Arts & Sciences Brown School McKelvey School Medicine Weekly Publications

WashU weekly Neuroscience publications

“Classification of temporal ICA components for separating global noise from fMRI data: Reply to Power” (2019) NeuroImage

Classification of temporal ICA components for separating global noise from fMRI data: Reply to Power
(2019) NeuroImage, 197, pp. 435-438. 

Glasser, M.F.a b c , Coalson, T.S.a , Bijsterbosch, J.D.d , Harrison, S.J.d e , Harms, M.P.f , Anticevic, A.g , Van Essen, D.C.a , Smith, S.M.d

a Department of Neuroscience, Washington University Medical School, Saint Louis, MI 63110, United States
b Department of Radiology, Washington University Medical School, Saint Louis, MI 63110, United States
c St. Luke’s Hospital, Saint Louis, MI 63017, United States
d Centre for Functional MRI of the Brain (FMRIB), Wellcome Centre for Integrative Neuroimaging, Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Headley Way, Oxford, OX3 9DU, United Kingdom
e Translational Neuromodeling Unit, University of Zurich & ETH Zurich, Wilfriedstrasse 6, Zurich, 8032, Switzerland
f Department of Psychiatry, Washington University Medical School, Saint Louis, MO, United States
g Department of Psychiatry, Yale University School of Medicine, 300 George Street, New Haven, CT 06511, United States

Abstract
We respond to a critique of our temporal Independent Components Analysis (ICA)method for separating global noise from global signal in fMRI data that focuses on the signal versus noise classification of several components. While we agree with several of Power’s comments, we provide evidence and analysis to rebut his major criticisms and to reassure readers that temporal ICA remains a powerful and promising denoising approach. © 2019 Elsevier Inc.

Document Type: Article
Publication Stage: Final
Source: Scopus

“Frontal theta activity and white matter plasticity following mindfulness meditation” (2019) Current Opinion in Psychology

Frontal theta activity and white matter plasticity following mindfulness meditation
(2019) Current Opinion in Psychology, 28, pp. 294-297. 

Tang, Y.-Y.a , Tang, R.b , Rothbart, M.K.c , Posner, M.I.c

a Department of Psychological Sciences, Texas Tech University, Lubbock, TX, United States
b Department of Psychological and Brain Sciences, Washington University in St. Louis, St. Louis, MO, United States
c Department of Psychology, University of Oregon, Eugene, OR, United States

Abstract
Both brain alpha and theta power have been examined in the mindfulness meditation literature and suggested as key biological signatures that potentially facilitate a successful meditative state. However, the exact role of how alpha and theta waves contribute to the initiation and maintenance of a meditative state remains elusive. In this perspective paper, we discuss the role of frontal midline theta (FMθ)activity in brain white matter plasticity following mindfulness meditation. In accordance with the previous studies in humans, we propose that FMθ activity indexes the control needed to maintain the meditation state; whereas alpha activity is related to the preparation needed to achieve the meditative state. Without enough mental preparation, one often struggles with and has difficulty achieving a meditative state. Animal work provides further evidence supporting the hypothesis that mindfulness meditation induces white matter changes through increasing FMθ activity. These studies shed light on how to effectively enhance brain plasticity through mindfulness meditation. © 2019 Elsevier Ltd

Document Type: Review
Publication Stage: Final
Source: Scopus

“Getting to precision psychopharmacology: Combining clinical and genetic information to predict fat gain from aripiprazole” (2019) Journal of Psychiatric Research

Getting to precision psychopharmacology: Combining clinical and genetic information to predict fat gain from aripiprazole
(2019) Journal of Psychiatric Research, 114, pp. 67-74. 

Oughli, H.a , Lenze, E.J.a , Locke, A.E.b , Yingling, M.D.a , Zhong, Y.c , Miller, J.P.d , Reynolds, C.F., IIIe , Mulsant, B.H.f , Newcomer, J.W.a g , Peterson, T.R.b , Müller, D.J.f , Nicol, G.E.a

a Washington University School of Medicine, Department of Psychiatry, Healthy Mind Lab, St. Louis, MO, United States
b Washington University School of Medicine, Department of Internal Medicine, St. Louis, MO, United States
c University of Pittsburgh Graduate School of Public Health, Department of Epidemiology, Pittsburgh, PA, United States
d Washington University School of Medicine, Division of Biostatistics, St. Louis, MO, United States
e University of Pittsburgh Medical Center, Department of Psychiatry, Pittsburgh, PA, United States
f University of Toronto, Department of Psychiatry and Center for Addiction and Mental Health, Toronto, Canada
g Florida Atlantic University, Charles E. Schmidt College of Medicine, Boca Raton, FL, United States

Abstract
Introduction: All atypical antipsychotics are associated with some degree of weight gain. We applied a novel statistical approach to identify moderators of aripiprazole-induced fat gain using clinical and genetic data from a randomized clinical trial (RCT) of treatment resistant depression in older adults. Materials and methods: Adults aged ≥60 years with non-response to a prospective trial of venlafaxine were randomized to 12 weeks of aripiprazole augmentation (n = 91) or placebo (n = 90). Dual energy x-ray absorptiometry (DEXA) measured adiposity at baseline and 12 weeks. Independent moderators of total body fat gain were used to generate two combined multiple moderators, one including clinical data alone and one including both clinical and genetic data to characterize individuals who gained fat during aripiprazole augmentation. Results: The value of the combined genetic + clinical multiple moderator (M cg ) was 0.57 [95% CI 0.46, 0.68] (effect size: 0.57), compared to the combined clinical moderator (M c ) value of 0.49 [0.34, 0.63] (effect size: 0.49). Individuals who gained adiposity in this study were more likely to be female and younger in age, have lower weight, fasting glucose and lipids at baseline and positive for the HTR2C polymorphism. Discussion: These results demonstrate a combined multiple moderator approach, including both clinical and genetic moderators, can be applied to existing clinical trial data to understand adverse treatment effects. This method allowed for more specific characterization of individuals at risk for the outcome of interest. Further work is needed to identify additional genetic moderators and to validate the approach. © 2019

Author Keywords
Adiposity;  Aripiprazole;  Older adults;  Treatment resistant depression

Document Type: Article
Publication Stage: Final
Source: Scopus

“Hippocampal volume and depression among young children” (2019) Psychiatry Research – Neuroimaging

Hippocampal volume and depression among young children
(2019) Psychiatry Research – Neuroimaging, 288, pp. 21-28. 

Barch, D.M.a b c , Tillman, R.b , Kelly, D.b , Whalen, D.b , Gilbert, K.b , Luby, J.L.b

a Department of Psychological & Brain Sciences, Washington University in St. Louis, United States
b Department of Psychiatry, Washington University in St. Louis, United States
c Department of Radiology, Washington University in St. Louis, United States

Abstract
Clinical depression can occur in young children as early as age three. This very early onset variant of depression shows the same clinical features with developmental adjustments as depression that onsets later in life. One robust neural feature of adult depression is reduced hippocampal volume. We measured hippocampal volume in a sample of 35 children aged 4–7 who were either in a clinical trial for preschool onset depression or were recruited from the community. We used T1 MPRAGE acquisitions on a Siemen’s Scanner, with Freesurfer 5.3 used to segment the hippocampus. Depression was measured using the K-SADS early childhood (K-SADS-EC) to create a dimensional depression severity score and the Child Behavior Checklist (CBCL) Depression T-Score. Multilevel models indicated that greater depression severity as measured by either the CBCL Depression Score or the K-SADS-EC was associated with lower hippocampal volume, even controlling for total gray matter, maternal depression, income-to-needs ratio, and stressful life events. These data indicate evidence for reduced hippocampal volume among children with PO-MDD who were more severely depressed. Findings are consistent with the idea that hippocampal volume reductions are an early occurring associated neural marker of MDD, particularly for more severe depression. © 2019

Author Keywords
Brain imaging;  Hippocampus;  Mood disorder;  Pediatric;  Preschool;  Structural imaging;  Volumetric

Document Type: Article
Publication Stage: Final
Source: Scopus

“Normal saline bolus use in pediatric emergency departments is associated with poorer pain control in children with sickle cell anemia and vaso-occlusive pain” (2019) American Journal of Hematology

Normal saline bolus use in pediatric emergency departments is associated with poorer pain control in children with sickle cell anemia and vaso-occlusive pain
(2019) American Journal of Hematology, 94 (6), pp. 689-696. 

Carden, M.A.a , Brousseau, D.C.b , Ahmad, F.A.c , Bennett, J.d , Bhatt, S.e , Bogie, A.f , Brown, K.g , Casper, T.C.h , Chapman, L.L.i , Chumpitazi, C.E.j , Cohen, D.k , Dampier, C.l m , Ellison, A.M.n , Grasemann, H.o , Hickey, R.W.p , Hsu, L.L.q , Leibovich, S.r , Powell, E.s , Richards, R.h , Sarnaik, S.t , Weiner, D.L.u , Morris, C.R.v w , on behalf of the Sickle Cell Disease Arginine Study Group and the Pediatric Emergency Care Applied Research Network (PECARN)x

a Departments of Pediatrics and Medicine, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, United States
b Department of Pediatrics, Division of Pediatric Emergency Medicine, Medical College of Wisconsin, Milwaukee, WI, United States
c Department of Pediatrics, Division of Pediatric Emergency Medicine, Washington University School of Medicine, St. Louis, MO, United States
d Department of Pediatrics, Division of Pediatric Emergency Medicine, Alfred I. DuPont Hospital for Children, Wilmington, DE, United States
e Department of Pediatrics, Division of Pediatric Emergency Medicine, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, United States
f Department of Pediatrics, Division of Pediatric Emergency Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States
g Department of Pediatrics, Division of Pediatric Emergency Medicine, Children’s National Medical Center, Washington, DC, United States
h Department of Pediatrics, Division of Pediatric Critical Care, University of Utah, Salt Lake City, UT, United States
i Alpert Medical School, Brown University, Providence, RI, United States
j Department of Pediatrics, Division of Pediatric Emergency Medicine, Baylor College of Medicine, Houston, TX, United States
k Department of Pediatrics, Division of Pediatric Emergency Medicine, Nationwide Children’s Hospital, Columbus, OH, United States
l Department of Pediatrics, Division of Hematology/Oncology, Emory University School of Medicine, Atlanta, GA, United States
m Department of Pediatrics, Division of Pediatric Emergency Medicine, The Aflac Cancer and Blood Disorders Center of Children’s Healthcare, Atlanta, GA, United States
n Department of Pediatrics, Division of Pediatric Emergency Medicine, The Children’s Hospital of Philadelphia, Philadelphia, PA, United States
o Department of Pediatrics, Division of Respiratory Medicine, The Hospital for Sick Children, Toronto, ON, Canada
p Department of Pediatrics, Division of Pediatric Emergency Medicine, Children’s Hospital of Pittsburgh of UPMC, Pittsburgh, PA, United States
q Department of Pediatrics, Division of Pediatric Hematology and Oncology, University of Illinois at Chicago, Chicago, IL, United States
r Department of Pediatrics, Division of Pediatric Emergency Medicine, UCSF-Benioff Children’s Hospital at Oakland, Oakland, CA, United States
s Department of Pediatrics, Division of Pediatric Emergency Medicine, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL, United States
t Department of Pediatrics, Division of Pediatric Emergency Medicine, Children’s Hospital of Michigan, Detroit, MI, United States
u Department of Pediatrics, Division of Pediatric Emergency Medicine, Boston Children’s Hospital, Boston, MA, United States
v Department of Pediatrics, Division of Pediatric Emergency Medicine, Emory University School of Medicine, Atlanta, GA, United States
w Department of Pediatrics, Division of Pediatric Emergency Medicine, Children’s Healthcare of Atlanta, Atlanta, GA, United States

