Oxytocin and social learning in socially anxious men and women.

OBJECTIVE: This study extended a classic self-referential learning paradigm by investigating the effects of intranasally-administered oxytocin in high and low socially anxious participants during social learning, as a function of social anxiety levels and sex. METHODS: In a randomized double-blinded design, 160 participants were either given intranasal oxytocin (24 I.U.) or placebo. Subsequently, while lying in an MR scanner, participants were shown neutral faces that were paired with positively, neutrally, or negatively valenced self-referential sentences, during which we measured self-reported arousal and sympathy of the facial stimuli, pupil dilation, and changes in the brain-oxygen-level dependent signal. Four-factor mixed analyses of variance with the between-subjects factors group (high socially anxious vs. low socially anxious), substance (oxytocin vs. placebo), and sex (male vs. female) and the within-subjects factor sentence valence (positive vs. neutral vs. negative) were conducted for each measure, respectively. RESULTS: Administration of intranasal oxytocin yielded an increase in sympathy ratings in high socially anxious compared to low socially anxious individuals and decreased arousal ratings for positively-conditioned faces in low socially anxious participants. As an objective physiological measure of arousal, pupil dilation mirrored the behavioral results. Oxytocin effects on neural activation in the insula interacted with anxiety levels and sex: low socially anxious individuals yielded lower activation under oxytocin than placebo; the converse was observed in high socially anxious individuals. This interaction also differed between sexes, as men yielded higher activation levels than women. These findings were more prominent for positively- and negatively-conditioned faces. Within the amygdala, high socially anxious men yielded higher activation than high socially anxious women in the left hemisphere, and low socially anxious men yielded higher activation than low socially anxious women from positively- and negatively-conditioned faces, though no influence of oxytocin was detected. CONCLUSION: These results suggest oxytocin-induced behavioral, physiological, and neural changes as a function of social learning in socially low and high anxious individuals. These findings challenge the amygdalocentric view of the role of emotions in social learning, instead contributing to the growing body of findings implicating the insula therein, revealing an interaction between oxytocin, sex, and emotional valence. Such discoveries raise an interesting set of questions regarding the computational goals of regions such as the insula in emotional learning and how neural activity can play a diagnostic or prognostic role in social anxiety, potentially leading to new treatment opportunities that may combine oxytocin and neurofeedback differentially for men and women.

How professional and academic pre-qualifications relate to success in medical education: Results of a multicentre study in Germany.

OBJECTIVE: Every year, many applicants want to study medicine. Appropriate selection procedures are needed to identify suitable candidates for the demanding curriculum. Although research on medical school admissions has shown good predictive validity for cognitive selection methods (undergraduate GPA, aptitude tests), the literature on applicants with professional and/or academic experience prior to entering medical school remains slim. In our study, we therefore aimed to examine the association between academic success in medical school and having previously completed vocational training in the medical field, voluntary service (≥11 months) or an academic degree. METHODS: Data were collected in a multicentre, cross-sectional study at five medical schools in Germany (Baden-Wuerttemberg) from students during medical school (i.e. 3rd-, 6th-, and 10th-semester and final-year students). Academic success was assessed according to scores on the first and second state examinations, the total number of examinations repeated and the number of semesters beyond the standard period of study. For the analysis we calculated ordinal logistic regression models for each outcome variable of academic success. RESULTS: A total of N = 2,370 participants (response rate: RR = 47%) participated in the study. Having completed vocational training was associated with a higher amount of repeated examinations (small effect), while having an academic degree was associated with worse scores on the second state examination (medium effect). No significant association emerged between voluntary service and academic success. CONCLUSION: The results indicate that professional and academic pre-qualifications pose no advantage for academic success. Possible associations with the financing of study and living conditions of students with pre-qualifications were analysed and discussed in an exploratory manner. However, the operationalisation of academic success from objective and cognitive data should be critically discussed, as the benefits of prior experience may be captured by personal qualities rather than examination results.

Childhood Maltreatment and Amygdala Response to Interpersonal Threat in a Transdiagnostic Adult Sample: The Role of Trait Dissociation.

