Psychometric properties of the revised children’s anxiety and depression scale (RCADS) for autistic youth without co-occurring intellectual disability

Autistic youth often present with comorbid anxiety and depression yet there is a dearth of validated assessment tools. The Revised Children’s Anxiety and Depression Scale (RCADS) assesses internalizing symptoms but there is little psychometric data in autistic youth. Treatment-seeking autistic youth with anxiety or obsessive-compulsive symptoms (N = 74; age 6–14 years), and caregivers, were administered the RCADS-Parent, RCADS-Child, and assessments of internalizing, externalizing symptoms and social impairment indicative of autism. RCADS-Parent and RCADS-Child total anxiety scores demonstrated excellent internal consistency, and the six subscales demonstrated acceptable-to-good internal consistency. The RCADS-Child and Parent total anxiety scores were weakly correlated, and neither child age nor gender altered the strength of this association. Convergent validity was supported by moderate-to-strong correlations with clinician and parent-reported anxiety symptoms. Support for divergent validity was mixed. Results provide support for the RCADS-Parent and RCADS-Child as reliable, valid measures of internalizing symptoms in autistic youth

Truncating SRCAP variants outside the Floating-Harbor syndrome locus cause a distinct neurodevelopmental disorder with a specific DNA methylation signature

Truncating variants in exons 33 and 34 of the SNF2-related CREBBP activator protein (SRCAP) gene cause the neurodevelopmental disorder (NDD) Floating-Harbor syndrome (FLHS), characterized by short stature, speech delay, and facial dysmorphism. Here, we present a cohort of 33 individuals with clinical features distinct from FLHS and truncating (mostly de novo) SRCAP variants either proximal (n = 28) or distal (n = 5) to the FLHS locus. Detailed clinical characterization of the proximal SRCAP individuals identified shared characteristics: developmental delay with or without intellectual disability, behavioral and psychiatric problems, non-specific facial features, musculoskeletal issues, and hypotonia. Because FLHS is known to be associated with a unique set of DNA methylation (DNAm) changes in blood, a DNAm signature, we investigated whether there was a distinct signature associated with our affected individuals. A machine-learning model, based on the FLHS DNAm signature, negatively classified all our tested subjects. Comparing proximal variants with typically developing controls, we identified a DNAm signature distinct from the FLHS signature. Based on the DNAm and clinical data, we refer to the condition as "non-FLHS SRCAP-related NDD.'' All five distal variants classified negatively using the FLHS DNAm model while two classified positively using the proximal model. This suggests divergent pathogenicity of these variants, though clinically the distal group presented with NDD, similar to the proximal SRCAP group. In summary, for SRCAP, there is a clear relationship between variant location, DNAm profile, and clinical phenotype. These results highlight the power of combined epigenetic, molecular, and clinical studies to identify and characterize genotype-epigenotype-phenotype correlations

Early treatments associated with optimal outcome in children with autism spectrum disorders

A growing body of evidence supports the notion that early intensive behavioral intervention is associated with positive gains in individuals with autism spectrum disorders (ASD), although it is not yet possible to draw definitive conclusions with respect to whether early intervention is both necessary and sufficient in achieving the most positive outcomes (i.e., optimal outcome ) from ASD. A recent report by Sutera et al. (2007) described a sample of 13 children diagnosed with ASD at approximately two years of age who, at re-evaluation at approximately four years of age, no longer met diagnostic criteria for ASD and scored within the average range on standardized measures of cognitive and adaptive functioning. ^ Aims of the present study are twofold: (1) to confirm and expand upon the findings of Sutera et al. (2007) utilizing a larger sample size; and (2) to examine associations between the age of onset of intervention and type(s) and number of hours of intervention services young children with ASD have received and a variety of outcome measures including cognitive functioning, adaptive skills, autistic symptomatology, and diagnostic status at around four years of age. ^ Consistent with Sutera et al.\u27s (2007) findings, early motor skills predicted outcome. Further, in the present study, a number of additional variables predicted outcome, including repetitive behavior symptoms, cognitive and adaptive skills and expressive language. Results revealed no significant predictive value of any of the treatment-related variables included in the present investigation, including age at which intervention began; total number of intervention hours provided before the age of 3; and intensity of intervention between the ages of 2.5 and 3 years. These findings and limitations of the current study are discussed within the context of the substantial body of research documenting the importance and effectiveness of early intervention in children with ASD.

