JAK inhibition decreases the autoimmune burden in Down syndrome.

Background: Individuals with Down syndrome (DS), the genetic condition caused by trisomy 21 (T21), display clear signs of immune dysregulation, including high rates of autoimmunity and severe complications from infections. Although it is well established that T21 causes increased interferon responses and JAK/STAT signaling, elevated autoantibodies, global immune remodeling, and hypercytokinemia, the interplay between these processes, the clinical manifestations of DS, and potential therapeutic interventions remain ill defined.

Methods: We report a comprehensive analysis of immune dysregulation at the clinical, cellular, and molecular level in hundreds of individuals with DS, including autoantibody profiling, cytokine analysis, and deep immune mapping.

Parent Perspectives on Parent-Mediated Intervention for Young Children With Down Syndrome.

Background: Parent-mediated intervention (PMI) is a potentially scalable approach for tailored interventions in neurogenetic conditions like Down syndrome (DS). Because PMIs require ongoing parent engagement, they must be developed in alignment with the needs of intended users. The present study examined caregiver opinions and preferences to inform the development of syndrome-informed interventions for children with DS.

JAK inhibition in Down Syndrome Regression Disorder.

Down Syndrome Regression Disorder (DRSD) is an uncommon but devastating condition affecting primarily adolescents and young adults with Down syndrome (DS). Individuals with DS display a dysregulated immune system associated with hyperactive interferon signaling, which is associated with a high incidence of autoimmune conditions. While the cause of DSRD is unknown, increasing evidence indicates that it may have an immune basis, and some individuals with DSRD have responded to intravenous immunoglobulin therapy.

Identifying Three Psilocybin Use Patterns by Frequency and Quantity.

Objective: Patterns of psilocybin use in non-clinical settings are not well described in the literature. Psilocybin use can involve infrequent, large (i.e.

JAK inhibition decreases the autoimmune burden in Down syndrome.

Individuals with Down syndrome (DS), the genetic condition caused by trisomy 21 (T21), display clear signs of immune dysregulation, including high rates of autoimmune disorders and severe complications from infections. Although it is well established that T21 causes increased interferon responses and JAK/STAT signaling, elevated autoantibodies, global immune remodeling, and hypercytokinemia, the interplay between these processes, the clinical manifestations of DS, and potential therapeutic interventions remain ill defined. Here, we report a comprehensive analysis of immune dysregulation at the clinical, cellular, and molecular level in hundreds of individuals with DS.

Implications of Using the BRIEF-Preschool With School-Age Children With Down Syndrome.

This study evaluated the appropriateness of scoring the Behavior Rating Inventory of Executive Function-Preschool (BRIEF-P) using age-equivalent scores generated from multiple measures of cognition and language among school-age children with Down syndrome (DS). Subscale T scores for 95 children with DS were contrasted using standard scoring on the Behavior Rating Inventory of Executive Function-Second edition (BRIEF-2; based on chronological age) to alternate scoring using the BRIEF-P (based on age-equivalent) for patterns of subscale intercorrelations, differences in mean scores, and agreement on findings from clinical cut-off scores. Results with children with DS suggested using (1) the BRIEF-P for children ages 2-5 years old, (2) the BRIEF-2 with chronological-age scoring or the BRIEF-P with age-equivalent scoring (with some caveats) for research on children ages 5-10 years old, and (3) the BRIEF-2 for children ages 11 and older.

Preliminary psychometric properties of an inhibition task in young children with Down syndrome.

Executive function (EF) skills are important treatment targets for people with Down syndrome (DS); however, few EF measures have been evaluated for use with young children in this population. : The present study evaluated preliminary psychometric properties of a measure of the EF component of inhibition. Participants were 73 children with DS between 2.

Longitudinal Predictors of Neurodevelopmental Outcomes in Children with Down Syndrome.

This study examined longitudinal predictors of neurodevelopmental outcomes in children with Down syndrome (DS). Participants were assessed at Wave 1 during infancy on measures of looking behavior and caregivers provided infant sensory ratings. At Wave 2, child-age participants completed a developmental assessment and caregivers provided ratings of executive function, ADHD symptoms, and autism symptoms.

