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An increasing number of studies have been investigating the co-occurrence of posttraumatic symptoms and dissociation in trauma-exposed samples. As traumatized refugees are particularly susceptible to developing posttraumatic stress disorder (PTSD), the aim of this study was to investigate the relationship between PTSD and dissociation in a traumatized refugee sample. Cross-sectional data from a clinical refugee sample ( N  = 526) were collected. Latent class analysis (LCA) examined different classes of PTSD, based on the Clinician Administered PTSD Scale for DSM-5 (CAPS-5) items. Subsequently, it was examined whether cumulative trauma, sexual trauma and general psychopathology predicted class membership. The LCA identified five classes. The classes were summarized as (1) "High PTSD," (2) "Moderate PTSD," (3) "High PTSD with high loss of interest," (4) "High PTSD with moderate loss of interest," and (5) "PTSD-DS." PTSD DS (10% of the sample) was characterized by high PTSD symptoms, as well as high depersonalization and derealization symptoms. The majority (61.4%) of this group has been exposed to sexual trauma. Overall endorsement of PTSD symptoms was extremely high in this clinical sample of refugees. A group evidencing the PTSD dissociative subtype was identified.

Background: The International Trauma Questionnaire (ITQ) is a recent self-report measure to assess the severity and probable posttraumatic stress disorder (PTSD) and complex PTSD (CPTSD) as defined by the 11th revision of the International Classification of Diseases . Few studies have examined the psychometric properties of full and short ITQ versions in depth. Therefore, we aimed to evaluate the psychometric properties of the Dutch-translated 28-item ITQ and the 12-item version., Method: Data were used from existing clinical studies and routine clinical assessments for the 28-item ( n = 956) and 12-item ( N = 4,944) ITQ versions in trauma-exposed treatment-seeking individuals in the Netherlands. Internal consistency and factor validity were assessed, and rates of probable PTSD and CPTSD were estimated. In addition, convergent and discriminant validity were examined by correlations with similar and dissimilar measures., Results: Both versions of the ITQ showed good internal consistency and convergent validity. Confirmatory factor analysis showed that both a first-order correlated six-factor model and a two-factor second-order model were a good representation of the latent structure for the ITQ-12. The ITQ-12 resulted in higher CPTSD rates compared to the ITQ-28 (47% vs. 36.3%), while a similar number of patients met the criteria for either PTSD or CPTSD (70.6% vs. 76.4%)., Conclusion: Internal consistency and convergent validity for the ITQ-12 and ITQ-28 were supported. The factorial validity was good for the ITQ-12 and acceptable for the ITQ-28. The discrepancy in CPTSD rates between the ITQ-12 and ITQ-28 calls for further testing of scoring methods against diagnostic clinical interviews for CPTSD. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Background: While treatment of posttraumatic stress disorder (PTSD) in refugees is generally effective, many refugees remain symptomatic after treatment. Coping styles could be relevant to PTSD treatment response and as such may be a potential focus of PTSD treatment., Aims: The study aims to examine 1) if baseline coping styles are related to treatment response after EMDR therapy or stabilization, and 2) if coping styles change during these treatments., Method: Seventy-two refugees with PTSD were randomly allocated to 12 hours of EMDR therapy or stabilization. A coping questionnaire (COPE-easy) and clinical interview for PTSD (CAPS-IV) were administered before and after treatment and at three-month follow-up. The association between baseline coping styles and PTSD symptom change was examined using regression analysis and a t-test. Changes in coping styles were analyzed using mixed design ANOVA., Results: No significant relations between baseline coping style levels and PTSD symptom changes were found. Additionally, coping style levels did not change significantly after either treatment., Conclusion: Contrary to the hypothesis, we did not find any evidence that treatment was related to (changes in) coping style. Addressing pre-treatment coping styles among refugees receiving short-term therapy, may not be required for reducing PTSD. Changing coping styles may need a longer or different type of treatment., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 van Heemstra et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: Although highly intensive trauma treatment programs show promising results in the treatment of patients with posttraumatic stress disorder (PTSD), it remains uncertain if patients with complex forms of PTSD can benefit equally from these intensive programs. To investigate whether patients with the dissociative subtype of PTSD (PTSD + DS) and patients with probable complex PTSD (CPTSD) draw equal benefits from a highly intensive trauma treatment program as patients with PTSD., Method: In this clinical cohort study, patients were included who attended a 5-day intensive program consisting of eye movement desensitisation reprocessing, exposure in vivo and trauma-sensitive yoga components. PTSD with DS was assessed with the Clinician-Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders, fifth edition (CAPS-5), and a provisional diagnosis of CPTSD was assessed with the International Trauma Questionnaire. Primary outcome measure was self-reported PTSD-symptom severity measured by PTSD Checklist for DSM -5 at the start of the program (T1) and a week after the program (T2)., Results: Both groups, PTSD + DS ( d = 0.85) and probable CPTSD ( d = 0.85) benefitted significantly in terms of PTSD-symptom severity reduction and the size of the decrease was not significantly different from that of patients with PTSD., Conclusions: Patients with both forms of PTSD complexity can benefit even from a very brief intensive treatment program, which extends previous studies. The diagnoses of PTSD + DS and CPTSD seem helpful to assess the initial severity of the symptoms, but do not imply contra-indications to benefit from intensive treatment. Highly intensive treatment programs are promising interventions to effectively treat complex forms of PTSD and should be studied further in randomized clinical trials. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Heterozygous de novo mutations in the Activity-Dependent Neuroprotective Homeobox (ADNP) gene underlie Helsmoortel-Van der Aa syndrome (HVDAS). Most of these mutations are situated in the last exon and we previously demonstrated escape from nonsense-mediated decay by detecting mutant ADNP mRNA in patient blood. In this study, wild-type and ADNP mutants are investigated at the protein level and therefore optimal detection of the protein is required. Detection of ADNP by means of western blotting has been ambiguous with reported antibodies resulting in non-specific bands without unique ADNP signal. Validation of an N-terminal ADNP antibody (Aviva Systems) using a blocking peptide competition assay allowed to differentiate between specific and non-specific signals in different sample materials, resulting in a unique band signal around 150 kDa for ADNP, above its theoretical molecular weight of 124 kDa. Detection with different C-terminal antibodies confirmed the signals at an observed molecular weight of 150 kDa. Our antibody panel was subsequently tested by immunoblotting, comparing parental and homozygous CRISPR/Cas9 endonuclease-mediated Adnp knockout cell lines and showed disappearance of the 150 kDa signal, indicative for intact ADNP. By means of both a GFPSpark and Flag-tag N-terminally fused to a human ADNP expression vector, we detected wild-type ADNP together with mutant forms after introduction of patient mutations in E. coli expression systems by site-directed mutagenesis. Furthermore, we were also able to visualize endogenous ADNP with our C-terminal antibody panel in heterozygous cell lines carrying ADNP patient mutations, while the truncated ADNP mutants could only be detected with epitope-tag-specific antibodies, suggesting that addition of an epitope-tag possibly helps stabilizing the protein. However, western blotting of patient-derived hiPSCs, immortalized lymphoblastoid cell lines and post-mortem patient brain material failed to detect a native mutant ADNP protein. In addition, an N-terminal immunoprecipitation-competent ADNP antibody enriched truncating mutants in overexpression lysates, whereas implementation of the same method failed to enrich a possible native mutant protein in immortalized patient-derived lymphoblastoid cell lines. This study aims to shape awareness for critical assessment of mutant ADNP protein analysis in Helsmoortel-Van der Aa syndrome., (© 2024. The Author(s).)

