Dissociative Experiences, Borderline Personality Disorder Features, and Childhood Trauma: Generating Hypotheses from Data-Driven Network Analysis in an International Sample.

Dissociation is a multifaceted phenomenon that occurs in various mental disorders, including borderline personality disorder (BPD), but also in non-clinical populations. Severity of childhood trauma (abuse, neglect) plays an important role in the development of dissociation and BPD. However, the complex interplay of different dissociative symptoms, BPD features, and self-reported childhood trauma experiences is not yet fully understood. Graph-theoretical network analysis can help to better understand such multivariate interrelations. Objective: This study aimed to investigate associations between self-reported dissociation, BPD features, and childhood trauma experiences using a graph-theoretical approach. Data was collected online via international mental health platforms and research sites. N = 921 individuals (77.4% female) were included; 40% reported pathological levels of dissociation. Variables were assessed with established psychometric scales (Dissociative Experiences Scale; Personality Assessment Inventory Borderline Features Scale; Childhood Trauma Questionnaire) and analyzed within a partial correlation network. Positive bivariate correlations between all variables were found. When accounting for their mutual influence on each other, dissociation was predominantly connected to BPD features with effect sizes between rp = .028 and rp = .126, while still showing a slight unique relationship with physical neglect (rp = .044). Findings suggest close associations between dissociative experiences and BPD features. While childhood trauma plays an important role in the development of dissociation and BPD, its recall may not fully explain their current co-occurrence. Prospective studies are needed to shed more light on causal pathways to better understand which factors contribute to dissociation and its link to BPD (features).

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.

Psychological Factors Linked to Intimate Partner Violence and Childhood Maltreatment: On Dissociation as a Possible Bridge Symptom.

Intimate partner violence (IPV) is a serious health concern, occurring worldwide in various forms and settings. Over the past years, multiple sources reported an increase of IPV globally, partly related to COVID-19 restrictions. Childhood maltreatment enhances the risk of IPV, possibly via alterations in emotion regulation, attachment, maladaptive core beliefs, dissociation, and psychopathological symptoms. However, studies investigating these associations simultaneously are still needed. This study aimed to investigate association between IPV, childhood maltreatment severity, maladaptive schemata (mistrust, alienation, enmeshment), attachment anxiety, social support, emotion regulation, dissociation, posttraumatic stress disorder (PTSD), and borderline personality disorder (BPD) symptoms. We further explored the complex interplay of all factors, accounting for their shared associations. An anonymous online survey was posted on international online platforms for people experiencing domestic violence and on research platforms. Regression analyses and graph-theoretical network analysis were used to explore associations between all variables. N = 434 participants (40% in treatment) completed the survey. IPV perpetration and victimization were highly correlated. Both were significantly associated with childhood maltreatment severity, early maladaptive schemata, dissociation, BPD features, and PTSD symptoms. When including all variables in one model, IPV was associated with dissociation, which indirectly linked it to childhood maltreatment experiences, PTSD symptoms, withdrawal, and self-blame. Our findings suggest that IPV perpetration and victimization often co-occur. Dissociation may be an important bridge symptom, linking IPV to childhood maltreatment experiences, PTSD symptoms, and maladaptive coping. Prospective studies are needed to corroborate these findings and to establish psychological mechanisms underlying IPV.

Shame, self-disgust, and envy: An experimental study on negative emotional response in borderline personality disorder during the confrontation with the own face.

Background: A markedly negative self-image and pervasive shame proneness have consistently been associated with borderline personality disorder (BPD). The present experimental study investigated the intensity of negative emotional responses with a focus on shame in BPD compared to healthy control persons (HCs) during an experimental paradigm promoting self-awareness, self-reflection, and self-evaluation. Furthermore, the relationship between levels of state shame during the experiment and shame proneness in BPD compared to HCs was examined. Methods: A sample of 62 individuals with BPD and 47 HCs participated in the study. During the experimental paradigm, participants were presented with photos of (i) the own face, (ii) the face of a well-known person, and (iii) of an unknown person. They were asked to describe positive facets of these faces. Participants rated the intensity of negative emotions induced by the experimental task as well the pleasantness of the presented faces. Shame-proneness was assessed using the Test of the Self-Conscious Affect (TOSCA-3). Results: Individuals with BPD experienced significantly higher levels of negative emotions than HCs both before and during the experimental task. While HC participants responded to their own face particularly with an increase in shame compared to the other-referential condition, the BPD patients responded above all with a strong increase of disgust. Furthermore, the confrontation with an unknown or well-known face resulted in a strong increase of envy in BPD compared to HC. Individuals with BPD reported higher levels of shame-proneness than HCs. Higher levels of shame-proneness were related to higher levels of state shame during the experiment across all participants. Conclusion: Our study is the first experimental study on negative emotional responses and its relationship to shame proneness in BPD compared to HC using the own face as a cue promoting self-awareness, self-reflection, and self-evaluation. Our data confirm a prominent role of shame when describing positive features of the own face, but they emphasize also disgust and envy as distinct emotional experience characterizing individuals with BPD when being confronted with the self.