Psychometric evaluation of a working memory assessment measure in young children with Down syndrome.

Background: Working memory involves the temporary storage and manipulation of information and is frequently an area of challenge for individuals with Down syndrome (DS). Despite the potential benefits of intervention, laboratory assessments of working memory that could capture intervention effects have not undergone rigorous evaluation for use with young children with DS. It is critical to evaluate assessments of working memory in young children with DS to ensure the reliable and accurate measurement of performance.

Using the Social Skills Improvement System (SSiS) Rating Scales to assess social skills in youth with Down syndrome.

Introduction And Methods: This study provides preliminary data on the Social Skills Improvement System (SSiS) Rating Scales Parent Form to measure social skills in a sample of 124 children and adolescents with Down syndrome (DS) ages 6-17 years.

Results: Overall, participants demonstrated relatively mild symptoms, with the sample's average standard score falling within 1 standard deviation from the mean of the normative sample for the social skills ( = 92,  = 15) and problem behaviors ( = 104,  = 12) domains (normative sample  = 100,  = 15 for both domains). However, a wide range of scores was observed across the sample for the composite and subscale scores.

Evaluating Processing Speed and Reaction Time Outcome Measures in Children and Adolescents with Down Syndrome.

Reliable and valid cognitive outcome measures, including examiner-administered and computer-facilitated assessments of processing speed and reaction time, are necessary for future clinical trials that include individuals with Down syndrome (DS). The current study evaluated the score distributions and psychometric properties of four examiner-administered and three computerized processing speed and reaction time measures. Participants included 97 individuals with DS, aged 6 to 17 (M = 12.

Cognitive flexibility assessment in youth with Down syndrome: Reliability, practice effects, and validity.

Background: Cognitive flexibility refers to the ability to switch between different mental sets, tasks, or strategies and is challenging for some individuals with Down syndrome (DS). The lack of reliable and valid cognitive flexibility measures for individuals with DS is a major barrier to clinical trials and intervention studies designed to address cognitive challenges specific to DS. To avoid measurement limitations that could confound interpretations of performance in clinical trials in children with DS, it is critical to use phenotype-sensitive and psychometrically sound measures of cognitive flexibility.

Outreach and Engagement Efforts in Research on Down Syndrome: An NIH INCLUDE Working Group Consensus Statement.

The National Institutes of Health formulated the Outreach and Engagement Working Group in Fall of 2019 to support the objectives of the INCLUDE Project (INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE). This Working Group consisted of a multi-disciplinary team of stakeholders in research on Down syndrome that met to discuss best practices for outreach and engagement to Down syndrome communities, with an emphasis on representation and diversity. This review and consensus paper describes the importance of increasing representation in DS research for future cohort building and summarizes the priority issues identified by the Working Group members.

Profiles of Caregiver-Reported Executive Function in Children with Down Syndrome.

Children with Down syndrome (DS) are at risk for challenges with aspects of executive function (EF). The current study explores whether heterogeneity in EF profiles can be detected within a sample of children with DS. Participants were 69 children with DS, ages 3-10 years (M = 6.

Considerations for measuring individual outcomes across contexts in Down syndrome: Implications for research and clinical trials.

Individuals with Down syndrome (DS) are increasingly involved in clinical trials that target developmental outcomes, like cognition and behavior. The increased focus on treatment in DS has led to ongoing discussions regarding the selection of outcome measures using syndrome-informed criteria. This discourse is warranted as clinical trials can fail if the outcome measures selected are inappropriate for individuals with DS or do not take into account the behavioral phenotype commonly associated with DS.

Defining Expressive Language Benchmarks for Children with Down Syndrome.