Abstract
Vaso-occlusive pain events (VOE) are the leading cause of emergency department (ED) visits in sickle cell anemia (SCA). This study assessed the variability in use of intravenous fluids (IVFs), and the association of normal saline bolus (NSB), on pain and other clinical outcomes in children with SCA, presenting to pediatric emergency departments (PED) with VOE. Four-hundred charts of children age 3-21 years with SCA/VOE receiving parenteral opioids at 20 high-volume PEDs were evaluated in a retrospective study. Data on type and amount of IVFs used were collected. Patients were divided into two groups: those who received NSB and those who did not. The association of NSB use on change in pain scores and admission rates was evaluated. Among 400 children studied, 261 (65%) received a NSB. Mean age was 13.8 ± 4.9 years; 46% were male; 92% had hemoglobin-SS. The IVFs (bolus and/or maintenance) were used in 84% of patients. Eight different types of IVFs were utilized and IVF volume administered varied widely. Mean triage pain scores were similar between groups, but improvement in pain scores from presentation-to-ED-disposition was smaller in the NSB group (2.2 vs 3.0, P =.03), while admission rates were higher (71% vs 59%, P =.01). Use of NSB remained associated with poorer final pain scores and worse change in pain scores in our multivariable model. In conclusion, wide variations in practice utilizing IVFs are common. NSB is given to >50% of children with SCA/VOE, but is associated with poorer pain control; a controlled prospective trial is needed to determine causality. © 2019 Wiley Periodicals, Inc.

Author Keywords
emergency department;  normal saline bolus;  Pediatric Emergency Care Applied Research Network (PECARN);  sickle cell anemia;  vaso-occlusive pain

Document Type: Article
Publication Stage: Final
Source: Scopus

“The association of fatigue and social participation in multiple sclerosis as assessed using two different instruments” (2019) Multiple Sclerosis and Related Disorders

The association of fatigue and social participation in multiple sclerosis as assessed using two different instruments
(2019) Multiple Sclerosis and Related Disorders, 31, pp. 165-172. 

Salter, A.a , Fox, R.J.b , Tyry, T.c , Cutter, G.d , Marrie, R.A.e

a Department of Biostatistics, Washington University, St. Louis, MO, United States
b Mellen Center for Multiple Sclerosis, Cleveland Clinic Foundation, Cleveland, OH, United States
c Dignity Health, St. Joseph’s Hospital and Medical Center, Phoenix, AZ, United States
d Department of Biostatistics, University of Alabama in Birmingham School of Public Health, Birmingham, AL, United States
e Departments of Internal Medicine and Community Health Sciences, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada

Abstract
Introduction: Fatigue is an important aspect of health-related quality of life and a commonly reported symptom by many persons with multiple sclerosis (MS). There are multiple validated instruments available to assess fatigue in MS with differing benefits for each instrument. Objective: We aimed to assess the relationship between the PROMIS Fatigue instrument and the Fatigue Performance Scale (FPS) in the NARCOMS registry. Additionally, we aimed to examine the association of fatigue with social participation. Methods: The NARCOMS registry is a voluntary, self-report registry, which has enrolled participants with MS who provide semi-annual updates regarding their MS. The Fall 2016 semi-annual survey included the PROMIS Fatigue and Ability to Participate in Social Roles and Activities questionnaires, in addition to demographic and clinical information. We examined the association between instruments using Spearman correlations. Linear and ordinal regression models were used to evaluate associations with fatigue using the PROMIS Fatigue and the FPS. Results: Of the 7,006 Fall 2016 respondents, 6,883 (98.2%) completed the PROMIS instruments. Respondents were mostly female (79.5%) and Caucasian (87.4%), had a mean (SD) age of 59.9 (10.2) years and moderate disability level (median Patient Determined Disease Steps [PDDS] 4 [early cane]). The mean (SD) PROMIS Fatigue T-score was 56.8 (11.0) and median (25th, 75th) FPS was 3 [moderate] (1 [minimal], 4 [severe]). Fatigue measures were strongly correlated (r = 0.83, 95% CI: [0.827, 0.842]). Factors consistently associated with fatigue were PDDS level, depression and pain functionality scales, and symptoms worsening. The ability to participate in social roles and activities was strongly associated with fatigue and had an independent effect on fatigue after adjusting for PDDS, depression and pain levels. Conclusion: A high proportion of respondents experience some level of fatigue and it is independently associated with reduced social participation. © 2019 Elsevier B.V.

Author Keywords
Fatigue;  Multiple sclerosis;  Patient reported outcomes;  PROMIS;  Social participation

Document Type: Article
Publication Stage: Final
Source: Scopus

“The structure of amyloid-β dimers in Alzheimer’s disease brain: a step forward for oligomers” (2019) Brain : a journal of neurology

The structure of amyloid-β dimers in Alzheimer’s disease brain: a step forward for oligomers
(2019) Brain : a journal of neurology, 142 (5), pp. 1168-1169. 

Bateman, R.J.a b c , Mawuenyega, K.G.a , Wildburger, N.C.a

a Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
b Knight Alzheimer’s Disease Research Center, Washington University School of Medicine, St. Louis, MO, United States
c Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, United States

Document Type: Article
Publication Stage: Final
Source: Scopus

“Clinical, pathophysiological and genetic features of motor symptoms in autosomal dominant Alzheimer’s disease” (2019) Brain : a journal of neurology

Clinical, pathophysiological and genetic features of motor symptoms in autosomal dominant Alzheimer’s disease
(2019) Brain : a journal of neurology, 142 (5), pp. 1429-1440. 

Vöglein, J.a b , Paumier, K.c , Jucker, M.d e , Preische, O.d e , McDade, E.c , Hassenstab, J.c , Benzinger, T.L.c , Noble, J.M.f , Berman, S.B.g , Graff-Radford, N.R.h , Ghetti, B.i , Farlow, M.R.i , Chhatwal, J.j , Salloway, S.k , Xiong, C.c , Karch, C.M.c , Cairns, N.c , Mori, H.l , Schofield, P.R.m n , Masters, C.L.o , Goate, A.p , Buckles, V.c , Fox, N.q , Rossor, M.q , Chrem, P.r , Allegri, R.r , Ringman, J.M.s , Höglinger, G.a t u , Steiner, H.a v , Dieterich, M.a b u w , Haass, C.a u v , Laske, C.d x , Morris, J.C.c , Bateman, R.J.c , Danek, A.a b , Levin, J.a b u , Dominantly Inherited Alzheimer Networky

a German Center for Neurodegenerative Diseases (DZNE), Munich, Germany
b Department of Neurology, Ludwig-Maximilians-Universität München, Munich, Germany
c Washington University School of Medicine, 660 South Euclid, Saint Louis, MO, USA
d German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany
e Hertie Institute for Clinical Brain Research, University of Tübingen, Germany
f Department of Neurology, Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, and Gertrude H. Sergievsky Center, Columbia University Irving Medical Center, 710 West 168th Street Box 176, New York, NY, USA
g University of Pittsburgh, Pittsburgh, PA, United States
h Department of Neurology, Mayo Clinic, Jacksonville, FL, United States
i Indiana University School of Medicine, Indianapolis, IN, United States
j Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
k Butler Hospital, 345 Blackstone Boulevard, Providence, RI, United States
l Osaka City University Medical School, Asahimachi ,Abenoku, Osaka, 545-8585, Japan
m Neuroscience Research Australia, Sydney, Australia
n School of Medical Sciences, University of New South Wales, Sydney, Australia
o Florey Institute, University of Melbourne, Level 5, Kenneth Myer Building, 30 Royal Parade, Parkville, Victoria, 3010, Australia
p Department of Neuroscience, Icahn School of Medicine at Mount Sinai, 1425 Madison Ave, B1065, New York, NY, USA
q Dementia Research Centre, Institute of Neurology, University College London, Queen Square, London, United Kingdom
r FLENI, Montañeses 2325 (C1428AQK), Bs As, Argentina
s Keck School of Medicine of University of Southern California, Center for the Health Professionals, 1540 Alcazar Street, Los Angeles, CA, United States
t Department of Neurology, Technical University of Munich, Munich, Germany
u Munich Cluster for Systems Neurology (SyNergy), Munich, Germany
v Biomedical Center (BMC), Metabolic Biochemistry, LMU Munich, Germany
w German Center for Vertigo and Balance Disorders, Ludwig Maximilians University, Munich, Germany
x Section for Dementia Research, Hertie Institute for Clinical Brain Research and Department of Psychiatry and Psychotherapy, University of Tübingen, 72076 Tübingen, Germany

