Journal of Neurodevelopmental Disorders最新文献

{"title":"Differential cognitive and behavioral development from 6 to 24 months in autism and fragile X syndrome","authors":"Lindsay J. Mullin, Joshua Rutsohn, Julia L. Gross, Kelly E. Caravella, Rebecca L. Grzadzinski, Leigh Anne Weisenfeld, Lisa Flake, Kelly N. Botteron, Stephen R. Dager, Annette M. Estes, Juhi Pandey, Robert T. Schultz, Tanya St. John, Jason J. Wolff, Mark D. Shen, Joseph Piven, Heather C. Hazlett, Jessica B. Girault","doi":"10.1186/s11689-024-09519-y","DOIUrl":"https://doi.org/10.1186/s11689-024-09519-y","url":null,"abstract":"Specifying early developmental differences among neurodevelopmental disorders with distinct etiologies is critical to improving early identification and tailored intervention during the first years of life. Recent studies have uncovered important differences between infants with fragile X syndrome (FXS) and infants with familial history of autism spectrum disorder who go on to develop autism themselves (FH-ASD), including differences in brain development and behavior. Thus far, there have been no studies longitudinally investigating differential developmental skill profiles in FXS and FH-ASD infants. The current study contrasted longitudinal trajectories of verbal (expressive and receptive language) and nonverbal (gross and fine motor, visual reception) skills in FXS and FH-ASD infants, compared to FH infants who did not develop ASD (FH-nonASD) and typically developing controls. Infants with FXS showed delays on a nonverbal composite compared to FH-ASD (as well as FH-nonASD and control) infants as early as 6 months of age. By 12 months an ordinal pattern of scores was established between groups on all domains tested, such that controls > FH-nonASD > FH-ASD > FXS. This pattern persisted through 24 months. Cognitive level differentially influenced developmental trajectories for FXS and FH-ASD. Our results demonstrate detectable group differences by 6 months between FXS and FH-ASD as well as differential trajectories on each domain throughout infancy. This work further highlights an earlier onset of global cognitive delays in FXS and, conversely, a protracted period of more slowly emerging delays in FH-ASD. Divergent neural and cognitive development in infancy between FXS and FH-ASD contributes to our understanding of important distinctions in the development and behavioral phenotype of these two groups.","PeriodicalId":16530,"journal":{"name":"Journal of Neurodevelopmental Disorders","volume":"28 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140168867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Social skills in neurodevelopmental disorders: a study using role-plays to assess adolescents and young adults with 22q11.2 deletion syndrome and autism spectrum disorders","authors":"Clémence Feller, Laura Ilen, Stephan Eliez, Maude Schneider","doi":"10.1186/s11689-024-09527-y","DOIUrl":"https://doi.org/10.1186/s11689-024-09527-y","url":null,"abstract":"Social skills are frequently impaired in neurodevelopmental disorders and genetic conditions, including 22q11.2 deletion syndrome (22q11DS) and autism spectrum disorders (ASD). Although often assessed with questionnaires, direct assessment provides a more valid estimate of the constructs. Role-plays (i.e., simulates situational settings) therefore appear to be an appropriate indicator of social skills in daily life. This co-registered study involved 53 individuals with 22q11DS, 34 individuals with ASD, and 64 typically developing (TD) peers aged 12–30 years. All participants were assessed with role-plays as well as parent-reported questionnaires and clinical interviews focusing on social skills, functioning and anxiety. Both clinical groups showed impaired social skills compared to TD, but distinct social profiles emerged between the groups. Individuals with 22q11DS displayed higher social appropriateness and clarity of speech but weaker general argumentation and negotiation skills, with the opposite pattern observed in participants with ASD. No association was found between social skills measured by direct observation and caregiver reports. Social anxiety, although higher in clinical groups than in TD, was not associated with role-plays. This study highlights the need to train social skills through tailored interventions to target the specific difficulties of each clinical population. It also highlights the importance of combining measures as they do not necessarily provide the same outcome.","PeriodicalId":16530,"journal":{"name":"Journal of Neurodevelopmental Disorders","volume":"88 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140147314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Using team-based precision medicine to advance understanding of rare genetic brain disorders.","authors":"Steven U Walkley, Sophie Molholm, Bryen Jordan, Robert W Marion, Melissa Wasserstein","doi":"10.1186/s11689-024-09518-z","DOIUrl":"10.1186/s11689-024-09518-z","url":null,"abstract":"<p><p>We describe a multidisciplinary teamwork approach known as \"Operation IDD Gene Team\" developed by the Rose F. Kennedy Intellectual and Developmental Disabilities Research Center (RFK IDDRC) at