Journal of Neurodevelopmental Disorders最新文献

{"title":"Common and rare variant analyses implicate late-infancy cerebellar development and immune genes in ADHD.","authors":"Yuanxin Zhong, Larry W Baum, Justin D Tubbs, Rui Ye, Lu Hua Chen, Tian Wu, Se-Fong Hung, Chun-Pan Tang, Ting-Pong Ho, Robert Moyzis, James Swanson, Chi-Chiu Lee, Pak C Sham, Patrick W L Leung","doi":"10.1186/s11689-025-09626-4","DOIUrl":"10.1186/s11689-025-09626-4","url":null,"abstract":"<p><strong>Objective: </strong>Attention-deficit hyperactivity disorder (ADHD) is a common neuropsychiatric disorder with a significant genetic component. The latest genome-wide association study (GWAS) meta-analysis of ADHD identified 27 whole-genome significant risk loci in the European population. However, genetic risk factors for ADHD are less well-characterized in the Asian population, especially for low-frequency / rare variants.</p><p><strong>Methods: </strong>In this study, we aimed to investigate the contributions of both common and low-frequency / rare variants to ADHD in a Hong Kong sample. Our sample comprised 279 cases and 432 controls who underwent genotyping using the Illumina Infinium Global Screening Array. We employed various analytical methods at different levels, while also leveraging multi-omics data and large-scale summary statistics to comprehensively analyze the genetic basis of ADHD.</p><p><strong>Results: </strong>We identified 41 potential genomic risk loci with a suggestive association (p < 1e^-4), pointing to 111 candidate risk genes, which were enriched for genes differentially expressed during late infancy brain development. Furthermore, tissue enrichment analysis implicated the involvement of the cerebellum. At the polygenic level, we also discovered a strong genetic correlation with resting-state functional MRI connectivity of the cerebellum involved in the attention/central executive and subcortical-cerebellum networks. In addition, an accumulation of ADHD common-variant risks found in European ancestry samples was found to be significantly associated with ADHD in the current study. In low-frequency / rare variant analyses, we discovered the correlations between ADHD and collapsing effects of rare damaging variants in TEP1, MTMR10, DBH, TBCC, and ANO1. Based on biological and functional profiles of the potential risk genes and gene sets, both common and low-frequency / rare variant analyses demonstrated that ADHD genetic risk was associated with immune processes.</p><p><strong>Conclusions: </strong>These findings re-validate the abnormal development of the neural system in ADHD and extend the existing neuro-dysfunction hypothesis to a multi-system perspective. The current study identified convergent risk factors from common and low-frequency / rare variants, which implicates vulnerability in late-infancy brain development, affecting especially the cerebellum, and the involvement of immune processes.</p>","PeriodicalId":16530,"journal":{"name":"Journal of Neurodevelopmental Disorders","volume":"17 1","pages":"34"},"PeriodicalIF":4.1,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12180188/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Developmental milestones and cognitive trajectories in school-aged children with 16p11.2 deletion.","authors":"Jente Verbesselt, Jeroen Breckpot, Inge Zink, Ann Swillen","doi":"10.1186/s11689-025-09615-7","DOIUrl":"10.1186/s11689-025-09615-7","url":null,"abstract":"<p><strong>Background: </strong>16p11.2 deletion syndrome (16p11.2DS) is a recurrent CNV that occurs de novo in approximately 70% of cases and confers risk for neurodevelopmental disorders, including intellectual disability (ID) and autism spectrum disorders (ASD). The current study focusses on developmental milestones, cognitive profiles and longitudinal cognitive trajectories.</p><p><strong>Methods: </strong>In-person assessments, digital medical records and parental interviews on developmental history of 24 children (5-16 years) with a confirmed BP4-BP5 16p11.2DS were reviewed and analysed for developmental milestones (motor, language, continence). Standardised intelligence tests were administered in all children, and longitudinal IQ-data were available for a subgroup (79%, 19/24).</p><p><strong>Results: </strong>Motor, language, and continence milestones were delayed. Average IQ was in the borderline range (IQ 71) with 46% (11/24) having borderline IQ (IQ 70-84). Both intra- and interindividual variability were found across the five cognitive domains with significant discrepancies between verbal and non-verbal skills in 55% (11/20). Longitudinal IQ-data indicate that school-aged children with 16p11.2DS perform statistically significantly lower at the second time point (p < 0.001) with 58% showing a growing into deficit trajectory.