On the interplay of borderline personality features, childhood trauma severity, attachment types, and social support.

BACKGROUND: Adverse childhood experiences (ACE) have consistently been associated with borderline personality disorder (BPD). Still, it is not yet entirely understood if and how different types of ACE (emotional, physical, sexual abuse, neglect) relate to different BPD subdomains (affective instability, identity disturbance, negative relationships, self-harm). Insecure attachment and lower perceived social support are associated with both ACE and BPD and may therefore contribute to their relationship. No study so far integrated all these variables in one model, while accounting for their mutual influence on each other. We investigated the interplay of BPD subdomains, ACE, attachment, and perceived social support using a graph-theoretical approach. METHODS: An international sample of 1692 participants completed the Childhood Trauma Questionnaire (CTQ), the Borderline Feature Scale from the Personality Assessment Inventory (PAI-BOR), the Adult Attachment Scale (AAS), and Multidimensional Scale of Perceived Social Support (MSPSS) via an online survey. We estimated a partial correlation network including subscales of the CTQ and the PAI-BOR as nodes. We extended the network by including subscales of the AAS and MSPSS as additional nodes. RESULTS: Emotional abuse was the most central node in both networks and a bridge between other types of ACE and BPD features. All domains of BPD except affective instability were associated with emotional abuse. Identity disturbances was the most central node in the BPD network. The association between ACE and BPD features was partly but not fully explained by attachment and social support. CONCLUSION: Our findings suggest that emotional abuse is an important link in the association between ACE and BPD features, also when taking attachment and social support into account. Findings further suggest an outstanding role of identity disturbance, linking emotional abuse to affective instability and being strongly associated with attachment anxiety.

Trustworthiness judgments and Borderline Personality Disorder: an experimental study on the interplay of happiness and trustworthiness appraisals and the effects of wearing face masks during the Covid-19 pandemic in Germany.

BACKGROUND: Judging positive emotional states or the trustworthiness of others is important for forming and maintaining social affiliations. Past studies have described alterations in these appraisal processes in Borderline Personality Disorder (BPD), which might have been exacerbated during the Covid-19 pandemic by the requirement to wear face masks. In the present study, we investigated in an online-survey a) whether social judgments are particularly strongly affected in individuals with BPD when they have to judge happiness and trustworthiness in facial stimuli covered by a mask, b) whether appraising a positive emotional state affects trustworthiness appraisals differentially in BPD and healthy individuals and c) whether social judgments are related to how individuals with BPD experience wearing masks during the pandemic. METHODS: Participants (67 HC, 75 BPD) judged happiness and trustworthiness of faces with calm expression with and without masks. Additionally, data on participants' confidence in their judgments, the experience of the burden induced by wearing masks, the protective benefits of masks, and compliance to wearing masks were collected. RESULTS: Happiness and trustworthiness were evaluated less confidently and less intense in the BPD group compared to HC. Masks reduced happiness and trustworthiness ratings in both groups. Lower happiness appraisals contributed to lower trustworthiness appraisals except for those with BPD and low levels of symptom severity. Lower trustworthiness ratings were associated with a higher burden, attributing a lower benefit to masks and lower compliance with wearing masks in BPD. CONCLUSIONS: Masks do not exacerbate deficits in social judgments. However, lower trustworthiness appraisals in general were linked with more negative evaluations of wearing masks in the BPD group. TRIAL REGISTRATION: The aims and hypotheses were preregistered together with the design and planned analyses ( https://aspredicted.org/f5du7.pdf ). For findings of an additionally preregistered research question on the impact of adverse childhood experiences see supplementary material.

Social Touch, Social Isolation, and Loneliness in Borderline Personality Disorder During the COVID-19 Pandemic.