BACKGROUND: Childhood maltreatment (CM) confers risk for different mental disorders as well as transdiagnostic symptoms such as dissociation. Aberrant amygdala response to interpersonal threat may link CM to transdiagnostic psychopathology and has recently been shown to depend on type and developmental timing of CM experiences. Still, most studies on CM and threat-related amygdala response employ categorical disorder-specific perspectives and fail to consider type and timing of CM exposure. We aimed to investigate associations between CM, amygdala response to interpersonal threat, and dimensional psychopathological symptoms including trait dissociation in a transdiagnostic adult sample, specifically considering type, timing, and duration of CM. METHODS: We conducted a cross-sectional neuroimaging study in 141 participants with varying levels of CM, including mostly female participants with major depressive disorder (n = 36), posttraumatic stress disorder (n = 34), and somatic symptom disorder (n = 35) and healthy volunteers (n = 36). Participants underwent functional magnetic resonance imaging during an emotional face-matching task, completed the brief German interview version of the Maltreatment and Abuse Chronology of Exposure scale, and answered self-report measures of transdiagnostic CM-related symptoms including trait dissociation. Data were analyzed using a machine learning-based model comparison procedure. RESULTS: In our transdiagnostic sample, neither type nor timing or duration of CM predicted amygdala response to interpersonal threat. Instead, trait dissociation predicted blunted bilateral amygdala response and emerged as a possible mediator between CM and amygdala function. CONCLUSIONS: Trait dissociation may be an important confounder in the widely documented association between CM and threat-related amygdala response, which should be considered in future longitudinal studies.

Stress and reward in the maternal brain of mothers with borderline personality disorder: a script-based fMRI study.

Borderline personality disorder (BPD) is associated with altered neural activity in regions of salience and emotion regulation. An exaggerated sensitization to emotionally salient situations, increased experience of emotions, and dysfunctional regulative abilities could be reasons for increased distress also during parenting. Mothers with BPD tend to have less reciprocal mother-child interactions (MCI) and reveal altered cortisol and oxytocin reactivity in the interaction with their child, which could indicate altered processing of stress and reward. Here, we studied underlying neural mechanisms of disrupted MCI in BPD. Twenty-five mothers with BPD and 28 healthy mothers participated in a script-driven imagery functional magnetic resonance imaging (fMRI)-paradigm. Scripts described stressful or rewarding MCI with the own child, or situations in which the mother was alone. Mothers with BPD showed larger activities in the bilateral insula and anterior cingulate cortex (ACC) compared to healthy mothers during the imagination of MCI and non-MCI. Already in the precursory phase while listening to the scripts, a similar pattern emerged with stronger activity in the left anterior insula (AINS), but not in the ACC. This AINS activity correlated negatively with the quality of real-life MCI for mothers with BPD. Mothers with BPD reported lower affect and higher arousal. An exaggerated sensitization to different, emotionally salient situations together with dysfunctional emotion regulation abilities, as reflected by increased insula and ACC activity, might hinder sensitive maternal behavior in mothers with BPD. These results underline the importance for psychotherapeutic interventions to improve emotional hyperarousal and emotion regulation in patients with BPD, especially in affected mothers caring for young children.

Evidence for a shared genetic contribution to loneliness and borderline personality disorder.