</p><p><strong>Conclusion: </strong>Delayed motor, language and continence milestones are common in 16p11.2DS carriers. School-aged children with 16p11.2DS show increasing cognitive impairments over time, pointing to the need for early diagnosis, regular cognitive follow-up and individualised intervention. The high prevalence of disharmonic IQ-profiles highlights the importance of expanding the focus beyond full-scale IQ (FSIQ) outcomes. Future studies in larger cohorts including carrier relatives are needed to gain more insight into the penetrance and phenotypic variability of 16p11.2DS.</p>","PeriodicalId":16530,"journal":{"name":"Journal of Neurodevelopmental Disorders","volume":"17 1","pages":"33"},"PeriodicalIF":4.1,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12178036/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neural excitation/inhibition imbalance and neurodevelopmental pathology in human copy number variant syndromes: a systematic review.","authors":"Amy L Sylvester, Eva Hensenne, Dimo Ivanov, Benedikt A Poser, David E J Linden, Thérèse van Amelsvoort, Claudia Vingerhoets","doi":"10.1186/s11689-025-09614-8","DOIUrl":"10.1186/s11689-025-09614-8","url":null,"abstract":"<p><p>Cumulative evidence suggests neurodevelopmental disorders are closely related. The risk of these disorders is increased by a series of copy number variant syndromes - phenotypically heterogeneous genetic disorders, present in a minority of the population. Recent models suggest that a disruption in the balance between excitatory and inhibitory neural activity may contribute to the aetiology of neurodevelopmental disorders, and may be additionally disturbed in copy number variant syndromes. In this systematic review, the databases PubMed, Embase, and Scopus were searched for studies of excitation/inhibition imbalance in relation to neurodevelopmental disorders in human copy number variant samples. A total of 53 studies were included, representing a variety of copy number variants and research methodologies. The resulting data suggests excitation/inhibition balance is indeed disrupted in different copy number variant populations, providing insight into a putative mechanism of both idiopathic and genetic neurodevelopmental disorders. However, the high level of heterogeneity in the data set, alongside emerging techniques for excitation/inhibition assessment, prompts further investigation of this field.</p>","PeriodicalId":16530,"journal":{"name":"Journal of Neurodevelopmental Disorders","volume":"17 1","pages":"31"},"PeriodicalIF":4.1,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12147258/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing the discriminatory power of polygenic scores for ADHD and autism in clinical and non-clinical samples.","authors":"James J Li, Quanfa He, Stephen Dorn, Zihang Wang, Qiongshi Lu","doi":"10.1186/s11689-025-09620-w","DOIUrl":"10.1186/s11689-025-09620-w","url":null,"abstract":"<p><strong>Background: </strong>Polygenic scores (PGS) are widely used in psychiatric genetic associations studies due to their predictive power for focal outcomes. However, they lack discriminatory power, in part due to the high degree of genetic overlap between psychiatric disorders. The lack of prediction specificity limits the clinical utility of psychiatric PGS, particularly for diagnostic applications. The goal of the study was to enhance the discriminatory power of psychiatric PGS for two highly comorbid and genetically correlated neurodevelopmental disorders in ADHD and autism spectrum disorder (ASD).</p><p><strong>Methods: </strong>Genomic structural equation modeling (GenomicSEM) was used to generate novel PGS for ADHD and ASD by accounting for the genetic overlap between these disorders (and eight others) to achieve greater discriminatory power in non-focal outcome predictions. PGS associations were tested in two large independent samples - the Philadelphia Neurodevelopmental Cohort (N = 4,789) and the Simons Foundation Powering Autism Research for Knowledge (SPARK) ASD and sibling controls (N = 5,045) cohort.</p><p><strong>Results: </strong>PGS from GenomicSEM achieved superior discriminatory power in terms of showing significantly attenuated associations with non-focal outcomes relative to traditionally computed PGS for these disorders. Additionally, genetic correlations between GenomicSEM PGS for ASD and ADHD were significantly attenuated in cross-trait associations with other psychiatric disorders and outcomes.