Differential methylation of OPRK1 in borderline personality disorder is associated with childhood trauma.

According to a growing body of neurobiological evidence, the core symptoms of borderline personality disorder (BPD) may be linked to an opioidergic imbalance between the hedonic and stimulatory activity of mu opioid receptors (MOR) and the reward system inhibiting effects of kappa opioid receptors (KOR). Childhood trauma (CT), which is etiologically relevant to BPD, is also likely to lead to epigenetic and neurobiological adaptations by extensive activation of the stress and endogenous opioid systems. In this study, we investigated the methylation differences in the promoter of the KOR gene (OPRK1) in subjects with BPD (N = 47) and healthy controls (N = 48). Comparing the average methylation rates of regulatorily relevant subregions (specified regions CGI-1, CGI-2, EH1), we found no differences between BPD and HC. Analyzing individual CG nucleotides (N = 175), we found eight differentially methylated CG sites, all of which were less methylated in BPD, with five showing highly interrelated methylation rates. This differentially methylated region (DMR) was found on the falling slope (5') of the promoter methylation gap, whose effect is enhanced by the DMR hypomethylation in BPD. A dimensional assessment of the correlation between disease severity and DMR methylation rate revealed DMR hypomethylation to be negatively associated with BPD symptom severity (measured by BSL-23). Finally, analyzing the influence of CT on DMR methylation, we found DMR hypomethylation to correlate with physical and emotional neglect in childhood (quantified by CTQ). Thus, the newly identified DMR may be a biomarker of the risks caused by CT, which likely epigenetically contribute to the development of BPD.

Consequences of the Lockdown: Domestic Violence During the COVID-19 Pandemic.

BACKGROUND: The global pandemic of the coronavirus disease 2019 (COVID-19) has presented many unique challenges to health systems. The hidden impact of COVID-19 and its associated lockdown have been an increased prevalence of domestic violence. OBJECTIVE: To increase our understanding of the connection between COVID-19 containment measures, domestic violence, and mental health in Germany, we conducted an online self-assessment survey of 98 domestic violence victims and 276 controls. All participants answered questions concerning domestic violence, emotional regulation skills, limitations due to and acceptance of containment measures, and quality of their contact experiences. RESULTS: There was no significant effect of "gender" x "domestic violence." Among victims of domestic violence, the number of women was considerably higher than the number of men. In addition, the factors "negative contact quality," "emotional regulation," and "resilience" differed significantly between the victims of domestic violence and the control group. CONCLUSIONS: The COVID-19 outbreak and associated containment and quarantine measures resulted in a "hidden pandemic" of domestic violence for which prevention programs and early victim assistance through the expansion of digital technologies are urgently needed. Prospective studies should expand empirical data to focus on the long-term psychological effects of domestic violence and biomarkers that can serve as warning signs of stress-related disorders.

Body plasticity in borderline personality disorder: A link to dissociation.

INTRODUCTION: Patients with borderline personality disorder (BPD) often report an unstable sense of self, which is further enhanced in dissociative states. As one consequence, BPD patients show a labile body percept, which might result in a higher degree of body plasticity. However, experimental data on body plasticity in BPD are not yet available. MATERIALS AND METHODS: The rubber hand illusion (RHI) probes the plasticity of one's body by inducing the feeling of ownership for an artificial limb. We tested the proneness to perceive the RHI in female patients with current and remitted BPD compared to healthy controls, and related their perceptions to state and trait dissociation. RESULTS: Participants with current BPD, compared to healthy controls, reported higher proneness to perceive the RHI (p<.05, with an effect size [Cohen's d] of 0.68). Remission was associated with a stabilization of perceptions. RHI vividness was positively related to state and trait dissociation across the groups, and specifically in current BPD when controlling for symptom severity (all Pearson's r≥.30, p<.05). DISCUSSION: These results indicate enhanced body plasticity related to dissociation in BPD, point to shared neurobiological mechanisms, and might help to elucidate the body-related perceptual disturbances associated with BPD. CONCLUSION: The results provide initial empirical evidence for significant alterations in body ownership processing associated with a current BPD diagnosis, resulting in enhanced body plasticity. Dissociation significantly correlated with illusory limb ownership experiences, making body plasticity a marker for BPD.

