And/or Autism Spectrum Disorder Research Articles

Whole Exome Sequencing and Panel-Based Analysis in 176 Spanish Children with Neurodevelopmental Disorders: Focus on Autism Spectrum Disorder and/or Intellectual Disability/Global Developmental Delay

Background: Neurodevelopmental disorders (NDDs) represent a significant challenge in pediatric genetics, often requiring advanced diagnostic tools for the accurate identification of genetic variants. Objectives: To determine the diagnostic yield of whole exome sequencing (WES) with targeted gene panels in children with neurodevelopmental disorders (NDDs). Methods: This observational, prospective study included a total of 176 Spanish-speaking pediatric patients with neurodevelopmental disorders (NDDs), encompassing intellectual disability (ID), global developmental delay (GDD), and/or autism spectrum disorder (ASD). Participants were recruited from January 2019 to January 2023 at a University Hospital in Madrid, Spain. Clinical and sociodemographic variables were recorded, along with genetic study results. The age range of the subjects was 9 months to 16 years, and the percentage of males was 72.1%. The diagnostic yield of whole exome sequencing (WES) was calculated both before and after parental testing via Sanger DNA sequencing. Results: The study included 176 children: 67 (38.1%) with ID, 62 (35.2%) with ASD, and 47 (26.7%) with ASD + ID. The diagnostic yield of proband-only exome sequencing was 12.5% (22/176). By group, the diagnostic yield of proband-only exome sequencing was 3.2% in the ASD, 12.7% in the ASD + ID, and 20.8% in the ID group. Variants of uncertain significance (VUS) were found in 39.8% (70/176). After parental testing, some variants were reclassified as “likely pathogenic”, increasing the diagnostic yield by 4.6%, with an overall diagnostic yield of 17.1%. Diagnostic yield was higher in patients with syndromic ID (70.6%% vs. 29.4%; p = 0.036). Conclusions: A sequential approach utilizing WES followed by panel-based analysis, starting with the index case and, when appropriate, including the parents, proves to be a cost-effective strategy. WES is particularly suitable for complex conditions, as it allows for the identification of potentially causative genes beyond those covered by targeted panels, providing a more comprehensive analysis. Including parental testing enhances the diagnostic yield and improves accuracy, especially in cases with variants of uncertain significance (VUS), thereby advancing our understanding of NDDs.

Homelessness—The perspectives of people with intellectual disability and/or Autistic spectrum disorder and their families

AbstractPeople with intellectual disability (ID) and/or autism spectrum disorder (ASD) are over‐represented in the homelessness population. A lack of available and suitable social housing leads to an over‐reliance on a private rental market where high rents are prevalent. Yet, people with ID and/or ASD, are more at risk of living in poverty and as such excluded from the private rental market. The current study reports on the lived experience of homelessness for a sample of people with ID and/or ASD and families supporting adult /children with ID/ASD. Their stories illuminate the complexity and challenges in securing a stable, safe and secure home.

A cohort study of neurodevelopmental disorders and/or congenital anomalies using high resolution chromosomal microarrays in southern Brazil highlighting the significance of ASD

