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Autism spectrum disorder (ASD) is a neurodevelopmental disorder (NDD) that affects approximately 4% of males and 1% of females in the United States. While causes of ASD are multi-factorial, single rare genetic variants contribute to around 20% of cases. Here, we report a case series of seven unrelated probands (6 males, 1 female) with ASD or another variable NDD phenotype attributed to de novo heterozygous loss of function or missense variants in the gene LARP1 (La ribonucleoprotein 1). LARP1 encodes an RNA-binding protein that post-transcriptionally regulates the stability and translation of thousands of mRNAs, including those regulating cellular metabolism and metabolic plasticity. Using lymphocytes collected and immortalized from an index proband who carries a truncating variant in one allele of LARP1, we demonstrated that lower cellular levels of LARP1 protein cause reduced rates of aerobic respiration and glycolysis. As expression of LARP1 increases during neurodevelopment, with higher levels in neurons and astrocytes, we propose that LARP1 haploinsufficiency contributes to ASD or related NDDs through attenuated metabolic activity in the developing fetal brain.

Summary: Autism spectrum disorder (ASD) is a neurodevelopmental disorder (NDD) that affects approximately 4% of males and 1% of females in the United States. While causes of ASD are multi-factorial, single rare genetic variants contribute to around 20% of cases. Here, we report a case series of seven unrelated probands (6 males, 1 female) with ASD or another variable NDD phenotype attributed to de novo heterozygous loss of function or missense variants in the gene LARP1 (La ribonucleoprotein 1). LARP1 encodes an RNA-binding protein that post-transcriptionally regulates the stability and translation of thousands of mRNAs, including those regulating cellular metabolism and metabolic plasticity. Using lymphocytes collected and immortalized from an index proband who carries a truncating variant in one allele of LARP1, we demonstrated that lower cellular levels of LARP1 protein cause reduced rates of aerobic respiration and glycolysis. As expression of LARP1 increases during neurodevelopment, with higher levels in neurons and astrocytes, we propose that LARP1 haploinsufficiency contributes to ASD or related NDDs through attenuated metabolic activity in the developing fetal brain.

Abstract Background Neurodevelopmental disorders (NDDs) are disabilities in brain functioning that cause impairments in cognition, communication, behavior, and sometimes motor skills. The goal of this study was to measure burnout and anxiety among parents of children with neurodevelopmental disorders compared to parents of children with typical development in Saudi Arabia. Results Four hundred twenty-five parents of healthy and parents of children with NDDs, including attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and intellectual disability (ID), and their parents. Parents of children with NDD had more anxiety and burnout relative to parents of typically developing children, and parents of children with ADHD experienced higher levels of anxiety and depression than parents of children with ASD or ID. Conclusion Parents of children with various neurodevelopmental disorders face a greater degree of psychological distress than parents of typically developing children. Parents of children with NDDs should be provided with interventions and resources to reduce stress and enhance their standard of living.

Background: Neurodevelopmental disorders (NDDs) are disabilities in brain functioning that cause impairments in cognition, communication, behavior, and sometimes motor skills. The goal of this study was to measure burnout and anxiety among parents of children with neurodevelopmental disorders compared to parents of children with typical development in Saudi Arabia. Results: Four hundred twenty-five parents of healthy and parents of children with NDDs, including attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and intellectual disability (ID), and their parents. Parents of children with NDD had more anxiety and burnout relative to parents of typically developing children, and parents of children with ADHD experienced higher levels of anxiety and depression than parents of children with ASD or ID. Conclusion: Parents of children with various neurodevelopmental disorders face a greater degree of psychological distress than parents of typically developing children. Parents of children with NDDs should be provided with interventions and resources to reduce stress and enhance their standard of living. [ABSTRACT FROM AUTHOR]

Several studies have supported the association between maternal immune activation (MIA) caused by exposure to pathogens or inflammation during critical periods of gestation and an increased susceptibility to the development of various psychiatric and neurological disorders, including autism and other neurodevelopmental disorders (NDDs), in the offspring. In the present work, we aimed to provide extensive characterization of the short- and long-term consequences of MIA in the offspring, both at the behavioral and immunological level. To this end, we exposed Wistar rat dams to Lipopolysaccharide and tested the infant, adolescent and adult offspring across several behavioral domains relevant to human psychopathological traits. Furthermore, we also measured plasmatic inflammatory markers both at adolescence and adulthood. Our results support the hypothesis of a deleterious impact of MIA on the neurobehavioral development of the offspring: we found deficits in the communicative, social and cognitive domains, together with stereotypic-like behaviors and an altered inflammatory profile at the systemic level. Although the precise mechanisms underlying the role of neuroinflammatory states in neurodevelopment need to be clarified, this study contributes to a better understanding of the impact of MIA on the risk of developing behavioral deficits and psychiatric illness in the offspring. [ABSTRACT FROM AUTHOR]

