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

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-structured Clinical 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 the Child 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 ≤ κ ≤ 0.94). With some exceptions, internal consistencies (0.60 ≤ α ≤ 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 CBCL Externalizing Problems were moderate to high. Finally, the ILF-EXTERNAL scales were significantly more strongly associated with the CBCL Externalizing Problems than with the Internalizing 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

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Molecular characterization of the cyclic nucleotide-gated cation channel of bovine rod outer segments

The cyclic nucleotide-gated (CNG) cation channel of rod photoreceptors plays an important role in the perception of light. The channel gating is the final step in the visual transduction cascade. The cloning (Kaupp et al., 1989) of what is now known to be the CNG channel α subunit facilitated its molecular characterization. A heterologous expression system was developed to examine molecular aspects of the α and β subunits of the CNG channel. Expression in mammalian cells helped resolve confusion regarding the JVL of the rod CNG channel a subunit. Although the cDNA codes for an 80 kDa protein, the a subunit exists in the rod outer segment as a 63 kDa protein suggesting the existence of a processing mechanism. PCR was used to construct cDNA clones which code for both the 63 and 80 kDa forms of the a subunit of the rod CNG channel. A polyclonal antibody, generated to specifically label the 80 kDa α subunit, was used in conjunction with a monoclonal antibody specific for the 63 kDa α subunit in labeling studies. These antibodies were shown to be mono-specific, capable of differentiating between the two size forms of the a subunit. Immunohistochemical studies demonstrated that the 63 kDa α subunit is the predominant species in the rod outer segment while the 80 kDa form is present in very low quantities. Rod outer segment (ROS) purification on sucrose gradients also showed that the 80 kDa form co-sediments with the 63 kDa α subunit indicating that the two size forms coexist in the outer segment. Examining the α subunits of the photoreceptors of another species demonstrated similar processing of the CNG α subunit polypeptides, however, an olfactory a subunit did not appear to undergo similar processing. The cloned CNG channel β subunit cDNA codes for a protein with a predicted molecular mass of 155 kDa (Korschen et al, 1995). Heterologous expression of the β subunit cDNA yielded a 240 kDa protein, positively identifying the 240 kDa protein in ROS which co-purifies with the a subunit as the CNG β subunit. Construction and expression of a truncated form of the (3 subunit demonstrated that it is the glutamic acidrich N-terminal portion of the (3 subunit that is responsible for its anomalous migration on an SDS gel. Co-expression of both subunits in mammalian cells indicated that the 3 subunit was not responsible for the processing of the α subunit. As seen for the subunits of the native CNG channel the heterologously expressed α and β subunits coimmunoprecipitated. The subunit interaction was not dependent on the 92 N terminal amino acids of the 80 kDa α subunit or on the glutamic acid-rich portion of the P subunit. A method for reconstitution of the heterologously expressed CNG channel was also developed. The expressed a subunit reconstituted alone did not generate functional cGMP-gated channels. Reconstitution of the heterologously expressed channel complex comprising the 80 kDa α and complete β subunits generated functional channels. Compared to the native CNG channel, 10% of the heterologously expressed channel complex exhibited cGMP-gated channel activity. This is the first example of reconstitution of a heterologously expressed cation channel into lipid vesicles for Ca²⁺ efflux measurements. The system presented here will be useful to further define CNG α and β subunit interactions and to carry out structure-function studies on the channel using a biochemical efflux assay.Medicine, Faculty ofBiochemistry and Molecular Biology, Department ofGraduat

Functional Impairment in Children With Externalizing Behavior Disorders: Psychometric Properties of the Weiss Functional Impairment Rating Scale-Parent Report in a German Clinical Sample

Objective: To examine the psychometric properties of a German adaptation of the Weiss Functional Impairment Rating Scale-Parent Report (WFIRS-P) in a clinical sample of children (4-12 years) with externalizing behavior disorders. Method: Data were collected within two clinical trials (N = 264). Factorial validity, reliability, and divergent validity from symptoms of ADHD and oppositional defiant disorder (ODD) were assessed. Results: Confirmatory factor analyses revealed that a bifactor model consistent with the theoretical assumption of a general construct of impairment (total scale) and additional specific factors (subscales) provided satisfactory data fit. Model-based reliability estimates showed that both the general construct and specific factors accounted for item variance. Internal consistencies were >.70, part-whole corrected item-scale correlations mostly >.30. Correlations between the WFIRS-P Scales and ADHD and ODD symptoms were low to moderate. Conclusion: The results support the factorial validity, reliability, and divergent validity of the WFIRS-P

