New insights into the effects of type and timing of childhood maltreatment on brain morphometry.

Childhood maltreatment (CM) is known to influence brain development. To obtain a better understanding of related brain alterations, recent research has focused on the influence of the type and timing of CM. We aimed to investigate the association between type and timing of CM and local brain volume. Anatomical magnetic resonance images were collected from 93 participants (79 female/14 male) with a history of CM. CM history was assessed with the German Interview Version of the "Maltreatment and Abuse Chronology of Exposure" scale, "KERF-40 + ". Random forest regressions were performed to assess the impact of CM characteristics on the volume of amygdala, hippocampus and anterior cingulate cortex (ACC). The volume of the left ACC was predicted by neglect at age 3 and 4 and abuse at age 16 in a model including both type and timing of CM. For the right ACC, overall CM severity and duration had the greatest impact on volumetric alterations. Our data point to an influence of CM timing on left ACC volume, which was most pronounced in early childhood and in adolescence. We were not able to replicate previously reported effects of maltreatment type and timing on amygdala and hippocampal volume.

Assessing complex PTSD and PTSD: validation of the German version of the International Trauma Interview (ITI).

Background: With the introduction of the ICD-11 into clinical practice, the reliable distinction between Posttraumatic Stress Disorder (PTSD) and Complex Posttraumatic Stress Disorder (CPTSD) becomes paramount. The semi-structured clinician-administered International Trauma Interview (ITI) aims to close this gap in clinical and research settings.Objective: This study investigated the psychometric properties of the German version of the ITI among trauma-exposed clinical samples from Switzerland and Germany.Method: Participants were 143 civilian and 100 military participants, aged M = 40.3 years, of whom 53.5% were male. Indicators of reliability and validity (latent structure, internal reliability, inter-rater agreement, convergent and discriminant validity) were evaluated. Confirmatory factor analysis (CFA) and partial correlation analysis were conducted separately for civilian and military participants.Results: Prevalence of PTSD was 30% (civilian) and 33% (military) and prevalence of CPTSD was 53% (civilians) and 21% (military). Satisfactory internal consistency and inter-rater agreement were found. In the military sample, a parsimonious first-order six-factor model was preferred over a second-order two-factor CFA model of ITI PTSD and Disturbances in Self-Organization (DSO). Model fit was excellent among military participants but no solution was supported among civilian participants. Overall, convergent validity was supported by positive correlations of ITI PTSD and DSO with DSM-5 PTSD. Discriminant validity for PTSD symptoms was confirmed among civilians but low in the military sample.Conclusions: The German ITI has shown potential as a clinician-administered diagnostic tool for assessing ICD-11 PTSD and CPTSD in primary care. However, further exploration of its latent structure and discriminant validity are indicated.

This study validated the German International Trauma Interview (ITI), a semi-structured clinician-administered diagnostic interview for ICD-11 Posttraumatic Stress Disorder and Complex Posttraumatic Stress Disorder.Internal reliability, inter-rater agreement, latent structure, and convergent validity were explored in trauma-exposed clinical and military samples from five different in- and outpatient centres in Germany and German-speaking Switzerland.The findings supported the German ITI's reliability, inter-rater agreement, convergent validity and usefulness from a patient perspective. Future research should explore its factor structure and discriminant validity, for which differences between the samples were found.

[Diagnosis and admission center : Establishment and evaluation of an integrated translational infrastructure for clinical psychiatric research]. / Diagnose- und Aufnahmezentrum : Etablierung und Evaluation einer integrierten translationalen Infrastruktur für die klinisch-psychiatrische Forschung.

The routine in-depth characterization of patients with methods of clinical and scale-based examination, neuropsychology, based on biomaterials, and sensor-based information opens up transformative possibilities on the way to personalized diagnostics, treatment and prevention in psychiatry, psychotherapy, and psychosomatics. Effective integration of the additional temporal and logistical effort into everyday care as well as the acceptance by patients are critical to the success of such an approach but there is little evidence on this to date. We report here on the establishment of the Diagnosis and Admission Center (DAZ) at the Central Institute of Mental Health (ZI) in Mannheim. The DAZ is an outpatient unit upstream of other care structures for clinical and scientific phenotyping across diagnoses as a starting point for data-driven, individualized pathways to further treatment, diagnostics or research. We describe the functions, goals, and implementation of the newly created clinical scientific translational structure, provide an overview of the patient populations it has reached, and provide data on its acceptance. In this context, the close integration with downstream clinical processes enables a better coordinated and demand-oriented allocation. In addition, DAZ enables a faster start of disorder-specific diagnostics and treatment. Since its launch in April 2021 up to the end of 2022, 1021 patients underwent psychiatric evaluation at DAZ during a pilot phase. The patient sample corresponded to a representative sample from standard care and the newly established processes were regarded as helpful by patients. In summary, the DAZ uniquely combines the interests and needs of patient with the collection of scientifically relevant data.