Background: Helsmoortel-Van der Aa syndrome is a neurodevelopmental disorder in which patients present with autism, intellectual disability, and frequent extra-neurological features such as feeding and gastrointestinal problems, visual impairments, and cardiac abnormalities. All patients exhibit heterozygous de novo nonsense or frameshift stop mutations in the Activity-Dependent Neuroprotective Protein (ADNP) gene, accounting for a prevalence of 0.2% of all autism cases worldwide. ADNP fulfills an essential chromatin remodeling function during brain development. In this study, we investigated the cerebellum of a died 6-year-old male patient with the c.1676dupA/p.His559Glnfs*3 ADNP mutation., Results: The clinical presentation of the patient was representative of the Helsmoortel-Van der Aa syndrome. During his lifespan, he underwent two liver transplantations after which the child died because of multiple organ failure. An autopsy was performed, and various tissue samples were taken for further analysis. We performed a molecular characterization of the cerebellum, a brain region involved in motor coordination, known for its highest ADNP expression and compared it to an age-matched control subject. Importantly, epigenome-wide analysis of the ADNP cerebellum identified CpG methylation differences and expression of multiple pathways causing neurodevelopmental delay. Interestingly, transcription factor motif enrichment analysis of differentially methylated genes showed that the ADNP binding motif was the most significantly enriched. RNA sequencing of the autopsy brain further identified downregulation of the WNT signaling pathway and autophagy defects as possible causes of neurodevelopmental delay. Ultimately, label-free quantification mass spectrometry identified differentially expressed proteins involved in mitochondrial stress and sirtuin signaling pathways amongst others. Protein-protein interaction analysis further revealed a network including chromatin remodelers (ADNP, SMARCC2, HDAC2 and YY1), autophagy-related proteins (LAMP1, BECN1 and LC3) as well as a key histone deacetylating enzyme SIRT1, involved in mitochondrial energy metabolism. The protein interaction of ADNP with SIRT1 was further biochemically validated through the microtubule-end binding proteins EB1/EB3 by direct co-immunoprecipitation in mouse cerebellum, suggesting important mito-epigenetic crosstalk between chromatin remodeling and mitochondrial energy metabolism linked to autophagy stress responses. This is further supported by mitochondrial activity assays and stainings in patient-derived fibroblasts which suggest mitochondrial dysfunctions in the ADNP deficient human brain., Conclusion: This study forms the baseline clinical and molecular characterization of an ADNP autopsy cerebellum, providing novel insights in the disease mechanisms of the Helsmoortel-Van der Aa syndrome. By combining multi-omic and biochemical approaches, we identified a novel SIRT1-EB1/EB3-ADNP protein complex which may contribute to autophagic flux alterations and impaired mitochondrial metabolism in the Helsmoortel-Van der Aa syndrome and holds promise as a new therapeutic target., (© 2024. The Author(s).)

