With the use of real-time functional magnetic resonance imaging neurofeedback (NF), amygdala activitiy can be visualized in real time. In this study, continuous amygdala NF was provided to patients with borderline personality disorder (BPD) with the instruction to down-regulate. During four sessions of NF training, patients viewed aversive pictures and received feedback from a thermometer display, which showed the amygdala blood oxygenation level-dependent signal. Conditions of regulation and viewing without regulation were presented. Each session started with a resting-state scan and was followed by a transfer run without NF. Amygdala regulation, task-related and resting-state functional brain connectivity were analyzed. Self-ratings of dissociation and difficulty in emotion regulation were collected. BPD patients down-regulated right amygdala activation but there were no improvements over time. Task-related amygdala-ventromedial prefrontal cortex connectivity was altered across the four sessions, with an increased connectivity when regulating vs viewing pictures. Resting-state amygdala-lateral prefrontal cortex connectivity was altered and dissociation, as well as scores for 'lack of emotional awareness', decreased with training. Results demonstrated that amygdala NF may improve healthy brain connectivity, as well as emotion regulation. A randomized-controlled trial is needed to investigate whether amygdala NF is instrumental for improving neural regulation and emotion regulation in BPD patients.

The objective of this study was to investigate the hypothesis that borderline personality disorder (BPD) and bipolar disorder (BD) share genetic variation through analysis of known genetic risk factors for BD in a well-characterized BPD case-control cohort. Genotyping of five genome-wide significant variants identified for BD (in CACNA1C, ANK3, and ODZ4) was performed in 673 BPD cases and 748 controls. A nominally significant association with BPD was found for rs1006737 in CACNA1C (P=0.0498). Sex-specific analysis showed that this signal was present only in women. This is the first report of an association between a BD risk gene and BPD where selection was not based on a priori hypotheses about its function, but on an unbiased hypothesis-free screening of the genome. Genome-wide association data of large samples of BPD are warranted and will eventually identify new risk genes and the overlap between BPD and BD if it exists.

Early experiences of childhood sexual or physical abuse are often associated with functional impairments, reduced well-being and interpersonal problems in adulthood. Prior studies have addressed whether the traumatic experience itself or adult psychopathology is linked to these limitations. To approach this question, individuals with posttraumatic stress disorder (PTSD) and healthy individuals with and without a history of child abuse were investigated. We used global positioning system (GPS) tracking to study temporal and spatial limitations in the participants' real-life activity space over the course of one week. The sample consisted of 228 female participants: 150 women with PTSD and emotional instability with a history of child abuse, 35 mentally healthy women with a history of child abuse (healthy trauma controls, HTC) and 43 mentally healthy women without any traumatic experiences in their past (healthy controls, HC). Both traumatized groups-i.e. the PTSD and the HTC group-had smaller movement radii than the HC group on the weekends, but neither spent significantly less time away from home than HC. Some differences between PTSD and HC in movement radius seem to be related to correlates of PTSD psychopathology, like depression and physical health. Yet group differences between HTC and HC in movement radius remained even when contextual and individual health variables were included in the model, indicating specific effects of traumatic experiences on activity space. Experiences of child abuse could limit activity space later in life, regardless of whether PTSD develops.

Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders.

Adverse experiences can lead to severe mental health problems, such as posttraumatic stress disorder (PTSD), throughout the lifespan. In individuals with PTSD, both global and local brain volume reductions have been reported-especially in the amygdala and hippocampus-while the literature on childhood maltreatment suggests a strong dependency on the timing of adverse events. In the present study, we pooled data from two studies to contrast the effects of reported trauma exposure during neurodevelopmentally sensitive periods in early life with trauma exposure during adulthood. A total of 155 women were allocated into one of six age-matched groups according to the timing of traumatization (childhood vs adulthood) and psychopathology (PTSD vs trauma-exposed healthy vs trauma-naïve healthy). Volumes of the amygdala and hippocampus were compared between these groups. Six additional exploratory regions of interest (ROI) were included based on a recent meta-analysis. Amygdala volume was strongly dependent on the timing of traumatization: Smaller amygdala volumes were observed in participants with childhood trauma and PTSD compared to the healthy control groups. In contrast, larger amygdala volumes were observed in both groups with trauma exposure during adulthood compared to the trauma-naïve control group. Hippocampal volume comparisons revealed no statistically significant differences, although the descriptive pattern was similar to that found for the amygdala. The remaining exploratory ROIs showed significant group effects, but no timing effects. The timing might be an important moderator for adversity effects on amygdala volume, potentially reflecting neurodevelopmental factors. Albeit confounded by characteristics like trauma type and multiplicity, these findings pertain to typical childhood and adulthood trauma as often observed in clinical practice and speak against a simple association between traumatic stress and amygdala volume.