Chromosomal microarray (CMA) is the reference in evaluation of copy number variations (CNVs) in individuals with neurodevelopmental disorders (NDDs), such as intellectual disability (ID) and/or autism spectrum disorder (ASD), which affect around 3–4% of the world’s population. Modern platforms for CMA, also include probes for single nucleotide polymorphisms (SNPs) that detect homozygous regions in the genome, such as long contiguous stretches of homozygosity (LCSH). These regions result from complete or segmental chromosomal homozygosis and may be indicative of uniparental disomy (UPD), inbreeding, population characteristics, as well as replicative DNA repair events. In this retrospective study, we analyzed CMA reading files requested by geneticists and neurologists for diagnostic purposes along with available clinical data. Our objectives were interpreting CNVs and assess the frequencies and implications of LCSH detected by Affymetrix CytoScan HD (41%) or 750K (59%) platforms in 1012 patients from the south of Brazil. The patients were mainly children with NDDs and/or congenital anomalies (CAs). A total of 206 CNVs, comprising 132 deletions and 74 duplications, interpreted as pathogenic, were found in 17% of the patients in the cohort and across all chromosomes. Additionally, 12% presented rare variants of uncertain clinical significance, including LPCNVs, as the only clinically relevant CNV. Within the realm of NDDs, ASD carries a particular importance, owing to its escalating prevalence and its growing repercussions for individuals, families, and communities. ASD was one clinical phenotype, if not the main reason for referral to testing, for about one-third of the cohort, and these patients were further analyzed as a sub-cohort. Considering only the patients with ASD, the diagnostic rate was 10%, within the range reported in the literature (8–21%). It was higher (16%) when associated with dysmorphic features and lower (7%) for "isolated" ASD (without ID and without dysmorphic features). In 953 CMAs of the whole cohort, LCSH (≥ 3 Mbp) were analyzed not only for their potential pathogenic significance but were also explored to identify common LCSH in the South Brazilians population. CMA revealed at least one LCSH in 91% of the patients. For about 11.5% of patients, the LCSH suggested consanguinity from the first to the fifth degree, with a greater probability of clinical impact, and in 2.8%, they revealed a putative UPD. LCSH found at a frequency of 5% or more were considered common LCSH in the general population, allowing us to delineate 10 regions as potentially representing ancestral haplotypes of neglectable clinical significance. The main referrals for CMA were developmental delay (56%), ID (33%), ASD (33%) and syndromic features (56%). Some phenotypes in this population may be predictive of a higher probability of indicating a carrier of a pathogenic CNV. Here, we present the largest report of CMA data in a cohort with NDDs and/or CAs from the South of Brazil. We characterize the rare CNVs found along with the main phenotypes presented by each patient and show the importance and usefulness of LCSH interpretation in CMA results that incorporate SNPs, as well as we illustrate the value of CMA to investigate CNV in ASD.

Can a nation-wide e-cohort of ADHD and ASD in childhood be established using Welsh routinely available datasets?

ObjectivesWe investigated the feasibility and validity of establishing a nationwide e-cohort of individuals with a diagnosis of attention deficit hyperactivity disorder (ADHD) and/or autism spectrum disorder (ASD) for future longitudinal...

Teachers’ relational competence: perceptions of teachers and students with and without ADHD and ASD

ABSTRACT This study examined whether teachers’ professional development of their relational competence with students with attention deficit hyperactivity disorder (ADHD) and/or autism spectrum disorder (ASD) modifies teachers’ and students’ perceptions of their teacher-student relationships (TSR). Participants comprised teachers (n = 33) and students (n = 232) from two elementary schools: one intervention school (InS) and one control school (CoS). InS teachers reported significant TSR improvements, regardless of student group or gender (p = .03). Among InS students, significant results were driven by female neurodiverse (ND) students and neurotypical (NT) male students (p = .03). Nevertheless, positive effects were solely observed among ND female students, while NT male students, conversely, reported decreased TSR during follow-up tests. No significant effects were found at the CoS irrespective of teacher or student ratings. The findings suggest that enhancing teachers’ understanding of relational competence concerning ND students will not only improve their own perceptions of their TSR but also those of ND female students. Nonetheless, directing teachers’ focus towards one student group (ND students) risks diminishing teachers’ attention towards other student groups, potentially explaining the poorer follow-up results among NT boys. The finding warrants further investigation, as it indicates a challenge for teachers to establish sufficient relational engagement with all students.

The Effects of the Exercise Intervention on Fundamental Movement Skills in Children with Attention Deficit Hyperactivity Disorder and/or Autism Spectrum Disorder: A Meta-Analysis

To explore the effect of exercise intervention on fundamental movement skills (FMS) of children with attention deficit hyperactivity disorder (ADHD) and/or autism spectrum disorder (ASD). Following the principle of PICOS, randomized controlled trials of the effect of exercise intervention on the FMS of ADHD/ASD children were searched. A total of 12 articles and 396 participants were included. Review Manager5.4 and Stata16.0 software were used to process and analyze the data. The results revealed that (1) exercise intervention can improve the gross motor skills of children with ADHD/ASD (p < 0.00001). Aquatic therapy (SMD = 56.54, 95% CI = 38.83–74.25) has a better effect on stability skills, and FMS intervention (SMD = 17.58, 95% CI = 1.78–33.38) has a better effect on locomotor skills and object control skills. (2) Exercise intervention can improve the fine motor skills of children with ADHD/ASD (p = 0.001). Table tennis exercise (SMD = 9.91, 95% CI = 0.23–19.59) and horse-riding program (SMD = 9.50, 95% CI = 5.20–13.80) have better effects on fine manual control and hand–eye coordination. (3) The closed-skill intervention for 60 min each time, twice a week, for at least 12 weeks had the best effect on the improvement in the FMS in children with ADHD/ASD (p < 0.00001). Exercise intervention may effectively improve FMS in children with ADHD/ASD. Intervention form, time, frequency, and duration are important moderator variables that positively impact the FMS of children with ADHD/ASD.

