SUMMARY SCA1, a fatal neurodegenerative disorder, is caused by a CAG expansion encoding a polyglutamine stretch in the protein ATXN1. We used RNA sequencing to profile cerebellar gene expression in Pcp2-ATXN1[82Q] mice with ataxia and progressive pathology and Pcp2-ATXN1[30Q]D776 animals having ataxia in absence of Purkinje cell progressive pathology. Weighted Gene Coexpression Network Analysis of the cerebellar expression data revealed two gene networks that significantly correlated with disease and have an expression profile correlating with disease progression ATXN1[82Q] Purkinje cells. The Magenta Module provides a signature of suppressed transcriptional programs reflecting disease progression in Purkinje cells, while the Lt Yellow Module, reflects transcriptional programs activated in response to disease in Purkinje cells as well as other cerebellar cell types. Furthermore, we found that upregulation of cholecystokinin (Cck) and subsequent interaction with the Cck1 receptor likely underlies the lack of progressive Purkinje cell pathology in Pcp2-ATXN1[30Q]D776 mice.

The Pediatric Symptom Checklist-17 (PSC-17) is a widely used, briefer version of the PSC-35, a parent-completed measure of children's psychosocial functioning. Despite the extensive use of the PSC-17 over the past 15 years there has not been a large-scale replication of the original derivation study.

CONCLUSIONS: Minimally trained PCPs can administer the M-CHAT/F reliably and efficiently during regular well-child visits, increasing PPV without compromising detection.

Accuracy of autism screening using M-CHAT plus the Follow-Up Interview (M-CHAT/F) for children screened positive at 18-months was compared to screening at 24-months. Formal ASD testing was criterion for a community sample of M-CHAT positive children (n=98), Positive Predictive Value (PPV) was 0.40 for the M-CHAT and 0.58 for the M-CHAT/F. MCHAT/F PPV was 0.69 among children 20+ months compared to 0.36 for <20 months. Multivariate analyses incorporating data from the Ages and Stages Questionnaire, MacArthur-Bates Communicative Development Inventory, M-CHAT and M-CHAT/F results, and M-CHAT items suggest language variables carry greatest relative importance in contributing to an age-based algorithm with potential to improve PPV for toddlers <20 months to the same level as observed in older toddlers.

This report describes a school-based screening project to improve early identification of children at risk for attention-deficit/hyperactivity disorder (ADHD) and communicate these concerns to parents, recommending that they contact their child’s primary care provider (PCP). Of 17,440 eligible children in first through fifth grades in five school districts, 47.0% of parents provided required written consent, and teachers completed 70.4% of the online screeners (using the Vanderbilt AD/HD Diagnostic Teacher Rating Scale). Of 5,772 screeners completed, 18.1% of children (n = 1,044) were identified as at risk. Parents of at-risk children were contacted to explain risk status and recommended to visit their child’s PCP for further evaluation. It was not possible to contact 39.1% of parents of at-risk children. Of the 636 parents of at-risk children who could be contacted, 53.1% (n = 338) verbally accepted the recommendation to follow-up with their PCP, which was not related to ADHD symptom severity. Parents of children with IEPs or related services were more likely to accept the recommendation to visit the PCP. Our exploration of the potential for school-based screening for ADHD identified a number of barriers to successful execution, but the data also indicated that this is an important problem to address.