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Laura C Politte, Lawrence Scahill, Janet Figueroa, James T McCracken, Bryan King, Christopher J McDougle
In a prior report, we showed that extended-release guanfacine (GEXR) is safe and effective for children with autism spectrum disorder (ASD) accompanied by ADHD symptoms. Here, we examine the impact of GEXR on oppositional behavior, anxiety, repetitive behavior, and sleep disturbance. Sixty-two subjects with ASD (53 boys, 9 girls; ages 5-14 years) were randomly assigned to GEXR (n = 30) or placebo (n = 32) for 8 weeks. Outcomes include the Home Situation Questionnaire-Modified for ASD (HSQ-ASD), Anxiety scale of the Child and Adolescent Symptom Inventory (CASI), Children's Yale-Brown Obsessive-Compulsive Scale-Modified for ASD (CYBOCS-ASD), and Children's Sleep Habits Questionnaire (CSHQ)...
February 27, 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Cynthia R Johnson, Tristram Smith, Alexandra DeMand, Luc Lecavalier, Victoria Evans, Matthew Gurka, Naomi Swiezy, Karen Bearss, Lawrence Scahill
BACKGROUND AND PURPOSE: Sleep disturbances in autism spectrum disorder (ASD) are common and may impair daytime functioning as well as add to parental burden. In this well characterized sample of young children with ASD and disruptive behaviors, we examine the association of age and IQ in sleep disturbances using the Child Sleep Habits Questionnaire modified for ASD (CSHQ-ASD). We also test whether children with poor sleep have greater daytime behavioral problems than those with better sleep...
April 2018: Sleep Medicine
Lora Minkova, Sarah Gregory, Rachael I Scahill, Ahmed Abdulkadir, Christoph P Kaller, Jessica Peter, Jeffrey D Long, Julie C Stout, Ralf Reilmann, Raymund A Roos, Alexandra Durr, Blair R Leavitt, Sarah J Tabrizi, Stefan Klöppel
Huntington's disease (HD) is a progressive neurodegenerative disorder that can be genetically confirmed with certainty decades before clinical onset. This allows the investigation of functional and structural changes in HD many years prior to disease onset, which may reveal important mechanistic insights into brain function, structure and organization in general. While regional atrophy is present at early stages of HD, it is still unclear if both hemispheres are equally affected by neurodegeneration and how the extent of asymmetry affects domain-specific functional decline...
2018: NeuroImage: Clinical
Lauren M Byrne, Filipe B Rodrigues, Eileanoir B Johnson, Enrico De Vita, Kaj Blennow, Rachael Scahill, Henrik Zetterberg, Amanda Heslegrave, Edward J Wild
Biomarkers of Huntington's disease (HD) in cerebrospinal fluid (CSF) could be of value in elucidating the biology of this genetic neurodegenerative disease, as well as in the development of novel therapeutics. Deranged synaptic and immune function have been reported in HD, and concentrations of the synaptic protein neurogranin and the microglial protein TREM2 are increased in other neurodegenerative diseases. We therefore used ELISAs to quantify neurogranin and TREM2 in CSF samples from HD mutation carriers and controls...
March 9, 2018: Scientific Reports
Terry Katz, Amy M Shui, Cynthia R Johnson, Amanda L Richdale, Ann M Reynolds, Lawrence Scahill, Beth A Malow
Sleep problems are common in children with autism spectrum disorder (ASD) and adversely impact daytime functioning. Although no questionnaires have been developed to assess sleep in children with ASD, the 33-item Children's Sleep Habits Questionnaire (CSHQ) is widely used in this population. We examined the factor structure of the CSHQ in 2872 children (age 4-10 years) enrolled in the Autism Treatment Network. A four-factor solution (Sleep Initiation and Duration, Sleep Anxiety/Co-Sleeping, Night Waking/Parasomnias, and Daytime Alertness) with 5-6 items per factor explained 75% of the total variation...
