functioning in BPD. Future research employing multimodal EEG-MRI approaches may provide deeper insights into the neural mechanisms underlying BPD and guide personalized therapeutic strategies.

Background Previous eye-tracking research on autistic individuals has mostly examined the gaze behavior of one individual in response to social stimuli presented on a computer screen, suggesting that there is atypical gaze behavior. However, it is unknown how these findings translate to the interactive dynamics of gaze behavior during “face-to-face” encounters between two individuals. Only by analyzing the gaze behaviour of both interaction partners is it possible to determine the frequency of actual eye-contact and who initiates or breaks such periods of mutual eye gaze. The knowledge gained from this analysis could contribute to theorizing about the psychological mechanisms (e.g., gaze avoidance vs. gaze indifference) underlying autism. Methods The present study applied a novel dual eye-tracking setup that allows the assessment and analysis of the interactive dynamics of gaze behavior regarding (i) mutual eye gaze (i.e., eye contact), (ii) initiations, and (iii) break-ups of eye contact. Participants (37 autistic individuals, 37 age- and IQ-matched neurotypical individuals) performed a semi-standardized social interaction (i.e., Fast Friends Procedure) with a confederate (trained to interact in a standardized manner). Results Eye contact was reduced in interactions involving autistic individuals. Additional analyses revealed that this reduction was primarily due to the more frequent breaking of eye contact by these individuals. We also found considerable heterogeneity among autistic individuals, with atypical gaze behavior present in only about half of the sample. Limitations Further research is required to determine whether the interactive dynamics of gaze behavior observed in this dual eye-tracking setup can be generalized to real-world situations. Future studies could also include arousal-related physiological measures. Conclusions By tracking the gaze behavior of two interacting individuals, this study reveals specific atypicalities in the interactive dynamics of gaze behavior in a subset of autistic individuals, potentially informing diagnostic and therapeutic decisions. More broadly, our study highlights the added value of dual eye-tracking in elucidating the interactive nature of social encounters in both neurodiverse and neurotypical individuals. Trial registration The study was registered as a clinical trial before starting data collection ( https://drks.de/search/en/trial/DRKS00018957 ; Registration Date: 12/17/2019).

Deep brain stimulation (DBS) of the supero-lateral medial forebrain bundle (slMFB) is associated with rapid and sustained antidepressant effects in treatment-resistant depression (TRD). Beyond that, improvements in social functioning have been reported. However, it is unclear whether social skills, the basis of successful social functioning, are systematically altered following slMFB DBS. Therefore, the current study investigated specific social skills (affective empathy, compassion, and theory of mind) in patients with TRD undergoing slMFB DBS in comparison to healthy subjects. 12 patients with TRD and 12 age- and gender-matched healthy subjects (5 females) performed the EmpaToM, a video-based naturalistic paradigm differentiating between affective empathy, compassion, and theory of mind. Patients were assessed before and three months after DBS onset and compared to an age- and gender-matched sample of healthy controls. All data were analyzed using non-parametric Mann-Whitney U tests. DBS treatment significantly affected patients’ affective responsiveness towards emotional versus neutral situations (i.e. affective empathy): While their affective responsiveness was reduced compared to healthy subjects at baseline, they showed normalized affective responsiveness three months after slMFB DBS onset. No effects occurred in other domains with persisting deficits in compassion and intact socio-cognitive skills. Active slMFB DBS resulted in a normalized affective responsiveness in patients with TRD. This specific effect might represent one factor supporting the resumption of social activities after recovery from chronic depression. Considering the small size of this unique sample as well as the explorative nature of this study, future studies are needed to investigate the robustness of these effects.

Binge eating disorder (BED) is maintained by increased food-related incentive salience, which is reflected by an attentional bias for food. Oxytocin attenuates this attentional bias in patients with anorexia nervosa and reduces hedonic (i.e., mainly reward-driven) food intake in males with normal or increased body weight, but results in individuals with BED are inconclusive. We assessed the acute effect of oxytocin on the processing of food stimuli and on eating behavior in BED in a double-blind, placebo-controlled cross-over study. Females with BED (n = 48) and female control participants with overweight (OWC; n = 46) or normal weight (NWC; n = 40) received intranasal oxytocin after a standardized breakfast following an overnight fast; in participants with natural menstrual cycle, sessions were scheduled during consecutive luteal phases. Participants completed a food-related dot-probe task with concurrent eye tracking and a bogus taste test measuring snack intake. Dwell time bias on food stimuli as well as calorie intake were the main dependent variables. We found an increase in dwell time bias due to oxytocin compared to placebo in the BED relative to the OWC group, in which this relationship was reversed. Contrary to our hypothesis, oxytocin significantly increased hedonic food intake across groups. The latter effect was restricted to females taking hormonal contraception. These results provide support for the assumption of disorder- and, respectively, sex-specific effects of oxytocin on food-related incentive salience and hedonic food intake. They moreover suggest that sex hormones determine the acute effect of oxytocin on eating behavior in females.

