The Prevalence of Suicidal Behavior in Autism Spectrum Disorder.

Background: Suicidal ideation (SI) and suicide attempts (SA) are common in autistic individuals, but prevalence rates have not yet been estimated with meta-analysis. Aims: This meta-analysis aims to estimate SI and SA prevalence rates in autistic individuals and identify subgroup differences based on sample characteristics and study quality. Methods: A systematic search identified 52 studies with 88,509 autistic participants reporting SI and SA. Pooled prevalence estimates were calculated using a random-effects model. Results: Pooled prevalence estimates of lifetime SI and SA were 37.2% [95% CI 25.3-50.8] and 15.3% [95% CI 9.5-23.6], respectively. For 12-month prevalence, this was 25.4% [95% CI 19.0-33.2] and 14.1% [95% CI 7.4-25.2], respectively. Subgroup analyses revealed significant differences based on age (SI), region (SI), data collection (SI), measurement scales used to define autism and suicidality (SA), and representation of the study sample (SI and SA). Heterogeneity measures were high for all outcomes (I2 = 60.3-99.1%). Limitations: The heterogeneity of the included studies may limit the generalizability of our findings. Conclusion: The high rates of suicidal problems in autistic individuals call for a systematic evaluation of suicidality in clinical practice and adequate therapeutic interventions to improve this condition.

Clinical stance on response initiation in autistic adults: co-creating an integrative approach based on theory and lived experiences to act from language, via motor movement to wellbeing.

Getting 'stuck', literally and figuratively, is a common experience for autistic people. Literally 'stuck' means exhibiting limited response initiation due to immobility with tense muscles and inability to move. Figuratively 'stuck' means loneliness, passivity or captivity in activities that do not offer long-term satisfaction. To further conceptualize this complex phenomenon of limited response initiation in autistic individuals, we performed qualitative interviews and focus groups with autistic people and their family members, followed by brainstorm sessions and a Delphi study with input from a larger panel of experts from multiple backgrounds. We aimed to co-create the outline of an integrative approach to support autistic people in moving away from this 'stuck state' to more flexible, limber 'supple states' in order to live freer, more meaningful, satisfying and peaceful lives. Over time, in interaction with all participants, our shared insight grew. Based on this, we here stipulate a conceptual framework, in which the described 'stuck state' at the micro-level of the muscles/behavior of one individual, probably is caused by feeling/being 'stuck' or 'cramped' at several overarching (i.e., meso and macro) levels. For instance, stuck in relationships with unhealthy dynamics, stuck at home creating short-term calm, trance-like states (e.g., gaming), stuck at an educational level that might fit the individuals' current social-emotional state rather than their potential cognitive level, stuck in a job that pays the bills but does not feel meaningful, nor contributes to a satisfying life with opportunities for personal development. Stuck in a mental/public health care system where ever ongoing changes in policies hinder sustained support to suit care-needs. Stuck in a regulated societal system making it likely to repeatedly get stuck. Is this phenomenon specific to autism? Formally we have only conducted interviews with this population, but in another smaller, related project we also spoke to people from the general population with careers that are considered successful in the general society. These people actually voiced similar experiences. Therefore, we hypothesize that this numbing state of being or feeling 'stuck' may be a prevalent phenomenon that needs to be addressed. In this article, we discuss several types of interventive approaches (i.e., language-based talking therapies, affective experiential expressive therapies, physical therapies and systemic therapies), prevention as well as intervention programs, directed at different primary stakeholders, that can complement and enrich each other in an integrative policy, that leads to tailor-made, personalized trajectories of interdisciplinary support to enable people to live satisfying, meaningful, dignified and peaceful lives.

Parental perspectives on Phelan-McDermid syndrome: Results of a worldwide survey.

Phelan-McDermid syndrome (PMS) is a rare neurodevelopmental disorder characterised by hypotonia, speech problems, intellectual disability and mental health issues like regression, autism and mood disorders. In the development, implementation and dissemination of a new clinical guideline for a rare genetic disorder like PMS, the parental experienced perspective is essential. As information from literature is scarce and often conflicting the European Phelan-McDermid syndrome guideline consortium created a multi-lingual survey for parents of individuals with PMS to collect their lived experiences with care needs, genotypes, somatic issues, mental health issues and parental stress. In total, we analysed 587 completed surveys from 35 countries worldwide. Based on parental reporting, PMS appeared to be caused by a deletion of chromosome 22q13.3 in 78% (379/486) of individuals and by a variant in the SHANK3 gene in 22% (107/486) of the individuals. Parents reported a wide variety of developmental, neurological, and other clinical issues in individuals with PMS. The most frequently experienced issues were related to speech and communication, learning disabilities/intellectual disability, and behaviour. While most reported issues were present across all age groups and genotypes, the prevalence of epilepsy, lymphoedema, and mental health issues do appear to vary with age. Developmental regression also appeared to begin earlier in this cohort than described in literature. Individuals with PMS due to a 22q13.3 deletion had a higher rate of kidney issues and lymphoedema compared to individuals with SHANK3 variants. Parental stress was high, with specific contributing factors being child and context related in accordance with the PMS phenotype. The survey results led to various validated recommendations in the European PMS guideline including an age specific surveillance scheme, specific genetic counselling, structured healthcare evaluations on sleep and communication and a focus on family well-being.