Background: Interpersonal impairments in borderline personality disorder (BPD) are characterised by a lack in the sense of belonging and the fear of being excluded. One feature of interactions that can promote a sense of social belonging is interpersonal touch. While some studies suggest that individuals with BPD experience social touch as less pleasurable than healthy individuals (HCs), there are no studies that investigated whether this difference is associated with feeling less socially connected. This question is particularly important during the COVID-19 pandemic, since one central behavioural recommendation is "social distancing". An increase in loneliness has been discussed as a consequence and it has been suggested that individuals with BPD may be particularly burdened. However, the primary goal of "social distancing" is not preventing social contacts, but physical proximity. In our study we investigated the interplay between feeling close to others, contact frequency and the appraisal of social touch in BPD. We were additionally interested in whether these factors contribute to the burden through "physical distancing". Methods: We assessed subjective and objective social isolation, the need, importance, and liking of social touch, as well as the burden through "physical distancing" policies in 130 women (61 BPD and 69 HCs). Results: Participants of the BPD group reported higher loneliness, less social contacts and a lower need for, importance and liking of social touch compared to HCs. Larger social networks, higher frequency of in-person contacts and higher liking and importance of social touch were associated with lower levels of loneliness. Both groups did not differ regarding their burden through "physical distancing". A higher need for and lower importance of social touch predicted a higher burden through "physical distancing". Conclusions: A positive appraisal of social touch was associated with less loneliness, independently of an individual's objective social isolation. In BPD, impairments of this fundamental facet of social interaction might hamper forming and strengthening of social bonds and contribute to the patients' interpersonal dysfunction. Changing the attitude towards social touch and in consequence its liking and importance in social interaction might provide one avenue to improve the sense of social connectedness in these patients.

Radiographic cortical thickness parameters as predictors of rotational alignment in proximal tibial shaft fractures: a cadaveric study.

AIM: The treatment of tibial fractures with an intramedullary nail is an established procedure. However, torsional control remains challenging using intraoperatively diagnostic tools. Radiographic tools such as the Cortical Step Sign (CSS) and the Diameter Difference Sign (DDS) may serve as tools for diagnosing a relevant malrotation. The aim of this study was to investigate the effect of torsional malalignment on CSS and DDS parameters and to construct a prognostic model to detect malalignment. METHODS: A proximal tibial shaft fracture was set in human tibiae. Torsion was set stepwise from 0° to 30° in external and internal torsion. Images were obtained with a C-arm and transferred to a PC for measuring the medical cortical thickness (MCT), lateral cortical thickness (LCT), tibial diameter (TD) in AP and the anterior cortical thickness (ACT) as well as the posterior cortical thickness (PCT) and the transverse diameter (TD) of the proximal and the distal main fragment. RESULTS: There were significant differences between the various degrees of torsion for each of the absolute values of the examined variables. The parameters with the highest correlation were TD, LCT and ACT. A model combining ACT, LCT, PCT and TD lateral was most suitable model in identifying torsional malalignment. The best prediction of clinically relevant torsional malalignment, namely 15°, was obtained with the TD and the ACT. CONCLUSION: This study shows that the CSS and DDS are useful tools for the intraoperative detection of torsional malalignment in proximal tibial shaft fractures and should be used to prevent maltorsion.

Trustworthiness appraisals of faces wearing a surgical mask during the Covid-19 pandemic in Germany: An experimental study.

BACKGROUND: 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. METHODS: All participants (N = 165) judged the intensity of happiness and trustworthiness in calm facial stimuli presented with and without a surgical mask covering part of the face. We analysed the relationship of changes in judgements evoked by MNCs to participants' evaluations of MNCs as protective tools and explored their associations with the burden experienced by wearing MNCs, compliance to behaviour recommendations, their risk associated with the pandemic, and their levels of psychological distress. RESULTS: Overall, calm facial stimuli covered with MNCs were evaluated as less trustworthy and, to an even stronger extent, less happy than uncovered facial stimuli. However, participants varied in whether they showed a negative or positive evaluation of faces with MNCs; the negative bias was stronger in those participants who attributed lower protective potential to MNCs, experienced a higher burden while wearing MNCs, wore MNCs less often, and experienced a higher level of psychological distress. CONCLUSIONS: A negative bias in trustworthiness appraisals of faces with a positive emotional expression covered by MNCs is linked to a participant's evaluation of MNCs as inefficient and burdening and their experience of high psychological distress.

Using Bioinformatics to Treat Hospitalized Smokers: Successes and Challenges of a Tobacco Treatment Service.