Smaller total and subregional cerebellar volumes in posttraumatic stress disorder: a mega-analysis by the ENIGMA-PGC PTSD workgroup.

Although the cerebellum contributes to higher-order cognitive and emotional functions relevant to posttraumatic stress disorder (PTSD), prior research on cerebellar volume in PTSD is scant, particularly when considering subregions that differentially map on to motor, cognitive, and affective functions. In a sample of 4215 adults (PTSD n = 1642; Control n = 2573) across 40 sites from the ENIGMA-PGC PTSD working group, we employed a new state-of-the-art deep-learning based approach for automatic cerebellar parcellation to obtain volumetric estimates for the total cerebellum and 28 subregions. Linear mixed effects models controlling for age, gender, intracranial volume, and site were used to compare cerebellum volumes in PTSD compared to healthy controls (88% trauma-exposed). PTSD was associated with significant grey and white matter reductions of the cerebellum. Compared to controls, people with PTSD demonstrated smaller total cerebellum volume, as well as reduced volume in subregions primarily within the posterior lobe (lobule VIIB, crus II), vermis (VI, VIII), flocculonodular lobe (lobule X), and corpus medullare (all p-FDR < 0.05). Effects of PTSD on volume were consistent, and generally more robust, when examining symptom severity rather than diagnostic status. These findings implicate regionally specific cerebellar volumetric differences in the pathophysiology of PTSD. The cerebellum appears to play an important role in higher-order cognitive and emotional processes, far beyond its historical association with vestibulomotor function. Further examination of the cerebellum in trauma-related psychopathology will help to clarify how cerebellar structure and function may disrupt cognitive and affective processes at the center of translational models for PTSD.

Examining the association between posttraumatic stress disorder and disruptions in cortical networks identified using data-driven methods.

Posttraumatic stress disorder (PTSD) is associated with lower cortical thickness (CT) in prefrontal, cingulate, and insular cortices in diverse trauma-affected samples. However, some studies have failed to detect differences between PTSD patients and healthy controls or reported that PTSD is associated with greater CT. Using data-driven dimensionality reduction, we sought to conduct a well-powered study to identify vulnerable networks without regard to neuroanatomic boundaries. Moreover, this approach enabled us to avoid the excessive burden of multiple comparison correction that plagues vertex-wise methods. We derived structural covariance networks (SCNs) by applying non-negative matrix factorization (NMF) to CT data from 961 PTSD patients and 1124 trauma-exposed controls without PTSD. We used regression analyses to investigate associations between CT within SCNs and PTSD diagnosis (with and without accounting for the potential confounding effect of trauma type) and symptom severity in the full sample. We performed additional regression analyses in subsets of the data to examine associations between SCNs and comorbid depression, childhood trauma severity, and alcohol abuse. NMF identified 20 unbiased SCNs, which aligned closely with functionally defined brain networks. PTSD diagnosis was most strongly associated with diminished CT in SCNs that encompassed the bilateral superior frontal cortex, motor cortex, insular cortex, orbitofrontal cortex, medial occipital cortex, anterior cingulate cortex, and posterior cingulate cortex. CT in these networks was significantly negatively correlated with PTSD symptom severity. Collectively, these findings suggest that PTSD diagnosis is associated with widespread reductions in CT, particularly within prefrontal regulatory regions and broader emotion and sensory processing cortical regions.

Amygdala-related electrical fingerprint is modulated with neurofeedback training and correlates with deep-brain activation: proof-of-concept in borderline personality disorder.