Understanding the Impact of Home Confinement on Children and Young People with ADHD and ASD During the COVID-19 Pandemic

To understand whether the mental health of children and young people (CYP) with and without attention-deficit/hyperactivity disorder (ADHD) and/or autism spectrum disorder (ASD) were differentially affected by COVID-19. We analysed data (n = 6507) from the Co-Space study, a UK web-based longitudinal survey. CYP with ADHD (n = 160;2.5%), ASD (n = 465;7%), and ADHD + ASD (n = 155;2.4%) were compared with a reference group (n = 5727;88%) using parent-completed questionnaires [Strengths and Difficulties Questionnaire (SDQ) & Pandemic Anxiety Scale (PAS)]. Baseline to 1-month follow-up differences were compared using linear regression models. CYP with ADHD and/or ASD had higher scores at baseline than other CYP. At follow-up, CYP with ASD showed small but significant improvements in symptoms (SDQ), compared with the reference group. CYP with ASD experienced a worsening of disease anxiety (PAS) and CYP with ADHD a deterioration in functional impairment. These findings indicate a mixed pattern of pandemic-related impact for CYP with ADHD and/or ASD.

Sexting experiences and motivations among adolescents with ADHD and ASD

Sexting (i.e., to send and receive self-produced sexual materials) has become a common element in adolescents’ socio-sexual exploration. Although often harmless, sexting also involves the risk of abuse, and potentially more so for some adolescents than for others. Adolescents with attention deficit disorder (ADHD) and/or autism spectrum disorder (ASD) have been pointed out as potentially more vulnerable online, yet research to support or reject these concerns is sparse. Focusing on sending sexts, this study compares sexting rates, sexting experiences, and sexting motivations of Swedish adolescents with ADHD and/or ASD to adolescents without these diagnoses. In all, 1063 adolescents (aged 15 to 19), 164 of whom self-reported ADHD and/or ASD, completed a survey about their sexting experiences. The results revealed both differences and similarities between groups. Adolescents with ADHD sexted more and reported more pressure to sext. No group differences were noted in terms of reporting positive or negative experiences. Sexting motivations were also similar between groups, although sexting for aggravated reasons was more common among adolescents with ADHD and/or ASD. Our findings suggest that adolescents with ADHD and ASD mainly use sexting for sexual gratification and exploration, but also report experiences and motivations that may indicate increased vulnerability in relation to sexting.

Career Intent Factors of Special Education Teachers Serving Students With Intellectual Disability, Developmental Delay, and Autism Spectrum Disorder

AbstractLimited research exists on special education teachers (SETs) of students with intellectual disability (ID), developmental delay (DD), and/or autism spectrum disorder (ASD), their intent to leave or stay in the teaching profession, and the working conditions impacting those decisions. Through an online survey, we investigated working conditions of SETs who teach students with ID, DD, and ASD and their career intent, with attention to teacher demographic characteristics. Our investigation (n = 564) found Black/African American, Asian, Hawaiian/Pacific Islander SETs of students with ID, DD, or ASD reported higher intent to leave, as well as male SETs, compared to White SETs. Other differences are reported between groups. Results emphasize a need to focus on ways to retain SETs from underrepresented groups. Implications for practice and research related to working conditions are discussed.

Language and Communication Deficits in Chromosome 16p11.2 Deletion Syndrome.

