Development and examination of the reactive attachment disorder and disinhibited social engagement disorder assessment interview

The fifth edition of the Diagnostic and Statistical Manual ( DSM) categorizes reactive attachment disorder (RAD) and disinhibited social engagement disorder (DSED) as two separate disorders, and their criteria are revised. For DSED, the core symptoms focus on abnormal social disinhibition, and symptoms regarding lack of selective attachment have been removed. The core symptoms of RAD are the absence of attachment behaviors and emotional dysregulation. In this study, an international team of researchers modified the Child and Adolescent Psychiatric Assessment for RAD to update it from DSM-IV to DSM-5 criteria for RAD and DSED. We renamed the interview the reactive attachment disorder and disinhibited social engagement disorder assessment (RADA). Foster parents of 320 young people aged 11 to 17 years completed the RADA online. Confirmatory factor analysis of RADA items identified good fit for a three-factor model, with one factor comprising DSED items (indiscriminate behaviors with strangers) and two factors comprising RAD items (RAD1: failure to seek/accept comfort, and RAD2: withdrawal/hypervigilance). The three factors showed differential associations with clinical symptoms of emotional and social impairment. Time in foster care was not associated with scores on RAD1, RAD2, or DSED. Higher age was associated with lower scores on DSED, and higher scores on RAD1

Statins enhance the efficacy of HER2-targeting radioligand therapy in drug-resistant gastric cancers

Human epidermal growth factor receptor 2 (HER2) is overexpressed in various cancer types. HER2-targeting trastuzumab plus chemotherapy is used as first-line therapy for HER2-positive recurrent or primary metastatic gastric cancer, but intrinsic and acquired trastuzumab resistance inevitably develop over time. To overcome gastric cancer resistance to HER2-targeted therapies, we have conjugated trastuzumab with a beta-emitting therapeutic isotope, lutetium-177, to deliver radiation locally to gastric tumors with minimal toxicity. Because trastuzumab-based targeted radioligand therapy (RLT) requires only the extramembrane domain binding of membrane-bound HER2 receptors, HER2-targeting RLT can bypass any resistance mechanisms that occur downstream of HER2 binding. Leveraging our previous discoveries that statins, a class of cholesterol-lowering drugs, can enhance the cell surface-bound HER2 to achieve effective drug delivery in tumors, we proposed that the combination of statins and

Deletion of Asxl1 results in myelodysplasia and severe developmental defects in vivo

Somatic Addition of Sex Combs Like 1 (ASXL1) mutations occur in 10-30% of patients with myeloid malignancies, most commonly in myelodysplastic syndromes (MDSs), and are associated with adverse outcome. Germline ASXL1 mutations occur in patients with Bohring-Opitz syndrome. Here, we show that constitutive loss of Asxl1 results in developmental abnormalities, including anophthalmia, microcephaly, cleft palates, and mandibular malformations. In contrast, hematopoietic-specific deletion of Asxl1 results in progressive, multilineage cytopenias and dysplasia in the context of increased numbers of hematopoietic stem/progenitor cells, characteristic features of human MDS. Serial transplantation of Asxl1-null hematopoietic cells results in a lethal myeloid disorder at a shorter latency than primary Asxl1 knockout (KO) mice. Asxl1 deletion reduces hematopoietic stem cell self-renewal, which is restored by concomitant deletion of Tet2, a gene commonly co-mutated with ASXL1 in MDS patients. Moreover, compound Asxl1/Tet2 deletion results in an MDS phenotype with hastened death compared with single-gene KO mice. Asxl1 loss results in a global reduction of H3K27 trimethylation and dysregulated expression of known regulators of hematopoiesis. RNA-Seq/ChIP-Seq analyses of Asxl1 in hematopoietic cells identify a subset of differentially expressed genes as direct targets of Asxl1. These findings underscore the importance of Asxl1 in Polycomb group function, development, and hematopoiesisclos

Le Conners CBRS : un questionnaire MULTI-INFORMANTS à large spectre de psychopathologie

Le Conners CBRS (Comprehensive behavior rating scale) est un questionnaire permettant d’évaluer un large spectre de psychopathologie chez les enfants. Il est peu connu au Québec, car il n’était pas disponible en français jusqu’à tout récemment. Il a été publié en 2008, puis révisé en 2014 avec l’arrivée du DSM-5. Nous l’avons traduit l’année dernière dans le cadre d’un projet de recherche, avec l’accord de l’éditeur et nous désirons le faire connaître aux cliniciens et chercheurs du Québec, puisqu’il nous apparaît comme une addition intéressante pour l’évaluation psychologique d’enfants et d’adolescents.The Conners CBRS (Comprehensive behavior rating scale) is a questionnaire intended to assess a broad spectrum of psychopathology in children. It is barely known in Quebec because the French edition wasn't available until recently. It was published in 2008 and revised in 2014 with the arrival of the DSM-5. With the agreement of the publisher, we translated it last year as part of a research project. Our aim is to make it known to clinicians and researchers in Quebec, since it appears to us as an interesting support for the psychological assessment of children and adolescents