Loneliness, influenced by genetic and environmental factors such as childhood maltreatment, is one aspect of interpersonal dysfunction in Borderline Personality Disorder (BPD). Numerous studies link loneliness and BPD and twin studies indicate a genetic contribution to this association. The aim of our study was to investigate whether genetic predisposition for loneliness and BPD risk overlap and whether genetic risk for loneliness contributes to higher loneliness reported by BPD patients, using genome-wide genotype data. We assessed the genetic correlation of genome-wide association studies (GWAS) of loneliness and BPD using linkage disequilibrium score regression and tested whether a polygenic score for loneliness (loneliness-PGS) was associated with case-control status in two independent genotyped samples of BPD patients and healthy controls (HC; Witt2017-sample: 998 BPD, 1545 HC; KFO-sample: 187 BPD, 261 HC). In the KFO-sample, we examined associations of loneliness-PGS with reported loneliness, and whether the loneliness-PGS influenced the association between childhood maltreatment and loneliness. We found a genetic correlation between the GWAS of loneliness and BPD in the Witt2017-sample (rg = 0.23, p = 0.015), a positive association of loneliness-PGS with BPD case-control status (Witt2017-sample: NkR² = 2.3%, p = 2.7*10-12; KFO-sample: NkR² = 6.6%, p = 4.4*10-6), and a positive association between loneliness-PGS and loneliness across patient and control groups in the KFO-sample (ß = 0.186, p = 0.002). The loneliness-PGS did not moderate the association between childhood maltreatment and loneliness in BPD. Our study is the first to use genome-wide genotype data to show that the genetic factors underlying variation in loneliness in the general population and the risk for BPD overlap. The loneliness-PGS was associated with reported loneliness. Further research is needed to investigate which genetic mechanisms and pathways are involved in this association and whether a genetic predisposition for loneliness contributes to BPD risk.

The mediating role of attachment and anger: exploring the impact of maternal early-life maltreatment on child abuse potential.

Background: Maternal early-life maltreatment (ELM) increases the risk of subsequent child maltreatment, but the underlying mechanisms of these intergenerational effects remain largely unknown. Identifying these mechanisms is crucial for developing preventive interventions that can break the cycle of abuse. Notably, previous research has shown that ELM often results in attachment insecurity and altered anger characteristics. Therefore, this study determines whether these characteristics mediate the relationship between maternal history of ELM and child abuse potential. Methods: The study sample included 254 mothers, of whom 149 had experienced ELM to at least a moderate degree. Maternal ELM was assessed using the Childhood Experience of Care and Abuse (CECA) interview. Attachment insecurity, trait anger and anger expression, and maternal abuse potential were assessed using the Vulnerable Attachment Questionnaire (VASQ), State-Trait Anger Expression Inventory (STAXI), and Child Abuse Potential Inventory (CAPI), respectively. Results: The severity of maternal ELM predicted higher child abuse potential, with attachment insecurity and anger suppression mediating this effect. Specifically, higher levels of maternal ELM were associated with greater attachment insecurity and increased anger suppression, resulting in a higher child abuse potential. Although higher levels of trait anger were directly associated with higher child abuse potential, this parameter did not mediate the relationship with ELM. In addition, no significant associations were observed between outwardly expressed anger and ELM or child abuse potential. All analyses were adjusted for maternal mental disorders, years of education, and relationship status. Discussion: Attachment insecurity and anger suppression may serve as pathways linking the maternal history of ELM to the risk of child abuse, even when considering maternal psychopathology. Overall, our findings indicate that interventions aimed at strengthening attachment and improving anger suppression may be beneficial for all mothers with ELM history and high child abuse potential, not just those who suffer from mental illness.

Prevalence of COVID-19 and Psychotropic Drug Treatment in Psychiatric In-patients in Germany in 2020: Results from a Nationwide Pilot Survey.