Applying the Bifactor S-1 Model to Ratings of ADHD/ODD Symptoms: A Commentary on Burns et al. (2019) and a Re-Analysis

To examine the construct validity of attention-deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD), the bifactor S-1 approach has been applied as an alternative to the fully symmetrical bifactor models in order to eliminate anomalous results and to allow for an unambiguous interpretation of g- and s-factors. We compared and contrasted our results with those of Burns et al. (2019) and extended their analyses by taking into account a two- vs. a three-factor structure of ADHD. Data from our previous research were reanalyzed and reinterpreted in accordance with the bifactor S-1 approach, constructing different models with hyperactivity (HY), impulsivity (IM) or hyperactivity/impulsivity (HI) as the general factor. No anomalous results were observed. All factor loadings were significant. Our results were comparable to those reported by Burns et al. (2019), although items from the specific subscales inattention (IN) and ODD accounted for more variance in our sample. Model fit for our HI model was comparable to that in Burns et al. (2019). In our sample, model fit was best when solely HY or IM was chosen as a general reference factor. However, in these cases, the remaining specific factor IM or HY was weakly defined. Overall, we were able to replicate the results found by Burns et al. 2019), although our factor loadings on the g-factor were slightly lower and our specificity regarding IN and ODD was slightly higher. Our results support a two-factor structure of ADHD/ODD in a clinical population

The Improvement of Individually Defined Problem Behaviors During a Telephone-Assisted Self-Help Intervention for Parents of Pharmacologically Treated Children with ADHD

Background: This study examined change in individually defined problem behaviors during a telephone-assisted self-help (LASH) intervention for parents of children with attention-deficit/hyperactivity disorder (ADHD). Method: Parents of children with ADHD and functional impairment despite methylphenidate treatment participated in a 12-month TASH intervention (8 self-help booklets plus up to 14 counseling telephone calls).The severity of three individually defined target problems, of ADHD symptoms, and oppositional symptoms were rated at baseline and after 6 and 12 months; parental satisfaction with the intervention was assessed after 12 months. The problems were categorized according to the type of behavior and the disorder to which they were related (ADHD vs. oppositional symptoms). Results: Repeated measures analyses of variance revealed a significant decrease in problem severity during the intervention. The change in problem severity was greater than the change in ADHD and oppositional symptoms. Correlations between problem severity and symptom severity were low to moderate. Correlations between the change in problem severity and parental satisfaction were moderate. Discussion: The decrease in the individual problem severity during TASH is stronger than the decrease in ADHD and oppositional symptoms. Individually defined problems should be attended to in psychotherapy research to avoid underestimating the benefit of interventions by solely considering standardized measures

Psychometric properties of a modified version of the Weiss Functional Impairment Rating Scale-Parent Report (WFIRS-P) in a clinical sample of children with aggressive behavior

PurposeTo evaluate the psychometric properties of a German modification of the Weiss Functional Impairment Rating ScaleParent Report for children with aggressive and oppositional behavior problems (WFIRS-P for ODD/CD).MethodsData were collected from a clinical sample of children (6-12 years; 96% boys) with oppositional defiant disorder (ODD) and conduct disorder (CD) (N=219). The WFIRS-P conceptual framework was evaluated using confirmatory factor analyses (CFA). Reliability was estimated using internal consistency (Cronbach's alpha) and omega statistics. Validity was assessed through correlations between WFIRS-P for ODD/CD domain scores and parent-rated scales on symptoms of ODD, CD, attention-deficit/hyperactivity disorder (ADHD), a broad range of other behavioral and emotional problems, and scales on health-related quality of life and family burden.ResultsCFA of the WFIRS-P for ODD/CD revealed that a bifactor model, with a general factor accounting for common variance ((H)=0.23-0.48) and independent specific group factors accounting for additional variance in item scores ((S)=0.37-0.60), best fits the data. Thus, CFA confirmed the theoretical assumption of a general construct of impairment (total scale) and additional specific impairments (subscales, e.g., family, social activities). Cronbach's alpha coefficient exceeded 0.70 for all subscales. Omega statistics showed that both the general construct and specific factors accounted for item variance. As expected, correlations with symptoms scales for ODD/CD and ADHD were low to moderate.ConclusionsThe use of the parent-rated WFIRS for ODD/CD in identifying ODD- and CD-related impairment in children is psychometrically supported. The scale can be employed to assess functional impairment in children with aggressive behavior problems