Aggression in Children with 7q11.23 Duplication Syndrome

7q11.23 duplication syndrome (Dup7) is a recently identified genetic disorder that is caused by a duplication of the same set of genes deleted in Williams syndrome (WS). Dup7 is highly variable and associated with several cognitive, behavioral, and medical characteristics, a wide range of cognitive abilities, language delay, childhood apraxia of speech, autism spectrum disorders (ASD), anxiety disorders, developmental coordination disorder, and epilepsy. A recent examination of individuals with Dup7 indicated high levels of social anxiety and elevated aggression and oppositional behavior compared to same-aged peers; however, detailed characterization of behavioral outcomes and factors that may contribute to variability in functioning have not been explored. The aim of this study was to characterize the presence and severity of aggression in children with Dup7 and identify potential contributions to levels of aggression utilizing a multi-method, multi-informant approach. Participants included 63 children with Dup7 between the ages of 4 and 18. Results indicate elevated levels of aggression and oppositional behavior. Children who were young and had language delays were more likely to demonstrate aggression as rated by an examiner. Intellectual functioning, expressive language functioning, and ASD severity were not related to aggression; however, children who were rated by their parents as demonstrating behaviors associated with Social Anxiety Disorder were more likely to be rated as demonstrating behaviors consistent with Oppositional Defiant Disorder. This finding suggests that the presence of social anxiety may contribute to the presence of aggression in children with Dup7. Overall, this study’s findings suggest that the genes in the 7q11.23 region duplicated in Dup7, in transaction with the environment, may contribute to aggressive behavior

Changes in Depressive Symptoms Among Adolescents with ASD Completing the PEERS® Social Skills Intervention

Depression is a common concern among people with autism spectrum disorder (ASD) and is often associated with social skills and relationship challenges. The present data, from a randomized controlled trial, examined the effect of PEERS® on self-reported depressive symptoms via the Children’s Depression Inventory (CDI) among 49 adolescents with ASD. Findings revealed that many CDI subscale scores declined (p’s \u3c 0.05) and were related to direct social contact on the Quality of Socialization Questionnaire at posttest (p’s \u3c 0.05). Exploratory analyses uncovered that suicidality was less evident following PEERS®. Findings support the notion that social functioning and depression may be intimately intertwined in ASD; therefore, bolstering social skills in ASD may positively influence other domains of functioning, including mental health

Social Difficulties in Youth with Autism With and Without Anxiety and ADHD Symptoms

Social difficulties inherent to autism spectrum disorder are often linked with co‐occurring symptoms of anxiety and attention deficit hyperactivity disorder (ADHD). The present study sought to examine the relation between such co‐occurring symptoms and social challenges. Parents of adolescents with autism (N = 113) reported upon social challenges via the social responsiveness scale (SRS) and anxiety and ADHD symptomatology via the Child Behavior Checklist. Results revealed differences in SRS scores across co‐occurring symptom subgroups (Anxiety, ADHD, Both, Neither)—namely, adolescents with autism and anxiety as well as those with autism, anxiety, and ADHD showed greater scores on the SRS than the other groups. Implications for research and clinical practice are discussed and recommendations are offered. Lay Summary Anxiety and attention deficit hyperactivity disorder (ADHD) symptoms are related to greater social challenges for adolescents with autism spectrum disorder. The present study found that autism with anxiety and autism with anxiety and ADHD, was related to greater social difficulties than autism alone. Findings provide further support for the intertwined nature of anxiety and ADHD symptoms in autism. What this may mean for research and clinical practice is considered and recommendations are suggested

Social Difficulties in Youth with Autism With and Without Anxiety and ADHD Symptoms