BACKGROUND: Hospitals face increasing regulations to provide and document inpatient tobacco treatment, yet few blueprint data exist to implement a tobacco treatment service (TTS). METHODS: A hospitalwide, opt-out TTS with three full-time certified counselors was developed in a large tertiary care hospital to proactively treat smokers according to Chronic Care Model principles and national treatment guidelines. A bioinformatics platform facilitated integration into the electronic health record to meet evolving Centers for Medicare & Medicaid Services meaningful use and Joint Commission standards. TTS counselors visited smokers at the bedside and offered counseling, recommended smoking cessation medication to be ordered by the primary clinical service, and arranged for postdischarge resources. RESULTS: During a 3.5-year span, 21,229 smokers (31,778 admissions) were identified; TTS specialists reached 37.4% (7,943), and 33.3% (5,888) of daily smokers received a smoking cessation medication order. Adjusted odds ratios (AORs) of receiving a chart order for smoking cessation medication during the hospital stay and at discharge were higher among patients the TTS counseled > 3 minutes and recommended medication: inpatient AOR = 7.15 (95% confidence interval [CI] = 6.59-7.75); discharge AOR = 5.3 (95% CI = 4.71-5.97). As implementation progressed, TTS counseling reach and medication orders increased. To assess smoking status ≤ 1 month postdischarge, three methods were piloted, all of which were limited by low follow-up rates (4.5%-28.6%). CONCLUSION: The TTS counseled approximately 3,000 patients annually, with increases over time for reach and implementation. Remaining challenges include the development of strategies to engage inpatient care teams to follow TTS recommendations, and patients postdischarge in order to optimize postdischarge smoking cessation.

Electronic Cigarette Use Among Counseled Tobacco Users Hospitalized in 2015.

OBJECTIVES: Few studies have examined the prevalence of electronic cigarette use among the inpatient population regardless of the patients' cessation goals. The objectives of this study were to examine the prevalence of electronic cigarette use among counseled tobacco users admitted to 2 academic hospitals. METHODS: Cross-sectional data of hospitalized adult tobacco users who were admitted between January 1, 2015 and December 31, 2015 and who received bedside tobacco cessation counseling from a tobacco treatment service counselor were examined. Demographic and smoking history items were compared as a function of electronic cigarette use using chi-square and independent t tests. Logistic regression was used to test independent associations with electronic cigarette use. RESULTS: Of 2194 hospitalized tobacco users counseled, 22% had used an electronic cigarette. Most of these patients used electronic cigarettes to quit or reduce use of combustible cigarettes. Adjusted odds of electronic cigarette use were higher for females (adjusted odds ratio [AOR] 0.60 for male patients, 95% confidence interval [CI] 0.47-0.76), younger patients (AOR 0.98 for older patients, 95% CI 0.97-0.99), and individuals who initiated tobacco use earlier in life (AOR 0.97 for later smoking initiation, 95% CI 0.95-0.99). CONCLUSIONS: Screening hospitalized cigarette smokers for electronic cigarette use offers an opportunity to counsel all patients on evidence-based quit aids. Young, female patients are most likely to use electronic cigarettes and may benefit most from directed discussions about electronic cigarette use and Federal Drug Administration-approved cessation methods during smoking cessation counseling.

Processing of fair and unfair offers in the ultimatum game under social observation.

Social context influences social decisions and outcome processing, partially depending on inter-individual differences. The present study investigated social context-dependent modulation of behavior and feedback processing in the ultimatum game (UG) in relation to inter-individual differences in social anxiety. Thirty-two healthy adults completed the UG both under social observation and without observation. Offers were allegedly either randomly generated by the computer or drawn from a pool of offers from previous human players. Overall, fewer unfair than fair offers were accepted. Observation decreased acceptance rates for unfair offers. The feedback-locked feedback-related negativity (FRN) but not the P3 was modulated by observation and fairness, with stronger differential coding of unfair/fair under observation. This effect was strongly correlated with individual levels of social anxiety, with higher levels associated with stronger differential fairness coding in the FRN under observation. Behavioral findings support negative reciprocity in the UG, suggesting that (implicit) social norms overwrite explicit task instructions even in the absence of (alleged) social interaction. Observation enhances this effect. Fairness coding in the FRN was modulated by observation as a function of social anxiety, supporting the notion that altered sensitivity to equality in a social context may contribute to social avoidance in socially anxious individuals.

A Cholesterol-Based Allostery Model of T Cell Receptor Phosphorylation.