</p><p><strong>Conclusions: </strong>Psychiatric PGS associations are likely inflated by the high degree of genetic overlap between the psychiatric disorders. Methods such as GenomicSEM can be used to refine PGS signals to be more disorder-specific, thereby enhancing their discriminatory power for future diagnostic applications.</p>","PeriodicalId":16530,"journal":{"name":"Journal of Neurodevelopmental Disorders","volume":"17 1","pages":"32"},"PeriodicalIF":4.1,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12150501/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Remote EEG acquisition in Angelman syndrome using PANDABox-EEG.","authors":"Kimberly Gálvez-Ortega, Roslyn Harold, Wei Siong Neo, Orlando S Hoilett, Amanda M Borosh, Alexa Friesen-Haarer, Stephanie Gombas, Dan Foti, Bridgette Kelleher","doi":"10.1186/s11689-025-09611-x","DOIUrl":"10.1186/s11689-025-09611-x","url":null,"abstract":"<p><strong>Objective: </strong>We describe the development and validation of PANDABox-EEG, a novel protocol for remote EEG assessment with no on-site technician, tailored for Angelman syndrome (AS). We argue that this protocol is reliable, valid, and widely acceptable for use in families affected by Angelman syndrome.</p><p><strong>Background: </strong>AS is a rare neurogenetic condition characterized by developmental delays, sleep problems, seizures, and a happy demeanor. People with AS are frequently monitored via EEG to inform clinical care, and EEG-measured delta activity has been proposed as a reliable biomarker to monitor treatment effectiveness. Traditional EEG assessments pose logistical and financial burdens for families due to the need to travel to a medical center to complete assessments. Telehealth methods, however, offer a pathway forward.</p><p><strong>Methods: </strong>PANDABox-EEG was developed through multidisciplinary collaboration with psychologists, psychophysiologists, engineers, and special-education scholars, incorporating caregiver feedback and user-centered design principles. It pairs PANDABox, a telehealth platform for biobehavioral assessment in rare disorders, with a dry electrode EEG system. Twenty-eight participants (7 AS, 7 siblings, 14 caregivers) completed three 5-min EEG sessions each over the course of a week. Caregivers were asked to provide feedback on acceptability of the design, and EEG data was quantified and assessed for metrics of reliability and validity.</p><p><strong>Results: </strong>PANDABox-EEG demonstrated high feasibility and acceptability, with 91% of caregivers reporting strong satisfaction assessment comfort. EEG data quality was promising, with high internal consistency (split-half reliability range for children with AS: r = .96-.98) and test-retest reliability for delta power among (test-retest reliability range for children with AS: ρ = .88-.96). Finally, we successfully detected the characteristic increased delta power in AS (effect size between AS and non-AS siblings: d = 1.56-2.85) and its association with age (effect size between non-AS siblings and caregivers: d = 2.19-2.72).</p><p><strong>Conclusion: </strong>PANDABox-EEG provides a feasible, cost-effective, and reliable method for remote EEG assessment in AS. Its high caregiver satisfaction and ability to capture relevant neurophysiological markers suggest potential for broader application. With further validation, PANDABox-EEG can enhance accessibility and inclusivity, benefiting clinical management and research in AS and other clinical populations in need of frequent EEG monitoring by eliminating the need to travel.</p>","PeriodicalId":16530,"journal":{"name":"Journal of Neurodevelopmental Disorders","volume":"17 1","pages":"29"},"PeriodicalIF":4.1,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12102843/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acceptability and safety of a probiotic beverage supplementation (Bio-K +) and feasibility of the proposed protocol in children with a diagnosis of autism spectrum disorder.","authors":"Ghizlane Gaougaou, Riham Zahra, Sophia Morel, Véronique Bélanger, Inga Sophia Knoth, Dominique Cousineau, Baudouin Forgeot D'Arc, Kelly Grzywacz, Guy Rousseau, Eric Déziel, Roger Godbout, Sarah Lippé, Mathieu Millette, Valérie Marcil","doi":"10.1186/s11689-025-09617-5","DOIUrl":"10.1186/s11689-025-09617-5","url":null,"abstract":"<p><strong>Background: </strong>Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders defined by stereotyped behavior and challenges in social communication and social interaction. ASD is associated with various comorbidities, including anxiety, gastrointestinal (GI) symptoms and sleep disorders. Evidence supports an association between intestinal dysbiosis and the severity of ASD-related symptoms. Probiotic intake was suggested to restore microbial homeostasis and decrease neurobehavioral, GI and sleep symptoms in individuals diagnosed with autism.