Background: Refugees often suffer from trauma-related psychopathology, specifically posttraumatic stress disorder (PTSD). Negative world assumptions are strongly correlated with the development, course, and severity of PTSD. Objective: This study aimed to investigate whether there are distinct profiles of PTSD and negative world assumptions (NWA) and examine whether trauma load, torture, and gender differentially predict such symptom profiles. Method: In a sample of 225 treatment-seeking refugees who had resettled in the Netherlands, latent profile analysis was used to identify subgroups of patients sharing the same profile of PTSD and NWA symptoms. Predictors of profile membership were analyzed via multinomial logistic regression. Results: A three-profile solution yielded the best model fit: a low PTSD/low NWA profile (23.6%), a high PTSD/high NWA profile (41.8%), and a high PTSD/low NWA profile (34.7%). Participants who reported a higher trauma load, were more likely to be part of the high PTSD/high NWA profile or the high PTSD/low NWA profile in comparison to low PTSD/low NWA profile. Participants who reported having experienced torture were more likely to be part of the high PTSD/high NWA profile in comparison to low PTSD/low NWA profile. Gender did not differentiate between the profiles. Conclusions: This study reveals that among treatment-seeking refugees resettled in the Netherlands, there are distinct profiles of PTSD and NWA. These profiles indicate that PTSD and NWA are not uniformly experienced among refugees, emphasizing the diversity in their psychological responses to trauma. Among individuals experiencing severe PTSD symptoms, a subgroup was identified of individuals who additionally exhibited negative assumptions about themselves, others, and the world. Recognizing this heterogeneity is crucial in both research and clinical practice, particularly in the context of refugee mental health. Directions for future research are discussed.

Background: During peacekeeping missions, military personnel may be involved in or exposed to potentially morally injurious experiences (PMIEs), such as an inability to intervene due to a limited mandate. While exposure to such morally transgressive events has been shown to lead to moral injury in combat veterans, research on moral injury in peacekeepers is limited. Objective: We aimed to determine patterns of exposure to PMIEs and associated outcome- and exposure-related factors among Dutch peacekeepers stationed in the former Yugoslavia during the Srebrenica genocide. Method: Self-report data were collected among Dutchbat III veterans ( N  = 431). We used Latent Class Analysis to identify subgroups of PMIE exposure as assessed by the Moral Injury Scale-Military version. We investigated whether deployment location, posttraumatic stress disorder (PTSD), posttraumatic growth, resilience, and quality of life differentiated between latent classes. Results: The analysis identified a three-class solution: a high exposure class ( n  = 79), a moderate exposure class ( n  = 261), and a betrayal and powerlessness-only class ( n  = 135). More PMIE exposure was associated with deployment location and higher odds of having probable PTSD. PMIE exposure was not associated with posttraumatic growth. Resilience and quality of life were excluded from analyses due to high correlations with PTSD. Conclusions: Peacekeepers may experience varying levels of PMIE exposure, with more exposure being associated with worse outcomes 25 years later. Although no causal relationship may be assumed, the results emphasize the importance of better understanding PMIEs within peacekeeping.