Abstract
Owing to an early and marked deposition of amyloid-β in the basal ganglia, autosomal dominant Alzheimer’s disease could distinctly involve motor symptoms. Therefore, we aimed to assess the prevalence and characteristics of motor signs in autosomal dominant Alzheimer’s disease. Baseline Unified Parkinson Disease Rating Scale part three scores (UPDRS-III) from 433 participants of the Dominantly Inherited Alzheimer’s Network observational study were analysed. Motor symptoms were scrutinized with respect to associations with mutation carrier status, mutation site within PSEN1, basal ganglia amyloid-β as measured by Pittsburgh compound B PET, estimated years to symptom onset and Clinical Dementia Rating Scale-Sum of Boxes. Motor findings in mutation carriers were compared to patients with sporadic Alzheimer’s disease using data of the National Alzheimer’s Coordination Center. Mutation carriers showed motor findings at a higher frequency (28.4% versus 12.8%; P < 0.001) and severity (mean UPDRS-III scores 2.0 versus 0.4; P < 0.001) compared to non-carriers. Eleven of the 27 UPDRS-III items were statistically more frequently affected in mutation carriers after adjustment for multiple comparisons. Ten of these 11 items were subscale components of bradykinesia. In cognitively asymptomatic mutation carriers, dysdiadochokinesia was more frequent compared to non-carriers (right hand: 3.8% versus 0%; adjusted P = 0.023; left: 4.4% versus 0.6%; adjusted P = 0.031). In this cohort, the positive predictive value for mutation carrier status in cognitively asymptomatic participants (50% a priori risk) of dysdiadochokinesia was 100% for the right and 87.5% for the left side. Mutation carriers with motor findings more frequently were basal ganglia amyloid-β positive (84% versus 63.3%; P = 0.006) and showed more basal ganglia amyloid-β deposition (Pittsburgh compound B-standardized uptake value ratio 2.472 versus 1.928; P = 0.002) than those without. Frequency and severity of motor findings were greater in post-codon 200 PSEN1 mutations (36%; mean UPDRS-III score 3.03) compared to mutations pre-codon 200 PSEN1 (19.3%, P = 0.022; 0.91, P = 0.013). In mutation carriers, motor symptom severity was significantly positively correlated with basal ganglia amyloid-β deposition, Clinical Dementia Rating scores and estimated years to symptom onset. Mutation carriers with a Clinical Dementia Rating global score of 2 exhibited more pronounced motor symptoms than sporadic Alzheimer’s disease patients with the same Clinical Dementia Rating global score (mean UPDRS-III scores 20.71 versus 5.96; P < 0.001). With a prevalence of approximately 30% and increasing severity with progression of dementia, motor symptoms are proven as a clinically relevant finding in autosomal dominant Alzheimer’s disease, in particular in advanced dementia stages, that correlates with deposition of amyloid-β in the basal ganglia. In a very small per cent of cognitively asymptomatic members of families with autosomal dominant Alzheimer’s disease, dysdiadochokinesia may increase the chance of an individual’s status as mutation carrier. © The Author(s) (2019). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Author Keywords
Alzheimer’s disease;  amyloid-β;  genetics;  motor symptoms;  Unified Parkinson Disease Rating Scale

Document Type: Article
Publication Stage: Final
Source: Scopus

“Effects of Early Auditory Deprivation on Working Memory and Reasoning Abilities in Verbal and Visuospatial Domains for Pediatric Cochlear Implant Recipients” (2019) Ear and hearing

Effects of Early Auditory Deprivation on Working Memory and Reasoning Abilities in Verbal and Visuospatial Domains for Pediatric Cochlear Implant Recipients
(2019) Ear and hearing, 40 (3), pp. 517-528. 

Davidson, L.S.a , Geers, A.E.b , Hale, S.c , Sommers, M.M.c , Brenner, C.d , Spehar, B.a

a Department of Otolaryngology, Washington University School of Medicine, St. Louis, MO, United States
b Department of Behavioral and Brain Sciences, University of Texas Dallas, Dallas, TX, United States
c Department of Psychology, Washington University St. LouisMO, United States
d Moog Center for Deaf Education, St. Louis, MO, United States

Abstract
OBJECTIVES: The overall goal of this study was to compare verbal and visuospatial working memory in children with normal hearing (NH) and with cochlear implants (CI). The main questions addressed by this study were (1) Does auditory deprivation result in global or domain-specific deficits in working memory in children with CIs compared with their NH age mates? (2) Does the potential for verbal recoding affect performance on measures of reasoning ability in children with CIs relative to their NH age mates? and (3) Is performance on verbal and visuospatial working memory tasks related to spoken receptive language level achieved by children with CIs? DESIGN: A total of 54 children ranging in age from 5 to 9 years participated; 25 children with CIs and 29 children with NH. Participants were tested on both simple and complex measures of verbal and visuospatial working memory. Vocabulary was assessed with the Peabody Picture Vocabulary Test (PPVT) and reasoning abilities with two subtests of the WISC-IV (Wechsler Intelligence Scale for Children, 4th edition): Picture Concepts (verbally mediated) and Matrix Reasoning (visuospatial task). Groups were compared on all measures using analysis of variance after controlling for age and maternal education. RESULTS: Children with CIs scored significantly lower than children with NH on measures of working memory, after accounting for age and maternal education. Differences between the groups were more apparent for verbal working memory compared with visuospatial working memory. For reasoning and vocabulary, the CI group scored significantly lower than the NH group for PPVT and WISC Picture Concepts but similar to NH age mates on WISC Matrix Reasoning. CONCLUSIONS: Results from this study suggest that children with CIs have deficits in working memory related to storing and processing verbal information in working memory. These deficits extend to receptive vocabulary and verbal reasoning and remain even after controlling for the higher maternal education level of the NH group. Their ability to store and process visuospatial information in working memory and complete reasoning tasks that minimize verbal labeling of stimuli more closely approaches performance of NH age mates.

Document Type: Article
Publication Stage: Final
Source: Scopus

“Genetic Discovery of ATP-Sensitive K + Channels in Cardiovascular Diseases” (2019) Circulation. Arrhythmia and electrophysiology

Genetic Discovery of ATP-Sensitive K + Channels in Cardiovascular Diseases
(2019) Circulation. Arrhythmia and electrophysiology, 12 (5), p. e007322. Cited 1 time.

Huang, Y.a b , Hu, D.a b , Huang, C.a b , Nichols, C.G.c

a Department of Cardiology, Renmin Hospital of Wuhan University; Cardiovascular Research Institute, Wuhan University, PR China (Y.H., D.H., C.H.)
b Hubei Key Laboratory of Cardiology, PR China (Y.H., Wuhan, China
c Center for the Investigation of Membrane Excitability Diseases and Department of Cell Biology and Physiology, Washington University School of Medicine, Saint Louis, United States

Abstract
The ATP-sensitive K+ (KATP) channels are hetero-octameric protein complexes comprising 4 pore-forming (Kir6.x) subunits and 4 regulatory sulfonylurea receptor (SURx) subunits. They are prominent in myocytes, pancreatic β cells, and neurons and link cellular metabolism with membrane excitability. Using genetically modified animals and genomic analysis in patients, recent studies have implicated certain ATP-sensitive K+ channel subtypes in physiological and pathological processes in a variety of cardiovascular diseases. In this review, we focus on the causal relationship between ATP-sensitive K+ channel activity and pathophysiology in the cardiovascular system, particularly from the perspective of genetic changes in human and animal models.

Author Keywords
cardiovascular diseases;  cardiovascular system;  heart failure;  neuron;  sulfonylurea receptor

Document Type: Article
Publication Stage: Final
Source: Scopus

“Genome-wide association study identifies 30 loci associated with bipolar disorder” (2019) Nature Genetics

Genome-wide association study identifies 30 loci associated with bipolar disorder
(2019) Nature Genetics, 51 (5), pp. 793-803. 

Stahl, E.A.a b c , Breen, G.d e , Forstner, A.J.f g h i j , McQuillin, A.k , Ripke, S.l m n , Trubetskoy, V.m , Mattheisen, M.o p q r s , Wang, Y.t u , Coleman, J.R.I.d e , Gaspar, H.A.d e , de Leeuw, C.A.v , Steinberg, S.w , Pavlides, J.M.W.x , Trzaskowski, M.y , Byrne, E.M.y , Pers, T.H.c z , Holmans, P.A.aa , Richards, A.L.aa , Abbott, L.l , Agerbo, E.s ab , Akil, H.ac , Albani, D.ad , Alliey-Rodriguez, N.ae , Als, T.D.o p s , Anjorin, A.af , Antilla, V.n , Awasthi, S.m , Badner, J.A.ag , Bækvad-Hansen, M.s ah , Barchas, J.D.ai , Bass, N.k , Bauer, M.aj , Belliveau, R.l , Bergen, S.E.ak , Pedersen, C.B.s ab , Bøen, E.al , Boks, M.P.am , Boocock, J.an , Budde, M.ao , Bunney, W.ap , Burmeister, M.aq , Bybjerg-Grauholm, J.s ah , Byerley, W.ar , Casas, M.as at au av , Cerrato, F.l , Cervantes, P.aw , Chambert, K.l , Charney, A.W.b , Chen, D.l , Churchhouse, C.l n , Clarke, T.-K.ax , Coryell, W.ay , Craig, D.W.az , Cruceanu, C.aw ba , Curtis, D.bb bc , Czerski, P.M.bd , Dale, A.M.be bf bg bh , de Jong, S.d e , Degenhardt, F.h , Del-Favero, J.bi , DePaulo, J.R.bj , Djurovic, S.bk bl , Dobbyn, A.L.a b , Dumont, A.l , Elvsåshagen, T.bm bn , Escott-Price, V.aa , Fan, C.C.bh , Fischer, S.B.f j , Flickinger, M.bo , Foroud, T.M.bp , Forty, L.aa , Frank, J.bq , Fraser, C.aa , Freimer, N.B.br , Frisén, L.bs bt bu , Gade, K.ao bv , Gage, D.l , Garnham, J.bw , Giambartolomei, C.bx , Pedersen, M.G.s ab , Goldstein, J.l , Gordon, S.D.by , Gordon-Smith, K.bz , Green, E.K.ca , Green, M.J.cb cc , Greenwood, T.A.bg , Grove, J.o p s cd , Guan, W.ce , Guzman-Parra, J.cf , Hamshere, M.L.aa , Hautzinger, M.cg , Heilbronner, U.ao , Herms, S.f h j , Hipolito, M.ch , Hoffmann, P.f h j , Holland, D.be ci , Huckins, L.a b , Jamain, S.cj ck , Johnson, J.S.a b , Juréus, A.ak , Kandaswamy, R.d , Karlsson, R.ak , Kennedy, J.L.cl cm cn co , Kittel-Schneider, S.cp , Knowles, J.A.cq cr , Kogevinas, M.cs , Koller, A.C.h , Kupka, R.ct cu cv , Lavebratt, C.bs , Lawrence, J.cw , Lawson, W.B.ch , Leber, M.cx , Lee, P.H.l n cy , Levy, S.E.cz , Li, J.Z.da , Liu, C.db , Lucae, S.dc , Maaser, A.h , MacIntyre, D.J.dd de , Mahon, P.B.bj df , Maier, W.dg , Martinsson, L.bt , McCarroll, S.l dh , McGuffin, P.d , McInnis, M.G.di , McKay, J.D.dj , Medeiros, H.cr , Medland, S.E.by , Meng, F.ac di , Milani, L.dk , Montgomery, G.W.y , Morris, D.W.dl dm , Mühleisen, T.W.f dn , Mullins, N.d , Nguyen, H.a b , Nievergelt, C.M.bg do , Adolfsson, A.N.dp , Nwulia, E.A.ch , O’Donovan, C.bw , Loohuis, L.M.O.br , Ori, A.P.S.br , Oruc, L.dq , Ösby, U.dr , Perlis, R.H.ds dt , Perry, A.bz , Pfennig, A.aj , Potash, J.B.bj , Purcell, S.M.b df , Regeer, E.J.du , Reif, A.cp , Reinbold, C.S.f j , Rice, J.P.dv , Rivas, F.cf , Rivera, M.d dw , Roussos, P.a b dx , Ruderfer, D.M.dy , Ryu, E.dz , Sánchez-Mora, C.as at av , Schatzberg, A.F.ea , Scheftner, W.A.eb , Schork, N.J.ec , Shannon Weickert, C.cb cc , Shehktman, T.bg , Shilling, P.D.bg , Sigurdsson, E.ed , Slaney, C.bw , Smeland, O.B.ee ef , Sobell, J.L.eg , Søholm Hansen, C.s ah , Spijker, A.T.eh , St Clair, D.ei , Steffens, M.ej , Strauss, J.S.cn ek , Streit, F.bq , Strohmaier, J.bq , Szelinger, S.el , Thompson, R.C.di , Thorgeirsson, T.E.w , Treutlein, J.bq , Vedder, H.em , Wang, W.a b , Watson, S.J.di , Weickert, T.W.cb cc , Witt, S.H.bq , Xi, S.en , Xu, W.eo ep , Young, A.H.eq , Zandi, P.er , Zhang, P.es , Zöllner, S.di , Adolfsson, R.dp , Agartz, I.q al et , Alda, M.bw eu , Backlund, L.bt , Baune, B.T.ev ew , Bellivier, F.ex ey ez fa , Berrettini, W.H.fb , Biernacka, J.M.dz , Blackwood, D.H.R.ax , Boehnke, M.bo , Børglum, A.D.o p s , Corvin, A.dm , Craddock, N.aa , Daly, M.J.l n , Dannlowski, U.ew , Esko, T.c dh dk fc , Etain, B.ex ez fa fd , Frye, M.fe , Fullerton, J.M.cc ff , Gershon, E.S.ae fg , Gill, M.dm , Goes, F.bj , Grigoroiu-Serbanescu, M.fh , Hauser, J.bd , Hougaard, D.M.s ah , Hultman, C.M.ak , Jones, I.aa , Jones, L.A.bz , Kahn, R.S.b am , Kirov, G.aa , Landén, M.ak fi , Leboyer, M.ck ex fj , Lewis, C.M.d e fk , Li, Q.S.fl , Lissowska, J.fm , Martin, N.G.by fn , Mayoral, F.cf , McElroy, S.L.fo , McIntosh, A.M.ax fp , McMahon, F.J.fq , Melle, I.fr , Metspalu, A.dk fs , Mitchell, P.B.cb , Morken, G.ft fu , Mors, O.s fv , Mortensen, P.B.o s ab , Müller-Myhsok, B.ba fw fx , Myers, R.M.cz , Neale, B.M.c l n , Nimgaonkar, V.fy , Nordentoft, M.s fz , Nöthen, M.M.h , O’Donovan, M.C.aa , Oedegaard, K.J.ga gb , Owen, M.J.aa , Paciga, S.A.gc , Pato, C.cr gd , Pato, M.T.cr , Posthuma, D.v ge , Ramos-Quiroga, J.A.as at au av , Ribasés, M.as at av , Rietschel, M.bq , Rouleau, G.A.gf gg , Schalling, M.bs , Schofield, P.R.cc ff , Schulze, T.G.ao bj bq bv fq , Serretti, A.gh , Smoller, J.W.l gi gj , Stefansson, H.w , Stefansson, K.w ed , Stordal, E.gk gl , Sullivan, P.F.ak gm gn , Turecki, G.go , Vaaler, A.E.gp , Vieta, E.gq , Vincent, J.B.ek , Werge, T.s gr gs , Nurnberger, J.I.gt , Wray, N.R.x y , Di Florio, A.aa gn , Edenberg, H.J.gu , Cichon, S.f h j dn , Ophoff, R.A.am an br , Scott, L.J.bo , Andreassen, O.A.ee ef , Kelsoe, J.bg , Sklar, P.a b gv , eQTLGen Consortiumgw , BIOS Consortiumgw , the Bipolar Disorder Working Group of the Psychiatric Genomics Consortiumgx

a Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, United States
b Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, United States
c Medical and Population Genetics, Broad Institute, Cambridge, MA, United States
d MRC Social, Genetic and Developmental Psychiatry Centre, King’s College London, London, United Kingdom
e NIHR BRC for Mental Health, King’s College London, London, United Kingdom
f Department of Biomedicine, University of Basel, Basel, Switzerland
g Department of Psychiatry (UPK), University of Basel, Basel, Switzerland
h Institute of Human Genetics, University of Bonn School of Medicine & University Hospital Bonn, Bonn, Germany
i Centre for Human Genetics, University of Marburg, Marburg, Germany
j Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland
k Division of Psychiatry, University College London, London, United Kingdom
l Stanley Center for Psychiatric Research, Broad Institute, Cambridge, MA, United States
m Department of Psychiatry and Psychotherapy, Charité–Universitätsmedizin, Berlin, Germany
n Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, United States
o iSEQ, Center for Integrative Sequencing, Aarhus University, Aarhus, Denmark
p Department of Biomedicine–Human Genetics, Aarhus University, Aarhus, Denmark
q Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden
r Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital Würzburg, Würzburg, Germany
s iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark
t Institute of Biological Psychiatry, Mental Health Centre Sct. Hans, Copenhagen, Denmark
u Institute of Clinical Medicine, University of Oslo, Oslo, Norway
v Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam, Netherlands
w deCODE Genetics/Amgen, Reykjavik, Iceland
x Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia
y Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia
z Division of Endocrinology and Center for Basic and Translational Obesity Research, Boston Children’s Hospital, Boston, MA, United States
aa Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, United Kingdom
ab National Centre for Register-based Research and Centre for Integrated Register-based Research, Aarhus University, Aarhus, Denmark
ac Molecular & Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI, United States
ad Department of Neuroscience, Istituto Di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy
ae Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL, United States
af Department of Psychiatry, Berkshire Healthcare NHS Foundation Trust, Bracknell, United Kingdom
ag Department of Psychiatry, Rush University Medical Center, Chicago, IL, United States
ah Center for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark
ai Department of Psychiatry, Weill Cornell Medical College, New York, NY, United States
aj Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
ak Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
al Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway
am Psychiatry, UMC Utrecht Brain Center Rudolf Magnus, Utrecht, Netherlands
an Human Genetics, University of California, Los Angeles, Los Angeles, CA, United States
ao Institute of Psychiatric Phenomics and Genomics, University Hospital, LMU Munich, Munich, Germany
ap Department of Psychiatry and Human Behavior, University of California, Irvine, Irvine, CA, United States
aq Molecular & Behavioral Neuroscience Institute and Department of Computational Medicine & Bioinformatics, University of Michigan, Ann Arbor, MI, United States
ar Department of Psychiatry, University of California, San Francisco, San Francisco, CA, United States
as Instituto de Salud Carlos III, Biomedical Network Research Centre on Mental Health (CIBERSAM), Madrid, Spain
at Department of Psychiatry, Hospital Universitari Vall d´Hebron, Barcelona, Spain
au Department of Psychiatry and Forensic Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain
av Psychiatric Genetics Unit, Group of Psychiatry Mental Health and Addictions, Vall d´Hebron Research Institut, Universitat Autònoma de Barcelona, Barcelona, Spain
aw Department of Psychiatry, Mood Disorders Program, McGill University Health Center, Montreal, QC, Canada
ax Division of Psychiatry, University of Edinburgh, Edinburgh, United Kingdom
ay University of Iowa Hospitals and Clinics, Iowa City, IA, United States
az Translational Genomics, USC, Phoenix, AZ, United States
ba Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany
bb Centre for Psychiatry, Queen Mary University of London, London, United Kingdom
bc UCL Genetics Institute, University College London, London, United Kingdom
bd Department of Psychiatry, Laboratory of Psychiatric Genetics, Poznan University of Medical Sciences, Poznan, Poland
be Department of Neurosciences, University of California, San Diego, La Jolla, CA, United States
bf Department of Radiology, University of California, San Diego, La Jolla, CA, United States
bg Department of Psychiatry, University of California, San Diego, La Jolla, CA, United States
bh Department of Cognitive Science, University of California, San Diego, La Jolla, CA, United States
bi Applied Molecular Genomics Unit, VIB Department of Molecular Genetics, University of Antwerp, Antwerp, Belgium
bj Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, United States
bk Department of Medical Genetics, Oslo University Hospital Ullevål, Oslo, Norway
bl NORMENT, KG Jebsen Centre for Psychosis Research, Department of Clinical Science, University of Bergen, Bergen, Norway
bm Department of Neurology, Oslo University Hospital, Oslo, Norway
bn NORMENT, KG Jebsen Centre for Psychosis Research, Oslo University Hospital, Oslo, Norway
bo Center for Statistical Genetics and Department of Biostatistics, University of Michigan, Ann Arbor, MI, United States
bp Department of Medical & Molecular Genetics, Indiana University, Indianapolis, IN, United States
bq Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
br Center for Neurobehavioral Genetics, University of California, Los Angeles, Los Angeles, CA, United States
bs Department of Molecular Medicine and Surgery, Karolinska Institutet and Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden
bt Department of Clinical Neuroscience, Karolinska Institutet and Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden
bu Child and Adolescent Psychiatry Research Center, Stockholm, Sweden
bv Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Göttingen, Germany
bw Department of Psychiatry, Dalhousie University, Halifax, NS, Canada
bx Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA, United States
by Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
bz Department of Psychological Medicine, University of Worcester, Worcester, United Kingdom
ca School of Biomedical Sciences, Plymouth University Peninsula Schools of Medicine and Dentistry, University of Plymouth, Plymouth, United Kingdom
cb School of Psychiatry, University of New South Wales, Sydney, NSW, Australia
cc Neuroscience Research Australia, Sydney, NSW, Australia
cd Bioinformatics Research Centre, Aarhus University, Aarhus, Denmark
ce Biostatistics, University of Minnesota System, Minneapolis, MN, United States
cf Mental Health Department, University Regional Hospital, Biomedicine Institute (IBIMA), Málaga, Spain
cg Department of Psychology, Eberhard Karls Universität Tübingen, Tubingen, Germany
ch Department of Psychiatry and Behavioral Sciences, Howard University Hospital, Washington, DC, United States
ci Center for Multimodal Imaging and Genetics, University of California, San Diego, La Jolla, CA, United States
cj Psychiatrie Translationnelle, Inserm U955, Créteil, France
ck Faculté de Médecine, Université Paris Est, Créteil, France
cl Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Onatario, Canada
cm Neurogenetics Section, Centre for Addiction and Mental Health, Toronto, ON, Canada
cn Department of Psychiatry, University of Toronto, Toronto, ON, Canada
co Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada
cp Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Frankfurt am Main, Germany
cq Cell Biology, SUNY Downstate Medical Center College of Medicine, Brooklyn, NY, United States
cr Institute for Genomic Health, SUNY Downstate Medical Center College of Medicine, Brooklyn, NY, United States
cs ISGlobal, Barcelona, Spain
ct Psychiatry, Altrecht, Utrecht, Netherlands
cu Psychiatry, GGZ inGeest, Amsterdam, Netherlands
cv Psychiatry, VU Medisch Centrum, Amsterdam, Netherlands
cw Department of, rth East London NHS Foundation Trust, Ilford, United Kingdom
cx Department of Neurodegenerative Diseases and Geropsychiatry, University Hospital Bonn, Bonn, Germany
cy Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, MA, United States
cz HudsonAlpha Institute for Biotechnology, Huntsville, AL, United States
da Department of Human Genetics, University of Michigan, Ann Arbor, MI, United States
db Department of Psychiatry, University of Illinois at Chicago College of Medicine, Chicago, IL, United States
dc Max Planck Institute of Psychiatry, Munich, Germany
dd Mental Health, NHS 24, Glasgow, United Kingdom
de Division of Psychiatry, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom
df Department of Psychiatry, Brigham and Women’s Hospital, Boston, MA, United States
dg Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany
dh Department of Genetics, Harvard Medical School, Boston, MA, United States
di Department of Psychiatry, University of Michigan, Ann Arbor, MI, United States
dj Genetic Cancer Susceptibility Group, International Agency for Research on Cancer, Lyon, France
dk Estonian Genome Center, University of Tartu, Tartu, Estonia
dl Discipline of Biochemistry, Neuroimaging and Cognitive Genomics (NICOG) Centre, National University of Ireland, Galway, Galway, Ireland
dm Neuropsychiatric Genetics Research Group, Department of Psychiatry and Trinity Translational Medicine Institute, Trinity College Dublin, Dublin, Ireland
dn Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, Jülich, Germany
do Research/Psychiatry, Veterans Affairs San Diego Healthcare System, San Diego, CA, United States
dp Department of Clinical Sciences, Psychiatry, Umeå University Medical Faculty, Umeå, Sweden
dq Department of Clinical Psychiatry, Psychiatry Clinic, Clinical Center University of Sarajevo, Sarajevo, Bosnia and Herzegovina
dr Department of Neurobiology, Care Sciences, and Society, Karolinska Institutet and Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden
ds Department of Psychiatry, Harvard Medical School, Boston, MA, United States
dt Division of Clinical Research, Massachusetts General Hospital, Boston, MA, United States
du Outpatient Clinic for Bipolar Disorder, Altrecht, Utrecht, Netherlands
dv Department of Psychiatry, Washington University in Saint Louis, Saint Louis, MO, United States
dw Department of Biochemistry and Molecular Biology II, Institute of Neurosciences, Center for Biomedical Research, University of Granada, Granada, Spain
dx Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, United States
dy Medicine, Psychiatry, Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, United States
dz Department of Health Sciences Research, Mayo Clinic, Rochester, MN, United States
ea Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, United States
eb Rush University Medical Center, Chicago, IL, United States
ec Scripps Translational Science Institute, La Jolla, CA, United States
ed Faculty of Medicine, Department of Psychiatry, School of Health Sciences, University of Iceland, Reykjavik, Iceland
ee Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
ef NORMENT, University of Oslo, Oslo, Norway
eg Psychiatry and the Behavioral Sciences, University of Southern California, Los Angeles, CA, United States
eh Mood Disorders, PsyQ, Rotterdam, Netherlands
ei Institute for Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom
ej Research Division, Federal Institute for Drugs and Medical Devices (BfArM), Bonn, Germany
ek Centre for Addiction and Mental Health, Toronto, Onatario, Canada
el Neurogenomics, TGen, Phoenix, AZ, United States
em Department of Psychiatry, Psychiatrisches Zentrum Nordbaden, Wiesloch, Germany
en Computational Sciences Center of Emphasis, Pfizer Global Research and Development, Cambridge, MA, United States
eo Department of Biostatistics, Princess Margaret Cancer Centre, Toronto, Onatario, Canada
ep Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada
eq Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, United Kingdom
er Department of Mental Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, United States
es Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States
et NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Institute of Clinical Medicine and Diakonhjemmet Hospital, University of Oslo, Oslo, Norway
eu National Institute of Mental Health, Klecany, Czech Republic
ev Department of Psychiatry, University of Melbourne, Melbourne, VIC, Australia
ew Department of Psychiatry, University of Munster, Munster, Germany
ex Department of Psychiatry and Addiction Medicine, Assistance Publique–Hopitaux de Paris, Paris, France
ey Paris Bipolar and TRD Expert Centres, FondaMental Foundation, Paris, France
ez UMR-S1144 Team 1: Biomarkers of relapse and therapeutic response in addiction and mood disorders, INSERM, Paris, France
fa Department of Psychiatry, Université Paris Diderot, Paris, France
fb Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, United States
fc Division of Endocrinology, Children’s Hospital Boston, Boston, MA, United States
fd Centre for Affective Disorders, Institute of Psychiatry, Psychology and Neuroscience, London, United Kingdom
fe Department of Psychiatry & Psychology, Mayo Clinic, Rochester, MN, United States
ff School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia
fg Department of Human Genetics, University of Chicago, Chicago, IL, United States
fh Biometric Psychiatric Genetics Research Unit, Alexandru Obregia Clinical Psychiatric Hospital, Bucharest, Romania
fi Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden
fj INSERM, Paris, France
fk Department of Medical & Molecular Genetics, King’s College London, London, United Kingdom
fl Neuroscience Therapeutic Area, Janssen Research and Development, LLC, Titusville, NJ, United States
fm Cancer Epidemiology and Prevention, M. Sklodowska–Curie Cancer Center and Institute of Oncology, Warsaw, Poland
fn School of Psychology, The University of Queensland, Brisbane, QLD, Australia
fo Research Institute, Lindner Center of HOPE, Mason, OH, United States
fp Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, United Kingdom
fq Human Genetics Branch, Intramural Research Program, National Institute of Mental Health, Bethesda, MD, United States
fr Division of Mental Health and Addiction and Institute of Clinical Medicine, Oslo University Hospital and University of Oslo, Oslo, Norway
fs Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia
ft Mental Health, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology–NTNU, Trondheim, Norway
fu Department of Psychiatry, St Olavs University Hospital, Trondheim, Norway
fv Psychosis Research Unit, Aarhus University Hospital, Risskov, Denmark
fw Munich Cluster for Systems Neurology (SyNergy), Munich, Germany
fx University of Liverpool, Liverpool, United Kingdom
fy Psychiatry and Human Genetics, University of Pittsburgh, Pittsburgh, PA, United States
fz Mental Health Services in the Capital Region of Denmark, Mental Health Center Copenhagen, University of Copenhagen, Copenhagen, Denmark
ga Division of Psychiatry, Haukeland Universitetssjukehus, Bergen, Norway
gb Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway
gc Human Genetics and Computational Biomedicine, Pfizer Global Research and Development, Groton, CT, United States
gd College of Medicine Institute for Genomic Health, SUNY Downstate Medical Center College of Medicine, Brooklyn, NY, United States
ge Department of Clinical Genetics, Amsterdam Neuroscience, Vrije Universiteit Medical Center, Amsterdam, Netherlands
gf Department of Neurology and Neurosurgery, McGill University, Faculty of Medicine, Montreal, QC, Canada
gg Montreal Neurological Institute and Hospital, Montreal, QC, Canada
gh Department of Biomedical and NeuroMotor Sciences, University of Bologna, Bologna, Italy
gi Department of Psychiatry, Massachusetts General Hospital, Boston, MA, United States
gj Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, MA, United States
gk Department of Psychiatry, Hospital Namsos, Namsos, Norway
gl Department of Mental Health, Norwegian University of Science and Technology, Trondheim, Norway
gm Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States
gn Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States
go Department of Psychiatry, McGill University, Montreal, QC, Canada
gp Department of Psychiatry, Sankt Olavs Hospital Universitetssykehuset i Trondheim, Trondheim, Norway
gq Clinical Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Spain
gr Institute of Biological Psychiatry, MHC Sct. Hans, Mental Health Services Copenhagen, Roskilde, Denmark
gs Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
gt Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, United States
gu Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, United States
gv Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States