Social anxiety disorder (SAD) is a prevalent and disabling mental health condition, characterized by excessive fear and anxiety in social situations. Resting-state functional magnetic resonance imaging (fMRI) paradigms have been increasingly used to understand the neurobiological underpinnings of SAD in the absence of threat-related stimuli. Previous studies have primarily focused on the role of the amygdala in SAD. However, the amygdala consists of functionally and structurally distinct subregions, and recent studies have highlighted the importance of investigating the role of these subregions independently. Using multiband fMRI, we analyzed resting-state data from 135 participants (42 SAD, 93 healthy controls). By employing voxel-wise permutation testing, we examined group differences of fMRI connectivity and associations between fMRI connectivity and social anxiety symptoms to further investigate the classification of SAD as a categorical or dimensional construct. Seed-to-whole brain functional connectivity analysis using multiple ‘seeds’ including the amygdala and its subregions and the precuneus, revealed no statistically significant group differences. However, social anxiety severity was significantly negatively correlated with functional connectivity of the precuneus - perigenual anterior cingulate cortex and positively correlated with functional connectivity of the amygdala (specifically the superficial subregion) - parietal/cerebellar areas. Our findings demonstrate clear links between symptomatology and brain connectivity in the absence of diagnostic differences, with evidence of amygdala subregion-specific alterations. The observed brain-symptom associations did not include disturbances in the brain’s fear circuitry (i.e., disturbances in connectivity between amygdala - prefrontal regions) likely due to the absence of threat-related stimuli.

BACKGROUND:Social withdrawal is a key symptom of depression. The resulting loss of social reinforcement in turn contributes to chronic, recurrent courses of the disease. However, it is not clear whether depressed patients have less motivation to socially interact, or whether their skills in doing so are impaired. The current study investigates potential skill deficits in patients with treatment-resistant depression (TRD).METHODS:15 TRD patients and 19 age- and sex-matched healthy controls performed the EmpaToM, a paradigm which includes naturalistic video stimuli of either neutral or emotional valence and which differentiates between socio-affective (affective empathy, compassion) and socio-cognitive (theory of mind) skills.RESULTS:Controlling for the baseline affective state in neutral situations, TRD patients displayed significantly reduced affective empathy towards emotional situations compared to healthy controls. Furthermore, TRD patients were less compassionate in both neutral and emotional situations. In contrast, socio-cognitive skill performances did not differ between patients and healthy controls.LIMITATIONS:Further studies might explore socio-affective and socio-cognitive skills in TRD patients using socio-affective/-cognitive tasks involving face-to-face social interactions.CONCLUSION:Our study revealed a specific socio-affective deficit in TRD patients, while showing intact socio-cognitive skills. Patients were less able to affectively resonate with others (affective empathy) and exhibited generally reduced feelings of compassion. These deficits might interfere with providing and receiving social support. Our study contributes to a better understanding of the underlying causes of social withdrawal and stresses the need to specifically address pervasive socio-affective deficits in psychotherapy of TRD patients.

The amygdala is important for human fear processing. However, recent research has failed to reveal specificity, with evidence that the amygdala also responds to other emotions. A more nuanced understanding of the amygdala's role in emotion processing, particularly relating to fear, is needed given the importance of effective emotional functioning for everyday function and mental health. We studied 86 healthy participants (44 females), aged 18-49 (mean 26.12 ± 6.6) years, who underwent multiband functional magnetic resonance imaging. We specifically examined the reactivity of four amygdala subregions (using regions of interest analysis) and related brain connectivity networks (using generalized psycho-physiological interaction) to fear, angry, and happy facial stimuli using an emotional face-matching task. All amygdala subregions responded to all stimuli (p-FDR < .05), with this reactivity strongly driven by the superficial and centromedial amygdala (p-FDR < .001). Yet amygdala subregions selectively showed strong functional connectivity with other occipitotemporal and inferior frontal brain regions with particular sensitivity to fear recognition and strongly driven by the basolateral amygdala (p-FDR < .05). These findings suggest that amygdala specialization to fear may not be reflected in its local activity but in its connectivity with other brain regions within a specific face-processing network.