</p><p><strong>Methods: </strong>This study aims to evaluate the acceptability and safety of a Bio-K + probiotics beverage in autistic children aged 4 to 11 years and the feasibility of the proposed research protocol to measure its impact on behaviors and comorbidities. The 30-week study consisted of daily supplementation with Bio-K + probiotics for 14 weeks. Acceptability and safety were monitored throughout the study. Feasibility was assessed by comparing recruitment and completion rates to pre-established thresholds. Preliminary impact of supplementation on behaviors (Autism Treatment Evaluation Checklist (ATEC) score), GI symptoms and sleep disorders was evaluated.</p><p><strong>Results: </strong>Of the 23 children recruited (mean age 6.7 ± 2.2 years, 70% males), 65% had GI problems and 91% had sleep disorders. Probiotic supplementation was accepted by all participants and no product-related adverse event was reported. Feasibility rates exceeded pre-established thresholds for almost all study outcomes including recruitment rate, compliance, electroencephalography, actigraphy and completion of questionnaires. Preliminary data suggest an improvement in behaviors associated with autism assessed with the total ATEC score, and in GI symptoms and sleep disorders.</p><p><strong>Conclusion: </strong>This study demonstrates probiotic beverage acceptability and safety and protocol feasibility in autistic children. To further support our data, a double-blinded placebo-controlled study is needed to determine its efficacy.</p>","PeriodicalId":16530,"journal":{"name":"Journal of Neurodevelopmental Disorders","volume":"17 1","pages":"30"},"PeriodicalIF":4.1,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12102953/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Contribution of families using the GenIDA database to the description of MED13L syndrome and literature review.","authors":"Roseline Caumes, Pauline Burger, Jean-Louis Mandel, Hélène Béhal, Jamal Ghoumid, Thomas Smol","doi":"10.1186/s11689-025-09618-4","DOIUrl":"10.1186/s11689-025-09618-4","url":null,"abstract":"<p><p>The GenIDA project aims to improve the understanding and management of rare genetic forms of intellectual disability by fostering collaboration among patients, caregivers, healthcare professionals, and research professionals. Clinical data is provided by patients' families via a structured questionnaire to identify medically relevant insights and better understand the natural history of rare diseases. This study focused on MED13L syndrome, analyzing data from 41 patients in the GenIDA database and comparing it with 102 cases from the scientific literature and 6 new descriptions of patients from our medical center.The GenIDA series confirmed the key features of MED13L syndrome, including global developmental delay, poor speech, intellectual disability, and cardiac defects (OMIM #616789), at frequencies similar to those reported in the literature. The GenIDA series identified a higher prevalence of visual impairment (76%) and highlighted under-recognized musculoskeletal issues, such as foot deformities, which had previously received little attention. This study highlights the value of family-reported data in describing the full phenotype of rare syndromes. A comprehensive review of published cases showed that patients with missense variants have more severe impairments, including increased cardiac defects, global developmental delay, and a higher incidence of epilepsy, than patients with premature truncated variants.These findings highlight the importance of family involvement in rare disease research and the need for further studies to explore genotype-phenotype correlations to improve patient care and outcomes.