BACKGROUND: The modulation of brain circuits of emotion is a promising pathway to treat borderline personality disorder (BPD). Precise and scalable approaches have yet to be established. Two studies investigating the amygdala-related electrical fingerprint (Amyg-EFP) in BPD are presented: one study addressing the deep-brain correlates of Amyg-EFP, and a second study investigating neurofeedback (NF) as a means to improve brain self-regulation. METHODS: Study 1 combined electroencephalography (EEG) and simultaneous functional magnetic resonance imaging to investigate the replicability of Amyg-EFP-related brain activation found in the reference dataset (N = 24 healthy subjects, 8 female; re-analysis of published data) in the replication dataset (N = 16 female individuals with BPD). In the replication dataset, we additionally explored how the Amyg-EFP would map to neural circuits defined by the research domain criteria. Study 2 investigated a 10-session Amyg-EFP NF training in parallel to a 12-weeks residential dialectical behavior therapy (DBT) program. Fifteen patients with BPD completed the training, N = 15 matched patients served as DBT-only controls. RESULTS: Study 1 replicated previous findings and showed significant amygdala blood oxygenation level dependent activation in a whole-brain regression analysis with the Amyg-EFP. Neurocircuitry activation (negative affect, salience, and cognitive control) was correlated with the Amyg-EFP signal. Study 2 showed Amyg-EFP modulation with NF training, but patients received reversed feedback for technical reasons, which limited interpretation of results. CONCLUSIONS: Recorded via scalp EEG, the Amyg-EFP picks up brain activation of high relevance for emotion. Administering Amyg-EFP NF in addition to standardized BPD treatment was shown to be feasible. Clinical utility remains to be investigated.

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.

Incidental learning of faces during threat: No evidence for enhanced physiological responses to former threat identities.

Remembering an unfamiliar person and the contextual conditions of that encounter is important for adaptive future behavior, especially in a potentially dangerous situation. Initiating defensive behavior in the presence of former dangerous circumstances can be crucial. Recent studies showed selective electrocortical processing of faces that were previously seen in a threat context compared to a safety context, however, this was not reflected in conscious recognition performance. Here, we investigated whether previously seen threat-faces, that could not be remembered, were capable to activate defensive psychophysiological response systems. During an encoding phase, 50 participants with low to moderate levels of anxiety viewed 40 face pictures with neutral expressions (6 s each), without an explicit learning instruction (incidental learning task). Each half of the faces were presented with contextual background colors that signaled either threat-of-shock or safety. In the recognition phase, all old and additional new faces (total of 60) were presented intermixed without context information. Participants had to decide whether a face was new or had been presented previously in a threatening or a safe context. Results show moderate face recognition independent of context conditions. Startle reflex and skin conductance responses (SCR) were more pronounced for threat compared to safety during encoding. For SCR, this differentiation was enhanced with higher levels of depression and anxiety. There were no differential startle reflex or SCR effects during recognition. From a clinical perspective, these findings do not support the notion that perceptual biases and physiological arousal directly relate to threat-associated identity recognition deficits in healthy and clinical participants with anxiety and trauma-related disorders.

Treating nightmares in posttraumatic stress disorder with dronabinol: study protocol of a multicenter randomized controlled study (THC PTSD-trial).

BACKGROUND: Distressing nightmares are a core symptom of posttraumatic stress disorder (PTSD) and contribute to psychiatric comorbidity, impaired physical health and decreased social functioning. No specific pharmacological treatment for PTSD-related nightmares is yet approved. Preliminary clinical data indicate that cannabinoid agonists can improve nightmares and overall PTSD symptoms in patients with PTSD. The primary objective of the study is to examine the efficacy of oral dronabinol (BX-1) versus placebo in reducing nightmares in patients with PTSD. The secondary objectives of the study are to examine the efficacy of oral BX-1 in reducing other PTSD symptoms. METHODS: The study is designed as a multi-centric, double-blind, randomized (1:1), placebo-controlled, parallel group interventional trial. Eligible patients will be randomized to BX-1 or placebo, receiving a once-daily oral dose before bedtime for 10 weeks. Primary efficacy endpoint is the Clinician-Administered PTSD Scale (CAPS-IV) B2 score for the last week, measuring frequency and intensity of nightmares. Secondary efficacy endpoints are other disorder-specific symptoms in patients with PTSD. Further, tolerability and safety of dronabinol will be assessed. DISCUSSION: This randomized controlled trial will provide evidence whether treating patients with PTSD and nightmares with dronabinol is safe and efficacious. TRIAL REGISTRATION: NCT04448808, EudraCT 2019-002211-25.

[Evidence-based inpatient psychotherapy in borderline personality disorder]. / Evidenzbasierte stationäre Psychotherapie der Borderline-Persönlichkeitsstörung.

