Urban and rural differences in needs, service use and satisfaction among caregivers of autistic children in Morocco.

LAY ABSTRACT: It is very important to understand the needs of caregivers to be able to empower caregivers and to develop or improve services around the world. Therefore, research in different regions is needed to understand differences in caregivers needs between countries, but also between areas within countries. This study investigated differences in needs and service use between caregivers of autistic children in Morocco, living in urban and rural areas. A total of 131 Moroccan caregivers of autistic children took part in the study and responded to an interview survey. The results showed both similarities and differences between urban and rural living caregivers' challenges and needs. Autistic children from urban communities were much more likely to receive intervention and attend school than children from rural communities, even though age and verbal skills of the two groups of children were comparable. Caregivers expressed similar needs for improved care and education, but different challenges in caring. Limited autonomy skills in children were more challenging to rural caregivers, while limited social-communicational skills were more challenging to urban caregivers. These differences may inform healthcare policy-makers and program developers. Adaptive interventions are important to respond to regional needs, resources, and practices. In addition, the results showed the importance of addressing challenges as experienced by caregivers such as costs related to care, barriers in access to information, or stigma. Addressing these issues may help reduce both global and within-country differences in autism care.

Effects of Bumetanide on Neurocognitive Functioning in Children with Autism Spectrum Disorder: Secondary Analysis of a Randomized Placebo-Controlled Trial.

We present the secondary-analysis of neurocognitive tests in the 'Bumetanide in Autism Medication and Biomarker' (BAMBI;EUDRA-CT-2014-001560-35) study, a randomized double-blind placebo-controlled (1:1) trial testing 3-months bumetanide treatment (≤ 1 mg twice-daily) in unmedicated children 7-15 years with ASD. Children with IQ ≥ 70 were analyzed for baseline deficits and treatment-effects on the intention-to-treat-population with generalized-linear-models, principal component analysis and network analysis. Ninety-two children were allocated to treatment and 83 eligible for analyses. Heterogeneous neurocognitive impairments were found that were unaffected by bumetanide treatment. Network analysis showed higher modularity after treatment (mean difference:-0.165, 95%CI:-0.317 to - 0.013,p = .034) and changes in the relative importance of response inhibition in the neurocognitive network (mean difference:-0.037, 95%CI:-0.073 to - 0.001,p = .042). This study offers perspectives to include neurocognitive tests in ASD trials.

It's about more than just talking; Exploring computer-mediated communication in adolescents with selective mutism.

INTRODUCTION: Selective mutism (SM) is an anxiety disorder categorized by a persistent failure to speak in specific situations. In an attempt to facilitate interaction with individuals with SM, other forms of communication (e.g. computer-mediated communication; CMC) are often tried. However, CMC is understudied in individuals with SM, while, especially since the COVID-19 pandemic, the importance of CMC for education and social purposes only increased. METHODS: In this study, we explored CMC in 79 adolescents with either selective mutism (n = 34), or typical development (n = 45). All participants completed a survey concerning verbal and written CMC in three contexts (friends, family, and school). RESULTS: Results showed that adolescents with SM used not only verbal but also written CMC less frequently than the comparison group across contexts. While the comparison group preferred Face-to-Face communication over CMC, adolescents with SM were divided, especially in the school context. With family and friends, the majority of the SM group preferred Face-to-Face communication, even though this provoked more feelings of tension than CMC for part of the group. CONCLUSION: These findings support anecdotal reports that SM affects not only speech but extends to other communicative venues and includes written communication in many situations. This underlines the importance of addressing not just speaking behavior but also writing and CMC in the diagnostic evaluation and treatment plans for adolescents with SM.

Diagnosing selective mutism: a critical review of measures for clinical practice and research.