Understanding Behavior in Phelan-McDermid Syndrome.

Background: Phelan-McDermid syndrome (PMS) or 22q13.3 deletion syndrome is a rare genetic disorder characterized by developmental delay, hypotonia and severely delayed speech. Behavioral difficulties are often reported in PMS, although knowledge of behavioral profiles and the interpretation of reported behavior remains limited. Understanding the meaning of behavior requires considering the context as well as other domains of functioning, for example the individual's level of cognitive, social and emotional development. Combining structured direct in-person neurodevelopmental assessments with contextual assessments to enable meaningful interpretations of reported behavior on functional dimensions across multiple units of analysis, as proposed by the RDoc framework, is essential. Methods: In this article we present a structured multidisciplinary method of assessment through direct in-person neurodevelopmental assessments and assessment of contextual factors. Our study sample includes data of 33 children with an average age of 6.2 years (range 1.1 to 15.7) with PMS, obtained through individual in-person assessments in combination with parent informed questionnaires. We assessed developmental age using the Bayley-III, adaptive behavior was assessed with the Vineland screener, social-emotional development with the ESSEON-R and behavior by using the CBCL. Results: Our results show a great deal of variability in phenotypic presentation with regard to behavior, symptom expression and symptom severity in individuals with PMS. The data on behavior is interpreted in the context of the individual's level of cognitive, adaptive development and the (genetic) context. Behavioral data showed high levels of withdrawn behavior and attention problems. More than half of the children showed borderline or clinical symptoms related to Autism Spectrum Disorder (ASD). Conclusions: The interpretation of the meaning of certain behavior in PMS is often based on questionnaires and descriptions without taking the specific context of development into account. Combining questionnaires with direct in-person assessments measuring different domains of functioning should be considered a more accurate method to interpret the meaning of findings in order to understand behavior in rare genetic disorders associated with developmental delay such as PMS. Direct in-person assessment provides valuable and specific information relevant to understanding individual behavior and inform treatment as well as increase knowledge of the neurodevelopmental phenotype in individuals with PMS. More specific application of the proposed frameworks on behavior in PMS is desirable in making useful interpretations.

Development, behaviour and autism in individuals with SMC1A variants.

INTRODUCTION: Development and behaviour in Cornelia de Lange Syndrome (CdLS), including autism characteristics, have been described infrequently stratified to genetic cause and only a few studies have considered behavioural characteristics in relation to developmental level. Here, we describe the behavioural phenotype in individuals with CdLS with SMC1A variants. METHODS: We performed an international, interdisciplinary study on 51 individuals with SMC1A variants. Results of questionnaire studies are compared to those in individuals with Down Syndrome and with Autism Spectrum Disorder. Results on cognition and self-injurious behaviour (SIB) are compared to those in individuals with CdLS caused by NIPBL variants. For Dutch participants with SMC1A variants we performed direct in-person assessments of cognition, autism, and added an interview and questionnaire on adaptive behaviour and sensory processing. RESULTS: Individuals with SMC1A variants show a higher cognitive level and less SIB than individuals with NIPBL variants. Individuals with SMC1A variants without classic CdLS phenotype but with a Rett-like phenotype show more severe intellectual disability and more SIB compared to those with a CdLS phenotype. Autism is less present if outcomes in direct in-person assessments are evaluated taking developmental level into account compared to results based on a questionnaire. CONCLUSIONS: Behaviour in individuals with CdLS should be evaluated taking genetic cause into account. Detailed interdisciplinary approaches are of clinical importance to inform tailored care and may eventually improve quality of life of patients and families.

Phenotypes and genotypes in individuals with SMC1A variants.

SMC1A encodes one of the proteins of the cohesin complex. SMC1A variants are known to cause a phenotype resembling Cornelia de Lange syndrome (CdLS). Exome sequencing has allowed recognizing SMC1A variants in individuals with encephalopathy with epilepsy who do not resemble CdLS. We performed an international, interdisciplinary study on 51 individuals with SMC1A variants for physical and behavioral characteristics, and compare results to those in 67 individuals with NIPBL variants. For the Netherlands all known individuals with SMC1A variants were studied, both with and without CdLS phenotype. Individuals with SMC1A variants can resemble CdLS, but manifestations are less marked compared to individuals with NIPBL variants: growth is less disturbed, facial signs are less marked (except for periocular signs and thin upper vermillion), there are no major limb anomalies, and they have a higher level of cognitive and adaptive functioning. Self-injurious behavior is more frequent and more severe in the NIPBL group. In the Dutch group 5 of 13 individuals (all females) had a phenotype that shows a remarkable resemblance to Rett syndrome: epileptic encephalopathy, severe or profound intellectual disability, stereotypic movements, and (in some) regression. Their missense, nonsense, and frameshift mutations are evenly spread over the gene. We conclude that SMC1A variants can result in a phenotype resembling CdLS and a phenotype resembling Rett syndrome. Resemblances between the SMC1A group and the NIPBL group suggest that a disturbed cohesin function contributes to the phenotype, but differences between these groups may also be explained by other underlying mechanisms such as moonlighting of the cohesin genes.