Chromosome 16p11.2 deletion syndrome (OMIM #611913) is a rare genetic condition resulting from the partial deletion of approximately 35 genes located at Chromosome 16. Affected people exhibit a variable clinical profile, featuring mild dysmorphisms, motor problems, developmental delay, mild intellectual disability (ID), socialization deficits and/or autism spectrum disorder (ASD) traits, and problems with language. Specifically, a precise characterization of the speech, language, and communication (dis)abilities of people with this condition is still pending. We used standardized tests and samples of naturalistic speech to provide a longitudinal profile of the speech, language, and communication problems of a boy with Chromosome 16p11.2 deletion syndrome and without ID or ASD. The proband shows impaired expressive abilities as well as problems with receptive language, dysprosody, and ASD-like communication deficits, such as impaired interactive skills, perseverative verbal behavior, overabundance of tangential responses, and lack of metapragmatic awareness and communicative use of gaze, meeting the criteria for social pragmatic communication disorder. Our results support the view that language and communication impairment should be regarded as one core symptom of Chromosome 16p11.2 deletion syndrome, even without a diagnosis of ASD or ID. Clinical implications of our results, with a focus on therapeutic interventions for children with 16p11.2 deletion syndrome and no ASD or ID, are also discussed. https://doi.org/10.23641/asha.21561714.

Pharmacological management of psychopathology in people with intellectual disabilities and/or autism spectrum disorder

SUMMARYOn average, 49–63% of people with intellectual disabilities and/or autism spectrum disorder (ASD) are prescribed psychotropic medications to treat psychopathology, including psychiatric illness, behaviours that challenge and the core symptoms and associated behaviours of these developmental disorders. In many cases, psychotropics, particularly antipsychotics, are used off-label without a proper indication, particularly to manage behaviours that challenge. The RCTs show moderate evidence supporting the efficacy of low-dose risperidone and some preliminary evidence for aripiprazole in treating behaviours that challenge among children with ASD and/or intellectual disabilities. The RCT-based evidence for the other psychotropics is equivocal, so no definitive conclusions can be made on their efficacy. Polypharmacy and the use of high doses of antipsychotics are prevalent in this population, leading to the risk of adverse events and drug–drug interactions. Despite various national and international guidelines, and government initiatives encouraging reduced psychotropic use, there is little evidence of this happening; on the contrary, the use of antidepressants, mood stabilisers and benzodiazepines may be increasing. A concerted multi-agency effort is urgently needed to address this significant public health concern of the overmedication of people with intellectual disabilities and/or ASD.

Recruiting and exploring vulnerabilities among young people at risk, or in the early stages of serious mental illness (borderline personality disorder and first episode psychosis).

IntroductionMany gaps exist in our understanding of the developmental pathways to severe mental illness (SMI), including borderline personality disorder (BPD) and psychosis. However, those who have experienced adverse childhood experiences (ACEs) are at an increased risk and there is evidence to suggest that one of the earliest markers is emotional dysregulation. An area which has received relatively less research attention is the role neurodevelopmental disorders (NDDs) play. The aim of this feasibility study was therefore to explore the clinical profiles of young people early in the course of SMI, including their profiles of ACEs, emotional regulation difficulties, borderline personality traits and NDDs.MethodsA cross-sectional study of young people (aged 15–25) at risk of SMI, currently being seen within NHS mental health services, was conducted. This included those with early symptoms of psychosis and/or BPD as assessed by diagnostic interview. Eligible participants self-completed a battery of sociodemographic, clinical, and psychological measures in the company of a researcher. This included assessments of: symptoms of NDDs; borderline pathology traits; ACEs; and difficulties in emotional regulation. Statistical analyses included Mann–Whitney U tests and multiple regression.ResultsOf the 118 potentially eligible participants who were referred, 48 were ultimately included in the study. Young people early in the course of SMI reported a high prevalence of ACEs and deficits in emotional regulation. In total, 79% met criteria for attention deficit hyperactivity disorder (ADHD) and/or autism spectrum disorder (ASD). Emotional dysregulation was found to significantly mediate the association between both ACEs and the frequency of NDDs and borderline personality traits, however given the small sample size these results are preliminary in nature.ConclusionYoung people early in the course of SMI are at an increased risk of experiencing multiple childhood adversities and our results indicate a high prevalence of NDDs amongst them. Emotional dysregulation emerged as a potentially significant early marker of future clinical severity. We suggest that the clinical implications of our findings include routine screening for NDDs and ACEs and an increased recognition of the significance of emotional dysregulation. However, larger scale longitudinal studies are needed to investigate these preliminary findings further.