Selective mutism (SM) is an anxiety disorder (prevalence 1-2%), characterized by the consistent absence of speaking in specific situations (e.g., in school), while adequately speaking in other situations (e.g., at home). SM can have a debilitating impact on the psychosocial and academic functioning in childhood. The use of psychometrically sound and cross-culturally valid instruments is urgently needed.The aim of this paper is to identify and review the available assessment instruments for screening or diagnosing the core SM symptomatology. We conducted a systematic search in 6 databases. We identified 1469 studies from the last decade and investigated the measures having been used in a diagnostic assessment of SM. Studies were included if original data on the assessment or treatment of SM were reported. It was found that 38% of published studies on SM reporting original data did not report the use of any standardized or objective measure to investigate the core symptomatology. The results showed that many different questionnaires, interviews and observational instruments were used, many of these only once. The Selective Mutism Questionnaire (SMQ), Anxiety Disorders Interview Schedule (ADIS) and School Speech Questionnaire (SSQ) were used most often. Psychometric data on these instruments are emerging. Beyond these commonly used instruments, more recent developed instruments, such as the Frankfurt Scale of SM (FSSM) and the Teacher Telephone Interview for SM (TTI-SM), are described, as well as several interesting observational measures. The strengths and weaknesses of the instruments are discussed and recommendations are made for their use in clinical practice and research.

Development of the My Positive Health dialogue tool for children: a qualitative study on children's views of health.

BACKGROUND: Children's views of health were explored in order to develop a health dialogue tool for children. METHODS: A qualitative research design was used as part of a codesign process. Based on semi-structured interviews with both healthy children and children with a chronic condition (aged 8-18). Two approaches were applied. The first was an open exploration of children's views on health, which was then thematically analysed. Subsequently, a framework was used, based on the six-dimensional My Positive Health (MPH) dialogue tool for adults, to guide the second part of the interviews, focusing on reviewing the children's view on health within the context of the framework. For the final draft of the dialogue tool, a framework analysis was conducted and then validated by members of the 'children's council' of the Wilhelmina Children's Hospital. RESULTS: We interviewed 65 children, 45 of whom had a chronic condition and 20 were healthy. The children described a broad concept of health with the central themes of 'feeling good about yourself' and 'being able to participate'. Based on the subsequent framework analysis, the wording of two of the six dimensions of the MPH dialogue tool was adjusted and the related aspects were adapted for better alignment with the children's concept of health. After these modifications, the tool fully matched the children's concept of health. CONCLUSION: The MPH dialogue tool for children was developed for children with and without a chronic condition, to help them open up about what they consider important for their health and well-being, and to improve directorship over decisions and actions that would affect their health. The MPH dialogue tool aims to support healthcare professionals in providing the type of care and treatment that is in line with the needs of their young patients/clients.

The Validation of the Selective Mutism Questionnaire for Use in the Dutch Population.

Selective mutism (SM) is an anxiety disorder in children/adolescents, characterized by the absence of speaking in specific social situations, mostly at school. The selective mutism questionnaire (SMQ) is a parent report, internationally used to assess SM symptomatology and treatment outcomes. Since no assessment instrument for SM was available in the Netherlands, our aim was to investigate the psychometric properties of the Dutch translation of the SMQ, through reliability, confirmatory factor, and ROC analyses conducted on data obtained in 303 children (ages 3-17 years; clinical SM group n = 106, control group n = 197). The SMQ turned out to be highly reliable (α = 0.96 in the combined sample; 0.83 within the clinical group) and followed the expected factor structure. We conclude that the Dutch version of the SMQ is a reliable and valid tool both as a screening and clinical instrument to assess SM in Dutch speaking children.

Two-year-olds at elevated risk for ASD can learn novel words from their parents.

Children diagnosed with autism spectrum disorder (ASD) often have smaller vocabularies in infancy compared to typically-developing children. To understand whether their smaller vocabularies stem from problems in learning, our study compared a prospective risk sample of 18 elevated risk and 11 lower risk 24-month-olds on current vocabulary size and word learning ability using a paradigm in which parents teach their child words. Results revealed that both groups learned novel words, even though parents indicated that infants at elevated risk of ASD knew fewer words. This suggests that these early compromised vocabularies cannot be solely linked to difficulties in word formations.

Measurement invariance of the Childhood Autism Rating Scale (CARS) across six countries.