BACKGROUND: Borderline personality disorder (BPD) is frequent (prevalence in Germany between 0.7% and 4.5%) [11] and is associated with a high level of psychological stress and frequent emergency inpatient admissions. The provision of disorder-specific outpatient psychotherapy is still insufficient also in Germany. OBJECTIVE: This article provides an overview of the available data on the effectiveness of inpatient psychotherapy for BPD. MATERIAL AND METHODS: A qualitative review on the effectiveness and therapy outcome predictors was conducted based on a literature search in PubMed. RESULTS: Overall, very few randomized controlled trials are available; in contrast uncontrolled studies are predominant. Most evidence is available for dialectical behavior therapy (DBT) but other approaches, including psychodynamic procedures, have also been studied. DISCUSSION: The currently available data suggest an efficacy of inpatient psychotherapy for BPD; however, randomized trials with larger samples and sufficient representation including male patients are largely lacking. There is also no substantial direct evidence for the superiority of inpatient compared to outpatient psychotherapy.

The association between adverse childhood experiences and peripartal pain experience.

ABSTRACT: Adverse childhood experiences (ACEs) are associated with altered ongoing and evoked pain experiences, which have scarcely been studied for the peripartum period. We aimed to investigate how ACEs affect pain experience in pregnancy and labor. For this noninterventional trial with a short-term follow-up, pregnant women were divided into a trauma group (TG) with ACEs (n = 84) and a control group (CG) without ACEs (n = 107) according to the Childhood Trauma Questionnaire. Pain experience in pregnancy and labor was recorded by self-report and the German Pain Perception Scale. Pain sensitivity prepartum and postpartum was assessed by Quantitative Sensory Testing and a paradigm of conditioned pain modulation (CPM), using pressure pain thresholds (PPTs) and a cold pressor test. The TG showed higher affective and sensory scores for back pain and a more than doubled prevalence of preexisting back pain. Pelvic pain differences were nonsignificant. The TG also exhibited increased affective scores (1.71 ± 0.15 vs 1.33 ± 0.11), but not sensory scores for labor pain during spontaneous delivery. There were no group differences in prepartum pain sensitivity. While PPTs increased through delivery in the CG (clinical CPM), and this PPT change was positively correlated with the experimental CPM ( r = 0.55), this was not the case in the TG. The association of ACEs with increased peripartal pain affect and heightened risk for preexisting back pain suggest that such women deserve special care. The dissociation of impaired clinical CPM in women with ACEs and normal prepartum experimental CPM implies at least partly different mechanisms of these 2 manifestations of endogenous pain controls.

Posterior cingulate cortex targeted real-time fMRI neurofeedback recalibrates functional connectivity with the amygdala, posterior insula, and default-mode network in PTSD.

BACKGROUND: Alterations within large-scale brain networks-namely, the default mode (DMN) and salience networks (SN)-are present among individuals with posttraumatic stress disorder (PTSD). Previous real-time functional magnetic resonance imaging (fMRI) and electroencephalography neurofeedback studies suggest that regulating posterior cingulate cortex (PCC; the primary hub of the posterior DMN) activity may reduce PTSD symptoms and recalibrate altered network dynamics. However, PCC connectivity to the DMN and SN during PCC-targeted fMRI neurofeedback remains unexamined and may help to elucidate neurophysiological mechanisms through which these symptom improvements may occur. METHODS: Using a trauma/emotion provocation paradigm, we investigated psychophysiological interactions over a single session of neurofeedback among PTSD (n = 14) and healthy control (n = 15) participants. We compared PCC functional connectivity between regulate (in which participants downregulated PCC activity) and view (in which participants did not exert regulatory control) conditions across the whole-brain as well as in a priori specified regions-of-interest. RESULTS: During regulate as compared to view conditions, only the PTSD group showed significant PCC connectivity with anterior DMN (dmPFC, vmPFC) and SN (posterior insula) regions, whereas both groups displayed PCC connectivity with other posterior DMN areas (precuneus/cuneus). Additionally, as compared with controls, the PTSD group showed significantly greater PCC connectivity with the SN (amygdala) during regulate as compared to view conditions. Moreover, linear regression analyses revealed that during regulate as compared to view conditions, PCC connectivity to DMN and SN regions was positively correlated to psychiatric symptoms across all participants. CONCLUSION: In summary, observations of PCC connectivity to the DMN and SN provide emerging evidence of neural mechanisms underlying PCC-targeted fMRI neurofeedback among individuals with PTSD. This supports the use of PCC-targeted neurofeedback as a means by which to recalibrate PTSD-associated alterations in neural connectivity within the DMN and SN, which together, may help to facilitate improved emotion regulation abilities in PTSD.