INTRODUCTION: In patients with a pre-existing mental disorder, an increased risk for a first manifestation of a psychiatric disorder in COVID-19 patients, a more severe course of COVID-19 and an increased mortality have been described. Conversely, observations of lower COVID-19 incidences in psychiatric in-patients suggested protective effects of psychiatric treatment and/or psychotropic drugs against COVID-19. METHODS: A retrospective multi-center study was conducted in 24 German psychiatric university hospitals. Between April and December 2020 (the first and partly second wave of COVID-19), the effects of COVID-19 were assessed on psychiatric in-patient care, the incidence and course of a SARS-CoV-2 infection, and treatment with psychotropic drugs. RESULTS: Patients (n=36,322) were admitted to the hospitals. Mandatory SARS-CoV-2 tests before/during admission were reported by 23 hospitals (95.8%), while 18 (75%) conducted regular testing during the hospital stay. Two hundred thirty-two (0.6%) patients were tested SARS-CoV-2-positive. Thirty-seven (16%) patients were receiving medical treatment for COVID-19 at the psychiatric hospital, ten (4.3%) were transferred to an intermediate/intensive care unit, and three (1.3%) died. The most common prescription for SARS-CoV-2-positive patients was for second-generation antipsychotics (n=79, 28.2%) and antidepressants (SSRIs (n=38, 13.5%), mirtazapine (n=36, 12.9%) and SNRIs (n=29, 10.4%)). DISCUSSION: Contrary to previous studies, our results showed a low number of infections and mortality in SARS-CoV-2-positive psychiatric patients. Several preventive measures seem effective to protect this vulnerable group. Our observations are compatible with the hypothesis of a protective effect of psychotropic drugs against COVID-19 as the overall mortality and need for specific medical treatment was low.

Altered amygdalar emotion space in borderline personality disorder normalizes following dialectical behaviour therapy.

BACKGROUND: Borderline personality disorder (BPD) is a mental health condition characterized by an inability to regulate emotions or accurately process the emotional states of others. Previous neuroimaging studies using classical univariate analyses have tied such emotion dysregulation to aberrant activity levels in the amygdala of patients with BPD. However, multivariate analyses have not yet been used to investigate how representational spaces of emotion information may be systematically altered in patients with BPD. METHODS: Patients with BPD performed an emotional face matching task while undergoing MRI before and after a 10-week inpatient program of dialectical behavioural therapy. Representational similarity analysis (RSA) was applied to activity patterns (evoked by angry, fearful, neutral and surprised faces) in the amygdala and temporo-occipital fusiform gyrus of patients with BPD and in the amygdala of healthy controls. RESULTS: We recruited 15 patients with BPD (8 females, 6 males, 1 transgender male) to participate in the study, and we obtained a neuroimaging data set for 25 healthy controls for a comparative analysis. The RSA of the amygdala revealed a negative bias in the underlying affective space (in that activity patterns evoked by angry, fearful and neutral faces were more similar to each other than to patterns evoked by surprised faces), which normalized after therapy. This bias-to-normalization effect was present neither in activity patterns of the temporo-occipital fusiform gyrus of patients nor in amygdalar activity patterns of healthy controls. LIMITATIONS: Larger samples and additional questionnaires would help to better characterize the association between specific aspects of therapy and changes in the neural representational space. CONCLUSION: Our findings suggest a more refined role for the amygdala in the pathological processing of perceived emotions and may provide new diagnostic and prognostic imaging-based markers of emotion dysregulation and personality disorders.Clinical trial registration: DRKS00019821, German Clinical Trials Register (Deutsches Register Klinischer Studien).

[Personalized psychotherapy of posttraumatic stress disorder : Overview on the selection of treatment methods and techniques using statistical procedures]. / Personalisierte Psychotherapie der posttraumatischen Belastungsstörung : Übersicht zur Auswahl von Behandlungsmethoden und -techniken mittels statistischer Verfahren.

BACKGROUND: A relevant heterogeneity of treatment effects in posttraumatic stress disorder (PTSD) is discussed with respect to the debate about the necessity of phase-based treatment and in light of the new diagnosis of complex PTSD and has recently been proven; however, there has been little personalization in the treatment of PTSD. This article presents the current state of research on the personalized selection of specific psychotherapeutic methods for the treatment of PTSD based on patient characteristics using statistical methods. METHODS: A systematic literature search was conducted in the PubMed (including Medline), Embase, Web of Science Core Collection, Google Scholar, PsycINFO and PSYNDEX databases to identify clinical trials and reviews examining personalized treatment for PTSD. RESULTS: A total of 13 relevant publications were identified, of which 5 articles were predictor analyses in samples without control conditions and 7 articles showed analyses of randomized controlled trials (RCT) with a post hoc comparison of treatment effects in optimally and nonoptimally assigned patients. In addition, one article was a systematic review on the treatment of patients with comorbid borderline personality order and PTSD. DISCUSSION: The available manuscripts indicate the importance and benefits of personalized treatment in PTSD. The relevant predictor variables identified for personalization should be used as a suggestion to investigate them in future prospective studies.