Introduction: Unaccompanied refugee minors (URMs) are at increased risk of developing mental health problems, such as symptoms of posttraumatic stress disorder (PTSD) and depression. In addition, URMs face several barriers to mental health care. Few studies have evaluated trauma-focused interventions for URMs that target these issues. The current study evaluated a multimodal trauma-focused treatment approach for URMs. It aimed to provide an initial indication of the effectiveness of this treatment approach and to provide a qualitative evaluation assessing treatment satisfaction of the participating URMs., Methods: A mixed-methods study was conducted among ten URMs, combining quantitative data with qualitative data through triangulation. Quantitative data were collected using a non-concurrent multiple baseline design in which repeated, weekly assessments were carried out during a randomized baseline period, during treatment, and during a 4-week follow-up period. Questionnaires assessing PTSD (Children's Revised Impact of Event Scale) and symptoms of depression (The Patient Health Questionnaire-9, modified for adolescents) were used. In addition, treatment satisfaction was measured post-treatment using a semi-structured interview., Results: During the qualitative evaluation, all but one URM noted they found the trauma-focused treatment approach useful and felt the treatment had positively impacted their wellbeing. However, the results of the quantitative evaluation did not show clinically reliable symptom reductions at posttest or follow-up. Implications for clinical practice and research are discussed., Discussion: The current study presents our search in developing a treatment approach for URMs. It adds to the current knowledge about methodological considerations in evaluating treatments for URMs, the potential effects of trauma-focused treatments on URMs, and the implementation of treatments for URMs. Clinical trial registration: The study was registered in the Netherlands Trial Register (NL8519), 10 April 2020., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Van Es, Velu, Sleijpen, van der Aa, Boelen and Mooren.)

Objective: Police officers typically face multiple potentially traumatic events and consequently have a higher conditional probability of developing PTSD. Although most police officers with PTSD benefit from first-line treatment, it is unknown whether recommended intensification of treatment for low responders is effective and which factors contribute to response. This study aimed to examine the treatment response of a day clinic for police officers with PTSD and identify predictors of treatment response., Method: Between 2009 and 2019, routine outcome monitoring measurements consisting of PTSD symptom severity and general psychological distress were administered at two timepoints among 102 patients undergoing a day clinic treatment consisting of trauma-focused therapy, sociotherapy, and psychomotor therapy. Hierarchical regression was used to assess whether change in PTSD symptom severity was associated with baseline PTSD and depression severity, gender, age, and eligibility for a recognition procedure., Results: Significant improvements in PTSD symptom severity were found over the course of the treatment ( d = .59), with 47% of patients showing statistically reliable improvement in their symptoms. The only significant predictor of treatment response was eligibility for a recognition procedure, with the total model explaining approximately 10% of the variation in treatment response., Conclusions: Intensifying treatment for police officers with PTSD who do not respond to previous trauma-focused treatment appears beneficial for a substantial number of patients. However, eligibility for a recognition procedure may negatively impact treatment response. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Introduction: Migration puts refugees in a completely new social context when simultaneously some have to deal with previously experienced traumatic events and post-migration stressors. Social capital and sense of coherence could be key resources to improve mental health of refugees. This study aims to examine the interplay between social capital (structural and cognitive), sense of coherence and mental health of refugees in the Netherlands., Objective: The present study was conducted to i) examine if social capital (structural and cognitive) and mental health are related in a population of Dutch refugees, and ii) test if sense of coherence has a moderating and/or a mediating effect on this relation., Method: Data were collected through questionnaires (n = 154) in a cross-sectional survey at different locations throughout the Netherlands. The data were analysed with multiple regression analyses and nonparametric bootstrapping using SPSS., Results: Social capital (structural and cognitive) was positively related to mental health. In addition a positive relation between sense of coherence and mental health of refugees was found. The relationship between cognitive social capital and mental health was completely mediated by sense of coherence. No moderation effect of sense of coherence on the relation between social capital and mental health was found., Conclusions: The current study contributed to understanding the social mechanism that determines refugee mental health: participating in social groups (structural social capital) and having supportive and trusting relationships (cognitive social capital), whilst experiencing life as comprehensible, manageable, and meaningful (sense of coherence) are positively related to better mental health of refugees. Findings indicate that preventive interventions aiming to enhance refugees' mental health may be more effective when targeting and promoting both social capital and sense of coherence, from a relatively early stage after arrival in the Netherlands., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors.)

Exposure to morally injurious events may have a severe, prolonged negative impact on psychosocial functioning, known as moral injury (MI). Research into the prevalence of MI has mostly focused on event exposure rather than on psychosocial impact. Also, the relationship between MI and post-traumatic stress disorder (PTSD) remains a matter of interest. The aim of this study was to identify MI and PTSD symptom profiles among trauma-exposed, treatment-seeking police officers and military veterans, and to explore demographic and clinical differences between symptom profiles. Latent class and multinomial regression analyses were conducted in a sample of 1,703 participants, using the Clinician-Administered PTSD Scale for DSM-5 and the Brief Symptom Inventory. Four classes of participants were identified, labeled as a MI class ( n = 192; 11.27%), a MI-PTSD class ( n = 565; 33.18%), a PTSD class ( n = 644; 37.82%), and a Neither MI-nor PTSD class ( n = 302; 17.73%), resulting in 44.45% ( n = 757) of participants who met an MI symptom profile with or without PTSD. There were significant differences between the classes in terms of gender as well as PTSD and comorbid psychopathology symptom severity, the latter of which was highest in the MI-PTSD class. In conclusion, a substantial subgroup of trauma-exposed, treatment-seeking police officers and military veterans could be classified as suffering from MI. Routinely screening for MI in treatment-seeking police officers and military veterans is recommended, and interventions aimed at relieving MI in these populations may be indicated., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Mensink, van Schagen, van der Aa and ter Heide.)