The Childhood Autism Rating Scale (CARS) is a simple and inexpensive tool for Autism spectrum disorder (ASD) assessments, with evidenced psychometric data from different countries. However, it is still unclear whether ASD symptoms are measured the same way across different societies and world regions with this tool, since data on its cross-cultural validity are lacking. This study evaluated the cross-cultural measurement invariance of the CARS among children with ASD from six countries, for whom data were aggregated from previous studies in India (n = 101), Jamaica (n = 139), Mexico (n = 72), Spain (n = 99), Turkey (n = 150), and the United States of America (n = 186). We analyzed the approximate measurement invariance based on Bayesian structural equation modeling. The model did not fit the data and its measurement invariance did not hold, with all items found non-invariant across the countries. Items related to social communication and interaction (i.e., relating to people, imitation, emotional response, and verbal and nonverbal communication) displayed lower levels of cross-country non-invariance compared to items about stereotyped behaviors/sensory sensitivity (i.e., body and object use, adaptation to change, or taste, smell, and touch response). This study found that the CARS may not provide cross-culturally valid ASD assessments. Thus, cross-cultural comparisons with the CARS should consider first which items operate differently across samples of interest, since its cross-cultural measurement non-invariance could be a source of cross-cultural variability in ASD presentations. Additional studies are needed before drawing valid recommendations in relation to the cultural sensitivity of particular items.

Is It Fear? Similar Brain Responses to Fearful and Neutral Faces in Infants with a Heightened Likelihood for Autism Spectrum Disorder.

Individuals with autism spectrum disorder (ASD) show atypical processing of facial expressions. Research with autistic toddlers suggests that abnormalities in processing of spatial frequencies (SFs) contribute to such differences. The current event-related-potential (ERP) study investigated differences between 10-month-old infants with high- and low-likelihood for ASD in SF processing and in discrimination of fearful and neutral faces, filtered to contain specific SF. Results indicate no group differences in general processing of higher (HSF, detailed) and lower-SF (LSF, global) information. However, unlike low-likelihood infants, high-likelihood infants do not discriminate between facial expressions when either the LSF or HSF information is available. Combined with previous findings in toddlers, the current results indicate a developmental delay in efficient processing of facial expressions in ASD.

Effectiveness of a behavioral treatment protocol for selective mutism in children: Design of a randomized controlled trial.

Selective mutism (SM) is a relatively rare anxiety disorder, characterized by a child's consistent failure to speak in various specific social situations (e.g., at school), while being able to speak in other situations (e.g., at home). Prevalence rates vary from 0.2% to 1.9%. SM is usually identified between the ages of 3-5 years. It is often underdiagnosed and consequently children receive no or inadequate treatment, with negative consequences for school and social functioning. If left untreated, SM can result in complex, chronic anxiety and/or mood disorders in adolescence and impaired working careers in adulthood. Currently, no evidence-based treatment for SM is available in the Netherlands, therefore this study aims to [1] test the effectiveness of a treatment protocol for SM that is carried out at school, and to [2] identify baseline predictors for treatment success. This article presents the design of a randomized controlled trial into the effectiveness of a behavioral therapeutic protocol for selective mutism in children (age 3-18). The expected study population is n = 76. Results of the treatment group (n = 38) will be compared with those of a waiting list control group (WCG) (n = 38). Pre and post treatment assessments will be conducted at comparable moments in both groups, with baseline assessment at intake, the second assessment at 12 weeks and post-assessment at the end of treatment. If proven effective, we aim to structurally implement this protocol as evidence-based treatment for SM.

Serious Games as Potential Therapies: A Validation Study of a Neurofeedback Game.

Serious (biofeedback) games offer promising ways to supplement or replace more expensive face-to-face interventions in health care. However, studies on the validity and effectiveness of EEG-based serious games remain scarce. In the current study, we investigated whether the conditions of the neurofeedback game "Daydream" indeed trained the brain activity as mentioned in the game manual. EEG activity was assessed in 14 healthy male volunteers while playing the 2 conditions of the game. The participants completed a training of 5 sessions. EEG frequency analyses were performed to verify the claims of the manual. We found significant differences in α- to ß-ratio between the 2 conditions although only in the amplitude data, not in the power data. Within the conditions, mean α-amplitude only differed significantly from the ß-amplitude in the concentration condition. Our analyses showed that neither α nor ß brain activity differed significantly between game levels (higher level requiring increased brain activity) in either of the two conditions. In conclusion, we found only marginal evidence for the proposed claims stated in the manual of the game. Our research emphasizes that it is crucial to validate the claims that serious games make, especially before implementing them in the clinic or as therapeutic devices.

Paradoxical Benzodiazepine Response: A Rationale for Bumetanide in Neurodevelopmental Disorders?