Social difficulties inherent to autism spectrum disorder are often linked with co‐occurring symptoms of anxiety and attention deficit hyperactivity disorder (ADHD). The present study sought to examine the relation between such co‐occurring symptoms and social challenges. Parents of adolescents with autism (N = 113) reported upon social challenges via the social responsiveness scale (SRS) and anxiety and ADHD symptomatology via the Child Behavior Checklist. Results revealed differences in SRS scores across co‐occurring symptom subgroups (Anxiety, ADHD, Both, Neither)—namely, adolescents with autism and anxiety as well as those with autism, anxiety, and ADHD showed greater scores on the SRS than the other groups. Implications for research and clinical practice are discussed and recommendations are offered. Lay Summary Anxiety and attention deficit hyperactivity disorder (ADHD) symptoms are related to greater social challenges for adolescents with autism spectrum disorder. The present study found that autism with anxiety and autism with anxiety and ADHD, was related to greater social difficulties than autism alone. Findings provide further support for the intertwined nature of anxiety and ADHD symptoms in autism. What this may mean for research and clinical practice is considered and recommendations are suggested

A Psychometric Analysis of the Social Anxiety Scale for Adolescents Among Youth with Autism Spectrum Disorder: Caregiver–Adolescent Agreement, Factor Structure, and Validity

Social anxiety is common among adolescents with autism spectrum disorder (ASD). An ongoing challenge for both research and clinical practice in ASD is the assessment of anxious symptomatology. Despite its widespread use in samples of youth with ASD, the Social Anxiety Scale for Adolescents (SAS-A) has not received psychometric evaluation within this population; thus, the validity of its use in research and clinical practice for ASD remains unclear. The present study conducted a psychometric analysis of caregiver and adolescent SAS-A forms in a sample of adolescents with ASD (N = 197). Results revealed (1) poor caregiver–adolescent item-level agreement, (2) a two-factor structure, (3) lack of measurement invariance between reporters, and (4) modest evidence for convergent and discriminant validity. Overall, findings suggest that this measure demonstrates reasonable psychometric properties in an ASD sample. Lack of measurement invariance, however, calls for careful interpretation of research involving the SAS-A in ASD samples, particularly when the primary goal is to compare adolescent and caregiver reports. The implications of these findings for future research and clinical practice are discussed

Neurocognition across the spectrum of mucopolysaccharidosis type I: Age, severity, and treatment

OBJECTIVES: Precise characterization of cognitive outcomes and factors that contribute to cognitive variability will enable better understanding of disease progression and treatment effects in mucopolysaccharidosis type I (MPS I). We examined the effects on cognition of phenotype, genotype, age at evaluation and first treatment, and somatic disease burden. METHODS: Sixty patients with severe MPS IH (Hurler syndrome treated with hematopoietic cell transplant and 29 with attenuated MPS I treated with enzyme replacement therapy), were studied with IQ measures, medical history, genotypes. Sixty-seven patients had volumetric MRI. Subjects were grouped by age and phenotype and MRI and compared to 96 normal controls. RESULTS: Prior to hematopoietic cell transplant, MPS IH patients were all cognitively average, but post-transplant, 59% were below average, but stable. Genotype and age at HCT were associated with cognitive ability. In attenuated MPS I, 40% were below average with genotype and somatic disease burden predicting their cognitive ability. White matter volumes were associated with IQ for controls, but not for MPS I. Gray matter volumes were positively associated with IQ in controls and attenuated MPS I patients, but negatively associated in MPS IH. CONCLUSIONS: Cognitive impairment, a major difficulty for many MPS I patients, is associated with genotype, age at treatment and somatic disease burden. IQ association with white matter differed from controls. Many attenuated MPS patients have significant physical and/or cognitive problems and receive insufficient support services. Results provide direction for future clinical trials and better disease management

Factors Contributing to Executive Functioning in Children with Neurofibromatosis Type 1