Does self-harm have the desired effect? Comparing non-suicidal self-injury to high-urge moments in an ambulatory assessment design.

All theoretical models of non-suicidal self-injury (NSSI) posit that regulation of negative affect (NA) is a central motive for NSSI, and cross-sectional work supports this. However, previous ambulatory assessment (AA) studies that examined NSSI found mixed results. We investigated the affect regulation function of NSSI in 51 women with DSM-5 NSSI disorder in a 15-day AA study with five random daily prompts and self-initiated NSSI prompts. We extend previous work by i) comparing NSSI moments to moments of a high-urge for NSSI, ii) adding high-frequency sampling following NSSI and high-urge moments, and iii) including tension as a dependent variable. We hypothesized that NA and tension would show a steeper decrease following NSSI than following high-urge moments, if NSSI was effective in reducing NA and tension. Results showed that the significant linear NA decline following NSSI was not steeper than that following high-urge moments. For aversive tension, we found that NSSI was associated with a significant linear decrease in tension, whereas resisting an urge was not. High-urge moments were better described by an inverted U-shaped pattern, likewise leading to decreased NA and tension following the reported urge. In exploratory analyses, we provide visualized clustering of the NA and tension trajectories surrounding NSSI using k-means and relate these to participants' self-rated effectiveness of the NSSI events. Findings indicate that resisting an urge may also be effective in managing NA and tension and underline the utility of interventions such as urge-surfing.

Does the Augmentation of Trauma Informed Hatha Yoga Increase the Effect of Dialectical Behavior Therapy for Substance Use Disorders on Psychopathological Strain of Patients with Borderline Personality Disorder and Comorbid Substance Use Disorder? Results of a Quasi-Experimental Study.

BACKGROUND: Borderline personality disorder (BPD) is one of the most common personality disorders among persons with substance use disorders (SUDs) and is characterized by severe clinical symptoms. The aim of this study was to investigate if the effect of dialectical behavior therapy for substance use disorders (DBT-S) inpatient treatment on psychopathological symptom load in patients suffering from both BPD and SUD can be augmented by weekly 60-min "Trauma Informed Hatha Yoga" sessions. MATERIALS AND METHODS: Thirty-nine patients suffering from comorbid BPD and SUD were consecutively in time included in this quasi-experimental pilot study (first intervention then control group). In the intervention group, weekly Trauma Informed Hatha Yoga sessions were added to standard DBT-S for 8 weeks. The participants of the control group received standard DBT-S. All participants completed several self-report questionnaires to assess symptoms of depression, anxiety, symptoms of BPD, and their subjective stress perception at three points in time during the study course. RESULTS: A repeated measures analysis of variance with patients' psychopharmacological medication as covariate revealed a significant main effect of time for each of the psychometric scales (State and Trait Anxiety Inventory subscale for state anxiety [STAI-S] p = 0.001, Beck Depression Inventory [BDI] p < 0.001; Borderline Symptom List 23 [BSL] p = 0.036) indicating that the psychopathological symptom load of the patients was significantly lower at the end of the DBT-S therapy compared to the beginning in both study groups. Moreover, there was a significant interaction effect of group*time on the psychometric scales STAI-T (subscale for trait anxiety) sum score (p = 0.010) and the sum score of the Perceived Stress Scale (PSS) (p = 0.043). This was expressed by the fact that the participants of the intervention group showed a significant reduction of the STAI-T sum score as well as the sum score of the Perceived Stress Scale (PSS), while the control group did not. Due to the exploratory nature of this study, correction for multiple testing was omitted. CONCLUSION: Although they are very preliminary, our results suggest that practicing Trauma Informed Hatha Yoga on a regular basis in addition to DBT-S inpatient treatment seems to reduce the level of trait anxiety and perceived stress significantly more than DBT-S inpatient treatment alone. Nevertheless, the effectiveness of Trauma Informed Hatha Yoga in reducing trait anxiety and perceived stress in patients suffering from SUD und BPD must be tested in large randomized controlled trials.

Neurostructural associations with traumatic experiences during child- and adulthood.

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.

Social threat and safety learning in individuals with adverse childhood experiences: electrocortical evidence on face processing, recognition, and working memory.