Abstract Disclosure: C. Atila: None. F. Holze: None. R. Murugesu: None. N. Rommers: None. N. Hutter: None. N. Varghese: None. C.O. Sailer: None. A. Eckert: None. M. Heinrichs: None. M. Liechti: None. M. Christ-crain: None. Introduction: Despite adequate treatment, patients with arginine vasopressin deficiency (AVP-D), known as central diabetes insipidus (cDI), often report psychological symptoms such as heightened anxiety levels, difficulties describing emotions, and depressed mood. Given the anatomical proximity, disruptions of the hypothalamic-pituitary axis causing an AVP-D could also disturb the oxytocin (OXT) system. OXT regulates socio-emotional functioning, including fear reduction, attachment, emotion recognition, and empathy. Therefore, these psychological symptoms may be caused by an additional OXT deficiency. However, OXT deficiency has not been established as a pituitary entity, as no provocation test for OXT is currently available. Here, we aimed to investigate the OXT system stimulator 3,4-Methylenedioxymethamphetamine (MDMA, ‘ecstasy’) as a novel biochemical and psychoactive provocation test to reveal an OXT deficiency in patients with cDI. Methods: Randomized, placebo-controlled, double-blind, cross-over study in 15 patients with cDI and 15 matched healthy controls. Participants underwent a psychological baseline evaluation, including the assessment of anxiety levels using the State-Trait Anxiety Inventory (STAI), mood using the Beck’s Depression Inventory (BDI), and alexithymia using the Toronto Alexithymia Scale (TAS). Participants were randomized to receive either a single oral dose of MDMA (100 mg) or placebo first. OXT samples were collected at 0, 90, 120, 150, 180, and 300 minutes after drug intake. Subjective effects in response to MDMA were assessed throughout the experiment. The primary outcome was the area under the plasma OXT concentration curve (AUC) after MDMA intake. Results: Already at baseline, patients compared with healthy controls, showed significantly higher scores in anxiety (STAI: 41 points [IQR 34-48] vs. 28 points [24-31]; p=0.02), alexithymia (TAS: 47 points [38-59] vs. 30 points [29-37; p=0.04), and depression symptoms (BDI: 6 points [3-17] vs. 1 point [0-2]; p=0.04). In response to MDMA stimulation, in patients, there was only a minimal OXT change with 66 pg/ml [16-94], while in healthy controls, OXT increased by 658 pg/ml [355-914]. The AUC was 15.8 times (1485%), i.e., 85,678 pg/ml (95%-CI [-10,800 to -63,356], p<0.001), lower in patients compared with healthy controls. This lack of OXT in patients was associated with lower subjective effects such as ‘good drug effect,’ ‘feeling high,’ ‘satisfaction,’ ‘happy,’ ‘trust,’ ‘talkative,’ ‘openness,’ and ‘fear reduction’ compared with healthy controls. Conclusion: These results lay the groundwork for OXT deficiency as a hypothalamic-pituitary entity. In patients with cDI, this lack in OXT was associated with reduced pro-social, empathic, and anxiolytic effects. Presentation: Saturday, June 17, 2023

Social interactions and particularly affectionate touch are vital for mental and physical health. Research shows that affectionate touch is associated with release of oxytocin and has calming and stress reducing effects suggesting a regulatory effect of oxytocin on the hypothalamic pituitary adrenal (HPA) axis. Here, we aimed to systematically investigate the effects of repeated intranasal oxytocin administration on salivary cortisol. Furthermore, we focused on the moderating role of couples' affectionate touch on biopsychological stress outcomes in everyday life. 80 heterosexual romantic couples (N=160 individuals) completed ecologically momentary assessments over five days. Six times per day participants answered smartphone-based questions regarding affectionate touch and momentary stress levels providing concomitant saliva samples for cortisol assessment. Half of the sample was randomly assigned to an instructed positive appraisal task. In a randomized double-blind design, both partners self-administered oxytocin or placebo on five days twice during the early evening. Multilevel analyses showed that oxytocin administration was associated with higher cortisol in the following morning and stronger decreases during the day. Subjectively reported momentary stress was associated with increase of affectionate touch in couples. Moreover, results indicate that participants, who received affectionate touch from their partner showed significantly lower cortisol levels after oxytocin administration. These results suggest that oxytocin administration paired with affectionate touch in romantic couples can influence HPA axis regulation as indicated via diurnal cortisol levels. Thereby, the data shed light on the neuroendocrine underpinnings of the health-promoting effects of intimate social relationships.