Volatile organic compounds from exhaled breath in schizophrenia.

OBJECTIVES: This study aims to find out whether volatile organic compounds (VOCs) from exhaled breath differ significantly between patients with schizophrenia and healthy controls and whether it might be possible to create an algorithm that can predict the likelihood of suffering from schizophrenia. METHODS: To test this theory, a group of patients with clinically diagnosed acute schizophrenia as well as a healthy comparison group has been investigated, which have given breath samples during awakening response right after awakening, after 30 min and after 60 min. The VOCs were measured using Proton-Transfer-Reaction Mass Spectrometry. RESULTS: By applying bootstrap with mixed model analysis (n = 1000), we detected 10 signatures (m/z 39, 40, 59, 60, 69, 70, 74, 85, 88 and 90) showing reduced concentration in patients with schizophrenia compared to healthy controls. These could safely discriminate patients and controls and were not influenced by smoking. Logistic regression forward method achieved an area under the receiver operating characteristic curve (AUC) of 0.91 and an accuracy of 82% and a machine learning approach with bartMachine an AUC of 0.96 and an accuracy of 91%. CONCLUSION: Breath gas analysis is easy to apply, well tolerated and seems to be a promising candidate for further studies on diagnostic and predictive clinical utility.

EEG-vigilance regulation in Borderline Personality Disorder.

BACKGROUND: Borderline Personality Disorder (BPD) is characterized by emotional instability, impulsivity, disturbed cognition, sleeplessness and states of high inner tension. Altered arousal regulation which is regarded as a higher domain of functioning according to the research domain criteria of the NIMH and which has previously been reported in several psychiatric disorders, such as mania or major depression could be involved in these features of BPD. METHODS: 40 unmedicated patients with BPD and 42 matched healthy volunteers participated in a twenty minute resting-state EEG measurement with closed eyes. EEG-vigilance regulation was assessed with VIGALL2.0 (Vigilance Algorithm Leipzig), which allows a classification of consecutive 1-s segments in different vigilance stages ranging from high alertness/relaxed wakefulness (stages 0, A1, A2, A3) to drowsiness (B1, B2/3) and sleep onset (C). RESULTS: Across 20 min, both groups showed a similar decline from higher to lower vigilance stages, but patients with BPD remained in higher stages of vigilance compared to healthy volunteers across the whole measurement (p = .013). Contrary to this, pre-experimental ratings indicated enhanced subjective sleepiness but no differences in self-reported sleep quantity in the previous night in patients with BPD compared to healthy volunteers. CONCLUSIONS: The results of an elevated arousal regulation (in combination with increased subjective sleepiness) might reflect several symptoms, such as aversive inner tension and impoverished sense of self in patients with BPD. As arousal is linked to the noradrenergic system, further investigations in this field seem to be promising.

A view on Bartonella quintana endocarditis--confirming the molecular diagnosis by specific fluorescence in situ hybridization.

Culture-negative endocarditis is a frequent problem in cardiology, especially if caused by fastidious organisms. Among these, the diagnostic tools for the detection of Bartonella quintana are still unsatisfactory. In a culture-negative case of suspected endocarditis undergoing aortic valve replacement, polymerase chain reaction amplification and sequencing of the 16S rRNA gene indicated B. quintana infection. To develop a new diagnostic tool, independent from culture and amplification techniques, we designed and optimized an oligonucleotide fluorescence in situ hybridization (FISH) probe specific for B. quintana and suitable for FISH. FISH succeeded in simultaneous visualization and identification of vital microorganisms directly within the aortic valve tissue and in fast and univocal diagnosis of B. quintana endocarditis.