Background: Adverse childhood experiences (ACEs) are often associated with stress and anxiety-related disorders in adulthood, and learning and memory deficits have been suggested as a potential link between ACEs and psychopathology. Objective: In this preregistered study, the impact of social threat learning on the processing, encoding, and recognition of unknown faces as well as their contextual settings was measured by recognition performance and event-related brain potentials. Method: Sixty-four individuals with ACEs encoded neutral faces within threatening or safe context conditions. During recognition, participants had to decide whether a face was new or had been previously presented in what context (item-source memory), looking at old and new faces. For visual working memory, participants had to detect changes in low and high load conditions during contextual threat or safety. Results: Results showed a successful induction of threat expectation in persons with ACEs. In terms of face and source recognition, overall recognition of safe and new faces was better compared to threatening face-compounds, with more socially anxious individuals having an advantage in remembering threatening faces. For working memory, an effect of task load was found on performance, irrespective of threat or safety context. Regarding electrocortical activity, an old/new recognition effect and threat-selective processing of face-context information was observed during both encoding and recognition. Moreover, neural activity associated with change detection was found for faces in a threatening context, but only at high task load, suggesting reduced capacity for faces in potentially harmful situations when cognitive resources are limited. Conclusion: While individuals with ACE showed intact social threat and safety learning overall, threat-selective face processing was observed for item/source memory, and a threatening context required more processing resources for visual working memory. Further research is needed to investigate the psychophysiological processes involved in functional and dysfunctional memory systems and their importance as vulnerability factors for stress-related disorders.

Antecedentes: Las experiencias adversas en la infancia (ACEs, por su sigla en inglés) estan a menudo asociadas con trastornos relacionados con el estrés y la ansiedad en la edad adulta, y los déficits de aprendizaje y memoria han sido sugeridos como un vínculo potencial entre las ACEs y la psicopatología.Objetivo: En este estudio previamente registrado, el impacto del aprendizaje de amenazas sociales en el procesamiento, la codificación y el reconocimiento de rostros desconocidos, así como sus entornos contextuales, se midió mediante el rendimiento y los potenciales cerebrales relacionados con los eventos.Método: Sesenta y cuatro personas con ACEs codificaron rostros neutrales dentro de condiciones de contextos amenazantes o seguros. Durante el reconocimiento, los participantes tenían que decidir si una cara era nueva o se había presentado previamente en qué contexto (elemento-fuente de memoria), mirando caras antiguas y nuevas. Para la memoria de trabajo visual, los participantes tenían que detectar cambios en las condiciones de carga baja y alta durante la amenaza contextual o la seguridad.Resultados: Los resultados mostraron una inducción exitosa de la expectativa de amenaza en personas con ACEs. En términos de reconocimiento de rostros y fuentes, el reconocimiento general de rostros seguros y nuevos fue mejor en comparación con los compuestos de rostros amenazantes, y las personas más ansiosas socialmente tenían una ventaja para recordar rostros amenazantes. Para la memoria de trabajo, se encontró un efecto de la carga de tareas en el rendimiento, independientemente de la amenaza o el contexto de seguridad. Con respecto a la actividad electrocortical, se observó un efecto de reconocimiento antiguo/nuevo y un procesamiento selectivo de amenazas de la información del contexto facial durante la codificación y el reconocimiento. Además, se encontró actividad neuronal asociada con la detección de cambios para rostros en un contexto amenazante, pero solo con una gran carga de tareas, lo que sugiere una capacidad reducida para rostros en situaciones potencialmente dañinas cuando los recursos cognitivos son limitados.Conclusión: Si bien las personas con ACE mostraron un aprendizaje intacto de amenazas sociales y seguridad en general, se observó un procesamiento facial selectivo de amenazas para la memoria de elementos/fuentes, y un contexto amenazante requería más recursos de procesamiento para la memoria de trabajo visual. Se necesita más investigación para investigar los procesos psicofisiológicos involucrados en los sistemas de memoria funcional y disfuncional y su importancia como factores de vulnerabilidad para los trastornos relacionados con el estrés.

The effects of transient receptor potential cation channel inhibition by BI 1358894 on cortico-limbic brain reactivity to negative emotional stimuli in major depressive disorder.