Abstract
Bipolar disorder is a highly heritable psychiatric disorder. We performed a genome-wide association study (GWAS) including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 variants with P &lt; 1 × 10 −4 in an additional 9,412 cases and 137,760 controls. Eight of the 19 variants that were genome-wide significant (P &lt; 5 × 10 −8 ) in the discovery GWAS were not genome-wide significant in the combined analysis, consistent with small effect sizes and limited power but also with genetic heterogeneity. In the combined analysis, 30 loci were genome-wide significant, including 20 newly identified loci. The significant loci contain genes encoding ion channels, neurotransmitter transporters and synaptic components. Pathway analysis revealed nine significantly enriched gene sets, including regulation of insulin secretion and endocannabinoid signaling. Bipolar I disorder is strongly genetically correlated with schizophrenia, driven by psychosis, whereas bipolar II disorder is more strongly correlated with major depressive disorder. These findings address key clinical questions and provide potential biological mechanisms for bipolar disorder. © 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.

Document Type: Article
Publication Stage: Final
Source: Scopus

“Use of the PROMIS® depression scale and the beck depression inventory in patients with heart failure” (2019) Health Psychology

Use of the PROMIS® depression scale and the beck depression inventory in patients with heart failure
(2019) Health Psychology, 38 (5), pp. 369-375. Cited 1 time.

Freedland, K.E.a , Steinmeyer, B.C.a , Carney, R.M.a , Rubin, E.H.a , Rich, M.W.b

a Department of Psychiatry, Washington University, School of Medicine in St. LouisMO 63108, United States
b Department of Medicine, Washington University School of Medicine in St. Louis, United States

Abstract
Objective: This study evaluated agreement between the Patient-Reported Outcomes Measurement Information System® (PROMIS®) Depression scale and the Beck Depression Inventory (BDI-II) in patients with heart failure and comorbid major depression. Method: The BDI-II and the computerized adaptive test version of the PROMIS® Depression scale were administered at baseline to 158 participants in a randomized controlled trial of cognitive behavior therapy for major depression in patients with heart failure. A crosswalk table (Choi, Schalet, Cook, &Cella, 2014) was used to transform the PROMIS® scores into “linked” BDI-II equivalent scores. Bland-Altman plots, histograms, and scatterplots were used to visualize the agreement between these scores at baseline and 6 months, and intraclass correlation coefficients (ICCs) were calculated for each occasion to quantify the agreement. Treatment effects and change scores were also examined. Results: The measures agreed moderately at baseline (ICC 0.52, p <.0001) and strongly at 6 months (ICC 0.77, p <.0001), but on average, the linked and observed BDI-II scores differed by 3.1 points at baseline (p <.0001) and-0.17 points at 6 months (p.78). The discrepancies were considerably larger in many individual cases on both occasions. Conclusions: The PROMIS® Depression scale is likely to play an important role in research on depression in patients with heart failure, but for now, it should be used in addition to rather than instead of the BDI-II in studies in which the BDI-II would ordinarily be used. Additional research is needed to evaluate the validity and utility of the PROMIS® Depression scale in patients with heart failure. © 2019 American Psychological Association.