Fluorescence in situ hybridisation (FISH) accelerates identification of Gram-positive cocci in positive blood cultures.

Sepsis is a life-threatening disease with a high mortality rate. Rapid identification of blood culture isolates plays a crucial role in adequate antimicrobial therapy in sepsis patients. To accelerate microbiological diagnosis, a comprehensive panel of oligonucleotide probes for fluorescence in situ hybridisation (FISH) targeting Gram-positive cocci was compiled and evaluated on 428 positive blood culture specimens. By combining genus-specific and species-specific probes, the assay allowed discrimination of staphylococci, streptococci and enterococci as well as differentiation of therapy-relevant pathogens such as Staphylococcus aureus and Enterococcus faecium/durans. Furthermore, the newly designed FISH probes STREP2, ENCO and GRANU targeted Streptococcus pneumoniae/mitis, Enterococcus spp. (except E. faecalis) and Granulicatella adiacens group, respectively. The FISH assay achieved an overall sensitivity of 98.65% and a specificity of 99.0% and therefore allowed rapid and reliable molecular identification of Gram-positive cocci in blood culture specimens.

Involvement of Guggenheimella bovis in digital dermatitis lesions of dairy cows.

Digital dermatitis (DD) of cattle leads to lameness and a decrease of milk production and is responsible for major economic losses worldwide. Although a bacterial aetiology is generally accepted, it still is unclear which microorganisms cause and/or maintain the disease. Recently, a previously undiscovered bacterial species, Guggenheimella bovis, has been isolated from the front of two DD lesions in Swiss cattle and suggested as a potential pathogen. The aims of the present study were to determine the prevalence of G. bovis in 58 German cows suffering from DD via dot blot hybridization, and to analyse the spatial distribution of G. bovis within the affected tissue by fluorescence in situ hybridization (FISH). A species-specific probe, GUBO1, was designed and evaluated. In none of the 58 samples Guggenheimella could be detected, while cultured G. bovis was reliably identified by GUBO1. Further FISH experiments were carried out on two additional biopsies of Swiss cattle tested positive for G. bovis by quantitative PCR and permitted visualization of the newly discovered bacteria in situ. In these biopsies G. bovis proved to be tissue invasive forming characteristic spherical microcolonies not only within the bacterial biofilm but also in seemingly unaffected parts of the tissue not yet reached by the advancing bacterial front. Although the presence of G. bovis does not constitute an essential premise for DD, it seems likely that the bacterial species involved in DD vary, and that in some cases G. bovis is crucial for the development of DD lesions.

Epigenetics in Personality Disorders: Today's Insights.

Objective: Epigenetic mechanisms have been described in several mental disorders, such as mood disorders, anxiety disorders and schizophrenia. However, less is known about the influence of epigenetic mechanisms with regard to personality disorders (PD). Therefore, we conducted a literature review on existing original data with regards to epigenetic peculiarities in connection with personality disorders. Methods: Systematic literature review using PRISMA guidelines. Search was performed via NCBI PubMed by keywords and their combinations. Used search terms included "epigenetic," "methylation," "acetylation" plus designations of specified personality traits and disorders according to DSM-IV. Results: Search yielded in total 345 publications, 257 thereof with psychiatric topic, 72 on personality disorder or traits, 43 of which were in humans and epigenetic, 23 thereof were original studies. Lastly, 23 original publications fulfilled the intended search criteria and were included. Those are 13 studies on gene methylation pattern with aggressive, antisocial and impulsive traits, 9 with borderline personality disorder (BPD), and 2 with antisocial personality disorder (ASPD). The results of these studies showed significant associations of PD with methylation aberrances in system-wide genes and suggest evidence for epigenetic processes in the development of personality traits and personality disorders. Environmental factors, of which childhood trauma showed a high impact, interfered with many neurofunctional genes. Methylation alterations in ASPD and BPD repeatedly affected HTR2A, HTR3A, NR3C1, and MAOA genes. Summary: Epigenetic studies in PD seem to be a useful approach to elucidate the interaction of co-working risk factors in the pathogenesis of personality traits and disorders. However, the complexity of pathogenesis leads to divergent results and impedes an explicit interpretation. Differing methylation patterns within the selected PD could indicate subgroups which would benefit from patient-oriented therapeutic adjustments. They might play a major role in the future design and observation of early therapeutic intervention and thus could help to prevent severe dysfunctional conduct or full-blown personality disorder in risk subjects.