Background: Primary microcephaly (PM) is defined as a significant reduction in occipitofrontal circumference (OFC) of prenatal onset. Clinical and genetic heterogeneity of PM represents a diagnostic challenge., Methods: We performed detailed phenotypic and genomic analyses in a large cohort (n = 169) of patients referred for PM and could establish a molecular diagnosis in 38 patients., Results: Pathogenic variants in ASPM and WDR62 were the most frequent causes in non-consanguineous patients in our cohort. In consanguineous patients, microarray and targeted gene panel analyses reached a diagnostic yield of 67%, which contrasts with a much lower rate in non-consanguineous patients (9%). Our series includes 11 novel pathogenic variants and we identify novel candidate genes including IGF2BP3 and DNAH2. We confirm the progression of microcephaly over time in affected children. Epilepsy was an important associated feature in our PM cohort, affecting 34% of patients with a molecular confirmation of the PM diagnosis, with various degrees of severity and seizure types., Conclusion: Our findings will help to prioritize genomic investigations, accelerate molecular diagnoses, and improve the management of PM patients., (© 2021 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

Most genes associated with neurodevelopmental disorders (NDDs) were identified with an excess of de novo mutations (DNMs) but the significance in case-control mutation burden analysis is unestablished. Here, we sequence 63 genes in 16,294 NDD cases and an additional 62 genes in 6,211 NDD cases. By combining these with published data, we assess a total of 125 genes in over 16,000 NDD cases and compare the mutation burden to nonpsychiatric controls from ExAC. We identify 48 genes (25 newly reported) showing significant burden of ultra-rare (MAF < 0.01%) gene-disruptive mutations (FDR 5%), six of which reach family-wise error rate (FWER) significance (p < 1.25E-06). Among these 125 targeted genes, we also reevaluate DNM excess in 17,426 NDD trios with 6,499 new autism trios. We identify 90 genes enriched for DNMs (FDR 5%; e.g., GABRG2 and UIMC1); of which, 61 reach FWER significance (p < 3.64E-07; e.g., CASZ1). In addition to doubling the number of patients for many NDD risk genes, we present phenotype-genotype correlations for seven risk genes (CTCF, HNRNPU, KCNQ3, ZBTB18, TCF12, SPEN, and LEO1) based on this large-scale targeted sequencing effort.

Background: Most people who experience a potentially traumatic event (PTE) recover on their own. A small group of individuals develops psychological complaints, but this is often not detected in time or guidance to care is suboptimal. To identify these individuals and encourage them to seek help, a web-based self-help test called Mobile Insight in Risk, Resilience, and Online Referral (MIRROR) was developed. MIRROR takes an innovative approach since it integrates both negative and positive outcomes of PTEs and time since the event and provides direct feedback to the user., Objective: The goal of this study was to assess MIRROR's use, examine its psychometric properties (factor structure, internal consistency, and convergent and divergent validity), and evaluate how well it classifies respondents into different outcome categories compared with reference measures., Methods: MIRROR was embedded in the website of Victim Support Netherlands so visitors could use it. We compared MIRROR's outcomes to reference measures of PTSD symptoms (PTSD Checklist for DSM-5), depression, anxiety, stress (Depression Anxiety Stress Scale-21), psychological resilience (Resilience Evaluation Scale), and positive mental health (Mental Health Continuum Short Form)., Results: In 6 months, 1112 respondents completed MIRROR, of whom 663 also completed the reference measures. Results showed good internal consistency (interitem correlations range .24 to .55, corrected item-total correlations range .30 to .54, and Cronbach alpha coefficient range .62 to .68), and convergent and divergent validity (Pearson correlations range -.259 to .665). Exploratory and confirmatory factor analyses (EFA+CFA) yielded a 2-factor model with good model fit (CFA model fit indices: χ 2 19 =107.8, P<.001, CFI=.965, TLI=.948, RMSEA=.065), conceptual meaning, and parsimony. MIRROR correctly classified respondents into different outcome categories compared with the reference measures., Conclusions: MIRROR is a valid and reliable self-help test to identify negative (PTSD complaints) and positive outcomes (psychosocial functioning and resilience) of PTEs. MIRROR is an easily accessible online tool that can help people who have experienced a PTE to timely identify psychological complaints and find appropriate support, a tool that might be highly needed in times like the coronavirus pandemic., (©Merel Marjolein van Herpen, Manon A Boeschoten, Hans te Brake, Niels van der Aa, Miranda Olff. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 25.09.2020.)