Author Keywords
Depression;  Depressive disorders;  Heart failure;  Patient-reported outcome measures

Document Type: Article
Publication Stage: Final
Source: Scopus

“Axon degeneration: mechanistic insights lead to therapeutic opportunities for the prevention and treatment of peripheral neuropathy” (2019) Pain

Axon degeneration: mechanistic insights lead to therapeutic opportunities for the prevention and treatment of peripheral neuropathy
(2019) Pain, 160, pp. S17-S22. 

DiAntonio, A.a b

a Department of Developmental Biology, Washington University Medical School Saint Louis, Saint Louis, MO, United States
b Needleman Center for Neurometabolism and Axonal Therapeutics, Washington University Medical School Saint LouisMO, United States

Abstract
Peripheral neuropathy is the most common neurodegenerative disease affecting hundreds of millions of patients worldwide and is an important cause of chronic pain. Typical peripheral neuropathies are characterized by dysesthesias including numbness, crawling skin, a sensation of “pins and needles,” and burning and stabbing pain. In addition, peripheral neuropathy can affect the motor and autonomic systems leading to symptoms such as weakness, constipation, and dysregulation of blood pressure. Peripheral neuropathies can be either hereditary or acquired and are a common consequence of diabetes and treatment with chemotherapy agents. Many neuropathies are due to degeneration of long axons; however, the mechanisms driving axon loss were unknown, and so no therapies are available to preserve vulnerable axons and prevent the development of peripheral neuropathy. With the recent identification of SARM1 as an injury-activated NADase enzyme that triggers axon degeneration, there is now a coherent picture emerging for the mechanism of axonal self-destruction. Here, we will present evidence that inhibiting the SARM1 pathway can prevent the development of peripheral neuropathy, describe the emerging mechanistic understanding of the axon degeneration program, and discuss how these mechanistic insights may be translated to the clinic for the prevention and treatment of peripheral neuropathy and other neurodegenerative disorders.

Document Type: Article
Publication Stage: Final
Source: Scopus

“Reinfection rates following adherence to Infectious Diseases Society of America guideline recommendations in first cerebrospinal fluid shunt infection treatment” (2019) Journal of Neurosurgery: Pediatrics

Reinfection rates following adherence to Infectious Diseases Society of America guideline recommendations in first cerebrospinal fluid shunt infection treatment
(2019) Journal of Neurosurgery: Pediatrics, 23 (5), pp. 577-585. 

Simon, T.D.a c m , Kronman, M.P.a c , Whitlock, K.B.c , Browd, S.R.b , Holubkov, R.d , Kestle, J.R.W.e , Kulkarni, A.V.f , Langley, M.e , Limbrick, D.D., Jr.g , Luerssen, T.G.h , Jerry Oakes, W.i , Riva-Cambrin, J.e k , Rozzelle, C.i , Shannon, C.N.i l , Tamber, M.j , Wellons, J.C., IIIi l , Whitehead, W.E.h , Mayer-Hamblett, N.a c

a Departments of Pediatrics, University of Washington, Seattle Children’s Hospital, Seattle, United States
b Departments of Neurosurgery, University of Washington, Seattle Children’s Hospital, Seattle, United States
c Center for Clinical and Translational Research, Seattle Children’s Research Institute, Seattle, WA, United States
d Department of Pediatrics, University of Utah, Salt Lake City, United States
e Division of Pediatric Neurosurgery, Primary Children’s Medical Center, Department of Neurosurgery, University of Utah, Salt Lake City, UT, United States
f Division of Neurosurgery, Hospital for Sick Children, University of TorontoON, Canada
g Department of Neurosurgery, St. Louis Children’s Hospital, Washington University in St. LouisMO, United States
h Division of Pediatric Neurosurgery, Texas Children’s Hospital, Department of Neurosurgery, Baylor College of Medicine, Houston, TX, United States
i Section of Pediatric Neurosurgery, Children’s Hospital of Alabama, Division of Neurosurgery, University of Alabama–BirminghamAL, United States
j Division of Neurosurgery, Children’s Hospital of PittsburghPA, United States
k Department of Clinical Neurosciences, University of Calgary, Alberta, Canada
l Department of Neurosurgery, Vanderbilt University, Nashville, TN, United States

Abstract
OBJECTIVE CSF shunt infection treatment requires both surgical and antibiotic decisions. Using the Hydrocephalus Clinical Research Network (HCRN) Registry and 2004 Infectious Diseases Society of America (IDSA) guidelines that were not proactively distributed to HCRN providers, the authors previously found high adherence to surgical recommendations but poor adherence to intravenous (IV) antibiotic duration recommendations. In general, IV antibiotic duration was longer than recommended. In March 2017, new IDSA guidelines expanded upon the 2004 guidelines by including recommendations for selection of specific antibiotics. The objective of this study was to describe adherence to both 2004 and 2017 IDSA guideline recommendations for CSF shunt infection treatment, and to report reinfection rates associated with adherence to guideline recommendations. METHODS The authors investigated a prospective cohort of children younger than 18 years of age who underwent treatment for first CSF shunt infection at one of 7 hospitals from April 2008 to December 2012. CSF shunt infection was diagnosed by recovery of bacteria from CSF culture (CSF-positive infection). Adherence to 2004 and 2017 guideline recommendations was determined. Adherence to antibiotics was further classified as longer or shorter duration than guideline recommendations. Reinfection rates with 95% confidence intervals (CIs) were generated. RESULTS There were 133 children with CSF-positive infections addressed by 2004 IDSA guideline recommendations, with 124 at risk for reinfection. Zero reinfections were observed among those whose treatment was fully adherent (0/14, 0% [95% CI 0%–20%]), and 15 reinfections were observed among those whose infection treatment was nonadherent (15/110, 14% [95% CI 8%–21%]). Among the 110 first infections whose infection treatment was nonadherent, 74 first infections were treated for a longer duration than guidelines recommended and 9 developed reinfection (9/74, 12% [95% CI 6%–22%]). There were 145 children with CSF-positive infections addressed by 2017 IDSA guideline recommendations, with 135 at risk for reinfection. No reinfections were observed among children whose treatment was fully adherent (0/3, 0% [95% CI 0%–64%]), and 18 reinfections were observed among those whose infection treatment was nonadherent (18/132, 14% [95% CI 8%–21%]). CONCLUSIONS There is no clear evidence that either adherence to IDSA guidelines or duration of treatment longer than recommended is associated with reduction in reinfection rates. Because IDSA guidelines recommend shorter IV antibiotic durations than are typically used, improvement efforts to reduce IV antibiotic use in CSF shunt infection treatment can and should utilize IDSA guidelines. ©AANS 2019, except where prohibited by US copyright law

Author Keywords
Antibiotic;  Cerebrospinal;  Hydrocephalus;  Infection;  Shunt;  Treatment

Document Type: Article
Publication Stage: Final
Source: Scopus

“Arteriopathy Influences Pediatric Ischemic Stroke Presentation, but Sickle Cell Disease Influences Stroke Management” (2019) Stroke

Arteriopathy Influences Pediatric Ischemic Stroke Presentation, but Sickle Cell Disease Influences Stroke Management
(2019) Stroke, 50 (5), pp. 1089-1094. 

Guilliams, K.P.a , Kirkham, F.J.b , Holzhauer, S.c , Pavlakis, S.d , Philbrook, B.e , Amlie-Lefond, C.f , Noetzel, M.J.a , Dlamini, N.g , Sharma, M.h , Carpenter, J.L.i , Fox, C.K.j , Torres, M.k , Ichord, R.N.l , Jordan, L.C.m , Dowling, M.M.n

a From the Departments of Neurology and Pediatrics, Washington University School of Medicine, St Louis, United States
b Developmental Neurosciences and Biomedical Research Unit, UCL Great Ormond Street Institute of Child Health, London and Clinical and Experimental Sciences, University of Southampton, United Kingdom (F.J.K.)
c Department of Pediatric Hematology and Oncology Charité University Medicine, Germany (S.H.), Berlin, Germany
d Department of Pediatrics and Neurology, Brooklyn Hospital Center, Icahn School of Medicine at Mount Sinai, Brooklyn, Australia
e Department of Pediatrics, Pediatric Neurology, Emory University, Children’s Healthcare of Atlanta, United States
f Department of Neurology, University of Washington, Seattle Children’s Hospital, Australia
g Department of Neurology, Hospital for Sick Children, Toronto, Australia
h Department of Pediatric Hematology Oncology, Children’s Mercy Hospital, University of Missouri Kansas City School of Medicine (M.S.)
i Department of Pediatrics, Neurology, Neuroscience, George Washington University, Children’s National Medical Center, United States
j Departments of Neurology and Pediatrics, University of California San Francisco (C.K.F.)
k Department of Pediatric Hematology Oncology, Cook Children’s Medical Center, Fort Worth, United States
l Departments of Neurology and Pediatrics, Perlman School of Medicine at the University of Pennsylvania
m Department of Pediatrics, Division of Pediatric Neurology, Vanderbilt University Medical Center, Nashville, United States
n Departments of Pediatrics, Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center at Dallas and Children’s Health Dallas (M.M.D.)

Abstract
Background and Purpose- Sickle cell disease (SCD) and arteriopathy are pediatric stroke risk factors that are not mutually exclusive. The relative contributions of sickled red blood cells and arteriopathy to stroke risk are unknown, resulting in unclear guidelines for primary and secondary stroke prevention when both risk factors are present. We hypothesized that despite similarities in clinical presentation and radiographic appearance of arteriopathies, stroke evaluation and management differ in children with SCD compared with those without SCD. Methods- We compared presentation and management of children with and without SCD enrolled in the IPSS (International Pediatric Stroke Study) with acute arterial ischemic stroke, according to SCD and arteriopathy status. Regression modeling determined relative contribution of SCD and arteriopathy in variables with significant frequency differences. Results- Among 930 childhood arterial ischemic strokes, there were 98 children with SCD, 67 of whom had arteriopathy, and 466 without SCD, 392 of whom had arteriopathy. Arteriopathy, regardless of SCD status, increased likelihood of hemiparesis (odds ratio [OR], 1.94; 95% CI, 1.46-2.56) and speech abnormalities (OR, 1.67; 95% CI, 1.29-2.19). Arteriopathy also increased likelihood of headache but only among those without SCD (OR, 1.89; 95% CI, 1.40-2.55). Echocardiograms were less frequently obtained in children with SCD (OR, 0.58; 95% CI, 0.37-0.93), but the frequency of identified cardiac abnormalities was similar in both groups ( P=0.57). Children with SCD were less likely to receive antithrombotic therapy, even in the presence of arteriopathy (OR, 0.14; 95% CI, 0.08-0.22). Arteriopathy was associated with a significantly higher likelihood of antithrombotic therapy in children without SCD (OR, 5.36; 95% CI, 3.55-8.09). Conclusions- Arteriopathy, and not SCD status, was most influential of stroke presentation. However, SCD status influenced stroke management because children with SCD were less likely to have echocardiograms or receive antithrombotic therapy. Further work is needed to determine whether management differences are warranted.