Loneliness, social networks, and social functioning in borderline personality disorder.

Persistent loneliness is often reported by patients with borderline personality disorder (BPD). However, empirical studies investigating this aspect of BPD psychopathology are sparse. Studies from social psychology revealed that social isolation and low social functioning contribute to loneliness, that is, the subjective feeling of being alone. The aim of the present study was to contribute to the understanding of loneliness in BPD by investigating its relation to social isolation and functioning in different domains of life. Subjective experience of loneliness was measured in 80 women (40 BPD patients, 40 healthy controls) with the UCLA Loneliness Scale. Social isolation and social functioning were assessed with the Social Network Inventory and the Social Functioning Scale. In addition, we assessed global functioning with the Global Assessment of Functioning. BPD patients reported stronger feelings of loneliness compared to healthy participants. In general, the level of loneliness was linked to network size, social engagement, and prosocial behavior. Diversity of social networks and functioning in the domain of interpersonal communication were associated with the level of loneliness only in BPD. A reduced variety of roles in social life together with impairments in interpersonal communication were particularly relevant for the experience of loneliness in BPD, suggesting an indirect path to target this psychopathological feature in therapeutic interventions. However, both social isolation and social functioning were not sufficient to explain the severely increased loneliness experienced by these patients, stressing the need for further investigation of determinants of loneliness in this clinical population. (PsycINFO Database Record

Cortical Representation of Afferent Bodily Signals in Borderline Personality Disorder: Neural Correlates and Relationship to Emotional Dysregulation.

IMPORTANCE: The ability to perceive and regulate one's own emotions has been tightly linked to the processing of afferent bodily signals (interoception). Thus, disturbed interoception might contribute to the core feature of emotional dysregulation in borderline personality disorder (BPD), as increased levels of depersonalization, body image disturbances, and reduced sensitivity to physical pain suggest poor body awareness in BPD. OBJECTIVE: To determine neural correlates of disturbed body awareness in BPD and its associations with emotional dysregulation and to explore improvements in body awareness with BPD symptom remission. DESIGN, SETTING, AND PARTICIPANTS: Case-control study performed at Heidelberg University Hospital, Heidelberg, Germany. Heartbeat evoked potentials (HEPs), an indicator of the cortical representation of afferent signals from the cardiovascular system, were investigated in 34 medication-free patients with BPD, 31 healthy volunteers, and 17 medication-free patients with BPD in remission. The HEPs were assessed using 5-minute resting-state electroencephalograms and parallel electrocardiograms. Core BPD symptoms, history of childhood traumatization, and psychiatric disorders were assessed by means of self-reports and structured interviews. To measure neural correlates of disturbed body awareness, high-resolution T1-weighted structural magnetic resonance imaging scans were collected and analyzed using voxel-based morphometry and region-of-interest-based approaches. The study was performed between 2012 and 2014, and data analysis was performed in 2014. MAIN OUTCOMES AND MEASURES: Mean HEP amplitudes in resting-state electroencephalograms and their correlation with self-reported emotional dysregulation, as well as with gray matter volume. RESULTS: Patients with BPD had significantly reduced mean HEP amplitudes compared with healthy volunteers (F1,61 = 11.32, P = .001), whereas the mean HEP amplitudes of patients with BDP in remission lie somewhere in between these 2 groups of participants (P > .05). The HEP amplitudes were negatively correlated with emotional dysregulation (R = -0.30, P = .01) and positively associated with gray matter volume in the left anterior insula (R = 0.53, P < .05) and the bilateral dorsal anterior cingulate cortex (R = 0.47, P < .05), 2 structures that have been identified as core regions for interoception. CONCLUSIONS AND RELEVANCE: The results indicate state-dependent deficits in the cortical processing of bodily signals in patients with BPD, which appear to be associated with core features of BPD. The analysis of patients with BPD in remission suggests an improvement in cortical representation of bodily signals with symptom remission. Results recommend the integration of techniques to strengthen bodily awareness in psychotherapeutic interventions of BPD.