the Albert Einstein College of Medicine. This initiative brings families affected by rare genetic diseases that cause intellectual and developmental disability together with physicians, basic scientists, and their trainees. At team meetings, family members share their child's medical and personal history, physicians describe the broader clinical consequences of the condition, and scientists provide accessible tutorials focused on the fundamental biology of relevant genes. When appropriate, possible treatment approaches are also discussed. The outcomes of team meetings have been overwhelmingly positive, with families not only expressing deep gratitude, but also becoming empowered to establish foundations dedicated to their child's specific condition. Physicians, and in particular the scientists and their trainees, have gained a deeper understanding of challenges faced by affected families, broadening their perspective on how their research can extend beyond the laboratory. Remarkably, research by the scientists following the Gene Team meetings have often included focus on the actual gene variants exhibited by the participating children. As these investigations progress and newly created foundations expand their efforts, national as well as international collaborations are forged. These developments emphasize the importance of rare diseases as windows into previously unexplored molecular and cellular processes, which can offer fresh insights into both normal function as well as more common diseases. Elucidating the mechanisms of and treatments for rare and ultra-rare diseases thus has benefits for all involved-families, physicians, and scientists and their trainees, as well as the broader medical community. While the RFK IDDRC's Operation IDD Gene Team program has focused on intellectual disabilities affecting children, we believe it has the potential to be applied to rare genetic diseases impacting individuals of any age and encompassing a wide variety of developmental disorders affecting multiple organ systems.</p>","PeriodicalId":16530,"journal":{"name":"Journal of Neurodevelopmental Disorders","volume":"16 1","pages":"10"},"PeriodicalIF":4.1,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10941544/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140140294","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 Kinase A in neurological disorders.","authors":"Alexander G P Glebov-McCloud, Walter S Saide, Marie E Gaine, Stefan Strack","doi":"10.1186/s11689-024-09525-0","DOIUrl":"10.1186/s11689-024-09525-0","url":null,"abstract":"<p><p>Cyclic adenosine 3', 5' monophosphate (cAMP)-dependent Protein Kinase A (PKA) is a multi-functional serine/threonine kinase that regulates a wide variety of physiological processes including gene transcription, metabolism, and synaptic plasticity. Genomic sequencing studies have identified both germline and somatic variants of the catalytic and regulatory subunits of PKA in patients with metabolic and neurodevelopmental disorders. In this review we discuss the classical cAMP/PKA signaling pathway and the disease phenotypes that result from PKA variants. This review highlights distinct isoform-specific cognitive deficits that occur in both PKA catalytic and regulatory subunits, and how tissue-specific distribution of these isoforms may contribute to neurodevelopmental disorders in comparison to more generalized endocrine dysfunction.</p>","PeriodicalId":16530,"journal":{"name":"Journal of Neurodevelopmental Disorders","volume":"16 1","pages":"9"},"PeriodicalIF":4.1,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10936040/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140119740","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":"Etiologic heterogeneity, pleiotropy, and polygenicity in behaviorally defined intellectual and developmental disabilities.","authors":"Jessica B Girault, Olivia J Veatch, Hyejung Won","doi":"10.1186/s11689-024-09526-z","DOIUrl":"10.1186/s11689-024-09526-z","url":null,"abstract":"","PeriodicalId":16530,"journal":{"name":"Journal of Neurodevelopmental Disorders","volume":"16 1","pages":"8"},"PeriodicalIF":4.1,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10936123/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140119739","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":"Conducting head-mounted eye-tracking research with young children with autism and children with increased likelihood of later autism diagnosis","authors":"E. Perkovich, A. Laakman, S. Mire, H. Yoshida","doi":"10.1186/s11689-024-09524-1","DOIUrl":"https://doi.org/10.1186/s11689-024-09524-1","url":null,"abstract":"Over the past years, researchers have been using head-mounted eye-tracking systems to study young children’s gaze behaviors in everyday activities through which children learn about the world. This method has great potential to further our understanding of how millisecond-level gaze behaviors create multisensory experiences and fluctuate around social environments. While this line of work can yield insight into early perceptual experiences and potential learning mechanisms, the majority of the work is exclusively conducted with typically-developing children. Sensory sensitivities, social-communication difficulties, and challenging behaviors (e.g., disruption, elopement) are common among children with developmental disorders, and they may represent potential methodological challenges for collecting high-quality data. In this paper, we describe our research practices of using head-mounted eye trackers with 41 autistic children and 17 children with increased likelihood of later autism diagnosis without auditory or visual impairments, including those who are minimally or nonspeaking and/or have intellectual disabilities. The success rate in gathering data among children with autism was 92.68%. 