March 2, 2018: Journal of Autism and Developmental Disorders
Susanna W Chang, Joseph F McGuire, John T Walkup, Douglas W Woods, Lawrence Scahill, Sabine Wilhelm, Alan L Peterson, James Dziura, John Piacentini
This paper examined neurocognitive functioning and its relationship to behavior treatment response among youth with Tourette's Disorder (TD) in a large randomized controlled trial. Participants diagnosed with TD completed a brief neurocognitive battery assessing inhibitory functions, working memory, and habit learning pre- and post-treatment with behavior therapy (CBIT, Comprehensive Behavioral Intervention for Tics) or psychoeducation plus supportive therapy (PST). At baseline, youth with tics and Attention Deficit Hyperactivity Disorder (ADHD) exhibited some evidence of impaired working memory and simple motor inhibition relative to youth with tics without ADHD...
March 2018: Psychiatry Research
Emily J Ricketts, Joseph F McGuire, Susanna Chang, Deepika Bose, Madeline M Rasch, Douglas W Woods, Matthew W Specht, John T Walkup, Lawrence Scahill, Sabine Wilhelm, Alan L Peterson, John Piacentini
This study assessed the psychometric properties of a parent-reported tic severity measure, the Parent Tic Questionnaire (PTQ), and used the scale to establish guidelines for delineating clinically significant tic treatment response. Participants were 126 children ages 9 to 17 who participated in a randomized controlled trial of Comprehensive Behavioral Intervention for Tics (CBIT). Tic severity was assessed using the Yale Global Tic Severity Scale (YGTSS), Hopkins Motor/Vocal Tic Scale (HMVTS) and PTQ; positive treatment response was defined by a score of 1 (very much improved) or 2 (much improved) on the Clinical Global Impressions - Improvement (CGI-I) scale...
January 2018: Behavior Therapy
Sarah L Mason, Richard E Daws, Eyal Soreq, Eileanoir B Johnson, Rachael I Scahill, Sarah J Tabrizi, Roger A Barker, Adam Hampshire
OBJECTIVE: Huntington's disease (HD) gene-carriers can be identified prior to clinical diagnosis; however, statistical models for predicting when overt motor symptoms will manifest are too imprecise to be useful at the level of the individual. Perfecting this prediction is integral to the search for disease modifying therapies. This study aimed to identify an imaging marker capable of reliably predicting real-life clinical diagnosis in HD. METHOD: A multivariate machine learning approach was applied to resting-state and structural MRI scans from 19 pre-manifest HD gene carriers (preHD, 8 of whom developed clinical disease in the 5 years post-scanning) and 21 healthy controls...
February 5, 2018: Annals of Neurology
Eileanoir B Johnson, Lauren M Byrne, Sarah Gregory, Filipe B Rodrigues, Kaj Blennow, Alexandra Durr, Blair R Leavitt, Raymund A Roos, Henrik Zetterberg, Sarah J Tabrizi, Rachael I Scahill, Edward J Wild
OBJECTIVE: Neurofilament light (NfL) protein in blood plasma has been proposed as a prognostic biomarker of neurodegeneration in a number of conditions, including Huntington disease (HD). This study investigates the regional distribution of NfL-associated neural pathology in HD gene expansion carriers. METHODS: We examined associations between NfL measured in plasma and regionally specific atrophy in cross-sectional (n = 198) and longitudinal (n = 177) data in HD gene expansion carriers from the international multisite TRACK-HD study...
January 24, 2018: Neurology
Zaheer-Ud-Din Babar, Shane Scahill, Raveena Amee Nagaria, Louise E Curley
BACKGROUND: Healthcare is under significant pressure with the explosion of long term conditions, shift in worldwide demographics and is evolving through advances in technology. Aligned with this is the changing role of pharmacy from the traditional dispenser of medicines to having (in addition) a more advanced clinical role. This study aimed to understand what the pharmacy practice research agenda might look like from the viewpoint of pharmacy academics and practitioners across five high-income countries...