Development and Validation of a Measure of Attachment Disorders Based on DSM-5 Criteria: The Early TRAuma-Related Disorders Questionnaire (ETRADQ)

Background: A review of the scientific literature showed few valid tools for assessing reactive attachment disorder (RAD) and disinhibited social engagement disorder (DSED), two diagnostic entities traditionally grouped under “attachment disorders.” The Early TRAuma-related Disorders Questionnaire (ETRADQ), a caregiver report, was developed to assess attachment disorders in school-age children based on the Diagnostic and Statistical Manual of Mental Disorders–Fifth edition criteria. This study sought to validate this instrument. Method: Caregivers of school-age children from the community (n = 578) and caregivers of at-risk children adopted or in out-of-home care (n = 245) completed a sociodemographic questionnaire, the ETRADQ, the Relationship Problem Questionnaire, the RADA (RAD and DSED Assessment) interview, and the Barkley Functional Impairment Scale for Children and Adolescents. Results: Confirmatory factor analysis of the ETRADQ items supported the expected organization of the measure, that is, two second-order factors and five subfactors: (1) RAD scale (three subscales: Low selective attachment, Low social and emotional responsiveness, Emotional unpredictability) and (2) DSED scale (two subscales: Interactions with unfamiliar adults, Social disinhibition). All scales showed excellent internal consistency, test–retest reliability, convergent validity, and known-group validity. Conclusions: Results support the reliability and validity of the ETRADQ.publishedVersio

Potentially traumatic events in foster youth, and association with DSM -5 trauma- and stressor related symptoms

Background In DSM 5, three disorders are related to trauma and/or maltreatment: Posttraumatic Stress Disorder (PTSD), Reactive Attachment Disorder (RAD) and Disinhibited Social Engagement Disorder (DSED) but how these disorders relate to each other and to traumatic events is unknown. Objective We examined 1. Prevalence of Potentially Traumatic Events (PTEs) and poly-victimization for youths in foster care. 2. Associations between single/multiple PTEs and PTSD, DSED, and the two symptom-clusters that constitute RAD: Failure to seek/accept comfort (RAD A), and Low social-emotional responsiveness/ emotion dysregulation (RAD B). Participants, setting and methods Foster youth 11 to 17 years (N = 303) in Norway completed The Child and Adolescent Trauma Screen. Foster parents completed the RAD and DSED Assessment interview. Results Foster youth reported experiencing, on average, 3.44 PTEs each (range 0-15, SD 3.33), and 52.9 % reported PTSD symptoms at or above clinical cut off. The PTE sum score was associated with the latent factors PTSD (r = .66, p < 0.001), RAD cluster B symptoms (Low social-emotional responsiveness / emotion dysregulation, r = .28, p < 0.001) and DSED (r = .11, p = 0.046), but not with RAD cluster A symptoms (Failure to seek/accept comfort). Conclusions These findings raise new questions about the nature, mechanisms and timing of development of RAD and DSED. Maltreatment assessment needs to encompass a wide range of PTEs, and consider poly-victimization

Development and Validation of a Measure of Attachment Disorders Based on DSM-5 Criteria: The Early TRAuma-Related Disorders Questionnaire (ETRADQ)

Background: A review of the scientific literature showed few valid tools for assessing reactive attachment disorder (RAD) and disinhibited social engagement disorder (DSED), two diagnostic entities traditionally grouped under “attachment disorders.” The Early TRAuma-related Disorders Questionnaire (ETRADQ), a caregiver report, was developed to assess attachment disorders in school-age children based on the Diagnostic and Statistical Manual of Mental Disorders–Fifth edition criteria. This study sought to validate this instrument. Method: Caregivers of school-age children from the community (n = 578) and caregivers of at-risk children adopted or in out-of-home care (n = 245) completed a sociodemographic questionnaire, the ETRADQ, the Relationship Problem Questionnaire, the RADA (RAD and DSED Assessment) interview, and the Barkley Functional Impairment Scale for Children and Adolescents. Results: Confirmatory factor analysis of the ETRADQ items supported the expected organization of the measure, that is, two second-order factors and five subfactors: (1) RAD scale (three subscales: Low selective attachment, Low social and emotional responsiveness, Emotional unpredictability) and (2) DSED scale (two subscales: Interactions with unfamiliar adults, Social disinhibition). All scales showed excellent internal consistency, test–retest reliability, convergent validity, and known-group validity. Conclusions: Results support the reliability and validity of the ETRADQ