Depression and social isolation during the COVID-19 pandemic in a student population: the effects of establishing and relaxing social restrictions.

Introduction: In a quasi-naturalistic study design, we evaluate the change in psychopathological syndromes and general well-being after the alleviation of social restrictions. The aim of this study was to investigate the specific relationship between social isolation and depressive syndromes. Methods: At two timepoints, the first during maximal social restrictions, the second after social restrictions had widely ended for 9 months, depressive and other syndromes were measured in an online survey addressing the total cohort of students registered at Heidelberg University, Germany via e-mail (n = 27,162). The complete Patient Health Questionnaire (PHQ) was used with nine items for depressive syndromes. In addition, well-being was measured by the Well-Being Index WHO-5. In the quantitative and qualitative part of the study psychopathological syndromes and well-being were related to social isolation and feelings of loneliness. Results: After 1.5 years of pandemic-related social restrictions, "major" depressive syndromes were reported by 40.16% of the respondents to the PHQ in a sample of 2,318 university students. 72.52% showed a severely reduced Well-Being-Index. Nine months after the end of social restrictions, "major" depressive syndromes were reported by 28.50% of the participants. Well-being improved after the alleviation of social restrictions, as well: 53.96% showed a Well-Being Index of below 50 vs. 72.52% in the first study. The quantitative and qualitative analysis of the free texts of the respondents suggest that a significant amount of depressive syndromes and reduced well-being are related to social isolation and loneliness. While in the times of the pandemic restrictions the participants mostly reported "loneliness and social isolation" (24.2%) as their main problem, only 7.7% described these as their main problem after social restrictions had been loosened for 9 months. The qualitative analysis hints that at t2 participants were more likely to mention possible ways to actively deal with loneliness than at t1, which might be interpreted along the lines of the decrease in depressive syndromes. Discussion: Keeping the self-selection bias in mind our study results suggest that one third of "major" depressive syndromes and one quarter of severely reduced well-being accompany social restrictions or are even caused by them, with loneliness being an important factor. These results should be taken into account by health policies when coping with future pandemics.

Microsocial analysis of dyadic interactions with toddlers and mothers with borderline personality disorder.

Borderline personality disorder (BPD) is known for disruptions in mother-child interaction, but possible underlying patterns of micro-behavior are barely understood. This is the first study examining behavioral dyadic synchrony-the coordinated and reciprocal adaptation of behavior-and regulation on a micro-level and relating it to macro-behavior in mothers with BPD and their toddlers. Twenty-five mothers with BPD and 29 healthy mothers participated with their 18- to 36-month-old toddlers in a frustration-inducing paradigm. Mother and toddler behavior was continuously micro-coded for gaze, affect, and vocalization. Synchrony, operationalized as the simultaneous engagement in social gaze and positive affect, and (co-)regulative behaviors and their contingencies were analyzed and associated with borderline symptom severity, the overall quality of interaction, and child internalizing and externalizing behavioral problems. Dyads with mothers with BPD showed significantly less synchrony compared to dyads with healthy mothers. Low synchrony was associated with high BPD symptom severity and low overall interaction quality. Dyads with BPD used the same amount of regulative behaviors as dyads with healthy mothers. Though both groups equally responded to children's negative emotionality, mothers with BPD were less effective in drawing the dyad back into synchrony. For dyads with BPD, regulative behaviors were negatively associated with child externalizing behaviors. BPD symptomology may reduce the effectiveness of mothers' attempts to attune to their child's needs. An emphasis on synchrony and regulative behaviors may be an important therapeutic target for parenting programs in mothers with BPD.

Planetary health as a main topic for the qualification in digital teaching - a project report.