Background:  Refugees are at high risk for developing post-traumatic stress disorder (PTSD). Narrative exposure therapy (NET) is an evidence-based treatment of PTSD, designed for patients exposed to (multiple) traumatic events and recommended for patients with culturally diverse backgrounds. In clinical practice, adherence to the NET-protocol has been challenged because of psychosocial complexities and comorbid disorders. ., Objective: The current study investigated the feasibility of NET embedded in an outpatient day treatment programme for refugees and examined reduction in PTSD symptoms and improvement of global functioning as well as correlates of change. ., Method: Participants were patients who consecutively entered an outpatient daytreatment programme from 2013-2017. The majority had a history of prior unsuccessful treatment. PTSD was assessed with the Clinically Administered PTSD Scale (CAPS) before and after finishing NET. Global Assessment of Functioning (GAF) was used to examine changes in functioning. Changes in PTSD scores and functioning were analyzed using paired t-tests and reliable change indices. Patients showing significant improvement were compared to those who did not, on patient and treatment characteristics, including sex, age, region of origin, childhood trauma and treatment duration and dosage of NET. ., Results: Of 97 patients, 76 (78.4%) completed NET. Completers had a longer residency and were more likely to have a partner. Significant reductions in PTSD symptoms and improvements in global functioning were observed. Twenty-eight percent showed reliable improvement with large effect sizes. Four patients did no longer meet the criteria for PTSD. No strong moderators for changes were found. Patients who did not improve more often had a history of childhood trauma., Conclusions: NET embedded in an outpatient day treatment programme appears to be feasible. In those who improved, a substantial decline in symptoms and improvement of functioning were observed. The findings suggest that a socially supportive living environment enhances acceptability of trauma-focused treatment in refugees., Competing Interests: No potential conflict of interest was reported by the authors., (© 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Background: Western countries are facing many challenges hosting refugees from several regions in the world. Many of them are severely traumatized and suffer from a variety of mental health symptoms, which complicates the identification and treatment of refugees at risk. This study examined subgroups based on a broad range of psychopathology, and several predictors, including trauma characteristics and gender., Methods: Participants were 1147 treatment-seeking, traumatized refugees. Latent profile analysis was conducted to identify different subgroups based on levels of posttraumatic stress disorder (PTSD), depression, anxiety, and somatic symptoms. Multinomial logistic regression was used to identify predictors of subgroup membership., Results: Three distinct subgroups were identified, reflecting Moderate (10.2%), Severe (43.0%), and Highly Severe (45.9%) symptom severity levels, respectively. Symptom severity of all psychopathology dimensions was distributed equally between the subgroups. Participants in the Severe and Highly Severe Symptoms subgroups reported more types of traumatic events compared to the Moderate subgroup. In particular, traumatic events associated with human right abuses, lack of human needs and separation from others predicted subgroup membership, as did gender., Limitations: The results are confined to treatment-seeking, traumatized refugee populations., Conclusions: Distinguishable symptom severity profiles of PTSD, depression, anxiety and somatic complaints could be identified in this large treatment-seeking refugee population, without qualitative differences in symptom distribution. Instead of focusing on specific mental disorders, classification based on overall symptom severity is of interest in severely traumatized patients. This knowledge will help to identify individuals at risk and to enhance existing treatment programs for specific patient groups., Competing Interests: Declarations of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Many pathways have been involved in pathophysiology of the fragile X syndrome, one of the more frequent genetic causes of intellectual disability and autism. This review highlights the recent insights in the role the abnormalities in the GABAergic system play in the disorder. Since the initial observations showed that the expression of specific subunits of the GABA(A) receptor were underexpressed in the fragile X knockout mouse model more than a decade ago, evidence has accumulated that the expression of approximately half of the GABAergic system is compromised in multiple species, including in fragile X patients. Functional consequences of the GABAergic deficiencies could be measured using whole-cell voltage clamp recordings. Pharmalogical treatment with agonist of the receptor was been able to restore several behavioral deficits in the fragile X mouse model, including seizures, marble burying and, in part, prepulse inhibition. Trials in patients with the same agonist have demonstrated encouraging post-hoc results in the most severely affected patients, although no effect could be demonstrated in the patient group as a whole. In conclusion, there can be little doubt that the GABAergic system is compromised in the fragile X syndrome and that these abnormalities contribute to the clinical abnormalities observed. However, at the moment the difference in treatment effectiveness of agonist of the receptor in animal models as opposed to in patients remains unexplained., (Copyright © 2019 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)

