Anxiety Disorders in Williams Syndrome Contrasted with Intellectual Disability and the General Population: A Systematic Review and Meta-Analysis

Individuals with specific genetic syndromes associated with intellectual disability (ID), such as Williams syndrome (WS), are at increased risk for developing anxiety disorders. A systematic literature review identified sixteen WS papers that could generate pooled prevalence estimates of anxiety disorders for WS. A meta-analysis compared these estimates with prevalence estimates for the heterogeneous ID population and the general population. Estimated rates of anxiety disorders in WS were high. WS individuals were four times more likely to experience anxiety than individuals with ID, and the risk was also heightened compared to the general population. The results provide further evidence of an unusual profile of high anxiety in WS

Early predictors of language and social communication impairments at ages 9-11 years: A follow-up study of early-referred children

Purpose: In this study, the authors aimed to evaluate hypotheses that early sociocognition will predict later social communication and early phonology will predict later morphosyntax in clinically referred preschoolers. Method: Participants were 108 children ages 9–11 years who had been referred to clinical services with concerns about language at age 2½–3½ years. Predictors at Time 1 (T1) were measures of sociocognition, word/nonword repetition, and receptive language. Outcome measures at Time 3 (T3) included a social communication questionnaire completed by parents and tests of nonword repetition, morphosyntax, and receptive language. Results: Group- and case-level analyses revealed early sociocognition to be the strongest predictor of social communication problems, which by T3 affected almost one third of the sample. At the group level, early phonology, which was a significant problem for the majority of children at T1, was a weak predictor of morphosyntax at T3. However, at the case level the majority of children with poor morphosyntax and nonword repetition at outcome had had very low repetition scores at T1. Conclusions: In early language referrals, it is important to identify and address sociocognitive problems, a considerable risk for later social communication and autism spectrum disorders. The majority of early-referred children had phonological problems, often severe, but these require further investigation to determine their longer term significance for language

Anxiety disorders in children with Williams syndrome, their mothers, and their siblings: Implications for the etiology of anxiety disorders

This study examines the prevalence of anxiety disorders in children with Williams syndrome (WS), their sibling closest in age, and their mothers as well as the predictors of anxiety in these groups. The prevalence of anxiety disorders was assessed and compared to that in the general population. Children with WS had a significantly higher prevalence of specific phobia, generalized anxiety disorder (GAD), and separation anxiety in comparison to children in the general population. While mothers had a higher prevalence of GAD than population controls, the excess was accounted for by mothers who had onset after the birth of their WS child. The siblings had rates similar to the general population. This pattern of findings suggests the presence of a gene in the WS region whose deletion predisposes to anxiety disorders. It is also worthwhile to investigate relations between genes deleted in WS and genes previously implicated in anxiety disorders

Diverse Profiles of Anxiety Related Disorders in Fragile X, Cornelia de Lange and Rubinstein–Taybi Syndromes

Anxiety disorders are heightened in specific genetic syndromes in comparison to intellectual disability of heterogeneous aetiology. In this study, we described and contrasted anxiety symptomatology in fragile X (FXS), Cornelia de Lange (CdLS) and Rubinstein–Taybi syndromes (RTS), and compared the symptomatology to normative data for typically-developing children and children diagnosed with an anxiety disorder. Scores did not differ between children diagnosed with an anxiety disorder and (a) participants with FXS on social phobia, panic/agoraphobia, physical injury fears, and obsessive–compulsive subscales (b) participants with CdLS on separation anxiety, generalized anxiety, panic/agoraphobia, physical injury fears and obsessive–compulsive subscales, and (c) participants with RTS on panic/agoraphobia and obsessive–compulsive subscales. The results highlight divergent profiles of anxiety symptomatology between these groups