Immunolocalization of angiopoietin 1 in human peritoneal endometriotic lesions.

OBJECTIVE: To analyze the expression of angiopoietin 1 (ANGPT1) in pigmented and nonpigmented endometriosis implants and specify its role in the interaction of angiogenic factors. DESIGN: Experimental retrospective study. SETTING: University hospital. PATIENT(S): Eighty-two sections from 201 laparoscopic tissue samples of 43 female patients. INTERVENTION(S): Biopsies of peritoneal endometriotic lesions of macroscopically different forms. MAIN OUTCOME MEASURE(S): Angiopoietin 1 expression and location pattern in endothelial cells, periendothelial cells, glandular epithelium, and stromal structures. RESULT(S): Angiopoietin 1 is immunohistochemically detectable in endothelial cells, periendothelial cells, in the glandular epithelium, and in the stroma. Differences in the expression of pigmented and nonpigmented lesions are not statistically significant. CONCLUSION(S): Pigmented and nonpigmented endometriotic lesions differ according to their clinical activity and angiogenic potential. Angiopoietin 1 is an important representative of the angiogenic factors and is involved in the angiogenic processes of these lesions. There were no significant differences in the expression and location within different lesion types for ANGPT1. Thus, it is not a direct activity marker of a lesion.

Expression of angiopoietin 1 and 2 in ectopic endometrium on the chicken chorioallantoic membrane.

OBJECTIVE: To investigate the role of angiopoietin 1 and 2 (ANGPT1/ANGPT2) in angiogenesis of the ectopic endometrium as a crucial step in the development of an endometriotic lesion, we analyzed their expression patterns in an experimental model of endometriosis. DESIGN: Experimental prospective study. SETTING: University hospital. PATIENT(S): Endometrium samples obtained from healthy, ovulating women undergoing hysterectomy for benign gynecologic conditions. INTERVENTION(S): Endometrial fragments were transplanted to the chicken chorioallantoic membrane (CAM) and cultivated for 0, 24, 48, and 72 hours. MAIN OUTCOME MEASURE(S): Expression of ANGPT1 and ANGPT2 mRNA was quantified by competitive reverse transcriptase polymerase chain reaction (RT-PCR) and normalized to expression of the housekeeping gene human glyceraldehyde 3-phosphate dehydrogenase (GAPDH) mRNA. The expression of ANGPT1 and ANGPT2 protein was analyzed by immunohistochemical staining. RESULT(S): All grafts expressed ANGPT1 and ANGPT2 mRNA. The mRNA concentration of both factors decreased after cultivation, but the ANGPT2/ANGPT1 ratio increased considerably during the first 24 hours of cultivation. The immunohistochemical investigation for ANGPT1 and ANGPT2 revealed presence of both proteins at all the times but no obvious correlation with the duration of cultivation. CONCLUSION(S): The ratio of ANGPT2/ANGPT1 mRNA in endometrial grafts increased after 24 hours of cultivation on the chicken chorioallantoic membrane and shows a shift toward a more dominant role of ANGPT2. This agrees with the current model of angiopoietin action in angiogenesis and might indicate angiogenic activity in the endometrial graft. The angiopoietins are likely to play an important role in the pathogenesis of endometriosis.