Despite variability in the neurofibromatosis type 1 (NF1) cognitive phenotype, attention and executive functioning (EF) difficulties are often described, and high rates of attention-deficit/hyperactivity disorder (ADHD) have long been associated with NF1. Despite the known clinical relation between NF1 and ADHD, there is a paucity of research exploring potential factors that contribute to ADHD vulnerabilities in children and adolescents with NF1. Furthermore, recent research suggests that impairment in EF, a construct highly associated with ADHD, occurs in children with NF1 independent of ADHD diagnosis suggesting that the presence of EF impairment in children with NF1 may not be uniquely associated with ADHD. Given the complexity of EF and the relative lack of literature about factors that might contribute to EF performance in children with NF1, further research is warranted. The current study aims to characterize EF in children with NF1, compare EF from performance-based and functional measures, and explore potential neuropsychological, sociodemographic, and psychosocial factors that contribute to EF in children with NF1. Overall, results confirmed that children with NF1 demonstrate difficulty on performance and functional EF measures, and difficulties were more evident based on functional parent report of behavior. Over one-third of children with NF1 met diagnostic criteria for ADHD; however, children with NF1 as a group demonstrated similar EF profiles on performance measures, independent of ADHD diagnosis. On functional parent reported measures of EF, children with NF1 and ADHD demonstrated significantly higher levels of executive dysfunction compared to children with NF1 without ADHD. Relations between performance-based working memory and general cognitive functioning were found for children with NF1, as a group. Parent report of internalizing problems were related to parent report of functional emotional control, shifting/cognitive flexibility, and overall behavioral regulation. As hypothesized, parent reported sleep difficulties were related to functional EF. In addition, slower reaction times on a working memory task were related to parent report of snoring, and parent report of restlessness during sleep was related to functional EF. Group differences between children with NF1 who met cut-off criteria for a sleep-related breathing disorder and those that did not were apparent when examining parent report of functional inhibition, working memory, and self-monitoring difficulties. Overall, results highlight the utility of a multi-method assessment of EF and provide evidence for contributing factors of overall cognition, attention, internalizing problems, and sleep on various aspects of EF in children and adolescents with NF1

Differences in MPS I and MPS II Disease Manifestations

Mucopolysaccharidosis (MPS) type I and II are two closely related lysosomal storage diseases associated with disrupted glycosaminoglycan catabolism. In MPS II, the first step of degradation of heparan sulfate (HS) and dermatan sulfate (DS) is blocked by a deficiency in the lysosomal enzyme iduronate 2-sulfatase (IDS), while, in MPS I, blockage of the second step is caused by a deficiency in iduronidase (IDUA). The subsequent accumulation of HS and DS causes lysosomal hypertrophy and an increase in the number of lysosomes in cells, and impacts cellular functions, like cell adhesion, endocytosis, intracellular trafficking of different molecules, intracellular ionic balance, and inflammation. Characteristic phenotypical manifestations of both MPS I and II include skeletal disease, reflected in short stature, inguinal and umbilical hernias, hydrocephalus, hearing loss, coarse facial features, protruded abdomen with hepatosplenomegaly, and neurological involvement with varying functional concerns. However, a few manifestations are disease-specific, including corneal clouding in MPS I, epidermal manifestations in MPS II, and differences in the severity and nature of behavioral concerns. These phenotypic differences appear to be related to different ratios between DS and HS, and their sulfation levels. MPS I is characterized by higher DS/HS levels and lower sulfation levels, while HS levels dominate over DS levels in MPS II and sulfation levels are higher. The high presence of DS in the cornea and its involvement in the arrangement of collagen fibrils potentially causes corneal clouding to be prevalent in MPS I, but not in MPS II. The differences in neurological involvement may be due to the increased HS levels in MPS II, because of the involvement of HS in neuronal development. Current treatment options for patients with MPS II are often restricted to enzyme replacement therapy (ERT). While ERT has beneficial effects on respiratory and cardiopulmonary function and extends the lifespan of the patients, it does not significantly affect CNS manifestations, probably because the enzyme cannot pass the blood–brain barrier at sufficient levels. Many experimental therapies, therefore, aim at delivery of IDS to the CNS in an attempt to prevent neurocognitive decline in the patients