Maternal Western-style diet reduces social engagement and increases idiosyncratic behavior in Japanese macaque offspring

Recent evidence in humans and animals indicates an association between maternal obesity and offspring behavioral outcomes. In humans, increased maternal body mass index has been linked to an increased risk of children receiving a diagnosis of early-emerging neurodevelopmental disorders such as Attention Deficit/Hyperactivity Disorder (ADHD) and/or Autism Spectrum Disorder (ASD). However, a limited number of preclinical studies have examined associations between maternal Western-Style Diet (mWSD) exposure and offspring social behavior. To our knowledge, this is the first study to investigate relationships between mWSD exposure and social behavior in non-human primates. Since aberrant social behavior is a diagnostic criterion for several neurodevelopmental disorders, the current study focuses on examining the influence of maternal nutrition and metabolic state on offspring social behavior in Japanese macaques (Macaca fuscata). We found that mWSD offspring initiated less affiliative social behaviors as well as proximity to a peer. Using path analysis, we found that the association between mWSD consumption and reduced offspring social engagement was statistically mediated by increased maternal interleukin (IL)-12 during the third trimester of pregnancy. Additionally, mWSD offspring displayed increased idiosyncratic behavior, which was related to alterations in maternal adiposity and leptin in the third trimester. Together, these results suggest that NHP offspring exposed to mWSD exhibit behavioral phenotypes similar to what is described in some early-emerging neurodevelopmental disorders. These results provide evidence that mWSD exposure during gestation may be linked to increased risk of neurodevelopmental disorders and provides targets for prevention and intervention efforts.

Dental procedures in children with or without intellectual disability and autism spectrum disorder in a hospital setting.

This population-based cohort study investigated dental procedures in the hospital setting in Western Australian children with or without intellectual disability (ID) and/or autism spectrum disorder (ASD) aged up to 18 years. Considering previously reported disparities in dental disease between Indigenous and non-Indigenous Australian children, this study also investigated the effect of Indigenous status on dental procedures. Data on Western Australian live births from 1983 to 2010 from the Midwives Notification System were linked to the Intellectual Disability Exploring Answers database and the Hospital Morbidity Data collection. Primary admissions for relevant dental diagnoses were identified, and treatment procedures for dental hospitalization were investigated. Descriptive statistics and Pearson's chi-squared test of independence were used for analysis. Overall, 76 065 episodes of dental hospitalization were recorded. Amongst children with ID and/or ASD, Indigenous children experienced more extractions and fewer restorations (68.7% and 16.2%) compared to non-Indigenous children (51.5% and 25.9%). After 6 years, extraction occurred less often in children with ID and/or ASD than in those without, where most surgical dental extractions were in the age group of 13-18 years. This study indicates a need for further improvements in access to dental services and the quality of care provided in hospitals for children with ID/ASD. There is also concern that more vulnerable Indigenous and all disadvantaged children are receiving an inadequate level of dental services resulting in more emergency dental hospitalization and invasive treatment.

Working memory training in children with borderline intellectual functioning and neuropsychiatric disorders: a triple-blind randomised controlled trial.

BackgroundPoor working memory, lower IQ and maladaptive behaviour form a triple disability known to have negative effects on the academic and social development of children with borderline intellectual functioning (BIF; IQ: 70 < IQ < 85) and neuropsychiatric disorders [attention‐deficit hyperactivity disorder (ADHD) and/or autism spectrum disorder (ASD)]. Treatment possibilities for these children are scarce and hardly evidence based. This study primarily investigated whether adaptive computerised working memory training (WMT) may lead to significantly more improvement on a non‐trained visuospatial WM task compared with a non‐adaptive control WMT (placebo) in children with BIF and neuropsychiatric disorders. As secondary outcome measures, we used the scores on several non‐trained neuropsychological near‐transfer and far‐transfer tasks as well as behavioural measures.MethodWe conducted a triple‐blind placebo‐controlled randomised clinical trial in 72 children (aged 10;0–13;11 years, 53 boys, 19 girls) with BIF and comorbid neuropsychiatric disorders (ADHD = 37, ASD = 21, both = 14) that were referred to child and adolescent psychiatry care, between May 2012 and March 2019. Children completed the Dutch version of Cogmed WMT, either the adaptive training version or the non‐adaptive placebo version, 25 sessions (30–45 min a day), for 5 weeks. The primary outcome measure was the score on a non‐trained visuospatial working memory task. The primary outcome was measured before and directly after 5 weeks of WMT and again 6 months after training.ResultsA total of 375 children were screened for eligibility and 72 were randomised. No significantly higher levels of improvement over time were found on our primary outcome measure in the experimental WMT group compared with the placebo control WMT, nor in the secondary (near‐transfer and far‐transfer tasks) or tertiary (behavioural measures) outcome measures. However, this study did show changes over time for these measurements for both the experimental and placebo conditions.ConclusionsThis study was unable to document superior training effects over time of an adaptive WMT in children with BIF and neuropsychiatric disorders, compared with a placebo (non‐adaptive) WMT. The objectively documented changes over time in the non‐adaptive WMT arm suggest that these children with persistent impairments in WM may benefit from a structured learning environment that is associated with improvement of neurocognitive functioning and coping strategies. Further research is needed to examine which elements of cognitive training may be useful for which specific patients and to study long‐term effects of training.