Abnormal emotional processing in major depressive disorder (MDD) has been associated with increased activation to negative stimuli in cortico-limbic brain regions. The authors investigated whether treatment with BI 1358894, a small-molecule inhibitor of the transient receptor potential cation channel subfamily C leads to attenuated activity in these areas in MDD patients. 73 MDD patients were randomized to receive a single oral dose of BI 1358894 (100 mg), citalopram (20 mg), or matching placebo. Brain responses to emotional faces and scenes were investigated using functional magnetic resonance imaging. Primary endpoints were BOLD signal changes in response to negative faces in cortico-limbic brain regions, i.e. bilateral amygdala (AMY), dorsolateral prefrontal cortex, anterior insula (AI), and anterior cingulate cortex. Secondary endpoints were BOLD signal changes in response to negative scenes. For each region, separate ANOVA models were computed for the comparison of treatments (BI 1358894 or citalopram) vs. placebo. The adjusted treatment differences in the % BOLD signal changes in the faces task showed that BI 1358894 induced signal reduction in bilateral AMY and left AI. In the scenes task, BI 1358894 demonstrated significant signal reduction in bilateral AMY, AI, anterior cingulate cortex and left dorsolateral prefrontal cortex. Citalopram failed to induce any significant reductions in BOLD signal in both tasks. BI 1358894-mediated inhibition of the transient receptor potential cation channel subfamily resulted in strong signal reduction in cortico-limbic brain regions, thereby supporting development of this mechanism of action for MDD patients.

Anger instability and aggression in Borderline Personality Disorder - an ecological momentary assessment study.

BACKGROUND: Anger and aggression are core features of Borderline Personality Disorder (BPD), contributing strongly to the individual as well as the societal burden caused by the disorder. Across studies, patients with BPD have shown increased, more frequent and prolonged episodes of anger and reported an increased prevalence of reactive aggression. However, only a few studies have investigated anger and aggression in the patients' everyday lives and did not consider anger instability. In order to contribute knowledge about aggression and its association with anger intensity and anger instability in real-life in BPD the aim of the present study was to better characterize days with and without aggressive behaviors with regard to the patients' experienced anger. METHODS: Patients with BPD and high aggression as well as healthy participants took part in an ecological momentary assessment (EMA) study assessing state anger and aggression three times per day over two weeks. Multilevel modeling was conducted and anger instability was operationalized by squared successive differences. RESULTS: As expected, patients with BPD reported greater instability in their experienced anger compared to healthy participants. Most interestingly, in the BPD group the occurrence of aggressive behavior was significantly associated with anger intensity as well as anger instability. More precisely, on days when patients with BPD acted out aggressively, they reported higher anger intensity as well as greater anger instability than on days when they did not act out aggressively. CONCLUSION: Knowledge about what characterizes days with aggressive behaviors may help to improve interventions to reduce aggressive behavior and thus relieve the burden aggression causes for patients with BPD, their surroundings and society.

Measuring types and timing of childhood maltreatment: The psychometric properties of the KERF-40.

Childhood maltreatment, specifically during sensitive developmental periods, is a major risk factor for poor physical and mental health. Despite its enormous clinical relevance, there is still a lack of scales measuring different types, timing, and duration of childhood maltreatment. The current study sought to validate and determine the psychometric properties of the brief German version of the Maltreatment and Abuse Chronology of Exposure (MACE) scale, the KERF-40. The KERF-40 was administered as an interview (i.e., KERF-40-I) to 287 adult participants with and without mental disorders. Based on item response theory, items of the KERF-40-I were assigned to different types of maltreatment, resulting in a scaled version, the KERF-40+. Test-retest reliability was assessed in a small subsample (n = 14). Convergent and relative predictive validity were measured with correlations of the KERF-40+ and the Childhood Trauma Questionnaire (CTQ) as well as self-report measures of general and trauma-related psychopathology. Rasch analysis and fit statistics yielded a 49-item version, encompassing ten different types of maltreatment. The test-retest reliability of the KERF-40+ was shown to be acceptable to excellent for almost all global and subscale scores (.74 ≤ ρ ≤ 1.00), with the exception of the subscale emotional neglect (ρ = .55). Convergent validity with the CTQ was confirmed for both KERF-40+ global scores (.72 ≤ r ≤ .87) and corresponding subscale scores (.56 ≤ r ≤ .78). Relative predictive validity was reflected by significant small-to-moderate correlations between KERF-40+ global scores and indices of general and trauma-related psychopathology (.24 ≤ r ≤ .45). Taken together, the KERF-40+ appears to be suited for clinicians and researchers interested in retrospectively assessing different types, timing, and duration of childhood maltreatment experiences during sensitive periods in adults.

Severity of childhood maltreatment predicts reaction times and heart rate variability during an emotional working memory task in borderline personality disorder.

