Posttraumatic stress disorder (PTSD) after childhood abuse (CA) is often related to severe co-occurring psychopathology, such as symptoms of borderline personality disorder (BPD). The ICD-11 has ...included Complex PTSD as a new diagnosis, which is defined by PTSD symptoms plus disturbances in emotion regulation, self-concept, and interpersonal relationships. Unfortunately, the empirical database on psychosocial treatments for survivors of CA is quite limited. Furthermore, the few existing studies often have either excluded subjects with self-harm behaviour and suicidal ideation - which is common behaviour in subjects suffering from Complex PTSD. Thus, researchers are still trying to identify efficacious treatment programmes for this group of patients.We have designed DBT-PTSD to meet the specific needs of patients with Complex PTSD. The treatment programme is based on the rules and principles of dialectical behavioural therapy (DBT), and adds interventions derived from cognitive behavioural therapy, acceptance and commitment therapy and compassion-focused therapy. DBT-PTSD can be provided as a comprehensive residential programme or as an outpatient programme. The effects of the residential programme were evaluated in a randomised controlled trial. Data revealed significant reduction of posttraumatic symptoms, with large between-group effect sizes when compared to a treatment-as-usual wait list condition (Cohen's d = 1.5).The first aim of this project on hand is to evaluate the efficacy of the outpatient DBT-PTSD programme. The second aim is to identify the major therapeutic variables mediating treatment efficacy. The third aim is to study neural mechanisms and treatment sensitivity of two frequent sequelae of PTSD after CA: intrusions and dissociation.
To address these questions, we include female patients who experienced CA and who fulfil DSM-5 criteria for PTSD plus borderline features, including criteria for severe emotion dysregulation. The study is funded by the German Federal Ministry of Education and Research, and started in 2014. Participants are randomised to outpatient psychotherapy with either DBT-PTSD or Cognitive Processing Therapy. Formal power analysis revealed a minimum of 180 patients to be recruited. The primary outcome is the change on the Clinician-Administered PTSD Scale for DSM-5.
The expected results will be a major step forward in establishing empirically supported psychological treatments for survivors of CA suffering from Complex PTSD.
German Clinical Trials Register: registration number DRKS00005578, date of registration 19 December 2013.
•To date it has been unclear which aspects of psychopathology and emotion regulation may change with neurofeedback-aided amygdala down-regulation. The present study provides an empirical basis for ...informed decision-making on primary outcome measures for larger clinical trials of amygdala neurofeedback training.•Participants were able to down-regulate their amygdala BOLD response with neurofeedback.•After neurofeedback training, there was a decrease of borderline symptoms as assessed with the Zanarini rating Scale for Borderline Personality Disorder (ZAN-BPD).•Patients also indicated less affective instability, indicated by lower variability in negative affect and inner tension in daily life after training.•After training, patients showed decreased emotion-modulated startle to negative pictures, indicative of increased emotion regulation abilities.
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.
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.
Abstract Peer-interactions are particularly important during adolescence and teenagers display enhanced sensitivity toward rejection by peers. Social rejection has been shown to induce alterations in ...pain perception in humans. However, the neurobiological consequences of adolescent social rejection have yet to be extensively characterized, and no appropriate animal model is available. Here, we propose inadequate playful interactions in adolescent rats as a novel animal model for social peer-rejection and examine potential long-term consequences into adulthood. Acute social pairing of female adolescent Wistar rats with an age-matched rat from the less playful Fischer344 strain was found to alter social play and decrease pain reactivity, indicating Fischer rats as inadequate social partners for Wistar animals. Therefore, in a second experiment, adolescent female Wistar rats were either reared with another Wistar rat (adequate social rearing; control) or with a Fischer rat (inadequate social rearing; play-deprived). Beginning on day 50, all Wistar rats were group housed with same-strain partners and tested for behavioral, neurobiological and endocrine differences in adulthood. Playful peer-interactions were decreased during adolescence in play-deprived animals, without affecting social contact behavior. Consequently, adult play-deprived rats showed decreased pain sensitivity and increased startle reactivity compared to controls, but did not differ in activity, anxiety-related behavior or social interaction. Both groups also differed in their endocrine stress-response, and expression levels of the cannabinoid CB1 receptor were increased in the thalamus, whereas FAAH levels were decreased in the amygdala. The present animal model therefore represents a novel approach to assess the long-term consequences of peer-rejection during adolescence.