Both environmental (e.g. interpersonal traumatization during childhood and adolescence) and genetic factors may contribute to the development of Borderline Personality Disorder (BPD). Twin studies assessing borderline personality symptoms/features in the general population indicate that genetic factors underlying these symptoms/features are shared in part with the personality traits of the Five Factor Model (FFM) of personality-the "Big Five". In the present study, the genetic overlap of BPD with the Big Five -Openness to Experience, Conscientiousness, Extraversion, Agreeableness, and Neuroticism- was assessed. Linkage disequilibrium score regression was used to calculate genetic correlations between a genome-wide association study (GWAS) in central European populations on BPD (N = 2543) and GWAS on the Big Five (N = 76,551-122,886, Neuroticism N = 390,278). Polygenic scores (PGS) were calculated to test the association of the genetic disposition for the personality traits with BPD case-control status. Significant positive genetic correlations of BPD were found with Neuroticism (rg = 0.34, p = 6.3*10-5) and Openness (rg = 0.24, p = 0.036), but not with the other personality traits (all | rg | <0.14, all p > 0.30). A cluster and item-level analysis showed positive genetic correlations of BPD with the Neuroticism clusters "Depressed Affect" and "Worry", and with a broad range of Neuroticism items (N = 348,219-376,352). PGS analyses confirmed the genetic correlations, and found an independent contribution of the personality traits to BPD risk. The observed associations indicate a partially shared genetic background of BPD and the personality traits Neuroticism and Openness. Larger GWAS of BPD and the "Big Five" are needed to further explore the role of personality traits in the etiology of BPD.

During the Covid-19 pandemic, the negative effects of wearing a mouth-nose cover (MNC) on interpersonal functioning have been discussed in public media but empirical studies on how wearing MNCs affect social judgements are sparse. In the present study, we investigated the effects of MNCs on trustworthiness appraisals, the influence of changes due to MNCs in evaluating joy, and the relationship between a social-cognitive appraisal bias and a participant's characteristics.

Personality disorders (PD) are common and burdensome mental disorders. The treatment of individuals with PD represents one of the more challenging areas in the field of mental health and health care providers need evidence-based recommendations to best support patients with PDs. Clinical guidelines serve this purpose and are formulated by expert consensus and/or systematic reviews of the current evidence. In this review, European guidelines for the treatment of PDs are summarized and evaluated. To date, eight countries in Europe have developed and published guidelines that differ in quality with regard to recency and completeness, transparency of methods, combination of expert knowledge with empirical data, and patient/service user involvement. Five of the guidelines are about Borderline personality disorder (BPD), one is about antisocial personality disorder and three concern PD in general. After evaluating the methodological quality of the nine European guidelines from eight countries, results in the domains of diagnosis, psychotherapy and pharmacological treatment of PD are discussed. Our comparison of guidelines reveals important contradictions between recommendations in relation to diagnosis, length and setting of treatment, as well as the use of pharmacological treatment. All the guidelines recommend psychotherapy as the treatment of first choice. Future guidelines should rigorously follow internationally accepted methodology and should more systematically include the views of patients and users.

The biological underpinnings of borderline personality disorder (BPD) and its psychopathology including states of aversive tension and dissociation is poorly understood. Our goal was to examine transcriptional changes associated with states of tension or dissociation within individual patients in a pilot study. Dissociation is not only a critical symptom of BPD but has also been associated with higher risk for self-mutilation and depression. We conducted a whole blood gene expression profile analysis using quantitative PCR in 31 female inpatients with BPD. For each individual, two samples were drawn during a state of high tension and dissociation, while two samples were drawn at non-tension states. There was no association between gene expression and tension states. However, we could show that Interleukin-6 was positively correlated to dissociation scores, whereas Guanine nucleotide-binding protein G(s) subunit alpha isoforms, Mitogen-activated protein kinase 3 and 8, Guanine nucleotide-binding protein G(i) subunit alpha-2, Beta-arrestin-1 and 2, and Cyclic AMP-responsive element-binding protein were negatively correlated to dissociation. Our data point to a potential association of dissociation levels with the expression of genes involved in immune system regulation as well as cellular signalling/second-messenger systems. Major limitations of the study are the the possibly heterogeneous cell proportions in whole blood and the heterogeneous medication.