Aim: To do justice to the need for planetary health in medical education, these are the aims of the online elective course "Planetary Health in Medical Education" (ME elective):1. Enable students to plan and realize their own course sessions on planetary health;2. Encourage communication among university medical faculties regarding planetary health in medical education;3. Reinforce competency in digital teaching and amplify the expert role as multiplicator among students pursuing a Master's degree in Medicinal Education (MME). Method: The development of the ME elective followed Kern's six-step approach to curriculum development by means of cooperation between the German Medical Students' Association (Bundesvertretung der Medizinstudierenden in Deutschland, abbreviated as bvmd), and the MME study program. Based on general and specific needs analyses, core learning objectives regarding planetary health, medical education and digital education were identified in the National Catalogue of Learning Objectives in Undergraduate Medical Education (NKLM) and the MME study program and relevant teaching methods were selected. Results: The ME elective, consisting of two contact hours per week per semester, was established at 13 medical schools as a four-phase course:1. Introduction to medical education using examples from planetary health;2. Lesson planning on a topic in planetary health under the supervision of MME students;3. Course sessions held by the undergraduate students; and4. Networking with the MME study program through participation in digital courses on planetary health and the pilot OSCE on planetary health.A total of 24 students attended the pilot in the 2022 summer semester. Conclusion: The topic of planetary health combines interests that span many subjects and semester levels. As a collaborative, interdisciplinary and interprofessional subject, it lends itself to training students in a trans-institutional elective course to become multiplicators.

The refugee and asylum seeker mental health treatment screener (RAS-MT-screener): Feasibility and psychometric properties of a questionnaire detecting refugees' and asylum seekers' need and urgency for mental health treatment.

OBJECTIVE: Refugees and asylum seekers are highly vulnerable to the development of mental health problems, yet oftentimes their need is underestimated. We aimed to develop a culturally sensitive screening tool for primary care settings assessing the urgency and need for mental health treatment to close this gap. METHOD: Items for the screening tool were selected out of an item pool generated by a group of clinical experts based on the data obtained from n = 307 asylum seekers in a refugee state registration and reception center in Germany. Out of these, n = 111 attended a psychosocial walk-in clinic, and clinicians' ratings of urgency and need for mental health treatment were added. RESULTS: The resulting questionnaire comprised 8 items assessing urgency and 13 items assessing need for mental health treatment. Sensitivity was =0.74 and specificity =0.70. Participants of clinical and non-clinical samples differ highly significantly (p < .001). Cross-cultural validity was shown by comparing measurement invariance for different countries of origin. CONCLUSION: The RAS-MT-Screener is a clinically and cross-culturally valid screening tool in primary care settings for the urgency and need for mental health treatment with acceptable psychometric properties. Future research on its external and construct validity is warranted.

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.

Oxytocin effects on amygdala reactivity to angry faces in males and females with antisocial personality disorder.

The amygdala is a key region in current neurocircuitry models of reactive aggression as it is crucially involved in detecting social threat and provocation. An increased amygdala reactivity to angry faces has been reported in aggression-prone individuals and the neuropeptide oxytocin (OT) could dampen anger-related amygdala reactivity in a number of mental disorders. One example is the antisocial personality disorder (ASPD) which has so far only been studied in limited numbers. To address the question whether OT can normalize amygdala hyperreactivity to emotional faces, we conducted a functional magnetic resonance imaging experiment with 20 men and 18 women with ASPD and 20 male and 20 female healthy control (HC) participants in a double-blind, randomized, placebo (PLC)-controlled within-subject design. Participants were exposed to an emotion classification task (fearful, angry, and happy faces) after receiving an intranasal dose (24 IU) of synthetic OT or PLC. We found OT to attenuate right amygdala hyperactivity to angry faces in participants with ASPD to such an extent that the intensity of amygdala activity in the ASPD group in the OT condition decreased to the level of amygdala activity in the PLC condition in the HC group. There was also a trend that OT effects were generally larger in women than in men. These findings suggest that OT differentially modulates the amygdala following social threatening or provoking cues in dependence of psychopathology (ASPD vs. HC) and sex (male vs. female). Particularly female ASPD patients could benefit from OT in the treatment of reactive aggression.