3 of 41 children failed to complete the play-session, resulting in an 86.36% success rate among 1–4-year-olds and a 100.00% success rate among 5–8-year-olds. 1 of 17 children with increased likelihood of later autism diagnosis failed to complete the play-session, resulting in a success rate of 94.11%. There were numerous “challenging” behaviors relevant to the method. The most common challenging behaviors included taking the eye-tracking device off, elopement, and becoming distressed. Overall, among children with autism, 88.8% of 1–4-year-olds and 29.4% of 5–8-year-olds exhibited at least one challenging behavior. Research capitalizing on this methodology has the potential to reveal early, socially-mediated gaze behaviors that are relevant for autism screening, diagnosis, and intervention purposes. We hope that our efforts in documenting our study methodology will help researchers and clinicians effectively study early naturally-occuring gaze behaviors of children during non-experimental contexts across the spectrum and other developmental disabilities using head-mounted eye-tracking. Ultimately, such applications may increase the generalizability of results, better reflect the diversity of individual characteristics, and offer new ways in which this method can contribute to the field.","PeriodicalId":16530,"journal":{"name":"Journal of Neurodevelopmental Disorders","volume":"8 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140025539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Outcome measures in Angelman syndrome","authors":"Doesjka A. Hagenaar, Karen G. C. B. Bindels-de Heus, Maud M. van Gils, Louise van den Berg, Leontine W. ten Hoopen, Philine Affourtit, Johan J. M. Pel, Koen F. M. Joosten, Manon H. J. Hillegers, Henriëtte A. Moll, Marie-Claire Y. de Wit, Gwen C. Dieleman, Sabine E. Mous","doi":"10.1186/s11689-024-09516-1","DOIUrl":"https://doi.org/10.1186/s11689-024-09516-1","url":null,"abstract":"Angelman syndrome (AS) is a rare neurodevelopmental disorder characterized by severe intellectual disability, little to no expressive speech, visual and motor problems, emotional/behavioral challenges, and a tendency towards hyperphagia and weight gain. The characteristics of AS make it difficult to measure these children’s functioning with standard clinical tests. Feasible outcome measures are needed to measure current functioning and change over time, in clinical practice and clinical trials. Our first aim is to assess the feasibility of several functional tests. We target domains of neurocognitive functioning and physical growth using the following measurement methods: eye-tracking, functional Near-Infrared Spectroscopy (fNIRS), indirect calorimetry, bio-impedance analysis (BIA), and BOD POD (air-displacement plethysmography). Our second aim is to explore the results of the above measures, in order to better understand the AS phenotype. The study sample consisted of 28 children with AS aged 2–18 years. We defined an outcome measure as feasible when (1) at least 70% of participants successfully finished the measurement and (2) at least 60% of those participants had acceptable data quality. Adaptations to the test procedure and reasons for early termination were noted. Parents rated acceptability and importance and were invited to make recommendations to increase feasibility. The results of the measures were explored. Outcome measures obtained with eye-tracking and BOD POD met the definition of feasibility, while fNIRS, indirect calorimetry, and BIA did not. The most important reasons for early termination of measurements were showing signs of protest, inability to sit still and poor/no calibration (eye-tracking specific). Post-calibration was often applied to obtain valid eye-tracking results. Parents rated the BOD POD als most acceptable and fNIRS as least acceptable for their child. All outcome measures were rated to be important. Exploratory results indicated longer reaction times to high salient visual stimuli (eye-tracking) as well as high body fat percentage (BOD POD). Eye-tracking and BOD POD are feasible measurement methods for children with AS. Eye-tracking was successfully used to assess visual orienting functions in the current study and (with some practical adaptations) can potentially be used to assess other outcomes as well. BOD POD was successfully used to examine body composition. Registered d.d. 23-04-2020 under number ‘NL8550’ in the Dutch Trial Register: https://onderzoekmetmensen.nl/en/trial/23075 ","PeriodicalId":16530,"journal":{"name":"Journal