Early treatments associated with optimal outcome in children with autism spectrum disorders

A growing body of evidence supports the notion that early intensive behavioral intervention is associated with positive gains in individuals with autism spectrum disorders (ASD), although it is not yet possible to draw definitive conclusions with respect to whether early intervention is both necessary and sufficient in achieving the most positive outcomes (i.e., optimal outcome ) from ASD. A recent report by Sutera et al. (2007) described a sample of 13 children diagnosed with ASD at approximately two years of age who, at re-evaluation at approximately four years of age, no longer met diagnostic criteria for ASD and scored within the average range on standardized measures of cognitive and adaptive functioning. ^ Aims of the present study are twofold: (1) to confirm and expand upon the findings of Sutera et al. (2007) utilizing a larger sample size; and (2) to examine associations between the age of onset of intervention and type(s) and number of hours of intervention services young children with ASD have received and a variety of outcome measures including cognitive functioning, adaptive skills, autistic symptomatology, and diagnostic status at around four years of age. ^ Consistent with Sutera et al.\u27s (2007) findings, early motor skills predicted outcome. Further, in the present study, a number of additional variables predicted outcome, including repetitive behavior symptoms, cognitive and adaptive skills and expressive language. Results revealed no significant predictive value of any of the treatment-related variables included in the present investigation, including age at which intervention began; total number of intervention hours provided before the age of 3; and intensity of intervention between the ages of 2.5 and 3 years. These findings and limitations of the current study are discussed within the context of the substantial body of research documenting the importance and effectiveness of early intervention in children with ASD.

Neurocognitive and Neurobehavioral Phenotype of Youth with Schaaf-Yang Syndrome

Truncating variants of theMAGEL2gene, one of the protein-coding genes within the Prader-Willi syndrome (PWS) critical region on chromosome 15q11, cause Schaaf-Yang syndrome (SYS)-a neurodevelopmental disorder that shares several clinical features with PWS. The current study sought to characterize the neurobehavioral phenotype of SYS in a sample of 9 patients with molecularly-confirmed SYS. Participants received an assessment of developmental/intellectual functioning, adaptive functioning, autism symptomatology, and behavioral/emotional functioning. Compared to individuals with PWS, patients with SYS manifested more severe cognitive deficits, no obsessions or compulsions, and increased rates of autism spectrum disorder

Parent-led, Stepped-care Cognitive-behavioral Therapy for Youth with Autism and Co-occurring Anxiety: Study Rationale and Method

Anxiety disorders affect up to 50% of individuals with autism spectrum disorder (ASD) and are significantly impairing to the person affected, as well as to their loved ones. Cognitive-behavioral therapy (CBT) has been established as the gold-standard treatment for anxiety disorders among typically developing youth and adults, and demonstrates similar efficacy among youth with high-functioning autism (HFA). Many CBT interventions utilize a “full-package” treatment approach to treat co-occurring anxiety in youth with ASD. However, these service delivery systems are often therapist-intensive, costly, and impractical, thereby compromising full engagement and treatment adherence. This paper describes the design, rationale, and methodology of a study examining stepped-care CBT for youth with HFA and co-occurring anxiety – a clinical trial examining the efficacy of low-intensity, parent-led CBT as the first line of treatment and utilizing a more intensive, therapist-led intervention for nonresponders. The study will evaluate the potential benefits of stepped-care and parent-led therapist-assisted interventions, predictors of treatment response, and the economic value of using a stepped-care model. Implications for practice will be discussed