Factors associated with dental hospitalisations in children with intellectual disability or autism spectrum disorder: a Western Australian population-based retrospective cohort study

Purpose This study investigated dental hospitalisations in Western Australian (WA) children with intellectual disability (ID) and/or autism spectrum disorder (ASD) aged up to 18 years. Methods Data on WA live births from 1983 to 2004 from the WA Midwives Notification System were linked to the Intellectual Disability Exploring Answers database, the WA Hospital Morbidity Data System, and the Western Australian Birth Defects Registry databases. Children were followed from birth to 2010 and the data grouped into three age-groups. Primary and secondary admissions for relevant dental diagnoses were identified and factors associated with having a dental hospitalisation investigated. Results There were 1366, 1596, and 780 dental hospitalisations amongst 1122, 1154, and 609 children with ID and/or ASD in the 0–6, >6–12, and >12–18 year age groups, respectively. Children with severe ID were much more likely to be hospitalised than those with mild/moderate ID. More socioeconomically disadvantaged children were less likely to be hospitalised than children whose parents were socially advantaged. Conclusions There is concern that more vulnerable children in the WA community with ID or ASD are receiving an inadequate level of dental services compared with other groups resulting in potentially preventable hospitalisations, a situation in need of urgent remediation. Implications for rehabilitation Little is known about why some children with intellectual disability (ID) or autism are being hospitalised for their dental care and others are not. Children with disability whose families are socioeconomically disadvantaged should have equivalent opportunity to receive optimal dental care. Dental practitioners at all levels need training and confidence in treating children with ID.

Using electronic clinical records to investigate service use and in-patient care of adults with intellectual disability and/or autism spectrum disorder

AimsTo describe characteristics of adults with intellectual disability (ID) and/or autism spectrum disorder (ASD) accessing care in one mental health Trust.To explore factors associated with in-patient admission/risk of re-admission within 12 months of discharge.BackgroundThere is concern that adults with intellectual disability and those with autism spectrum disorder are frequently admitted to mental health hospitals. The evidence from NHS datasets suggests that this remains a significant issue and is associated with personal, social and economic costs.MethodAdults (≥ 18 years) with ICD-10 diagnosis of “mental retardation” and/or autism who had accessed care in the Camden and Islington Foundation Trust were identified using the Clinical Record Interactive Search (CRIS). The identification process was validated through cross checking of free text in the electronic clinical notes. We compared demographic and clinical characteristics and service use, including length of admission, of 315 individuals with ASD and 339 with ID (with or without ASD). Logistic regression was used to explore factors associated with in-patient admission and re-admission within 12 months of discharge.ResultA greater proportion of adults with ID (with or without ASD) had a diagnosis of psychosis, substance misuse, or dementia whereas diagnosis of anxiety disorder was greater in those with ASD. Antipsychotics and other psychotropics were twice as likely to be prescribed for the ID ± group. Admission to psychiatric in-patient care was greater in those with ID ± ASD (adjusted OR 4.00, 95% confidence interval (CI) 2.41-6.63), men (aOR 2.28, 95%CI 1.39-3.75), younger adults (aOR 0.98, 95%CI 0.97-1.00), and in those with a diagnosis of schizophrenia spectrum disorder (aOR 5.08, 95%CI 3.00-8.61), affective disorder (aOR 2.23, 95%CI 1.29-3.83), personality disorder (aOR 1.94, 95%CI 1.02-3.68), and record of previous inpatient admission (aOR 2.18, 95%CI 1.17-4.05). Having ASD alone was associated with a greater risk of re-admission within one year of discharge, although this difference was not statistically significant (aOR 0.70, 95% CI 0.32-1.52). Comorbid diagnoses of affective disorder or personality disorder were the only significant associations with re-admission (aOR 3.11, 95%CI 1.34-7.23 and aOR 8.28, 95%CI 2.85-24.04, respectively).ConclusionThese findings provide the first longitudinal investigation into the acute care pathway for adults with ID and/or ASD in the NHS. Replication in other trusts is now needed to inform “at risk of admission” registers and guide targeted interventions to prevent admission.