Adverse childhood experiences mediate the negative association between borderline personality disorder symptoms and plasma oxytocin.

Background Interpersonal dysfunction is a core symptom of borderline personality disorder (BPD) and may be closely linked to adverse childhood experiences. According to a recent model on the pathology of BPD, the neuropeptide oxytocin might play an important role in the development and maintenance of the disorder. However, so far, only few studies with small adult samples have reported reduced baseline oxytocin levels in BPD that may be linked to adverse childhood experiences. Methods We examined baseline plasma oxytocin levels in 131 female patients with BPD and 124 non-BPD female controls across a large age span (12-50 years). Additionally, 113 female patients with less than five DSM-IV BPD features were included to examine the association between plasma oxytocin levels and the number of fulfilled BPD criteria. We also explored associations between plasma oxytocin and adverse childhood experiences as well as depressive symptoms in BPD. Results Patients with BPD had reduced plasma oxytocin levels compared to non-BPD controls and this was independent of age. Plasma oxytocin was negatively associated with the number of fulfilled BPD criteria. The exploratory regression model revealed no association between plasma oxytocin and depressive symptoms but an association between plasma oxytocin and adverse childhood experiences, which in fact mediated the relationship between BPD criteria und plasma oxytocin. Conclusion In a large sample of individuals with BPD across a large age span, our results replicate and extend previous reports of reduced plasma oxytocin levels that might be related to adverse childhood experiences thus providing further evidence for a prominent role of oxytocin in BPD.

Your smile won't affect me: Association between childhood maternal antipathy and adult neural reward function in a transdiagnostic sample.

Aberrant activation in the ventral striatum (VS) during reward anticipation may be a key mechanism linking adverse childhood experiences (ACE) to transdiagnostic psychopathology. This study aimed to elucidate whether retrospectively reported ACE, specifically maternal antipathy, relate to monetary and social reward anticipation in a transdiagnostic adult sample. A cross-sectional neuroimaging study was conducted in 118 participants with varying levels of ACE, including 25 participants with posttraumatic stress disorder (PTSD), 32 with major depressive disorder (MDD), 29 with somatic symptom disorder (SSD), and 32 healthy volunteers (HVs). Participants underwent functional magnetic resonance imaging during a monetary and social incentive delay task, and completed a self-report measure of ACE, including maternal antipathy. Neural correlates of monetary and social reward anticipation and their association with ACE, particularly maternal antipathy, were analyzed. Participants showed elevated activation in brain regions underlying reward processing, including the VS, only while anticipating social, but not monetary rewards. Participants reporting higher levels of maternal antipathy exhibited reduced activation in the brain reward network, including the VS, only during social, but not monetary reward anticipation. Group affiliation moderated the association between maternal antipathy and VS activation to social reward anticipation, with significant associations found in participants with PTSD and HVs, but not in those with MDD and SSD. Results were not associated with general psychopathology or psychotropic medication use. Childhood maternal antipathy may confer risk for aberrant social reward anticipation in adulthood, and may thus be considered in interventions targeting reward expectations from social interactions.

An analgesic pathway from parvocellular oxytocin neurons to the periaqueductal gray in rats.

The hypothalamic neuropeptide oxytocin (OT) exerts prominent analgesic effects via central and peripheral action. However, the precise analgesic pathways recruited by OT are largely elusive. Here we discovered a subset of OT neurons whose projections preferentially terminate on OT receptor (OTR)-expressing neurons in the ventrolateral periaqueductal gray (vlPAG). Using a newly generated line of transgenic rats (OTR-IRES-Cre), we determined that most of the vlPAG OTR expressing cells targeted by OT projections are GABAergic. Ex vivo stimulation of parvocellular OT axons in the vlPAG induced local OT release, as measured with OT sensor GRAB. In vivo, optogenetically-evoked axonal OT release in the vlPAG of as well as chemogenetic activation of OTR vlPAG neurons resulted in a long-lasting increase of vlPAG neuronal activity. This lead to an indirect suppression of sensory neuron activity in the spinal cord and strong analgesia in both female and male rats. Altogether, we describe an OT-vlPAG-spinal cord circuit that is critical for analgesia in both inflammatory and neuropathic pain models.