Author Keywords
aspirin;  child;  headache;  heparin;  risk factor

Document Type: Article
Publication Stage: Final
Source: Scopus

“Risk Factors for Retinopathy in Type 1 Diabetes: The DCCT/EDIC Study” (2019) Diabetes care

Risk Factors for Retinopathy in Type 1 Diabetes: The DCCT/EDIC Study
(2019) Diabetes care, 42 (5), pp. 875-882. 

Hainsworth, D.P.a , Bebu, I.b , Aiello, L.P.c , Sivitz, W.d , Gubitosi-Klug, R.e , Malone, J.f , White, N.H.g , Danis, R.h , Wallia, A.i , Gao, X.b , Barkmeier, A.J.j , Das, A.j , Patel, S.k , Gardner, T.W.l , Lachin, J.M.m , Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) Research Groupn

a Mason Eye Institute, University of Missouri, Columbia, MO, United States
b Biostatistics Center, George Washington UniversityWA, United States
c Department of Ophthalmology, Joslin Diabetes Center, Boston, MA, United States
d Department of Internal Medicine, University of Iowa, Iowa City, IA, United States
e Rainbow Babies and Children’s Hospital, Cleveland, OH, United States
f Diabetes Center, University of South Florida, Tampa, FL, United States
g Pediatrics, Washington University, St. Louis, MO, United States
h University of Wisconsin, Madison, WI, United States
i Department of Medicine, Northwestern University, Evanston, IL, United States
j University of New Mexico, Albuquerque, NM, United States
k Vanderbilt University Medical Center, Nashville, TN, United States
l University of Michigan Kellogg Eye Center, Ann Arbor, MI, United States
m Biostatistics Center, George Washington UniversityWA, United States

Abstract
OBJECTIVE: The Diabetes Control and Complications Trial (DCCT) demonstrated that intensive therapy reduced the development and progression of retinopathy in type 1 diabetes (T1D) compared with conventional therapy. The Epidemiology of Diabetes Interventions and Complications (EDIC) study observational follow-up showed persistent benefits. In addition to glycemia, we now examine other potential retinopathy risk factors (modifiable and nonmodifiable) over more than 30 years of follow-up in DCCT/EDIC. RESEARCH DESIGN AND METHODS: The retinopathy outcomes were proliferative diabetic retinopathy (PDR), clinically significant macular edema (CSME), and ocular surgery. The survival (event-free) probability was estimated using the Kaplan-Meier method. Cox proportional hazards models assessed the association between risk factors and subsequent risk of retinopathy. Both forward- and backward-selection approaches determined the multivariable models. RESULTS: Rate of ocular events per 1,000 person-years was 12 for PDR, 14.5 for CSME, and 7.6 for ocular surgeries. Approximately 65%, 60%, and 70% of participants remained free of PDR, CSME, and ocular surgery, respectively. The greatest risk factors for PDR in descending order were higher mean HbA1c, longer duration of T1D, elevated albumin excretion rate (AER), and higher mean diastolic blood pressure (DBP). For CSME, risk factors, in descending order, were higher mean HbA1c, longer duration of T1D, and greater age and DBP and, for ocular surgeries, were higher mean HbA1c, older age, and longer duration of T1D. CONCLUSIONS: Mean HbA1c was the strongest risk factor for the progression of retinopathy. Although glycemic control is important, elevated AER and DBP were other modifiable risk factors associated with the progression of retinopathy. © 2019 by the American Diabetes Association.

Document Type: Article
Publication Stage: Final
Source: Scopus

“Untangling a canopy of spinal itch circuits” (2019) Pain

Untangling a canopy of spinal itch circuits
(2019) Pain, 160 (5), pp. 987-988. 

Grajales-Reyes, J.G.a b c , Samineni, V.K.a c

a Division of Basic Research, Department of Anesthesiology, Washington University in St. Louis, St. Louis, MO, United States
b Medical Scientist Training Program, Washington University in St. Louis, St. Louis, MO, United States
c Washington University Pain Center, Washington University in St. Louis, St. Louis, MO, United States

Document Type: Article
Publication Stage: Final
Source: Scopus

“Mutant huntingtin enhances activation of dendritic Kv4 K + channels in striatal spiny projection neurons” (2019) eLife

Mutant huntingtin enhances activation of dendritic Kv4 K + channels in striatal spiny projection neurons
(2019) eLife, 8, . 

Carrillo-Reid, L.a b , Day, M.a , Xie, Z.a , Melendez, A.E.a , Kondapalli, J.a , Plotkin, J.L.a c , Wokosin, D.L.a , Chen, Y.a , Kress, G.J.a d , Kaplitt, M.e , Ilijic, E.a , Guzman, J.N.a , Chan, S.S.a , Surmeier, D.J.a

a Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, United States
b Department of Developmental Neurobiology and Neurophysiology, Neurobiology Institute, National Autonomous University of MexicoQueretaro, Mexico
c Department of Neurobiology & Behavior, Stony Brook University School of Medicine, Stony Brook, United States
d Department of Neurology, Washington University School of Medicine, St. Louis, United States
e Department of Neurological Surgery, Weill Cornell Medical CollegeNY, United States

Abstract
Huntington’s disease (HD) is initially characterized by an inability to suppress unwanted movements, a deficit attributable to impaired synaptic activation of striatal indirect pathway spiny projection neurons (iSPNs). To better understand the mechanisms underlying this deficit, striatal neurons in ex vivo brain slices from mouse genetic models of HD were studied using electrophysiological, optical and biochemical approaches. Distal dendrites of iSPNs from symptomatic HD mice were hypoexcitable, a change that was attributable to increased association of dendritic Kv4 potassium channels with auxiliary KChIP subunits. This association was negatively modulated by TrkB receptor signaling. Dendritic excitability of HD iSPNs was rescued by knocking-down expression of Kv4 channels, by disrupting KChIP binding, by restoring TrkB receptor signaling or by lowering mutant-Htt (mHtt) levels with a zinc finger protein. Collectively, these studies demonstrate that mHtt induces reversible alterations in the dendritic excitability of iSPNs that could contribute to the motor symptoms of HD. © 2019, Carrillo-Reid et al.

Author Keywords
calcium imaging;  dendrite;  Huntington’s disease;  KChIP;  Kv4;  mouse;  neuroscience;  zinc finger protein

Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access

“Additional Approaches to Treatment of Depression” (2019) JAMA – Journal of the American Medical Association

Additional Approaches to Treatment of Depression
(2019) JAMA – Journal of the American Medical Association, 321 (16), pp. 1634-1635. 

Carney, R.M.

Department of Psychiatry, Washington University School of Medicine, St Louis, MO, United States

Document Type: Letter
Publication Stage: Final
Source: Scopus

“Detection of Pediatric Upper Extremity Motor Activity and Deficits With Accelerometry” (2019) JAMA network open

Detection of Pediatric Upper Extremity Motor Activity and Deficits With Accelerometry
(2019) JAMA network open, 2 (4), p. e192970. 

Hoyt, C.R.a b , Van, A.N.a , Ortega, M.a , Koller, J.M.c , Everett, E.A.a , Nguyen, A.L.a , Lang, C.E.a b d , Schlaggar, B.L.a c e f g h , Dosenbach, N.U.F.a b g h i

a Department of Neurology, Washington University School of Medicine in St Louis, St Louis, MO, United States
b Program in Occupational Therapy, Washington University School of Medicine in St Louis, St Louis, MO, United States
c Department of Psychiatry, Washington University School of Medicine in St Louis, St Louis, MO, United States
d Program in Physical Therapy, Washington University School of Medicine in St Louis, St Louis, MO, United States
e Department of Anatomy and Neurobiology, Washington University School of Medicine in St Louis, St Louis, MO, United States
f Kennedy Krieger Institute, Baltimore, MD, United States
g Department of Radiology, Washington University School of Medicine in St Louis, St Louis, MO, United States
h Department of Pediatrics, Washington University School of Medicine in St Louis, St Louis, MO, United States
i Department of Biomedical Engineering, Washington University School of Medicine in St Louis, St Louis, MO, United States

Abstract
Importance: Affordable, quantitative methods to screen children for developmental delays are needed. Motor milestones can be an indicator of developmental delay and may be used to track developmental progress. Accelerometry offers a way to gather real-world information about pediatric motor behavior. Objective: To develop a referent cohort of pediatric accelerometry from bilateral upper extremities (UEs) and determine whether movement can accurately distinguish those with and without motor deficits. Design, Setting, and Participants: Children aged 0 to 17 years participated in a prospective cohort from December 8, 2014, to December 29, 2017. Children were recruited from Ranken Jordan Pediatric Bridge Hospital, Maryland Heights, Missouri, and Washington University School of Medicine in St Louis, St Louis, Missouri. Typically developing children were included as a referent cohort if they had no history of motor or neurological deficit; consecutive sampling and matching ensured equal representation of sex and age. Children with diagnosed asymmetric motor deficits were included in the motor impaired cohort. Exposures: Bilateral UE motor activity was measured using wrist-worn accelerometers for a total of 100 hours in 25-hour increments. Main Outcomes and Measures: To characterize bilateral UE motor activity in a referent cohort for the purpose of detecting irregularities in the future, total activity and the use ratio between UEs were used to describe typically developing children. Asymmetric impairment was classified using the mono-arm use index (MAUI) and bilateral-arm use index (BAUI) to quantify the acceleration of unilateral movements. Results: A total of 216 children enrolled, and 185 children were included in analysis. Of these, 156 were typically developing, with mean (SD) age 9.1 (5.1) years and 81 boys (52.0%). There were 29 children in the motor impaired cohort, with mean (SD) age 7.4 (4.4) years and 16 boys (55.2%). The combined MAUI and BAUI (mean [SD], 0.86 [0.005] and use ratio (mean [SD], 0.90 [0.008]) had similar F1 values. The area under the curve was also similar between the combined MAUI and BAUI (mean [SD], 0.98 [0.004]) and the use ratio (mean [SD], 0.98 [0.004]). Conclusions and Relevance: Bilateral UE movement as measured with accelerometry may provide a meaningful metric of real-world motor behavior across childhood. Screening in early childhood remains a challenge; MAUI may provide an effective method for clinicians to measure and visualize real-world motor behavior in children at risk for asymmetrical deficits.

Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access

“A heteroscedastic hidden Markov mixture model for responses and categorized response times” (2019) Behavior research methods

A heteroscedastic hidden Markov mixture model for responses and categorized response times
(2019) Behavior research methods, 51 (2), pp. 676-696. 