</p>","PeriodicalId":16530,"journal":{"name":"Journal of Neurodevelopmental Disorders","volume":"17 1","pages":"28"},"PeriodicalIF":4.1,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12087057/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute administration of lovastatin had no pronounced effect on motor abilities, motor coordination, gait nor simple cognition in a mouse model of Angelman syndrome.","authors":"Timothy A Fenton, Stela P Petkova, Anna Adhikari, Jill L Silverman","doi":"10.1186/s11689-025-09616-6","DOIUrl":"10.1186/s11689-025-09616-6","url":null,"abstract":"<p><p>Translational research is needed to discover pharmacological targets and treatments for the diagnostic behavioral domains of neurodevelopmental disorders (NDDs), including autism spectrum disorders (ASDs) and intellectual disabilities (IDs). One NDD, associated with ASD and ID, is Angelman Syndrome (AS). AS is a rare genetic NDD for which there is currently no cure nor effective therapeutics. The genetic cause is known to be the loss of expression from the maternal allele of ubiquitin protein ligase E3A (UBE3A). The Ube3a maternal deletion mouse model of AS reliably demonstrates behavioral phenotypes of relevance to AS and therefore offers a suitable in vivo system in which to test potential therapeutics, with construct and face validity. Successes in reducing hyperexcitability and epileptogenesis have been reported in an AS model following acute treatment with lovastatin, an ERK inhibitor by reducing seizure threshold and percentage of mice exhibiting seizures. Since there has been literature reporting disruption of the ERK signaling pathway in AS, we chose to evaluate the effects of acute lovastatin administration in a tailored set of translationally relevant behavioral assays in a mouse model of AS. Unexpectedly, deleterious effects of sedation were observed in wildtype (WT), age matched littermate control mice and despite a baseline hypolocomotive phenotype in AS mice, even further reductions in exploratory activity, were observed post-acute lovastatin treatment. Limitations of this work include that chronic lower dose regimens, more akin to drug administration in humans were beyond the scope of this work, and may have produced a more favorable impact of lovastatin administration over single acute high doses. In addition, lovastatin's effects were not assessed in younger subjects, since our study focused exclusively on adult functional outcomes. Metrics of gait, as well as motor coordination and motor learning in rotarod, previously observed to be impaired in AS mice, were not improved by lovastatin treatment. Finally, cognition by novel object recognition task was worsened in WT controls and not improved in AS, following lovastatin administration. In conclusion, lovastatin did not indicate any major improvement to AS symptoms, and in fact, worsened behavioral outcomes in the WT control groups. Therefore, despite its attractive low toxicity, immediate availability, and low cost of the drug, further investigation for clinical study is unwarranted given the results presented herein.</p>","PeriodicalId":16530,"journal":{"name":"Journal of Neurodevelopmental Disorders","volume":"17 1","pages":"27"},"PeriodicalIF":4.1,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12085040/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Visual feedback and motor memory contributions to sustained motor control deficits in autism spectrum disorder across childhood and into adulthood.","authors":"Robin L Shafer, James Bartolotti, Abigail Driggers, Erin Bojanek, Zheng Wang, Matthew W Mosconi","doi":"10.1186/s11689-025-09607-7","DOIUrl":"10.1186/s11689-025-09607-7","url":null,"abstract":"<p><strong>Background: </strong>Autistic individuals show deficits in sustained fine motor control which are associated with an over-reliance on visual feedback. Motor memory deficits also have been reported during sustained fine motor control in autism spectrum disorders (ASD). The development of motor memory and visuomotor feedback processes contributing to sustained motor control issues in ASD are not known. The present study aimed to characterize age-related changes in visual feedback and motor memory processes contributing to sustained fine motor control issues in ASD.</p><p><strong>Methods: </strong>Fifty-four autistic participants and 31 neurotypical (NT) controls ages 10-25 years completed visually guided and memory guided sustained precision gripping tests by pressing on force sensors with their dominant hand index finger and thumb. For visually guided trials, participants viewed a stationary target bar and a force bar that moved upwards with increased force for 15s. During memory guided trials, the force bar was visible for 3s, after which participants attempted to maintain their force output without visual feedback for another 12s. To assess visual feedback processing, force accuracy, variability (standard deviation), and regularity (sample entropy) were examined. To assess motor memory, force decay latency, slope, and magnitude were examined during epochs without visual feedback.