The inclusion of the dissociative subtype of post-traumatic stress disorder (PTSD-DS) in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) reflects the importance of assessing PTSD-DS. We developed the Dissociative Subtype of PTSD Interview (DSP-I). This clinician-administered instrument assesses the presence and severity of PTSD-DS (i.e., symptoms of depersonalization or derealization) and contains a supplementary checklist that enables assessment and differentiation of other trauma-related dissociative symptoms (i.e., blanking out, emotional numbing, alterations in sensory perception, amnesia, and identity confusion). The psychometric properties were tested in 131 treatment-seeking individuals with PTSD and histories of multiple trauma, 17.6 % of whom met criteria for PTSD-DS in accordance with the DSP-I. The checklist was tested in 275 treatment-seeking individuals. Results showed the DSP-I to have high internal consistency, good convergent validity with PTSD-DS items of the CAPS-5, and good divergent validity with scales of somatization, anxiety and depression. The depersonalization and derealization scales were highly associated. Moreover, the DSP-I accounted for an additional variance in PTSD severity scores of 8% over and above the CAPS-5 and number of traumatic experiences. The dissociative experiences of the checklist were more strongly associated with scales of overall distress, somatization, depression, and anxiety than scales of depersonalization and derealization. In conclusion, the DSP-I appears to be a clinically relevant and psychometrically sound instrument that is valuable for use in clinical and research settings.

Objective: Exposure to potentially traumatic events (PTEs) has been identified as a risk factor for various psychological problems in adolescents generally and in young refugees. The aim of this study was to examine whether individual resilience (assessed as a personality characteristic) can protect adolescents in diverse contexts from negative effects of trauma exposure., Method: A path model was used to assess whether individual resilience buffered the negative effects of exposure to PTEs in a cross-sectional study of adolescent refugees (aged 12-17 years; n = 117) and their Dutch peers (n = 148). Measurements included the Children's Revised Impact of Event Scale, Strengths and Difficulties Questionnaire, Satisfaction with Life Scale and the Resilience Scale., Results: The moderating effects of individual resilience on the relationship between PTEs and mental health problems and life satisfaction were mixed: In the nonrefugee group, but not in the refugee group most moderation effects reached significance., Conclusion: Findings suggest that not all groups benefit similarly from individual-level resilience. Consequently, adolescents, who differ with regard to the risks to which they are exposed, may need different forms of support. This study points to the interplay of factors that contributes to demonstration of individual resilience. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Histones mediate dynamic packaging of nuclear DNA in chromatin, a process that is precisely controlled to guarantee efficient compaction of the genome and proper chromosomal segregation during cell division and to accomplish DNA replication, transcription, and repair. Due to the important structural and regulatory roles played by histones, it is not surprising that histone functional dysregulation or aberrant levels of histones can have severe consequences for multiple cellular processes and ultimately might affect development or contribute to cell transformation. Recently, germline frameshift mutations involving the C-terminal tail of HIST1H1E, which is a widely expressed member of the linker histone family and facilitates higher-order chromatin folding, have been causally linked to an as-yet poorly defined syndrome that includes intellectual disability. We report that these mutations result in stable proteins that reside in the nucleus, bind to chromatin, disrupt proper compaction of DNA, and are associated with a specific methylation pattern. Cells expressing these mutant proteins have a dramatically reduced proliferation rate and competence, hardly enter into the S phase, and undergo accelerated senescence. Remarkably, clinical assessment of a relatively large cohort of subjects sharing these mutations revealed a premature aging phenotype as a previously unrecognized feature of the disorder. Our findings identify a direct link between aberrant chromatin remodeling, cellular senescence, and accelerated aging., (Copyright © 2019 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Individuals diagnosed with posttraumatic stress disorder (PTSD) show remarkably different symptom presentations. Identification of diagnostic profiles of PTSD may contribute to knowledge about treatment modifications to enhance treatment effectiveness. The present study aimed to identify symptom severity classes among 236 Dutch veterans based on a broad range of psychopathology outcomes, including PTSD, using Latent Profile Analysis (LPA). Moreover, multinomial logistic regression was used to test whether class membership could be predicted by the number and characteristics of traumatic event types, coping and personality dimensions. LPA identified three classes of individuals, defined as average, severe, and highly severe symptom severity classes, respectively. No qualitative differences in the symptom dimensions emerged between classes. Veterans with higher amounts of traumatic experiences and specifically with regard to lack of basic human needs, as well as those using more avoidant and problem-focused coping strategies and with more dysfunctional personality characteristics regarding neuroticism and agreeableness were significantly more often in the severe and/or highly severe symptom classes. In conclusion, general symptom severity was found to be an important diagnostic characteristic in this population. Integrated treatments targeting the broad spectrum of mental health problems may be of importance in treating patients that show low therapeutic recovery., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The World Assumption Scale (WAS) is a frequently used measure in trauma research. The 32 items of the WAS are intended to represent eight assumptions about the benevolence of the world, the meaningfulness of events, and the worthiness of the self. Debate about the validity of the WAS is ongoing, particularly in terms of its empirical factor structure; some studies have confirmed a model of eight correlated factors whereas several other studies have not. The WAS items were administered to a clinical sample of patients who sought professional help because of posttraumatic complaints (n = 1,791) as well as a sample of healthcare professionals (n = 236). We split the clinical sample into three subsamples, then performed exploratory factor analysis using data from one subsample and tested the factor structure with confirmatory factor analysis using the other two subsamples. A consistent model of eight correlated factors was demonstrated, with almost all factors showing acceptable reliability, Cronbach's αs = .68-.84. We tested this factor model against data from the sample of healthcare professionals with increasingly stringent levels of invariance and found it to be scalar invariant (same structure, loadings, and thresholds). In a regression analysis, five factors showed significant associations with posttraumatic stress disorder (PTSD) symptoms, and two factors had unique associations with PTSD symptoms after we controlled for traumatic events: Self-Worth, β = -.31; and Luck, β = -.15. Future research should aim to distinguish between different assumptions and their individual influences on posttraumatic complaints., (© 2018 The Authors. International Society for Traumatic Stress Studies published by Wiley Periodicals, Inc. on behalf of Society for International Society for Traumatic Stress Studies.)