The availability of effective laboratory paradigms for inducing psychological stress is an important requirement for experimental stress research. Reliable protocols are scarce, usually laborious and manpower-intensive. In order to develop an economical, easily applicable standardized stress protocol, we have recently tailored the Mannheim Multicomponent Stress Test (MMST). This test has been shown to induce relatively high stress responses without focusing on social-evaluative components. In this study we evaluated changes in electrodermal activity and salivary cortisol in response to the MMST. The MMST simultaneously combines cognitive (mental arithmetic), emotional (affective pictures), acoustic (white noise) and motivational stressors (loss of money). This study comprised two independent experiments. For experiment 1, 80 female subjects were recruited; 30 subjects (15 females) participated in experiment 2. Significant changes in electrodermal activity and salivary cortisol levels in response to MMST exposure were found. Subjective stress and heart rate responses were significantly increased in both experiments. These results indicate that the MMST is an economical stress paradigm which is also applicable in larger cohorts or multicenter studies for investigating stress reactions. As social-evaluative threat is not the main stress component of the MMST, this procedure represents a useful and complementary alternative to other established stress protocols.

Real-time functional magnetic resonance imaging (fMRI) neurofeedback training of amygdala hemodynamic activity directly targets a neurobiological mechanism, which contributes to emotion regulation problems in borderline personality disorder (BPD). However, it remains unknown which outcome measures can assess changes in emotion regulation and affective instability, associated with amygdala downregulation in a clinical trial. The current study directly addresses this question. Twenty-four female patients with a DSM-IV BPD diagnosis underwent four runs of amygdala neurofeedback. Before and after the training, as well as at a six-weeks follow-up assessment, participants completed measures of emotion dysregulation and affective instability at diverse levels of analysis (verbal report, clinical interview, ecological momentary assessment, emotion-modulated startle, heart rate variability, and fMRI). Participants were able to downregulate their amygdala blood oxygen-dependent (BOLD) response with neurofeedback. There was a decrease of BPD symptoms as assessed with the Zanarini rating scale for BPD (ZAN-BPD) and a decrease in emotion-modulated startle to negative pictures after training. Further explorative analyses suggest that patients indicated less affective instability, as seen by lower hour-to-hour variability in negative affect and inner tension in daily life. If replicated by an independent study, our results imply changes in emotion regulation and affective instability for several systems levels, including behavior and verbal report. Conclusions are limited due to the lack of a control group. A randomized controlled trial (RCT) will be needed to confirm effectiveness of the training.

Cardiorespiratory fitness (CRF) seems to be prognostic prior to allogeneic stem cell transplantation (allo-HSCT). Influencing factors of CRF in allo-HSCT candidates have not been studied so far. Aim was to identify potentially influencing factors on CRF.

Dysfunctional fear responses play a central role in many mental disorders. New insights in learning and memory suggest that pharmacological and behavioural interventions during the reconsolidation of reactivated fear memories may increase the efficacy of therapeutic interventions. It has been proposed that interventions applied during reconsolidation may modify the original fear memory, and thus prevent the spontaneous recovery and reinstatement of the fear response.

Social affiliation is essential for many species and gains significant importance during adolescence. Disturbances in social affiliation, in particular social rejection experiences during adolescence, affect an individual's well-being and are involved in the emergence of psychiatric disorders. The underlying mechanisms are still unknown, partly because of a lack of valid animal models. By using a novel animal model for social peer-rejection, which compromises adolescent rats in their ability to appropriately engage in playful activities, here we report on persistent impairments in social behavior and dysregulations in the endocannabinoid (eCB) system. From postnatal day (pd) 21 to pd 50 adolescent female Wistar rats were either reared with same-strain partners (control) or within a group of Fischer 344 rats (inadequate social rearing, ISR), previously shown to serve as inadequate play partners for the Wistar strain. Adult ISR animals showed pronounced deficits in social interaction, social memory, processing of socially transmitted information, and decreased pain sensitivity. Molecular analysis revealed increased CB1 receptor (CB1R) protein levels and CP55, 940 stimulated [35S]GTPγS binding activity specifically in the amygdala and thalamus in previously peer-rejected rats. Along with these changes, increased levels of the eCB anandamide (AEA) and a corresponding decrease of its degrading enzyme fatty acid amide hydrolase (FAAH) were seen in the amygdala. Our data indicate lasting consequences in social behavior and pain sensitivity following peer-rejection in adolescent female rats. These behavioral impairments are accompanied by persistent alterations in CB1R signaling. Finally, we provide a novel translational approach to characterize neurobiological processes underlying social peer-rejection in adolescence.

There is a general agreement that physical pain serves as an alarm signal for the prevention of and reaction to physical harm. It has recently been hypothesized that "social pain," as induced by social rejection or abandonment, may rely on comparable, phylogenetically old brain structures. As plausible as this theory may sound, scientific evidence for this idea is sparse. This study therefore attempts to link both types of pain directly. We studied patients with borderline personality disorder (BPD) because BPD is characterized by opposing alterations in physical and social pain; hyposensitivity to physical pain is associated with hypersensitivity to social pain, as indicated by an enhanced rejection sensitivity.