January 11, 2018: Research in Social & Administrative Pharmacy: RSAP
Peter McColgan, Sarah Gregory, Kiran K Seunarine, Adeel Razi, Marina Papoutsi, Eileanoir Johnson, Alexandra Durr, Raymund A C Roos, Blair R Leavitt, Peter Holmans, Rachael I Scahill, Chris A Clark, Geraint Rees, Sarah J Tabrizi
BACKGROUND: The earliest white matter changes in Huntington's disease are seen before disease onset in the premanifest stage around the striatum, within the corpus callosum, and in posterior white matter tracts. While experimental evidence suggests that these changes may be related to abnormal gene transcription, we lack an understanding of the biological processes driving this regional vulnerability. METHODS: Here, we investigate the relationship between regional transcription in the healthy brain, using the Allen Institute for Brain Science transcriptome atlas, and regional white matter connectivity loss at three time points over 24 months in subjects with premanifest Huntington's disease relative to control participants...
March 1, 2018: Biological Psychiatry
Karen Bearss, T Lindsey Burrell, Saankari A Challa, Valentina Postorino, Scott E Gillespie, Courtney Crooks, Lawrence Scahill
Telehealth is a potential solution to limited access to specialized services for children with autism spectrum disorder (ASD) in rural areas. We conducted a feasibility trial of parent training with children ages 3-8 with ASD and disruptive behavior from rural communities. Fourteen children (mean age 5.8 ± 1.7) from four telehealth sites enrolled. Thirteen families (92.9%) completed treatment, with 91.6% of core sessions attended. Therapists attained 98% fidelity to the manual and 93% of expected outcome measures were collected at week 24...
November 23, 2017: Journal of Autism and Developmental Disorders
Jennifer L Anderson, Timothy S Mulligan, Meng-Chieh Shen, Hui Wang, Catherine M Scahill, Frederick J Tan, Shao J Du, Elisabeth M Busch-Nentwich, Steven A Farber
As model organism-based research shifts from forward to reverse genetics approaches, largely due to the ease of genome editing technology, a low frequency of abnormal phenotypes is being observed in lines with mutations predicted to lead to deleterious effects on the encoded protein. In zebrafish, this low frequency is in part explained by compensation by genes of redundant or similar function, often resulting from the additional round of teleost-specific whole genome duplication within vertebrates. Here we offer additional explanations for the low frequency of mutant phenotypes...
November 2017: PLoS Genetics
Frank H Lau, Kelly Vogel, John P Luckett, Maxwell Hunt, Alicia Meyer, Camille L Rogers, Oren Tessler, Charles L Dupin, Hugo St Hilaire, Kazi N Islam, Trivia Frazier, Jeffrey Gimble, Steven Scahill
White adipose tissue (WAT) is a critical organ in both health and disease. However, physiologically faithful tissue culture models of primary human WAT remain limited, at best. Here we describe a novel WAT culture system in which primary human WAT is sandwiched between tissue-engineered sheets of adipose-derived stromal cells. This construct, called "sandwiched white adipose tissue" (SWAT), can be defined as a Microphysiological System (MPS) since it is a tissue-engineered, multicellular, 3D organ construct produced using human cells...
November 16, 2017: Tissue Engineering. Part C, Methods
Eileanoir B Johnson, Sarah Gregory, Hans J Johnson, Alexandra Durr, Blair R Leavitt, Raymund A Roos, Geraint Rees, Sarah J Tabrizi, Rachael I Scahill
The selection of an appropriate segmentation tool is a challenge facing any researcher aiming to measure gray matter (GM) volume. Many tools have been compared, yet there is currently no method that can be recommended above all others; in particular, there is a lack of validation in disease cohorts. This work utilizes a clinical dataset to conduct an extensive comparison of segmentation tools. Our results confirm that all tools have advantages and disadvantages, and we present a series of considerations that may be of use when selecting a GM segmentation method, rather than a ranking of these tools...