Signaling through the T cell receptor (TCR) controls adaptive immune responses. Antigen binding to TCRαß transmits signals through the plasma membrane to induce phosphorylation of the CD3 cytoplasmic tails by incompletely understood mechanisms. Here we show that cholesterol bound to the TCRß transmembrane region keeps the TCR in a resting, inactive conformation that cannot be phosphorylated by active kinases. Only TCRs that spontaneously detached from cholesterol could switch to the active conformation (termed primed TCRs) and then be phosphorylated. Indeed, by modulating cholesterol binding genetically or enzymatically, we could switch the TCR between the resting and primed states. The active conformation was stabilized by binding to peptide-MHC, which thus controlled TCR signaling. These data are explained by a model of reciprocal allosteric regulation of TCR phosphorylation by cholesterol and ligand binding. Our results provide both a molecular mechanism and a conceptual framework for how lipid-receptor interactions regulate signal transduction.

Quantification of low molecular weight fatty acids in cave drip water and speleothems using HPLC-ESI-IT/MS -- development and validation of a selective method.

This study presents a novel method for the analysis of low molecular weight (LMW) fatty acids in cave drip water and speleothems. The method development included optimization of sample preparation procedures, e.g., blank reduction, solid phase extraction, concentration of extracts as well as liquid chromatography coupled to electrospray ion-trap mass spectrometry (HPLC-ESI-IT/MS) measurement parameters. Retention times for five analytes (lauric acid, myristic acid, palmitic acid, stearic acid and arachidic acid) were between 5 and 13.5 min. Spiking experiments were performed to accomplish external calibrations which ranged from 12.5 to 75 ng per spiked water sample. The correlation coefficient ranged from 0.9558 to 0.9989. Inter-batch precision, expressed as the relative standard deviation of three replicates, was <7 %. Limits of detection ranged from 0.77 to 55.97 ng for the diverse analytes; obtained recoveries varied from 30 to 103 %. For a first application, cave drip water and stalagmite samples from Herbstlabyrinth-Adventhöhle cave system were analyzed. Concentrations ranged from 38.37 to 9,982.54 ng L(-1) for water samples and 2.52 to 1,344.96 ng g(-1) for the stalagmite. Thereby, the different fatty acids showed a distinctive variation. Whereas shorter-chained fatty acids exhibited similarities, arachidic acid showed opposite trends. Diverse correlations were found, which could improve the understanding of different organic sources of the lipids transported by drip water and preserved in speleothems. This new method provides a more selective extraction process, particularly adjusted to LMW fatty acids and therefore reduces the required sample size. Furthermore, it is applicable to stalagmite as well as cave drip water samples.

Quantitative analysis of protein phosphorylations and interactions by multi-colour IP-FCM as an input for kinetic modelling of signalling networks.

BACKGROUND: To understand complex biological signalling mechanisms, mathematical modelling of signal transduction pathways has been applied successfully in last few years. However, precise quantitative measurements of signal transduction events such as activation-dependent phosphorylation of proteins, remains one bottleneck to this success. METHODOLOGY/PRINCIPAL FINDINGS: We use multi-colour immunoprecipitation measured by flow cytometry (IP-FCM) for studying signal transduction events to unrivalled precision. In this method, antibody-coupled latex beads capture the protein of interest from cellular lysates and are then stained with differently fluorescent-labelled antibodies to quantify the amount of the immunoprecipitated protein, of an interaction partner and of phosphorylation sites. The fluorescence signals are measured by FCM. Combining this procedure with beads containing defined amounts of a fluorophore allows retrieving absolute numbers of stained proteins, and not only relative values. Using IP-FCM we derived multidimensional data on the membrane-proximal T-cell antigen receptor (TCR-CD3) signalling network, including the recruitment of the kinase ZAP70 to the TCR-CD3 and subsequent ZAP70 activation by phosphorylation in the murine T-cell hybridoma and primary murine T cells. Counter-intuitively, these data showed that cell stimulation by pervanadate led to a transient decrease of the phospho-ZAP70/ZAP70 ratio at the TCR. A mechanistic mathematical model of the underlying processes demonstrated that an initial massive recruitment of non-phosphorylated ZAP70 was responsible for this behaviour. Further, the model predicted a temporal order of multisite phosphorylation of ZAP70 (with Y319 phosphorylation preceding phosphorylation at Y493) that we subsequently verified experimentally. CONCLUSIONS/SIGNIFICANCE: The quantitative data sets generated by IP-FCM are one order of magnitude more precise than Western blot data. This accuracy allowed us to gain unequalled insight into the dynamics of the TCR-CD3-ZAP70 signalling network.