Despite heritability estimates of 37-69%, research has identified few genetic risk variants for borderline personality disorder (BPD). The present collaborative candidate gene study of 987 BPD cases and 1110 healthy controls found an association between BPD and single nucleotide polymorphism rs12718541 in the dopa decarboxylase gene.

Affective hyper-reactivity and impaired cognitive control of emotional material are core features of borderline personality disorder (BPD). A high percentage of individuals with BPD experience stress-related dissociation, including emotional numbing and memory disruptions. So far little is known about how dissociation influences the neural processing of emotional material in the context of a working memory task in BPD. We aimed to investigate whole-brain activity and amygdala functional connectivity (FC) during an Emotional Working Memory Task (EWMT) after dissociation induction in un-medicated BPD patients compared to healthy controls (HC). Using script-driven imagery, dissociation was induced in 17 patients ('BPD_D'), while 12 patients ('BPD_N') and 18 HC were exposed to neutral scripts during fMRI. Afterwards, participants performed the EWMT with neutral vs. negative IAPS pictures vs. no distractors. Main outcome measures were behavioral performance (reaction times, errors) and whole-brain activity during the EWMT. Psychophysiological interaction analysis was used to examine amygdala connectivity during emotional distraction. BPD patients after dissociation induction showed overall WM impairments, a deactivation in bilateral amygdala, and lower activity in left cuneus, lingual gyrus, and posterior cingulate than BPD_N, along with stronger left inferior frontal gyrus activity than HC. Furthermore, reduced amygdala FC with fusiform gyrus and stronger amygdala FC with right middle/superior temporal gyrus and left inferior parietal lobule was observed in BPD_D. Findings suggest that dissociation affects reactivity to emotionally salient material and WM. Altered activity in areas associated with emotion processing, memory, and self-referential processes may contribute to dissociative states in BPD.

Deleterious effects of adverse childhood experiences (ACE) on human brain volume are widely reported. First evidence points to differential effects of ACE on brain volume in terms of timing of ACE. Upcoming studies additionally point towards the impact of different types (i.e., neglect and abuse) of ACE in terms of timing. The current study aimed to investigate the correlation between retrospectively reported severity of type (i.e., the extent to which subjects were exposed to abuse and/or neglect, respectively) and timing of ACE on female brain volume in a sample of prolonged traumatized subjects. A female sample with ACE (N = 68) underwent structural magnetic resonance imaging and a structured interview exploring the severity of ACE from age 3 up to 17 using the "Maltreatment and Abuse Chronology of Exposure" (MACE). Random forest regression with conditional interference trees was applied to assess the impact of ACE severity as well as the severity of ACE type, (i.e. to what extent individuals were exposed to neglect and/or abuse) at certain ages on pre-defined regions of interest such as the amygdala, hippocampus, and anterior cingulate (ACC) volume. Analyses revealed differential type and timing-specific effects of ACE on stress sensitive brain structures: Amygdala and hippocampal volume were affected by ACE severity during a period covering preadolescence and early adolescence. Crucially, this effect was driven by the severity of neglect.

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 (β = 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.

Patients with Borderline Personality Disorder (BPD) showed reduced volume of amygdala and hippocampus, but similar findings are evident in Posttraumatic Stress Disorder (PTSD). Applying voxel-based morphometry (VBM) in a larger cohort of patients with BPD, we sought to extend earlier findings of volume abnormalities in limbic regions and to evaluate the influence of co-occurring PTSD in BPD patients. We used voxel-based morphometry to study gray matter volume (GMV) in 60 healthy controls (HC) and 60 patients with BPD. Subgroup analyses on 53 patients concerning the role of co-occurring PTSD were conducted. Additionally, regression analyses were calculated to assess the relation between borderline symptom severity as well as dissociative experiences and GMV. Differences in local GMV between patients with BPD and HC were observed in the amygdale and hippocampus as well as in the fusiform and cingulate gyrus. Co-occurring PTSD was accompanied by increased GMV in the superior temporal gyrus and dorsolateral prefrontal cortex. Independent of co-occurring PTSD, severity of BPD symptoms predicted smaller GMV in the amygdala and dorsal ACC. Dissociation was positively related to GMV in the middle temporal gyrus. We could replicate earlier findings of diminished limbic GMV in patients with BPD and additionally show that patients with co-morbid PTSD feature increased GMV in prefrontal regions associated with cognitive control.