The Senses of Agency and Ownership in Patients With Borderline Personality Disorder

Patients with borderline personality disorder (BPD) not only experience a strong instability in their affect and interpersonal relations but also disturbances in their self-experience, including dissociation and body-alienation symptoms. It is not yet understood whether an altered sense of ownership (SoO) or sense of agency (SoA) may contribute to these disturbances. One recent hypothesis is that patients with BPD have a reduced sense of self and are therefore more likely to misattribute external objects or actions to their own self than healthy individuals. The present study followed up this hypothesis by investigating whether BPD patients have a more flexible body representation than healthy participants. More specifically, the active rubber hand illusion (aRHI) was applied to 21 patients with BPD and the same number of healthy participants. Using established subjective, electrodermal, and behavioral measures, the participants' SoO and SoA were assessed during the aRHI. The findings show self-reported evidence for higher SoO under anatomical hand congruency as compared to anatomical incongruency, but no evidence for group differences between BPD patients and healthy participants. This finding is inconsistent with previous findings of an enhanced SoO-related body plasticity in BPD patients. Regarding SoA, the findings show self-report evidence of higher SoA in BPD patients versus healthy participants, although this group difference was not evident in the implicit SoA measure (intentional binding). In summary, the present study only reveals partial evidence for a higher body plasticity in BPD patients. Instead, the observed variability in results appears better explainable by some generally elevated perceptual suggestibility of BPD individuals

Empirically based dimensions of externalizing symptoms in children and adolescents: a multitrait-multisource approach

The present study sought to refine knowledge about the structure underlying externalizing dimensions. From a top-down ICD/DSM-based perspective, externalizing symptoms can be categorized into attention-deficit/hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and conduct disorder (CD). From a bottom-up developmental theory-based perspective, disruptive behaviors can be meaningfully described as aggressive (AGG) and rule-breaking (RB) behaviors. We analyzed five large data sets comprising externalizing symptom ratings obtained with a screening instrument using different sources (parents, teachers, self-ratings) from different samples. Using confirmatory factor analyses, we evaluated several factor models (unidimensional; correlated factors; bifactor (S-1) models) derived from an ICD/DSM- and theory-based perspective. Our optimally fitting models were assessed for measurement invariance across all sources, sample settings, and sex. Following several model-based criteria (model fit indices; factor loadings; omega statistics; model parsimony), we discarded our models stepwise and concluded that both the ICD/DSM-based model with three correlated factors (ADHD, ODD, CD) and the developmental theory-based model with three correlated factors (ADHD, AGG, RB) displayed a statistically sound factor structure and allowed for straightforward interpretability. Furthermore, these two models demonstrated metric invariance across all five samples and across sample settings (community, clinical), as well as scalar invariance across sources and sex. While the dimensions AGG and RB may depict a more empirically coherent view than the categorical perspective of ODD and CD, at this point we cannot clearly determine whether one perspective really outperforms the other. Implications for model selection according to our model-based criteria and clinical research are discussed

Child-therapist and parent-therapist alliances and outcome in the treatment of children with oppositional defiant/conduct disorder

Objective This study examined the quality of therapeutic alliance from different rater perspectives (child, parent, therapist) in cognitive behavioural therapy for children with oppositional defiant disorder (ODD) and conduct disorder (CD), and its association with symptom severity. Further, a panel model with an autoregressive cross-lagged panel design was used to explore whether therapist-rated and parent-rated therapeutic alliance influences change in symptom severity, or vice versa. Methods Sixty boys aged 6-12 years with a principal diagnosis of ODD/CD, and their parents, received individually delivered social competence training for childhood aggressive behaviour problems. Child, therapist, and parent ratings of therapeutic alliance and symptom severity were measured twice. Results Our results indicate good to very good therapeutic alliance that was relatively stable over time. The cross-sectional analyses of the alliance-symptom association revealed moderate correlations. However, effects of early alliance on later treatment outcome or of early symptom severity on later alliance were marginal. The only significant association was found between early parent-rated therapist-parent alliance and later parent-rated symptom severity. Conclusion Our study shows a moderate correlation between simultaneously assessed therapeutic alliance and symptoms. The findings of the panel model indicate that an early good therapeutic alliance is a component of later therapeutic success (parent perspective)