Background : In 2013, the Clinician-Administered PTSD Scale, the golden standard to assess PTSD, was adapted to the DSM-5 (CAPS-5). Objective : This project aimed to develop a clinically relevant Dutch translation of the CAPS-5 and to investigate its psychometric properties. Method : We conducted a stepped translation including Delphi rounds with a crowd of 44 Dutch psychotrauma experts and five senior psychotrauma experts. Using partial crowd-translations, two professional translations and the official Dutch translation of the DSM-5, each senior expert aggregated one independent translation. Consensus was reached plenary. After back-translation, comparison with the original CAPS-5 and field testing, a last round with the senior experts resulted in the final version. After implementation clinicians conducted CAPS-5 interviews with 669 trauma-exposed individuals referred for specialized diagnostic assessment. Reliability of the Dutch CAPS-5 was investigated through internal consistency and interrater reliability analyses, and construct validity through confirmatory factor analysis (CFA). Results : CAPS-5 total severity score showed high internal consistency ( α  = .90) and interrater reliability (ICC = .98, 95% CI: .94-.99). CAPS-5 diagnosis showed modest interrater reliability (kappa = .59, 95% CI: .20-.98). CFA with alternative PTSD models revealed adequate support for the DSM-5 four-factor model, but a six-factor (Anhedonia) model fit the data best. Conclusions : The Dutch CAPS-5 is a carefully translated instrument with adequate psychometric properties. Current results add to the growing support for more refined (six and seven) factor models for DSM-5 PTSD indicating that the validity and clinical implications of these models should be objective of further research.

Objectives: Dissociation is a prevalent phenomenon among veterans with post-traumatic stress disorder (PTSD) that may interfere with the effectiveness of treatment. This study aimed to replicate findings of a dissociative PTSD subtype, to identify corresponding patterns in coping style, symptom type, and symptom severity, and to investigate its impact on post-traumatic symptom improvement., Methods: Latent profile analysis (LPA) was applied to baseline data from 330 predominantly (97%) male treatment-seeking veterans (mean age 39.5 years) with a probable PTSD. Multinomial logistic models were used to identify predictors of dissociative PTSD. Eighty veterans with PTSD that commenced with psychotherapy were invited for a follow-up measure after 6 months. The majority (n = 64, 80% response rate) completed the follow-up measure. Changes in post-traumatic stress between baseline and follow-up were explored as a continuous distal outcome., Results: Latent profile analysis revealed four distinct patient profiles: 'low' (12.9%), 'moderate' (33.2%), 'severe' (45.1%), and 'dissociative' (8.8%) PTSD. The dissociative PTSD profile was characterized by more severe pathology levels, though not post-traumatic reactions symptom severity. Veterans with dissociative PTSD benefitted equally from PTSD treatment as veterans with non-dissociative PTSD with similar symptom severity., Conclusions: Within a sample of veterans with PTSD, a subsample of severely dissociative veterans was identified, characterized by elevated severity levels on pathology dimensions. The dissociative PTSD subtype did not negatively impact PTSD treatment., Practitioner Points: The present findings confirmed the existence of a distinct subgroup veterans that fit the description of dissociative PTSD. Patients with dissociative PTSD subtype symptoms uniquely differed from patients with non-dissociative PTSD in the severity of several psychopathology dimensions. Dissociative and non-dissociative PTSD patients with similar post-traumatic severity levels showed similar levels of improvement after PTSD treatment. The observational design and small sample size caution interpretation of the treatment outcome data. The IES-R questionnaire does not assess all PTSD DSM-IV diagnostic criteria (14 of 17), although it is considered a valid measure for an indication of PTSD., (© 2018 The British Psychological Society.)