2017: Frontiers in Neurology
Jessica Bradshaw, Karen Bearss, Courtney McCracken, Tristram Smith, Cynthia Johnson, Luc Lecavalier, Naomi Swiezy, Lawrence Scahill
This study examines parent and child characteristics in young children with autism spectrum disorder and disruptive behavior who showed a positive response to a parent education program in a randomized clinical trial of parent training. Children with autism spectrum disorder (N = 180) were randomized to parent training (PT) or parent education program (PEP) for 6 months. Using the Clinical Global Impression-Improvement scale, masked independent evaluators rated positive response in 68.5% of children in PT compared to 39...
October 19, 2017: Journal of Clinical Child and Adolescent Psychology
David C Houghton, Matthew R Capriotti, Lawrence D Scahill, Sabine Wilhelm, Alan L Peterson, John T Walkup, John Piacentini, Douglas W Woods
Behavior therapy is effective for Persistent Tic Disorders (PTDs), but behavioral processes facilitating tic reduction are not well understood. One process, habituation, is thought to create tic reduction through decreases in premonitory urge severity. The current study tested whether premonitory urges decreased in youth with PTDs (N = 126) and adults with PTDs (N = 122) who participated in parallel randomized clinical trials comparing behavior therapy to psychoeducation and supportive therapy (PST). Trends in premonitory urges, tic severity, and treatment outcome were analyzed according to the predictions of a habituation model, whereby urge severity would be expected to decrease in those who responded to behavior therapy...
November 2017: Behavior Therapy
Suzannah Iadarola, Lynne Levato, Bryan Harrison, Tristram Smith, Luc Lecavalier, Cynthia Johnson, Naomi Swiezy, Karen Bearss, Lawrence Scahill
We report on parent outcomes from a randomized clinical trial of parent training (PT) versus psychoeducation (PEP) in 180 children with autism spectrum disorder (ASD) and disruptive behavior. We compare the impact of PT and PEP on parent outcomes: Parenting Stress Index (PSI), Parent Sense of Competence (PSOC), and Caregiver Strain Questionnaire (CGSQ). Mixed-effects linear models evaluated differences at weeks 12 and 24, controlling for baseline scores. Parents in PT reported greater improvement than PEP on the PSOC (ES = 0...
October 7, 2017: Journal of Autism and Developmental Disorders
Jeffrey D Long, James A Mills, Blair R Leavitt, Alexandra Durr, Raymund A Roos, Julie C Stout, Ralf Reilmann, Bernhard Landwehrmeyer, Sarah Gregory, Rachael I Scahill, Douglas R Langbehn, Sarah J Tabrizi
Importance: Predictive genetic testing in Huntington disease (HD) enables therapeutic trials in HTT gene expansion mutation carriers prior to a motor diagnosis. Progression-free survival (PFS) is the composite of a motor diagnosis or a progression event, whichever comes first. Objective: To determine if PFS provides feasible sample sizes for trials with mutation carriers who have not yet received a motor diagnosis. Design, Setting, and Participants: This study uses data from the 2-phase, longitudinal cohort studies called Track and from a longitudinal cohort study called the Cooperative Huntington Observational Research Trial (COHORT)...
November 1, 2017: JAMA Neurology
Muhammad Atif, Arslan Bashir, Nafees Ahmad, Razia Kaneez Fatima, Sehar Saba, Shane Scahill
BACKGROUND: Interim treatment outcomes at 6-months for multidrug-resistant tuberculosis (MDR-TB) treatment are among the most basic performance monitoring and key evaluation indicators in the Stop and End TB strategy of the World Health Organization (WHO). Therefore, this study was conducted to evaluate the interim treatment outcomes of MDR-TB patients in Pakistan. METHODS: This study was conducted at the Programmatic Management Unit for Drug-resistance TB (PMDT) site of the National Tuberculosis Program (NTP), Pakistan...
September 29, 2017: BMC Infectious Diseases
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