Validation of a new emotion regulation self-report questionnaire for children

Objective: To examine and validate the self-report Questionnaire on the Regulation of Unpleasant Moods in Children (FRUST), which is a modified and shortened version of the Questionnaire for the Assessment of Emotion Regulation in Children and Adolescents (FEEL-KJ). Methods: The data comprised child and parent ratings of a community-screened sample with differing levels of affective dysregulation (AD) (N = 391, age: M = 10.64, SD = 1.33, 56% male). We conducted latent factor analyses to establish a factor structure. Subsequently, we assessed measurement invariance (MI) regarding age, gender, and AD level and evaluated the internal consistencies of the scales. Finally, we examined the convergent and divergent validity of the instrument by calculating differential correlations between the emotion regulation strategy (ERS) scales and self- and parent-report measures of psychopathology. Results: A four-factor model, with one factor representing Dysfunctional Strategies and the three factors Distraction, Problem-Solving and Social Support representing functional strategies provided the best fit to our data and was straightforward to interpret. We found strong MI for age and gender and weak MI for AD level. Differential correlations with child and parent ratings of measures of psychopathology supported the construct validity of the factors. Conclusions: We established a reliable and valid self-report measure for the assessment of ERS in children. Due to the reduced number of items and the inclusion of highly specific regulatory behaviors, the FRUST might be a valuable contribution to the assessment of ER strategies for diagnostic, therapeutic, and research purposes

Irritability and Emotional Impulsivity as Core Feature of ADHD and ODD in Children (May, 10.1007/s10862-022-09974-8, 2022)

The categorical approach of diagnosing mental disorders entails the problem of frequently occurring comorbidities, suggesting a more parsimonious structure of psychopathology. In this study, we therefore aim to assess how affective dysregulation (AD) is associated with attention-deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) in children. To assess AD in children aged 8-12 years (n = 391), we employed the parent version of a newly constructed parent rating scale. Following item reduction, we conducted exploratory and confirmatory factor analyses to establish a factorial structure of AD. One core dimension was identified, comprising irritability and emotional impulsivity, and two smaller dimensions, comprising positive emotionality and exuberance. Subsequently, we examined five different latent factor models - a unidimensional model, a first-order correlated factor model, a second-order correlated factor model, a traditional bifactor model, and a bifactor S-1 model, in which the first-order factor AD-Irritability/Emotional Impulsivity (II) was modeled as the general reference factor. A bifactor S-1 model with the a priori defined general reference domain AD-II provided the best fit to our data and was straightforward to interpret. This model showed excellent model fit and no anomalous factor loadings. This still held true, when comparing it to bifactor S-1 models with ADHD/ODD-related reference factors. Differential correlations with emotion regulation skills and the established Parent Proxy Anger Scale validate the interpretation of the different dimensions. Our results suggest that irritability/emotional impulsivity might be a common core feature of ADHD and ODD

Toward a Dimensional Assessment of Externalizing Disorders in Children: Reliability and Validity of a Semi-Structured Parent Interview

Objective This study assesses the reliability and validity of the DSM-5-based, semi-structuredClinical Parent Interview for Externalizing Disorders in Children and Adolescents(ILF-EXTERNAL). Method Participant data were drawn from the ongoing ESCAschool intervention study. The ILF-EXTERNAL was evaluated in a clinical sample of 474 children and adolescents (aged 6-12 years, 92 females) with symptoms of attention-deficit/hyperactivity disorder (ADHD). To obtain interrater reliability, the one-way random-effects, absolute agreement models of the intraclass correlation (ICC) for single ICC(1,1) and average measurements ICC(1,3) were computed between the interviewers and two independent raters for 45 randomly selected interviews involving ten interviewers. Overall agreement on DSM-5 diagnoses was assessed using Fleiss' kappa. Further analyses evaluated internal consistencies, item-total correlations as well as correlations between symptom severity and the degree of functional impairment. Additionally, parents completed the German version of theChild Behavior Checklist(CBCL) and two DSM-5-based parent questionnaires for the assessment of ADHD symptoms and symptoms of disruptive behavior disorders (FBB-ADHS; FBB-SSV), which were used to evaluate convergent and divergent validity. Results ICC coefficients demonstrated very good to excellent interrater reliability on the item and scale level of the ILF-EXTERNAL [scale level: ICC(1,1) = 0.83-0.95; ICC(1,3) = 0.94-0.98]. Overall kappa agreement on DSM-5 diagnoses was substantial to almost perfect for most disorders (0.38 <= kappa <= 0.94). With some exceptions, internal consistencies (0.60 <= alpha <= 0.86) and item-total correlations (0.21 <= r(it)<= 0.71) were generally satisfactory to good. Furthermore, higher symptom severity was associated with a higher degree of functional impairment. The evaluation of convergent validity revealed positive results regarding clinical judgment and parent ratings (FBB-ADHS; FBB-SSV). Correlations between the ILF-EXTERNAL scales and the CBCLExternalizing Problemswere moderate to high. Finally, the ILF-EXTERNAL scales were significantly more strongly associated with the CBCLExternalizing Problemsthan with theInternalizing Problems, indicating divergent validity. Conclusion In clinically referred, school-age children, the ILF-EXTERNAL demonstrates sound psychometric properties. The ILF-EXTERNAL is a promising clinical interview and contributes to high-quality diagnostics of externalizing disorders in children and adolescents