The impact of traumatic childhood experiences on interoception: disregarding one's own body.

BACKGROUND: Deficient interoception, the processing and perception of internal bodily signals, has been discussed as a mechanism underlying various mental disorders. First results indicate a mediating role of interoception in the interplay of traumatic childhood experiences and adult mental disorders. Traumatic childhood experiences may hinder the adequate processing, integration, and trust in bodily signals that are important in order to understand and regulate own needs and emotions, thereby increasing the vulnerability for mental disorders. However, an overarching study investigating alterations in different interoceptive measures and trauma-related disorders as well as their mediating role between early trauma and emotion dysregulation is still missing. METHODS: One hundred thirty-six individuals with varying levels of traumatic childhood experiences who either had a current diagnosis of major depression, posttraumatic stress disorder, or somatic symptom disorder, or no mental disorder, took part in a multidimensional assessment of interoceptive processes, including interoceptive accuracy, sensibility, and awareness. Kruskal-Wallis tests were used to compare groups regarding interoceptive processes and associations with traumatic childhood experiences and emotion dysregulation were analyzed with Spearman correlations. Furthermore, mediation analyses were computed to examine and compare interoceptive processes as potential mediators between traumatic childhood experiences and emotion dysregulation. RESULTS: Only body dissociation, a measure for interoceptive sensibility, was significantly reduced in individuals with a current mental disorder. Body dissociation was also the only interoceptive measure significantly associated with traumatic childhood experiences and emotion dysregulation and the only significant mediator in the relationship between traumatic childhood experiences and emotion dysregulation across groups. CONCLUSION: Results suggest body dissociation, but not other interoceptive measures, as an important feature linking traumatic childhood experiences to current emotion dysregulation, an important transdiagnostic feature. As body dissociation refers to a habitual non-attendance or disregard of interoceptive signals, integrative therapeutic interventions could help affected individuals to overcome difficulties in emotion perception and regulation. TRIAL REGISTRATION: The general study design was preregistered; see the German Clinical Trials Register (DRKS-ID: DRKS00015182). This study's analysis plan was not preregistered.

Structural Correlates of Lifetime Voice-Hearing in Patients with Borderline Personality Disorder: A Pilot Study.

INTRODUCTION: Auditory verbal hallucinations (AVH) are transdiagnostic phenomena that can occur in several mental disorders, including borderline personality disorder (BPD). Despite the transdiagnostic relevance of these symptoms, very little is known about neural signatures of AVH in BPD. METHODS: We used structural magnetic resonance imaging to investigate multiple markers of brain morphology in BPD patients presenting with a lifetime history of AVH (AVH, n = 6) versus BPD patients without AVH (nAVH, n = 10) and healthy controls (HC, n = 12). The Computational Anatomy Toolbox (CAT12) was used for surface-based morphometric analyses that considered cortical thickness (CTh), gyrification (CG), and complexity of cortical folding (CCF). Factorial models were used to explore differences between AVH patients and HC, as well as between the patient groups. RESULTS: Compared to HC, AVH patients showed distinct abnormalities in key regions of the language network, i.e., aberrant CTh and CG in right superior temporal gyrus and abnormal CCF in left inferior frontal gyrus. Further abnormalities were found in right prefrontal cortex (CTh) and left orbitofrontal cortex (CCF). Compared to nAVH patients, individuals with AVH showed abnormal CTh in right prefrontal cortex, along with CCF differences in right transverse temporal, superior parietal, and parahippocampal gyri. CG differences between the patient groups were found in left orbitofrontal cortex. CONCLUSION: The data suggest a transdiagnostic neural signature of voice-hearing that converges on key regions involved in speech generation and perception, memory and executive control. It is possible that cortical features of distinct evolutionary and genetic origin, i.e., CTh and CG/CCF, differently contribute to AVH vulnerability in BPD.