Background: Difficulties in emotion regulation are a core symptom of borderline personality disorder (BPD) and often interfere with cognitive functions, such as working memory (WM). Traumatic childhood experiences, including severe maltreatment, can contribute to emotion dysregulation, possibly mediated by changes in high-frequency heart rate variability (HF-HRV). However, it is not yet entirely understood if HF-HRV alterations underlie impaired WM during emotional distraction in BPD and if this is related to traumatic childhood experiences and to comorbid post-traumatic stress disorder (PTSD). Objective: Our aim was to investigate performance (reaction times, RTs) and HF-HRV during an emotional working memory task (EWMT) in relation to childhood maltreatment severity and comorbid PTSD in BPD. Method: Eighty-one women (n = 28 healthy controls (HC) and n = 53 BPD patients of which n = 18 had comorbid PTSD) performed an adapted Sternberg item recognition WM task with neutral and negative social cues (interpersonal scenes from the International Affective Picture System (IAPS), and neutral, fearful, and angry faces) as distractors. Dependent variables were RTs of correct trials and HF-HRV. Childhood maltreatment was assessed with the Childhood Trauma Questionnaire. Results: Compared to healthy participants, patients with BPD showed prolonged RTs across all distractor conditions with social cues, regardless of their emotional valence. Patients with BPD, especially those with PTSD, demonstrated reduced HF-HRV both at rest and during EWMT. Severity of childhood maltreatment predicted longer RTs and lower HF-HRV during the EWMT. Conclusions: Findings suggest that adverse childhood experiences accelerate difficulties in shifting attention away from social information and that these are more pronounced in individuals with BPD. Reduced HF-HRV (low parasympathetic-tonus) may be an important psychophysiological mechanism underlying impaired WM in the presence of distracting social cues in patients with BPD, especially in those with comorbid PTSD. HIGHLIGHTS: This study provides evidence that childhood maltreatment experiences are associated with hypersensitivity to social information and reduced high-frequency heart rate variability during a working memory task in borderline personality disorder.

Antecedentes: las dificultades en la regulación emocional es un síntoma central del trastorno límite de la personalidad (TLP) y, a menudo, interfieren con las funciones cognitivas, como la memoria de trabajo (MT). Las experiencias traumáticas de la infancia, incluido el maltrato grave, pueden contribuir a la desregulación emocional, posiblemente mediada por cambios en la variabilidad de la frecuencia cardíaca de alta frecuencia (VFC-AF). Sin embargo, aún no se comprende del todo si las alteraciones de VFC-AF subyacen a la alteración de la MT durante la distracción emocional en el TLP y si esto está relacionado con experiencias traumáticas de la infancia y con el trastorno de estrés postraumático (TEPT) comórbido.Objetivo: Nuestro objetivo fue investigar el rendimiento (tiempos de reacción, TR) y VFC-AF durante una tarea de memoria de trabajo emocional (MTE) en relación con la gravedad del maltrato infantil y el TEPT comórbido en el TLP.Método: Ochenta y una mujeres (n=28 controles sanos (CS) y n=53 pacientes con TLP, de las cuales n=18 tenían TEPT comórbido) realizaron una tarea de MT de reconocimiento de elementos de Sternberg adaptada con señales sociales neutras y negativas (escenas interpersonales del Sistema internacional de imágenes afectivas (IAPS por sus siglas en ingles) y rostros neutrales, temerosos y enojados) como distractores. Las variables dependientes fueron TR de ensayos correctos y VFC-AF. El maltrato infantil se evaluó con el Cuestionario de Trauma Infantil.Resultados: En comparación con las participantes sanas, las pacientes con TLP mostraron TR prolongados en todas las condiciones de distracción con señales sociales, independientemente de su valencia emocional. Los pacientes con TLP, especialmente aquellos con TEPT, demostraron una reducción de VFC-AF tanto en reposo como durante MTE. La gravedad del maltrato infantil predijo TR más largos y VFC-AF más bajo durante el MTE.Conclusiones: Los resultados sugieren que las experiencias infantiles adversas refuerzan las dificultades para desviar la atención de la información social y que estas son más pronunciadas en las personas con TLP. La VFC-AF reducida (tono parasimpático bajo) puede ser un mecanismo psicofisiológico importante subyacente a la MT alterada en presencia de señales sociales que distraen en pacientes con TLP, especialmente en aquellos con TEPT comórbido.