Refine
Language
- English (4)
Has Fulltext
- yes (4)
Is part of the Bibliography
- no (4)
Keywords
Institute
- Psychologie (3)
- Medizin (1)
Pathophysiological models are urgently needed for personalized treatments of mental disorders. However, most potential neural markers for psychopathology are limited by low interpretability, prohibiting reverse inference from brain measures to clinical symptoms and traits. Neural signatures—i.e. multivariate brain-patterns trained to be both sensitive and specific to a construct of interest—might alleviate this problem, but are rarely applied to mental disorders. We tested whether previously developed neural signatures for negative affect and discrete emotions distinguish between healthy individuals and those with mental disorders characterized by emotion dysregulation, i.e. Borderline Personality Disorder (BPD) and complex Post-traumatic Stress Disorder (cPTSD). In three different fMRI studies, a total sample of 192 women (49 BPD, 62 cPTSD, 81 healthy controls) were shown pictures of scenes with negative or neutral content. Based on pathophysiological models, we hypothesized higher negative and lower positive reactivity of neural emotion signatures in participants with emotion dysregulation. The expression of neural signatures differed strongly between neutral and negative pictures (average Cohen's d = 1.17). Nevertheless, a mega-analysis on individual participant data showed no differences in the reactivity of neural signatures between participants with and without emotion dysregulation. Confidence intervals ruled out even small effect sizes in the hypothesized direction and were further supported by Bayes factors. Overall, these results support the validity of neural signatures for emotional states during fMRI tasks, but raise important questions concerning their link to individual differences in emotion dysregulation.
Pathophysiological models are urgently needed for personalized treatments of mental disorders. However, most potential neural markers for psychopathology are limited by low interpretability, prohibiting reverse inference from brain measures to clinical symptoms and traits. Neural signatures—i.e. multivariate brain-patterns trained to be both sensitive and specific to a construct of interest—might alleviate this problem, but are rarely applied to mental disorders. We tested whether previously developed neural signatures for negative affect and discrete emotions distinguish between healthy individuals and those with mental disorders characterized by emotion dysregulation, i.e. Borderline Personality Disorder (BPD) and complex Post-traumatic Stress Disorder (cPTSD). In three different fMRI studies, a total sample of 192 women (49 BPD, 62 cPTSD, 81 healthy controls) were shown pictures of scenes with negative or neutral content. Based on pathophysiological models, we hypothesized higher negative and lower positive reactivity of neural emotion signatures in participants with emotion dysregulation. The expression of neural signatures differed strongly between neutral and negative pictures (average Cohen’s d = 1.17). Nevertheless, a mega-analysis on individual participant data showed no differences in the reactivity of neural signatures between participants with and without emotion dysregulation. Confidence intervals ruled out even small effect sizes in the hypothesized direction and were further supported by Bayes factors. Overall, these results support the validity of neural signatures for emotional states during fMRI tasks, but raise important questions concerning their link to individual differences in emotion dysregulation.
Introduction: Evidence from a number of open-label, uncontrolled studies has suggested that rituximab may benefit patients with autoimmune diseases who are refractory to standard-of-care. The objective of this study was to evaluate the safety and clinical outcomes of rituximab in several standard-of-care-refractory autoimmune diseases (within rheumatology, nephrology, dermatology and neurology) other than rheumatoid arthritis or non-Hodgkin's lymphoma in a real-life clinical setting.
Methods: Patients who received rituximab having shown an inadequate response to standard-of-care had their safety and clinical outcomes data retrospectively analysed as part of the German Registry of Autoimmune Diseases. The main outcome measures were safety and clinical response, as judged at the discretion of the investigators.
Results: A total of 370 patients (299 patient-years) with various autoimmune diseases (23.0% with systemic lupus erythematosus, 15.7% antineutrophil cytoplasmic antibody-associated granulomatous vasculitides, 15.1% multiple sclerosis and 10.0% pemphigus) from 42 centres received a mean dose of 2,440 mg of rituximab over a median (range) of 194 (180 to 1,407) days. The overall rate of serious infections was 5.3 per 100 patient-years during rituximab therapy. Opportunistic infections were infrequent across the whole study population, and mostly occurred in patients with systemic lupus erythematosus. There were 11 deaths (3.0% of patients) after rituximab treatment (mean 11.6 months after first infusion, range 0.8 to 31.3 months), with most of the deaths caused by infections. Overall (n = 293), 13.3% of patients showed no response, 45.1% showed a partial response and 41.6% showed a complete response. Responses were also reflected by reduced use of glucocorticoids and various immunosuppressives during rituximab therapy and follow-up compared with before rituximab. Rituximab generally had a positive effect on patient well-being (physician's visual analogue scale; mean improvement from baseline of 12.1 mm).
Conclusions: Data from this registry indicate that rituximab is a commonly employed, well-tolerated therapy with potential beneficial effects in standard of care-refractory autoimmune diseases, and support the results from other open-label, uncontrolled studies.
Background: 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.
Methods: 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.
Discussion: The expected results will be a major step forward in establishing empirically supported psychological treatments for survivors of CA suffering from Complex PTSD.
Trial registration: German Clinical Trials Register: registration number DRKS00005578, date of registration 19 December 2013.