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

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

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

Negative parenting behaviour as a mediator of the effects of telephone-assisted self-help for parents of pharmacologically treated children with attention-deficit/hyperactivity disorder

A previous randomised controlled trial demonstrated the effects of a telephone-assisted self-help (TASH) intervention for parents of pharmacologically treated children with attention-deficit/hyperactivity disorder (ADHD) on ADHD symptoms, oppositional symptoms, functional impairment, and negative parenting behaviour (per-protocol analyses). In the current study, we examined whether changes in positive and negative parenting behaviour mediated the effects on symptoms and impairment. Parents in an enhancement group (n = 51) participated in a 12-month TASH intervention (eight booklets plus up to 14 telephone consultations) as an adjunct to routine clinical care, whereas parents in a waitlist control group (n = 52) received routine clinical care only. Parents completed measures of child symptoms, child functional impairment, and parenting behaviour at baseline, at 6 months, and at 12 months. The mediating effects of parenting behaviour were examined using regression analyses. Per-protocol analyses (n = 74) revealed a significant indirect intervention effect on functional impairment through negative parenting behaviour at 6 months as well as indirect intervention effects on oppositional symptoms and functional impairment through negative parenting behaviour at 12 months. The indirect effect on ADHD symptoms through negative parenting behaviour at 12 months just failed to reach significance. The analyses yielded no indirect intervention effects through positive parenting behaviour. The study provides some, albeit limited, support for the importance of changes in negative parenting behaviour to achieve changes in symptoms and functional impairment during parent training. In consideration of the inconsistent results of previous studies concerning the mediating role of positive and negative parenting behaviour, further research is required to better understand the mechanisms of change during parent training, also including other possible mediators like parenting stress and parental self-efficacy

Psychometric Properties of a German Parent and Self-Rating Scale for the Assessment of Anxiety Disorders

This study examined the psychometric properties of a German ICD-10 and DSM-IV-based external (parents) and self-reporting (children) rating scale for the assessment of anxiety disorders and obsessive-compulsive disorders (FBB-ANZ/SBB-ANZ) in two clinical samples (n = 182, n = 130). Additionally, their factor structures were analyzed using two community samples (n = 724, n = 281). In the clinical samples, most of the questionnaires' scales showed satisfactory internal consistency (.59 <= alpha <= .93). In all samples, exploratory factor analyses largely revealed factors concordant with the scales defined a priori based on ICD-10 and DSM-IV diagnoses of anxiety disorders. Intercorrelations between the subscales within the questionnaires varied from low to moderate, suggesting that they capture different constructs. Moderate agreement between the corresponding scales of the parents and children questionnaires was found. The results support the questionnaires' reliability and validity. Further research should concentrate on the convergent and divergent validity of the subscales