Abstract Introduction The current COVID-19 pandemic interferes with family lives across the world, particularly families of children with neurodevelopmental disorders (NDDs) are at a greater risk for being negatively impacted by the pandemic. Together with representatives from this caregiver population the aim was to explore the interference associated with normal family life caused by the COVID-19 pandemic. Method This is a descriptive study using a cross-sectional design. Following a strategic network sampling strategy, a user-developed national survey was completed by a larger sample (N = 1,186) of parents and informal caregivers of children with NDDs. The survey utilized a combination of both closed and open-ended questions, and a logistic regression analysis was carried out to assess the association between family characteristics, characteristics of the child, and COVID-19 related family life interference. Before carrying out the regression an inductive content analysis of the open-ended question on `How has the isolation affected the family´ was carried out to construct the outcome variable. Results The initial analysis indicated that the COVID-19 pandemic induced a shift in everyday family life and a lack of guidance and support related to managing the challenges they were facing. Caregivers who reported that COVID-19 had significantly interfered with their family life, were more likely to report having anxious children, and to have experienced an increased number of conflicts at home. The logistic regression showed that both anxious children and increased conflicts considerably increased the risk for reporting family life interference compared to those that reported no increased conflicts or anxious children. Discussion Considering how the COVID-19 related increased conflicts at home and anxious children threaten the family life of the NDD caregiver population, as an external source of family stress, which might lead to negative impact on their mental and physical well-being, the need for further research in collaboration with user representatives is apparent. Our study suggests that more information should be provided to healthcare providers, social professionals, peers, people with NDDs, and caregivers of people with NDDs about the potential threats that a stressful life event such as the current pandemic can pose to their mental and physical health and their family life.

Robotics has made it possible to change and improve many support processes for vulnerable people in different settings. In recent years, its use has been oriented toward supporting therapeutic interventions of neurodevelopmental disorders (NDD), including attention deficit hyperactivity disorder (ADHD). This review of the literature highlights how advances in robotics have evolved in different scenarios of ADHD treatment, its collaboration with other emerging technologies, its results, its limitations, and the research challenges for the future development of robotics in the field of supporting children with ADHD. The authors conducted a literature review based on the location of keywords ‘robotics’ and several NNDs such as ‘ADHD’, ’Autism Spectrum Disorder (ASD)’, ‘cerebral palsy’, and ‘dementia’ in titles, abstracts, and introduction of scientific articles in the Scopus and Web of Science (WoS) database. The reviewed literature was classified according to the type of therapy supported by the robots, the type of robot and the associated technologies. From this analysis, we can solve the research question: Which types of robots have the potential for specific applications in ADHD treatment? Furthermore, this article shows that despite favorable technical results, robotic technologies that support ADHD therapies require significant improvements in terms of scalability, human-machine interaction, and treatment and processing of acquired information to be applied effectively in real-world therapies. The most significant research challenges are proposed to drive research efforts to develop new approaches to enable robotic assistants to participate in ADHD therapies.

Introduction: The current COVID-19 pandemic interferes with family lives across the world, particularly families of children with neurodevelopmental disorders (NDDs) are at a greater risk for being negatively impacted by the pandemic. Together with representatives from this caregiver population the aim was to explore the interference associated with normal family life caused by the COVID-19 pandemic.Method: This is a descriptive study using a cross-sectional design. Following a strategic network sampling strategy, a user-developed national survey was completed by a larger sample (N = 1,186) of parents and informal caregivers of children with NDDs. The survey utilized a combination of both closed and open-ended questions, and a logistic regression analysis was carried out to assess the association between family characteristics, characteristics of the child, and COVID-19 related family life interference. Before carrying out the regression an inductive content analysis of the open-ended question on `How has the isolation affected the family´ was carried out to construct the outcome variable.Results: The initial analysis indicated that the COVID-19 pandemic induced a shift in everyday family life and a lack of guidance and support related to managing the challenges they were facing. Caregivers who reported that COVID-19 had significantly interfered with their family life, were more likely to report having anxious children, and to have experienced an increased number of conflicts at home. The logistic regression showed that both anxious children and increased conflicts considerably increased the risk for reporting family life interference compared to those that reported no increased conflicts or anxious children.Discussion: Considering how the COVID-19 related increased conflicts at home and anxious children threaten the family life of the NDD caregiver population, as an external source of family stress, which might lead to negative impact on their mental and physical well-being, the need for further research in collaboration with user representatives is apparent. Our study suggests that more information should be provided to healthcare providers, social professionals, peers, people with NDDs, and caregivers of people with NDDs about the potential threats that a stressful life event such as the current pandemic can pose to their mental and physical health and their family life. [ABSTRACT FROM AUTHOR]

Phenotypic heterogeneity in monogenic neurodevelopmental disorders can arise from differential severity of variants underlying disease, but how distinct alleles drive variable disease presentation is not well understood. Here, we investigate missense mutations in DNA methyltransferase 3A (DNMT3A), a DNA methyltransferase associated with overgrowth, intellectual disability, and autism, to uncover molecular correlates of phenotypic heterogeneity. We generate a Dnmt3a P900L/+ mouse mimicking a mutation with mild to moderate severity and compare phenotypic and epigenomic effects with a severe R878H mutation. P900L mutants exhibit core growth and behavioral phenotypes shared across models but show subtle epigenomic changes, while R878H mutants display extensive disruptions. We identify mutation-specific dysregulated genes that may contribute to variable disease severity. Shared transcriptomic disruption identified across mutations overlaps dysregulation observed in other developmental disorder models and likely drives common phenotypes. Together, our findings define central drivers of DNMT3A disorders and illustrate how variable epigenomic disruption contributes to phenotypic heterogeneity in neurodevelopmental disease. [Display omitted] • DNMT3A mutant phenotypes correlate with epigenomic and transcriptomic disruption • Analyzing multiple DNMT3A mutations reveals core disease-relevant genomic effects • DNMT3A mutants show concordant gene dysregulation with Rett and Sotos syndrome mice Beard et al. characterize a DNMT3A mutant mouse carrying a moderate severity mutation, comparing it with a severe mutation to uncover epigenomic and transcriptional drivers of phenotypic variability. They utilize these mice to identify DNA-methylation-dependent enhancer dysfunction, gene expression changes, and concordant gene dysregulation with other neurodevelopmental disorder models. [ABSTRACT FROM AUTHOR]