Background Several studies have investigated volumetric brain changes in patients with posttraumatic stress disorder (PTSD) and borderline personality disorder (BPD). Both groups exhibit volume ...reductions of the hippocampus and amygdala. Our aim was to investigate the influence of comorbid PTSD on hippocampus and amygdala volumes in patients with BPD. Methods We compared 2 groups of unmedicated female patients with BPD (10 with and 15 without comorbid PTSD) and 25 healthy female controls. We used T1 - and T2 -weighted magnetic resonance images for manual tracing and 3-dimensional reconstruction of the hippocampus and amygdala. Results Hippocampus volumes of patients with BPD and PTSD were smaller than those of healthy controls. However, there was no significant difference between patients with BPD but without PTSD and controls. Impulsiveness was positively correlated with hippocampus volumes in patients with BPD. Limitations Our study did not allow for disentangling the effects of PTSD and traumatization. Another limitation was the relatively small sample size. Conclusion Our findings highlight the importance of classifying subgroups of patients with BPD. Comorbid PTSD may be related to volumetric alterations in brain regions that are of central importance to our understanding of borderline psychopathology.
Background Previous studies have revealed altered affective pain processing in patients with borderline personality disorder (BPD) as well as in patients with posttraumatic stress disorder (PTSD). ...Reduced levels of activation in the amygdala might be related to antinociceptive mechanisms pertinent to both disorders. This study aimed at clarifying whether central antinoceptive mechanisms discriminate BPD patients with and without co-occurrent PTSD. Methods We investigated 29 medication-free female outpatients with BPD, 12 with and 17 without co-occurrent PTSD. Psychophysical characteristics were assessed, and functional magnetic resonance imaging was performed during heat stimulation with stimuli adjusted for equal subjective painfulness. Results No difference in pain sensitivity was found between both groups of patients. Amygdala deactivation, however, was more pronounced in BPD patients with co-occurrent PTSD compared with those without PTSD. Amygdala deactivation was independent of BPD symptom severity and dissociation. Conclusions Amygdala deactivation seems to differentiate patients who meet criteria for both BPD and PTSD from BPD patients without co-occurrent PTSD. On the basis of these preliminary findings it might be speculated that reduced pain sensitivity or at least the emotional component of it is associated with amygdala deactivation in patients with both disorders, whereas BPD patients without PTSD use different yet unknown antinociceptive mechanisms.
Evidence from randomized controlled trials (RCT) that exercise interventions have beneficial effects in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) is growing. ...However, intensive chemotherapy conditioning and glucocorticoid (GC) treatment is always part of an allo-HSCT and possibly affect exercise adherence and training response. Therefore, we aimed to examine whether various conditioning protocols or different doses of GC treatment affect exercise adherence and/or training response during the inpatient period.
We analyzed inpatient data from intervention groups of two large RCT in allo-HSCT patients (n = 113). The intervention incorporated partly supervised endurance and resistance exercise three to five times per week. According to the potentially interfering factors, the patients were divided into groups depending on intensity of conditioning (myeloablative conditioning (MAC), reduced-intensity conditioning (RIC), and nonmyeloablative conditioning (NMC)) and cumulative dose of GC treatment (GC low ≤9 mg·kg prednisone or GC high >9 mg·kg prednisone) and were compared.
Median exercise adherence (target value, five sessions weekly) during the inpatient period was 64% in MAC, 54% in RIC, and 63% in NMC. The proportion of prematurely terminated training sessions ranged from 11% to 15%. Tiredness was the most frequent cause of exercise termination in all groups. Exercise adherence, duration (min·wk) and type of training was significantly associated with GC dose. With regard to training response, results suggest that GC-low patients tend to respond better in knee extensor muscle strength.
