Translating discoveries in Attention-Deficit/Hyperactivity Disorder genomics to an outpatient child and adolescent psychiatric cohort

Objective Genomic discoveries should be investigated in generalizable child psychiatric samples to justify and inform studies that will evaluate their use for specific clinical purposes. In youth consecutively referred for neuropsychiatric evaluation, we examined: 1) the convergent and discriminant validity of attention-deficit/hyperactivity disorder (ADHD) polygenic risk scores (PRS) in relation to DSM-based ADHD phenotypes; 2) the association of ADHD PRS with phenotypes beyond ADHD that share its liability and have implications for outcome; and 3) the extent to which youth with high ADHD PRS manifest a distinctive clinical profile. Method Participants were 433 youth, ages 7 to 18, from the Longitudinal Study of Genetic Influences on Cognition. We used logistic/linear regression and mixed effects models to examine associations with ADHD-related polygenic variation from the largest ADHD GWAS to date. We replicated key findings in 5140 adult patients from a local health system biobank. Results Among referred youth, ADHD PRS associated with ADHD diagnoses, cross-diagnostic ADHD symptoms and academic impairment (OR’s ∼1.4; R2‘s ∼2-3%) as well as cross-diagnostic variation in aggression and working memory. In adults, ADHD PRS associated with ADHD and phenotypes beyond the condition that have public health implications. Finally, youth with a high ADHD polygenic burden showed a more severe clinical profile than those with low burden (beta’s∼.2). Conclusion Among child and adolescent outpatients, ADHD polygenic risk associated with ADHD and related phenotypes as well as clinical severity. Results extend the scientific foundation for studies of ADHD polygenic risk in the clinical setting and highlight directions for further research

Feasibility of a new intervention addressing group-based balance and high-intensity training, physical activity, and employment in individuals with multiple sclerosis: a pilot randomized controlled trial

Background and purpose: Impaired sensorimotor function, reduced physical activity and unemployment are common challenges in persons with multiple sclerosis (pwMS), even when disability is low. CoreDISTparticipation is a new, multidisciplinary intervention delivered across healthcare levels systematically addressing these elements. This study primarily aimed to evaluate the feasibility of CoreDISTparticipation in terms of process, resources, management, and scientific outcomes. The secondary aim was to evaluate initial efficacy in terms of possible short-term effects compared with the usual care on barriers to employment, balance, walking, health-related quality of life (HRQoL), and physical activity. Methods: This assessor-blinded prospective pilot randomized controlled trial included 29 pwMS [Expanded Disability Status Scale (EDSS): 0–3.5] randomly allocated to the intervention group (CoreDISTparticipation) (n = 15) or usual care (n = 14). CoreDISTparticipation consists of three phases: (1) hospital outpatient clinic: MS nurse work-focused session and physiotherapist exploring balance; (2) municipality: a digital meeting with pwMS, employer, MS nurse, and physiotherapist addressing employment and physical activity, 4 weeks indoor CoreDIST balance training (60 min × 2/week); and (3) 4 weeks outdoor CoreDIST balance training and high-intensity running/walking (60 min × 2/week). Assessments were undertaken at baseline and at weeks 6 and 11. Primary feasibility metric outcomes were the reporting of process, resources, management, and scientific outcomes. Efficacy measures included evaluation of the Multiple Sclerosis Work Difficulties Questionnaire-23 Norwegian Version (MSWDQ-23NV) and 6 Minute Walk-test as well as the Trunk Impairment Scalemodified Norwegian Version, Mini-Balance Evaluation Systems Test (MiniBESTest), Multiple Sclerosis Walking Scale-12, Multiple Sclerosis Impact Scale-29 Norwegian Version (MSIS-29NV), ActiGraph wGT3x-BT monitors, and AccuGait Optimized force platform. The statistical analyses included repeated-measures mixed models performed in IBM SPSS Version 29. Results: The primary feasibility metric outcomes demonstrated the need for minor adjustments in regard to the content of the intervention and increasing the number of staff. In regard to the efficacy measures, one person attended no postintervention assessments and was excluded, leaving 28 participants (mean EDSS: 1.8, SD: 1). The mean percentage employment was 46.3 (SD: 35.6) and 65.4 (SD: 39.3) in the CoreDISTparticipation and usual care group, respectively. No between-group differences were found. MSWDQ-23NV demonstrated a within-group difference of 5.7 points from baseline to Week 11 (P = 0.004; confidence interval: 2.2–9.3). MiniBESTest and MSIS-29NV demonstrated within-group differences. The study is registered in ClinicalTrials.gov (Identifier: NCT05057338). Discussion: The CoreDISTparticipation intervention is feasible to support pwMS when the identified feasibility metric outcomes in regard to process, resource, management, and scientific outcome metrics are adjusted to improve feasibility. Regarding efficacy measures, no between-group differences were detected; however, within-group differences in barriers to employment, balance, and HRQoL were detected for the CoreDISTparticipation group. A larger comparative trial is needed to explore between-group differences and should accurately and precisely define usual care and address the identified limitations of this study

Neuropsychological Function in a Child with 18p Deletion Syndrome

Interior of west annex building with ancestral spirit tablets and bronze vessels (ding form on the right); A single-gabled circular building, built on a single level of marble stone base. It is located south of the Hall of Prayer for Good Harvests and resembles it, but is smaller. It is surrounded by a smooth circular wall, the Echo Wall (3.7 m high, 193 m circumference), that can transmit sounds over large distances. Built in 1530 during the Ming Dynasty reign of Emperor Jiajing (Ming Shizong or Zhu Houcong); rebuilt in present form in 1752 by Emperor QianLong (Qing dynasty). The east and west annexes and the vault inside the Echo Wall compound were used to hold divine tablets of various gods worshipped at the Circular Mound Altar, spirit tablets of ancestors, and other ceremonial objects. Source: Wikipedia; http://en.wikipedia.org/wiki/Main_Page (accessed 6/3/2013

Cognitive Impairment Occurs in Children and Adolescents With Multiple Sclerosis

In the largest sample studied to date, we measured cognitive functioning in children and adolescents with pediatric multiple sclerosis (n = 187) as well as those with clinically isolated syndrome (n = 44). Participants were consecutively enrolled from six United States Pediatric Multiple Sclerosis Centers of Excellence. Participants had a mean of 14.8 ± 2.6 years of age and an average disease duration of 1.9 ± 2.2 years. A total of 65 (35%) children with multiple sclerosis and 8 (18%) with clinically isolated syndrome met criteria for cognitive impairment. The most frequent areas involved were fine motor coordination (54%), visuomotor integration (50%), and speeded information processing (35%). A diagnosis of multiple sclerosis (odds ratio = 3.60, confidence interval = 1.07, 12.36, P = .04) and overall neurologic disability (odds ratio = 1.47, confidence interval = 1.10, 2.10, P = .03) were the only independent predictors of cognitive impairment. Cognitive impairment may occur early in these patients, and prompt recognition is critical for their care