</p><p><strong>Results: </strong>Relative to NT controls, autistic individuals showed a greater magnitude and a trend for a steeper slope of force decay during memory guided trials. Across conditions, the ASD group showed reduced force accuracy (β = 0.41, R² = 0.043, t_79.3=2.36, p = .021) and greater force variability (β=-2.16, R² = 0.143, t_77.1=-4.04, p = .0001) and regularity (β=-0.52, R² = 0.021, t_77.4=-2.21, p = .030) relative to NT controls at younger ages, but these differences normalized by adolescence (age x group interactions). Lower force accuracy and greater force variability during visually guided trials and steeper decay slope during memory guided trials were associated with overall autism severity.</p><p><strong>Conclusions: </strong>Our findings that autistic individuals show a greater magnitude and tendency for a greater rate of force decay than NT individuals following the removal of visual feedback indicate that motor memory deficits contribute to fine motor control issues in ASD. Findings that sensorimotor differences in ASD were specific to younger ages suggest delayed development across multiple motor control processes.</p>","PeriodicalId":16530,"journal":{"name":"Journal of Neurodevelopmental Disorders","volume":"17 1","pages":"26"},"PeriodicalIF":4.1,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12083110/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protein-truncating variants and deletions of SHANK2 are associated with autism spectrum disorder and other neurodevelopmental concerns.","authors":"Hailey Silver, Rori Greenberg, Paige M Siper, Jessica Zweifach, Renee Soufer, Mustafa Sahin, Elizabeth Berry-Kravis, Latha Valluripalli Soorya, Audrey Thurm, Jonathan A Bernstein, Alexander Kolevzon, Dorothy E Grice, Joseph D Buxbaum, Tess Levy","doi":"10.1186/s11689-025-09600-0","DOIUrl":"https://doi.org/10.1186/s11689-025-09600-0","url":null,"abstract":"<p><strong>Background: </strong>SHANK2 disorder is a rare neurodevelopmental disorder caused by a deletion or pathogenic sequence variant of the SHANK2 gene and is associated with autism spectrum disorder (ASD), intellectual disability (ID), and developmental delay. To date, research in SHANK2 has focused on laboratory-based in vivo and in vitro studies with few prospective clinical studies in humans.</p><p><strong>Methods: </strong>A remote assessment battery was comprised of caregiver interviews with a psychiatrist, psychologists, and a genetic counselor, caregiver-reports, and review of records. Results from this cohort were reported using descriptive statistics. An age-matched sample of participants with SHANK3 haploinsufficiency (Phelan-McDermid syndrome, PMS) was used to compare adaptive behavior between the two groups.</p><p><strong>Results: </strong>All ten participants demonstrated delays in adaptive behavior, with most motor skills preserved and a weakness in communication. According to parent report, 90% of participants carried a formal diagnosis of ASD, 50% of participants carried a diagnosis of attention-deficit/hyperactivity disorder (ADHD), and mild-to-moderate developmental delays were noted. Sensory hyperreactivity and seeking behaviors were more pronounced than sensory hyporeactivity. Medical features included hypotonia, recurrent ear infections, and gastrointestinal abnormalities. No similar facial dysmorphic features were observed. Compared to PMS participants, individuals with SHANK2 disorder had significantly higher adaptive functioning.</p><p><strong>Conclusions: </strong>Consistent with previous studies of SHANK2 disorder, these results indicate mild to moderate developmental impairment. Overall, SHANK2 disorder is associated with developmental and adaptive functioning delays, high rates of autism, including sensory symptoms and repetitive behaviors, and ADHD. This study was limited by its remote nature, diverse age range, and the homogeneous racial and ethnic sample. Future studies should examine larger, diverse cohorts, add cognitive testing, capture longitudinal data, and include in-person assessments.</p>","PeriodicalId":16530,"journal":{"name":"Journal of Neurodevelopmental Disorders","volume":"17 1","pages":"25"},"PeriodicalIF":4.1,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12042525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144007253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}