Prader–Willi syndrome and autism spectrum disorders: an evolving story

Prader–Willi syndrome (PWS) is well-known for its genetic and phenotypic complexities. Caused by a lack of paternally derived imprinted material on chromosome 15q11–q13, individuals with PWS have mild to moderate intellectual disabilities, repetitive and compulsive behaviors, skin picking, tantrums, irritability, hyperphagia, and increased risks of obesity. Many individuals also have co-occurring autism spectrum disorders (ASDs), psychosis, and mood disorders. Although the PWS 15q11–q13 region confers risks for autism, relatively few studies have assessed autism symptoms in PWS or directly compared social, behavioral, and cognitive functioning across groups with autism or PWS. This article identifies areas of phenotypic overlap and difference between PWS and ASD in core autism symptoms and in such comorbidities as psychiatric disorders, and dysregulated sleep and eating. Though future studies are needed, PWS provides a promising alternative lens into specific symptoms and comorbidities of autism

Increased Secreted Amyloid Precursor Protein-α (sAPPα) in Severe Autism: Proposal of a Specific, Anabolic Pathway and Putative Biomarker

Autism is a neurodevelopmental disorder characterized by deficits in verbal communication, social interactions, and the presence of repetitive, stereotyped and compulsive behaviors. Excessive early brain growth is found commonly in some patients and may contribute to disease phenotype. Reports of increased levels of brain-derived neurotrophic factor (BDNF) and other neurotrophic-like factors in autistic neonates suggest that enhanced anabolic activity in CNS mediates this overgrowth effect. We have shown previously that in a subset of patients with severe autism and aggression, plasma levels of the secreted amyloid-β (Aβ) precursor protein-alpha form (sAPPα) were significantly elevated relative to controls and patients with mild-to-moderate autism. Here we further tested the hypothesis that levels of sAPPα and sAPPβ (proteolytic cleavage products of APP by α- and β-secretase, respectively) are deranged in autism and may contribute to an anabolic environment leading to brain overgrowth. We measured plasma levels of sAPPα, sAPPβ, Aβ peptides and BDNF by corresponding ELISA in a well characterized set of subjects. We included for analysis 18 control, 6 mild-to-moderate, and 15 severely autistic patient plasma samples. We have observed that sAPPα levels are increased and BDNF levels decreased in the plasma of patients with severe autism as compared to controls. Further, we show that Aβ1-40, Aβ1-42, and sAPPβ levels are significantly decreased in the plasma of patients with severe autism. These findings do not extend to patients with mild-to-moderate autism, providing a biochemical correlate of phenotypic severity. Taken together, this study provides evidence that sAPPα levels are generally elevated in severe autism and suggests that these patients may have aberrant non-amyloidogenic processing of APP

Optimising exposure for children and adolescents with anxiety, OCD and PTSD: a systematic review

Cognitive-behavioural therapy is an effective treatment for anxiety disorders in children and young people, however, many do not benefit. Behavioural exposure appears to be the critical ingredient in the treatment of anxiety disorders. Research with adults has identified innovative strategies to optimise exposure-based treatments, yet it is not clear how to optimise the effects of exposure for children and young people. This review was a preliminary exploration of the association between potential optimisation strategies and treatment procedures and outcomes for the treatment of child anxiety symptoms/disorders. We searched PsychInfo and Medline databases using a systematic search strategy and identified 29 articles. We found preliminary evidence that some specific strategies may enhance the effects of exposure, such as dropping safety behaviours, parents and therapists discouraging avoidance, and the use of homework. However, not one significant finding was replicated by another study for the same time point using the same methodology. To a large degree, this lack of replication reflects a limited number of studies combined with a lack of consistency across studies around conceptualisations, methodological approaches, and outcome measures making it difficult to make meaningful comparisons between studies and draw firm conclusions. Examination is needed of a wide range of theoretically-driven potential optimisation strategies using methodologically robust, preclinical studies with children and young people. Furthermore, the methods used in future research must enable comparisons across studies and explore developmental differences in the effects of particular optimisation strategies