Disentangling Symptoms of Externalizing Disorders in Children Using Multiple Measures and Informants

The trait impulsivity theory suggests that a single, highly heritable externalizing liability factor, expressed as temperamental trait impulsivity, represents the core vulnerability for externalizing disorders. The present study sought to test the application of latent factor models derived from this theory to a clinical sample of children. Participants were 474 German children (age 6-12 years, 81% male) with symptoms of attention-deficit/hyperactivity disorder and externalizing behavior problems participating in an ongoing multicenter intervention study. Using confirmatory factor analyses (CFA) and exploratory structural equation modeling (ESEM), we evaluated several factor models of externalizing spectrum disorders (unidimensional; first-order correlated factors; higher-order factor; fully symmetrical bifactor; bifactor S-1 model). Furthermore, we assessed our prevailing factor models for measurement invariance across raters (clinicians, parents, teachers) and assessment modes (interview, questionnaires). While both CFA and ESEM approaches provided valuable insights into the multidimensionality, ESEM solutions were generally superior since they showed a substantially better model fit and less biased factor loadings. Among the models tested, the bifactor S-1 CFA/ESEM models, with a general hyperactivity-impulsivity reference factor, displayed a statistically sound factor structure and allowed for straightforward interpretability. Furthermore, these models showed the same organization of factors and loading patterns, but not equivalent item thresholds across raters and assessment modes, highlighting cross-situational variability in child behavior. Our findings are consistent with the assumption of the trait impulsivity theory that a common trait, presented as hyperactivity-impulsivity symptoms, underlies all externalizing disorders

Genome-wide association study of germline variants and breast cancer-specific mortality

Abstract Background: We examined the associations between germline variants and breast cancer mortality using a large meta-analysis of women of European ancestry. Methods: Meta-analyses included summary estimates based on Cox models of twelve datasets using ~10.4 million variants for 96,661 women with breast cancer and 7697 events (breast cancer-specific deaths). Oestrogen receptor (ER)-specific analyses were based on 64,171 ER-positive (4116) and 16,172 ER-negative (2125) patients. We evaluated the probability of a signal to be a true positive using the Bayesian false discovery probability (BFDP). Results: We did not find any variant associated with breast cancer-specific mortality at P &lt; 5 × 10−8. For ER-positive disease, the most significantly associated variant was chr7:rs4717568 (BFDP = 7%, P = 1.28 × 10−7, hazard ratio [HR] = 0.88, 95% confidence interval [CI] = 0.84–0.92); the closest gene is AUTS2. For ER-negative disease, the most significant variant was chr7:rs67918676 (BFDP = 11%, P = 1.38 × 10−7, HR = 1.27, 95% CI = 1.16–1.39); located within a long intergenic non-coding RNA gene (AC004009.3), close to the HOXA gene cluster. Conclusions: We uncovered germline variants on chromosome 7 at BFDP &lt; 15% close to genes for which there is biological evidence related to breast cancer outcome. However, the paucity of variants associated with mortality at genome-wide significance underpins the challenge in providing genetic-based individualised prognostic information for breast cancer patients

Association analysis identifies 65 new breast cancer risk loci

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Polygenic risk scores for prediction of breast cancer and breast cancer subtypes

Abstract Stratification of women according to their risk of breast cancer based on polygenic risk scores (PRSs) could improve screening and prevention strategies. Our aim was to develop PRSs, optimized for prediction of estrogen receptor (ER)-specific disease, from the largest available genome-wide association dataset and to empirically validate the PRSs in prospective studies. The development dataset comprised 94,075 case subjects and 75,017 control subjects of European ancestry from 69 studies, divided into training and validation sets. Samples were genotyped using genome-wide arrays, and single-nucleotide polymorphisms (SNPs) were selected by stepwise regression or lasso penalized regression. The best performing PRSs were validated in an independent test set comprising 11,428 case subjects and 18,323 control subjects from 10 prospective studies and 190,040 women from UK Biobank (3,215 incident breast cancers). For the best PRSs (313 SNPs), the odds ratio for overall disease per 1 standard deviation in ten prospective studies was 1.61 (95%CI: 1.57–1.65) with area under receiver-operator curve (AUC) = 0.630 (95%CI: 0.628–0.651). The lifetime risk of overall breast cancer in the top centile of the PRSs was 32.6%. Compared with women in the middle quintile, those in the highest 1% of risk had 4.37- and 2.78-fold risks, and those in the lowest 1% of risk had 0.16- and 0.27-fold risks, of developing ER-positive and ER-negative disease, respectively. Goodness-of-fit tests indicated that this PRS was well calibrated and predicts disease risk accurately in the tails of the distribution. This PRS is a powerful and reliable predictor of breast cancer risk that may improve breast cancer prevention programs