Search

We report on parent outcomes from a randomized clinical trial of parent training (PT) versus psychoeducation (PEP) in 180 children with autism spectrum disorder (ASD) and disruptive behavior. We compare the impact of PT and PEP on parent outcomes: Parenting Stress Index (PSI), Parent Sense of Competence (PSOC), and Caregiver Strain Questionnaire (CGSQ). Mixed-effects linear models evaluated differences at weeks 12 and 24, controlling for baseline scores. Parents in PT reported greater improvement than PEP on the PSOC (ES = 0.34), CGSQ (ES = 0.50), and difficult child subdomain of the PSI (ES = 0.44). This is the largest trial assessing PT in ASD on parent outcomes. PT reduces disruptive behavior in children, and improves parental competence while reducing parental stress and parental strain.

Dilated cardiomyopathy is characterized by substantial locus, allelic, and clinical heterogeneity that necessitates testing of many genes across clinically overlapping diseases. Few studies have sequenced sufficient individuals; thus, the contributions of individual genes and the pathogenic variant spectrum are still poorly defined. We analyzed 766 dilated cardiomyopathy patients tested over 5 years in our molecular diagnostics laboratory. Patients were tested using gene panels of increasing size from 5 to 46 genes, including 121 cases tested with a multiple-cardiomyopathy next-generation panel covering 46 genes. All variants were reassessed using our current clinical-grade scoring system to eliminate false-positive disease associations that afflict many older analyses. Up to 37% of dilated cardiomyopathy cases carry a clinically relevant variant in one of 20 genes, titin (TTN) being the largest contributor (up to 14%). Desmoplakin (DSP), an arrhythmogenic right ventricular cardiomyopathy gene, contributed 2.4%, illustrating the utility of multidisease testing. The clinical sensitivity increased from 10 to 37% as gene panel sizes increased. However, the number of inconclusive cases also increased from 4.6 to 51%. Our data illustrate the utility of broad gene panels for genetically and clinically heterogeneous diseases but also highlight challenges as molecular diagnostics moves toward genome-wide testing. Genet Med 16 8, 601–608.

Background: Linking autism symptoms to cognitive abilities can expand phenotypic descriptions and facilitate investigations into the etiology and treatment of this multiplex disorder. Executive dysfunction is one of several potential cognitive phenotypes in autism. Method: Archival clinical data on 89 children diagnosed with Autism Spectrum Disorders and administered a large neuropsychological battery were evaluated for relationships between executive functioning and autism symptoms. Results: Significant relationships between both laboratory tasks and behavior rating scales of executive functions and autism symptoms were identified. Multiple regression analyses revealed that measures of semantic fluency, divided auditory attention, and behavioral regulation were significantly correlated with autism symptoms, even after accounting for the variance from correlated “nuisance variables,” such as vocabulary and age. Conclusions: Executive dysfunction is related to all three clusters of behavioral symptoms in A...

Research examining set-shifting has revealed significant difficulties for adults with autism spectrum disorders (ASDs). However, research with high-functioning children with ASDs has yielded mixed results. The current study tested 6- to 13-year-old high-functioning children with ASD and typically developing controls matched on age, gender, and IQ using the Intradimensional/Extradimensional (ID/ED) Shift Test from the Cambridge Neuropsychological Test Automated Battery. Children with ASDs completed as many ED shifts and reversal ED shifts as controls; however, they made significantly more errors than controls while completing the ED reversal shifts. Analyses on a subset of cases revealed a significant positive correlation between ED reversal errors and the number of repetitive behavior symptoms in the ASD group. These findings suggest that high-functioning children with ASDs require additional feedback to shift successfully. In addition, the relationship between set-shifting and non-social symptoms suggests its utility as a potentially informative intermediate phenotype in ASDs.

1. Regulation of vascular Nox2-containing NADPH oxidase by p47(phox) plays a pivotal role in the development of atherosclerotic lesions through the generation of superoxide. Reduced vascular nitric oxide (NO) bioavailability is a major contributing factor in the initiation of atherosclerosis because it leads to an increase in adhesion molecule expression for inflammatory cell recruitment into the vessel wall. 2. The aim of the present study was to examine whether the anti-oxidant and anti-inflammatory effects of endogenous NO involve inhibition of NADPH oxidase-dependent superoxide production. 3. To inhibit endogenous NO production, male C57Bl/6 wild-type (WT) mice or age-matched p47(phox-/-) mice were treated with N(G)-nitro-L-arginine methyl ester (L-NAME; 100 mg/kg per day for 4 weeks). Blood pressure was measured weekly via the tail-cuff method. Basal and phorbol dibutyrate (PDB)-stimulated aortic superoxide production was detected using lucigenin- and L-012-enhanced chemiluminescence, respectively. Aortic Nox2, p47(phox) and vascular cell adhesion molecule (VCAM)-1 expression were measured with western blotting. Plasma angiotensin (Ang) II levels were determined by radioimmunoassay. 4. Compared with vehicle (tap water)-treated WT mice (n = 4), L-NAME-treated WT mice had significantly higher systolic blood pressure (SBP; n = 6; P < 0.05) and basal and stimulated aortic extracellular superoxide production (n = 6-8; P < 0.05), but lower plasma AngII levels (P < 0.05). There was no change in Nox2 expression following l-NAME treatment of WT mice (n = 6); however, significant increases in both aortic p47(phox) (n = 6; P < 0.05) and VCAM-1 expression (n = 6; P < 0.05) were observed. In p47(phox-/-) mice, l-NAME treatment significantly increased SBP (n = 3-4; P < 0.05), but failed to increase aortic superoxide production and VCAM-1 expression. 5. In conclusion, endogenous NO suppresses vascular inflammation, via inhibition of p47(phox) expression, leading to attenuation of NADPH oxidase-dependent superoxide production.