Exercise adherence during inpatient period is significantly affected by dose of GC treatment but not by condition regimen. However, given the reasonable adherence rates also in the GC-high group, data support the feasibility and importance of exercising for all allo-HSCT patients during the inpatient period.
Background: A diagnosis of post-traumatic stress disorder (PTSD) requires the identification of one or more traumatic events, designated the index trauma, which serves as the basis for assessment of ...severity of PTSD. In patients who have experienced more than one traumatic event, severity may depend on the exact definition of the index trauma. Defining the index trauma as the worst single incident may result in PTSD severity scores that differ from what would be seen if the index trauma included multiple events.
Objective: This study aimed to investigate the impact of the definition of the index trauma on PTSD baseline severity scores and treatment outcome.
Method: A planned secondary analysis was performed on data from a subset (N = 58) of patients enrolled in a trial evaluating the efficacy of a 12 week residential dialectical behavioural therapy programme for PTSD related to childhood abuse (DBT-PTSD). Assessments of the severity of PTSD were conducted at admission, at the end of the 12 week treatment period, and at 6 and 12 weeks post-treatment, using the Clinician-Administered PTSD Scale. The index trauma was defined with respect to both the worst single incident and up to three qualitatively distinct traumatic events.
Results: When the index trauma included multiple traumas, PTSD severity scores were significantly higher and improvements from pre- to post-treatment were significantly lower than when the index trauma was defined as the worst single incident.
Conclusions: In patients with PTSD who have experienced multiple traumas, defining the index trauma as the worst single incident may miss some aspects of clinically relevant symptomatology, thereby leading to a possibly biased interpretation of treatment effects. In DBT-PTSD, treatment effects were lower when the index trauma included multiple traumatic events. More research is needed to determine the impact of the various index trauma definitions on the evaluation of other trauma-focused treatments.
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
; KFO-sample: NkR² = 6.6%, p = 4.4*10
), 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.
Zusammenfassung
Die dialektisch behaviorale Therapie für komplexe posttraumatische Belastungsstörungen (DBT-PTBS) ist ein modulares Behandlungsprogramm, das am Zentralinstitut für Seelische ...Gesundheit (ZI) der Universität Heidelberg in den Jahren 2005 bis 2021 entwickelt wurde. DBT-PTBS ist auf die Bedürfnisse von PatientInnen mit komplexer PTBS nach sexueller oder körperlicher Traumatisierung in der Kindheit und Jugend ausgerichtet. Sie wurde speziell für Betroffene konzipiert, die unter schweren Problemen der Emotionsregulation, anhaltenden Selbstverletzungen, chronischen Suizidgedanken sowie schweren dissoziativen Symptomen leiden und dabei ein ausgeprägtes negatives Selbstkonzept mit einem hohen Maß an Schuld, Scham, Selbstverachtung und zwischenmenschlichen Problemen zeigen. Um diese sehr unterschiedlichen Kernbereiche zu behandeln, kombiniert die DBT-PTBS evidenzbasierte therapeutische Strategien: Prinzipien, Regeln und Fertigkeiten der DBT, traumaspezifische kognitive und expositionsbasierte Techniken sowie imaginative Interventionen und Verfahren zur Verhaltensänderung. Das Behandlungsprogramm ist so konzipiert, dass es sowohl ambulant (45 Wochen) als auch stationär (12 Wochen) durchgeführt werden kann. Ergebnisse aus zwei randomisiert-kontrollierten Studien zeigen große Effektstärken auf unterschiedlichste Symptombereiche sowie eine signifikante Überlegenheit von DBT-PTBS im Vergleich zur „Cognitive Processing Therapy“ (CPT). Aufgrund dieser Ergebnisse ist die DBT-PTBS ein vielversprechendes evidenzbasiertes Behandlungsprogramm für alle Merkmale einer komplexen PTBS nach sexuellem Missbrauch in der Kindheit und Jugend.
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