of Neurodevelopmental Disorders","volume":"18 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140006272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Overcoming genetic and cellular complexity to study the pathophysiology of X-linked intellectual disabilities.","authors":"Dayne Martinez, Evan Jiang, Zhaolan Zhou","doi":"10.1186/s11689-024-09517-0","DOIUrl":"10.1186/s11689-024-09517-0","url":null,"abstract":"<p><p>X-linked genetic causes of intellectual disability (ID) account for a substantial proportion of cases and remain poorly understood, in part due to the heterogeneous expression of X-linked genes in females. This is because most genes on the X chromosome are subject to random X chromosome inactivation (XCI) during early embryonic development, which results in a mosaic pattern of gene expression for a given X-linked mutant allele. This mosaic expression produces substantial complexity, especially when attempting to study the already complicated neural circuits that underly behavior, thus impeding the understanding of disease-related pathophysiology and the development of therapeutics. Here, we review a few selected X-linked forms of ID that predominantly affect heterozygous females and the current obstacles for developing effective therapies for such disorders. We also propose a genetic strategy to overcome the complexity presented by mosaicism in heterozygous females and highlight specific tools for studying synaptic and circuit mechanisms, many of which could be shared across multiple forms of intellectual disability.</p>","PeriodicalId":16530,"journal":{"name":"Journal of Neurodevelopmental Disorders","volume":"16 1","pages":"5"},"PeriodicalIF":4.9,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10902969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139996492","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":"Correction: Endophenotype trait domains for advancing gene discovery in autism spectrum disorder.","authors":"Matthew W Mosconi, Cassandra J Stevens, Kathryn E Unruh, Robin Shafer, Jed T Elison","doi":"10.1186/s11689-024-09523-2","DOIUrl":"10.1186/s11689-024-09523-2","url":null,"abstract":"","PeriodicalId":16530,"journal":{"name":"Journal of Neurodevelopmental Disorders","volume":"16 1","pages":"4"},"PeriodicalIF":4.9,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10900778/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139990346","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":"Assessing the integrity of auditory sensory memory processing in CLN3 disease (Juvenile Neuronal Ceroid Lipofuscinosis (Batten disease)): an auditory evoked potential study of the duration-evoked mismatch negativity (MMN).","authors":"Tufikameni Brima, Edward G Freedman, Kevin D Prinsloo, Erika F Augustine, Heather R Adams, Kuan Hong Wang, Jonathan W Mink, Luke H Shaw, Emma P Mantel, John J Foxe","doi":"10.1186/s11689-023-09515-8","DOIUrl":"10.1186/s11689-023-09515-8","url":null,"abstract":"<p><strong>Background: </strong>We interrogated auditory sensory memory capabilities in individuals with CLN3 disease (juvenile neuronal ceroid lipofuscinosis), specifically for the feature of \"duration\" processing. Given decrements in auditory processing abilities associated with later-stage CLN3 disease, we hypothesized that the duration-evoked mismatch negativity (MMN) of the event related potential (ERP) would be a marker of progressively atypical cortical processing in this population, with potential applicability as a brain-based biomarker in clinical trials.</p><p><strong>Methods: </strong>We employed three stimulation rates (fast: 450 ms, medium: 900 ms, slow: 1800 ms), allowing for assessment of the sustainability of the auditory sensory memory trace. The robustness of MMN directly relates to the rate at which the regularly occurring stimulus stream is presented. As presentation rate slows, robustness of the sensory memory trace diminishes. By manipulating presentation rate, the strength of the sensory memory trace is parametrically varied, providing greater sensitivity to detect auditory cortical dysfunction. A secondary hypothesis was that duration-evoked MMN abnormalities in CLN3 disease would be more severe at slower presentation rates, resulting from greater demand on the sensory memory system.</p><p><strong>Results: </strong>Data from individuals with CLN3 disease (N = 21; range 6-28 years of age) showed robust MMN responses (i.e., intact auditory sensory memory processes) at the medium stimulation rate. However, at the fastest rate, MMN was significantly reduced, and at the slowest rate, MMN was not detectable in CLN3 disease relative to neurotypical controls (N = 41; ages 6-26 years).</p><p><strong>Conclusions: </strong>Results reveal emerging insufficiencies in this critical auditory perceptual system in individuals with CLN3 disease.</p>","PeriodicalId":16530,"journal":{"name":"Journal of Neurodevelopmental Disorders","volume":"16 1","pages":"3"},"PeriodicalIF":4.9,"publicationDate":"2024-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10770910/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139106224","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}