Establishing expressive language benchmarks (ELBs) for children with Down syndrome (DS), as developed by Tager-Flusberg et al. for children with autism, is critically needed to inform the development of novel treatments, identify individualized treatment targets, and promote accurate monitoring of progress. In the present study, we assessed ELB assignments in three language domains (phonology, vocabulary, and grammar) for 53 young children with DS (CA range: 2.

Comparison of Attention-Deficit Hyperactivity Disorder in Typically Developing Children and Children with Down Syndrome.

Objective: This study aimed to evaluate attention-deficit hyperactivity disorder (ADHD) symptom patterns among children with Down syndrome (DS) with or without ADHD and typically developing (TD) children with ADHD.

Methods: Parents and teachers rated symptoms of inattention, hyperactivity, and general behavioral concerns for 22 children with DS and comorbid diagnoses of ADHD (DS + ADHD), 66 gender-matched and age-matched children with DS with no diagnosis of ADHD (DS - ADHD), and 66 gender-matched and age-matched TD children with ADHD (TD + ADHD). Children with DS were recruited from the community.

Early Regulatory Skills and Social Communication Development in Infants with Down Syndrome.

Children with Down syndrome (DS) demonstrate substantial variability in communication and language outcomes. One potential source of variability in this skill area may be early regulatory function. Characterizing the early link between regulatory function and early social communication may benefit infants with DS at risk of difficulties with social communication and language skill acquisition.

Cognitive Profiles and Autism Symptoms in Comorbid Down Syndrome and Autism Spectrum Disorder.

Objective: The prevalence of comorbid autism spectrum disorder (ASD) in children with Down syndrome (DS) is estimated to be around 16%. This study aims to fill gaps in the literature by describing developmental and behavioral phenotypes in this group relative to those with DS or ASD in isolation.

Methods: Participants included 173 children (Mage = 73 months) with ASD, DS, or DS + ASD.

Sensory Processing and Maladaptive Behavior: Profiles Within the Down Syndrome Phenotype.

: Sensory processing impairments are well characterized in children with neurodevelopmental disorders, particularly autism, and have been associated with maladaptive behaviors. However, little is known regarding sensory processing difficulties within Down syndrome, or how these difficulties may influence maladaptive behavior. This study aims to characterize sensory processing difficulties within the Down syndrome phenotype and determine the influence of processing difficulties on maladaptive behavior.

Autism spectrum disorder (ASD) symptom profiles of children with comorbid Down syndrome (DS) and ASD: A comparison with children with DS-only and ASD-only.

Background: Down syndrome (DS) is associated with increased rates of autism spectrum disorder (ASD), characterized by social-communicative impairments (SOC-COM) and repetitive behaviors and interests (RBI). However, little is known about the ASD symptom presentation in children with DS + ASD.

Aims: The current study sought to describe parent-report of SOC-COM and RBI symptoms on the Autism Diagnostic Interview -Revised (ADI-R) in children with DS (n = 22), DS + ASD (n = 11), and ASD (n = 66).

Exploratory behavior and developmental skill acquisition in infants with Down syndrome.

Infants learn about objects by exploring them. Typically developing infants actively explore objects through visual, manual, and oral modalities. Attenuated exploratory behavior has been observed in various neurodevelopmental disorders, including Down syndrome (DS), presumably limiting learning options.

Personalized reading intervention for children with Down syndrome.

The purpose of this replication study was to evaluate the potential efficacy and feasibility of an early reading intervention for children with Down syndrome. The intervention was developed in alignment with the Down syndrome behavioral phenotype. Six children between the ages of seven and ten years participated in a series of multiple-probe across lessons single-case design studies.

Adaptive behavior in infants and toddlers with Down syndrome and fragile X syndrome.

Individuals with Down syndrome (DS) experience deficits across all domains of adaptive functioning, however little is known about the emergence and age-related changes of these impairments compared to other neurogenetic disorders with similar intellectual disability impairments, such as fragile X syndrome (FXS). Adaptive behavior is key for optimal functioning in these populations. Participants aged 5-45 months comprised three age-matched groups, DS (n = 64), FXS (n = 69), and typically developing controls (TD; n = 69).