Novel missense mutations in PTCHD1 alter its plasma membrane subcellular localization and cause intellectual disability and autism spectrum disorder.

The X‐linked PTCHD1 gene, encoding a synaptic membrane protein, has been involved in neurodevelopmental disorders with the description of deleterious genomic microdeletions or truncating coding mutations. Missense variants were also identified, however, without any functional evidence supporting their pathogenicity level. We investigated 13 missense variants of PTCHD1, including eight previously described (c.152G>A,p.(Ser51Asn); c.217C>T,p.(Leu73Phe); c.517A>G,p.(Ile173Val); c.542A>C,p.(Lys181Thr); c.583G>A,p.(Val195Ile); c.1076A>G,p.(His359Arg); c.1409C>A,p.(Ala470Asp); c.1436A>G,p.(Glu479Gly)), and five novel ones (c.95C>T,p.(Pro32Leu); c.95C>G,p.(Pro32Arg); c.638A>G,p.(Tyr213Cys); c.898G>C,p.(Gly300Arg); c.928G>C,p.(Ala310Pro)) identified in male patients with intellectual disability (ID) and/or autism spectrum disorder (ASD). Interestingly, several of these variants involve amino acids localized in structural domains such as transmembrane segments. To evaluate their potentially deleterious impact on PTCHD1 protein function, we performed in vitro overexpression experiments of the wild‐type and mutated forms of PTCHD1‐GFP in HEK 293T and in Neuro‐2a cell lines as well as in mouse hippocampal primary neuronal cultures. We found that six variants impaired the expression level of the PTCHD1 protein, and were retained in the endoplasmic reticulum suggesting abnormal protein folding. Our functional analyses thus provided evidence of the pathogenic impact of missense variants in PTCHD1, which reinforces the involvement of the PTCHD1 gene in ID and in ASD.

Quality of Life Changes during the COVID-19 Pandemic for Caregivers of Children with ADHD and/or ASD.

The COVID-19 pandemic has presented many challenges to caregivers of children. Families with children with attention-deficit/hyperactivity disorder (ADHD) and/or autism spectrum disorder (ASD) are an understudied but potentially vulnerable population to changes during the outbreak. As such, the aim of this study was to contrast quality of life for caregivers of children with ADHD and/or ASD, before and during the pandemic, compared to caregivers of neurotypical (NT) children. Total, Parent Health-Related Quality of Life, and Family Functioning Summary Scores from the Family Impact Module of the Pediatric Quality of Life InventoryTM were contrasted among caregivers of children with ADHD, ASD, comorbid ADHD and ASD, and NT development. For all scores, caregivers of ADHD and/or ASD children reported lower quality of life, both before and during the pandemic, in comparison to caregivers of NT children. For all diagnoses, quality of life decreased during the pandemic, but caregivers of children with ADHD and/or ASD reported a greater decrease in quality of life than caregivers for NT children. There are limitations to this study in terms of the composition of the sample and the survey methodology, but we are able to conclude that caregivers of children with ADHD and/or ASD have been disproportionately affected by the pandemic, and it is imperative that these families receive additional resources and support to improve their quality of life.

Melatonin Supplementation in Children: A Narrative Review of Indications, Safety, and Potential Long-Term Effects

Insomnia and sleep disturbance are common in children and adolescents. Parents and medical providers often wonder whether melatonin supplementation is a safe choice in these age groups. Small-scale studies suggest that long-term melatonin supplementation safely and effectively treats sleep onset insomnia in children with attention-deficit hyperactivity disorder (ADHD) and/or autism spectrum disorder (ASD). Documented side effects have been minimal and relatively benign. This paper is a brief review of the clinical indications, side effects, and potential long-term implications of supplementing melatonin in children.