The diuretic agent bumetanide has recently been put forward as a novel, promising treatment of behavioral symptoms in autism spectrum disorder (ASD) and related conditions. Bumetanide can decrease neuronal chloride concentrations and may thereby reinstate γ-aminobutyric acid (GABA)-ergic inhibition in patients with neurodevelopmental disorders. However, strategies to select appropriate candidates for bumetanide treatment are lacking. We hypothesized that a paradoxical response to GABA-enforcing agents such as benzodiazepines may predict the efficacy of bumetanide treatment in neurodevelopmental disorders. We describe a case of a 10-year-old girl with ASD, epilepsy, cortical dysplasia, and a 15q11.2 duplication who had exhibited marked behavioral arousal after previous treatment with clobazam, a benzodiazepine. We hypothesized that this response indicated the presence of depolarizing excitatory GABA and started bumetanide treatment with monitoring of behavior, cognition, and EEG. The treatment resulted in a marked clinical improvement in sensory behaviors, rigidity, and memory performance, which was substantiated by questionnaires and cognitive assessments. At baseline, the girl's EEG showed a depression in absolute α power, an electrographic sign previously related to ASD, which was normalized with bumetanide treatment. The effects of bumetanide on cognition and EEG seemed to mirror the "nonparadoxical" responses to benzodiazepines in healthy subjects. In addition, temporal lobe epilepsy and cortical dysplasia have both been linked to disturbed chloride homeostasis and seem to support our assumption that the observed paradoxical response was due to GABA-mediated excitation. This case highlights that a paradoxical behavioral response to GABA-enforcing drugs may constitute a framework for targeted treatment with bumetanide.

Stop and change: inhibition and flexibility skills are related to repetitive behavior in children and young adults with autism spectrum disorders.

Cognitive control dysfunctions, like inhibitory and attentional flexibility deficits are assumed to underlie repetitive behavior in individuals with autism spectrum disorders (ASD). In the present study, prepotent response inhibition and attentional flexibility were examined in 64 high-functioning individuals with ASD and 53 control participants. Performance under different task conditions were tested both in response to visual and auditory information, and requiring a motor or verbal response. Individuals with ASD showed significant more control dysfunctions than typically developing participants on the auditory computer task. Inhibitory control and attentional flexibility predicted RRB in everyday life. Specifically, response inhibition in reaction to visual information and task switching in reaction to auditory information predicted motor and sensory stereotyped behavior.

New Interview and Observation Measures of the Broader Autism Phenotype: Description of Strategy and Reliability Findings for the Interview Measures.

Clinical genetic studies confirm the broader autism phenotype (BAP) in some relatives of individuals with autism, but there are few standardized assessment measures. We developed three BAP measures (informant interview, self-report interview, and impression of interviewee observational scale) and describe the development strategy and findings from the interviews. International Molecular Genetic Study of Autism Consortium data were collected from families containing at least two individuals with autism. Comparison of the informant and self-report interviews was restricted to samples in which the interviews were undertaken by different researchers from that site (251 UK informants, 119 from the Netherlands). Researchers produced vignettes that were rated blind by others. Retest reliability was assessed in 45 participants. Agreement between live scoring and vignette ratings was very high. Retest stability for the interviews was high. Factor analysis indicated a first factor comprising social-communication items and rigidity (but not other repetitive domain items), and a second factor comprised mainly of reading and spelling impairments. Whole scale Cronbach's alphas were high for both interviews. The correlation between interviews for factor 1 was moderate (adult items 0.50; childhood items 0.43); Kappa values for between-interview agreement on individual items were mainly low. The correlations between individual items and total score were moderate. The inclusion of several factor 2 items lowered the overall Cronbach's alpha for the total set. Both interview measures showed good reliability and substantial stability over time, but the findings were better for factor 1 than factor 2. We recommend factor 1 scores be used for characterising the BAP.

Autism Diagnostic Interview-Revised (ADI-R) Algorithms for Toddlers and Young Preschoolers: Application in a Non-US Sample of 1,104 Children.

The current study aimed to investigate the Autism Diagnostic Interview-Revised (ADI-R) algorithms for toddlers and young preschoolers (Kim and Lord, J Autism Dev Disord 42(1):82-93, 2012) in a non-US sample from ten sites in nine countries (n = 1,104). The construct validity indicated a good fit of the algorithms. The diagnostic validity was lower, with satisfactorily high specificities but moderate sensitivities. Young children with clinical ASD and lower language ability were largely in the mild-to-moderate or moderate-to-severe concern ranges of the ADI-R, nearly half of the older and phrase speech ASD-group fell into the little-to-no concern range. Although broadly the findings support the toddler algorithms, further work is required to understand why they might have different properties in different samples to further inform research and clinical use.

New interview and observation measures of the broader autism phenotype: group differentiation.

To identify the broader autism phenotype (BAP), the Family History Interview subject and informant versions and an observational tool (Impression of Interviewee), were developed. This study investigated whether the instruments differentiated between parents of children with autism, and parents of children with Down syndrome (DS). The BAP scores of parents of 28 multiplex autism families were compared with parents from, 32 DS families. The BAP measures provided good group differentiation but when considered together, the subject interview did not improve group differentiation. The differentiation was better for fathers than mothers. The measures do carry an important degree of validity; whether they can differentiate the BAP from other social disorders should be tested.

Development of a Video-feedback Intervention to promote Positive Parenting for Children with Autism (VIPP-AUTI).

In this paper we describe the development and content of Video-feedback Intervention to promote Positive Parenting for Children with Autism (VIPP-AUTI). VIPP-AUTI is an adapted version of the evidence-based intervention VIPP. The lack of social responsiveness in children with autism often lowers the quality of the parent-child interaction. A wide range of early interventions exist to cope with the disorder. The majority of early interventions for children with autism focus on their deficits of (social) skills, but the number of evidence-based interventions to improve early parent-child interaction patterns is limited. The aim of VIPP-AUTI is to enhance parental sensitivity to children's autistic characteristics, in order to improve child developmental outcome by increased parental support.

Convergence of genes and cellular pathways dysregulated in autism spectrum disorders.

Rare copy-number variation (CNV) is an important source of risk for autism spectrum disorders (ASDs). We analyzed 2,446 ASD-affected families and confirmed an excess of genic deletions and duplications in affected versus control groups (1.41-fold, p = 1.0 × 10(-5)) and an increase in affected subjects carrying exonic pathogenic CNVs overlapping known loci associated with dominant or X-linked ASD and intellectual disability (odds ratio = 12.62, p = 2.7 × 10(-15), ∼3% of ASD subjects). Pathogenic CNVs, often showing variable expressivity, included rare de novo and inherited events at 36 loci, implicating ASD-associated genes (CHD2, HDAC4, and GDI1) previously linked to other neurodevelopmental disorders, as well as other genes such as SETD5, MIR137, and HDAC9. Consistent with hypothesized gender-specific modulators, females with ASD were more likely to have highly penetrant CNVs (p = 0.017) and were also overrepresented among subjects with fragile X syndrome protein targets (p = 0.02). Genes affected by de novo CNVs and/or loss-of-function single-nucleotide variants converged on networks related to neuronal signaling and development, synapse function, and chromatin regulation.

How to use the ADI-R for classifying autism spectrum disorders? Psychometric properties of criteria from the literature in 1,204 Dutch children.

The algorithm of the Autism Diagnostic Interview-Revised provides criteria for autism versus non-autism according to DSM-IV. Criteria for the broader autism spectrum disorders are needed. This study investigated the validity of seven sets of criteria from the literature, in 1,204 Dutch children (aged 3-18 years) with and without mental retardation. The original criteria (Rutter et al. in ADI-R Autism Diagnostic Interview Revised. Manual. Western Psychological Services, Los Angeles, 2003) well discriminated ASD from non-ASD in MR. All other criteria (IMGSAC in Am Soc Hum Genet 69:570-581 2001; Sung et al. in Am J Hum Genet 76: 68-81, 2005; Risi et al. in J Am Acad Child Adolesc Psychiatry 45: 1094-1103, 2006) were sensitive at the cost of specificity, bearing the risk of overinclusiveness. In the group without MR, clinicians should decide whether sensitivity or specificity is aimed for, to choose the appropriate criteria. Including the Autism Diagnostic Observation Schedule revised algorithms in the classification, the specificity increases, at the cost of sensitivity. This study adds to a more valid judgment on which criteria to use for specific objectives.