Molenaar, D.a , Rózsa, S.b , Bolsinova, M.c

a Department of Psychology, University of Amsterdam, Amsterdam, Netherlands
b Washington University School of Medicine, St. Louis, MO, United States
c Iowa City, IA, United States

Abstract
Various mixture modeling approaches have been proposed to identify within-subjects differences in the psychological processes underlying responses to psychometric tests. Although valuable, the existing mixture models are associated with at least one of the following three challenges: (1) A parametric distribution is assumed for the response times that-if violated-may bias the results; (2) the response processes are assumed to result in equal variances (homoscedasticity) in the response times, whereas some processes may produce more variability than others (heteroscedasticity); and (3) the different response processes are modeled as independent latent variables, whereas they may be related. Although each of these challenges has been addressed separately, in practice they may occur simultaneously. Therefore, we propose a heteroscedastic hidden Markov mixture model for responses and categorized response times that addresses all the challenges above in a single model. In a simulation study, we demonstrated that the model is associated with acceptable parameter recovery and acceptable resolution to distinguish between various special cases. In addition, the model was applied to the responses and response times of the WAIS-IV block design subtest, to demonstrate its use in practice.

Author Keywords
Hidden Markov models;  Item response theory;  Mixture models;  Response times

Document Type: Article
Publication Stage: Final
Source: Scopus

“Use of magnetic resonance imaging in severe pediatric traumatic brain injury: Assessment of current practice” (2019) Journal of Neurosurgery: Pediatrics

Use of magnetic resonance imaging in severe pediatric traumatic brain injury: Assessment of current practice
(2019) Journal of Neurosurgery: Pediatrics, 23 (4), pp. 471-479. 

Ferrazzano, P.A.a be , Rosario, B.L.d , Wisniewski, S.R.d , Shaf, N.I.e , Siefkes, H.M.f , Miles, D.K.g bb , Alexander, A.L.b c , Bell, M.J.h , Sarnaik, A.bg , Agrawal, S.i , Mahoney, S.j , Gupta, D.k , Beca, J.l , Loftis, L.m , Morris, K.n , Piper, L.o , Slater, A.p , Walson, K.q , Bennett, T.r , Kilbaugh, T.s , Iqbal O’Meara, A.M.t , Dean, N.u , Chima, R.S.v , Biagas, K.w , Wildschut, E.x , Peters, M.y , LaRovere, K.z , Balcells, J.aa , Robertson, C.ab , Gertz, S.ac , Deep, A.ad , Cooper, S.ae , Wainwright, M.af , Murphy, S.ag , Kuluz, J.ah , Butt, W.ai , O’Brien, N.aj , Thomas, N.ak , Buttram, S.al , Erickson, S.am , Mahil Samuel, J.an , Agbeko, R.ao , Edwards, R.ap , Ramakrishnan, K.A.aq , Winkler, M.ar , Borasino, S.ar , Natale, J.as , Giza, C.at , Hilfiker, M.au , Shellington, D.au , Figaji, A.av , Newell, E.aw , Truemper, E.ax , Clark, R.ay , Newth, K.az , Shafi, N.ba , Schober, M.bc , Zimmerman, J.bd , Pineda, J.bf

a Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States
b Department of Medical Physics, University of Wisconsin, Madison, Wisconsin, United States
c Department of Psychiatry, University of Wisconsin, Madison, Wisconsin, United States
d Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
e Department of Pediatrics, University of Tennessee, Memphis, Tennessee, United States
f Department of Pediatrics, University of California-Davis, Sacramento, California, United States
g Department of Pediatrics, University of Texas-Southwestern, Dallas, Texas, United States
h Department of Pediatrics, Children’s National Medical Center, Washington, DC, United States
i Addenbrookes Hospital, Cambridge, United Kingdom
j Alder Hey Children’s NHS Foundation Trust, Liverpool, United Kingdom
k All India Institute of Medical Sciences, New Delhi, India
l Auckland DHB Charitable Trust, Starship Children’s Hospital, Auckland, New Zealand
m Baylor College of Medicine, Houston, TX, United States
n Birmingham Children’s Hospital NHS Foundation Trust, Birmingham, United Kingdom
o Levine Children’s Hospital, Charlotte, NC, United States
p Children’s Health Queensland Hospital and Health Service, Brisbane, Australia
q Children’s Healthcare of Atlanta, Atlanta, GA, United States
r Children’s Hospital Colorado, Aurora, CO, United States
s Children’s Hospital of Philadelphia, Philadelphia, PA, United States
t Children’s Hospital of Richmond, Richmond, VA, United States
u Children’s National Medical Center, Washington, DC, United States
v Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, United States
w Columbia University, New York, NY, United States
x Erasmus Medical Center, Rotterdam, Netherlands
y Great Ormond St. Hospital NHS Foundation Trust, London, United Kingdom
z Boston Children’s Hospital, Boston, MA, United States
aa Hospital Vall d’Hebron, Barcelona, Spain
ab John Hopkins University, Baltimore, MD, United States
ac Joseph M. Sanzari Children’s Hospital, Hackensack University Medical Center, Hackensack, NJ, United States
ad King’s College Hospital NHS Foundation Trust, London, United Kingdom
ae Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom
af Lurie Children’s Hospital, Chicago, IL, United States
ag Massachusetts General Hospital, Boston, MA, United States
ah Miami Children’s Hospital, Miami, FL, United States
ai Murdoch Children’s Research Institute, Royal Children’s Hospital, Melbourne, Australia
aj Nationwide Children’s Hospital, Columbus, OH, United States
ak Pennsylvania State University, Hershey, PA, United States
al Phoenix Children’s Hospital, Phoenix, AZ, United States
am Princess Margaret Hospital, Perth, Australia
an Royal Manchester Children’s Hospital NHS Foundation Trust, Manchester, United Kingdom
ao Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle, United Kingdom
ap University Hospital Bristol NHS Foundation Trust, Bristol, United Kingdom
aq University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom
ar University of Alabama at Birmingham, Birmingham, AL, United States
as University of California, Davis, Sacramento, CA, United States
at University of California, Los Angeles, Los Angeles, CA, United States
au University of California, San Diego, San Diego, CA, United States
av Red Cross War Memorial Children’s Hospital, Cape Town, South Africa
aw University of Iowa Children’s Hospital, Iowa City, IA, United States
ax University of Nebraska Medical Center, Nebraska Medical Center, Omaha, NE, United States
ay University of Pittsburgh, Pittsburgh, PA, United States
az Children’s Hospital of Los Angeles, Los Angeles, CA, United States
ba Le Bon heur Children’s Hospital, Memphis, TN, United States
bb University of Texas Southwestern Medical Center, Dallas, TX, United States
bc University of Utah, Salt Lake City, UT, United States
bd University of Washington, Seattle, WA, United States
be University of Wisconsin, Madison, WI, United States
bf Washington University-St. Louis, St. Louis, MO, United States
bg Wayne State University, Detroit, MI, United States

Abstract
OBJECTIVE There is no consensus on the optimal timing and specific brain MRI sequences in the evaluation and management of severe pediatric traumatic brain injury (TBI), and information on current practices is lacking. The authors performed a survey of MRI practices among sites participating in a multicenter study of severe pediatric TBI to provide information for designing future clinical trials using MRI to assess brain injury after severe pediatric TBI. METHODS Information on current imaging practices and resources was collected from 27 institutions participating in the Approaches and Decisions after Pediatric TBI Trial. Multiple-choice questions addressed the percentage of patients with TBI who have MRI studies, timing of MRI, MRI sequences used to investigate TBI, as well as the magnetic feld strength of MR scanners used at the participating institutions and use of standardized MRI protocols for imaging after severe pediatric TBI. RESULTS Overall, the reported use of MRI in pediatric patients with severe TBI at participating sites was high, with 40% of sites indicating that they obtain MRI studies in > 95% of this patient population. Differences were observed in the frequency of MRI use between US and international sites, with the US sites obtaining MRI in a higher proportion of their pediatric patients with severe TBI (94% of US vs 44% of international sites reported MRI in at least 70% of patients with severe TBI). The reported timing and composition of MRI studies was highly variable across sites. Sixty percent of sites reported typically obtaining an MRI study within the first 7 days postinjury, with the remainder of responses distributed throughout the first 30-day postinjury period. Responses indicated that MRI sequences sensitive for diffuse axonal injury and ischemia are frequently obtained in patients with TBI, whereas perfusion imaging and spectroscopy techniques are less common. CONCLUSIONS Results from this survey suggest that despite the lack of consensus or guidelines, MRI is commonly obtained during the acute clinical setting after severe pediatric TBI. The variation in MRI practices highlights the need for additional studies to determine the utility, optimal timing, and composition of clinical MRI studies after TBI. The information in this survey describes current clinical MRI practices in children with severe TBI and identifies important challenges and objectives that should be considered when designing future studies. © AANS 2019.

Author Keywords
Magnetic resonance imaging;  Pediatric traumatic brain injury;  Survey;  Trauma

Document Type: Article
Publication Stage: Final
Source: Scopus

“Lithium chloride corrects weakness and myopathology in a preclinical model of LGMD1D” (2019) Neurology: Genetics

Lithium chloride corrects weakness and myopathology in a preclinical model of LGMD1D
(2019) Neurology: Genetics, 5 (2), art. no. e318, . 

Findlay, A.R.a b , Bengoechea, R.a b , Pittman, S.K.a b , Chou, T.-F.c , True, H.L.a d , Weihl, C.C.a b

a Washington University School of Medicine, Hope Center for Neurological Diseases, St. Louis, MO, United States
b Department of Neurology, Hope Center for Neurological Diseases, St. Louis, MO, United States
c Harbor-UCLA Medical Center, Department of Pediatrics, Division of Medical Genetics, Torrance, CA, United States
d Department of Cell Biology and Physiology, Saint Louis, MO, United States

Abstract
Objective: To understand DNAJB6’s function in skeletal muscle and identify therapeutic targets for limb-girdle muscular dystrophy 1D (LGMD1D). Methods: DNAJB6 knockout (KO) myoblasts were generated with Crispr/cas9 technology, and differentially accumulated proteins were identified using stable isotope labeling, followed by quantitative mass spectrometry. Cultured KO myotubes and mouse muscle from DNAJB6b-WT or DNAJB6b-F93L mice were analyzed using histochemistry, immunohistochemistry, and immunoblot. Mouse functional strength measures included forelimb grip strength and inverted wire hang. Results: DNAJB6 inactivation leads to the accumulation of sarcomeric proteins and hypertrophic myotubes with an enhanced fusion index. The increased fusion in DNAJB6 KO myotubes correlates with diminished glycogen synthase kinase-β (GSK3β) activity. In contrast, LGMD1D mutations in DNAJB6 enhance GSK3β activation and suppress β-catenin and NFAT3c signaling. GSK3β inhibition with lithium chloride improves muscle size and strength in an LGMD1D preclinical mouse model. Conclusions: Our results suggest that DNAJB6 facilitates protein quality control and negatively regulates myogenic signaling. In addition, LGMD1D-associated DNAJB6 mutations inhibit myogenic signaling through augmented GSK3β activity. GSK3β inhibition with lithium chloride may be a therapeutic option in LGMD1D. © 2019 American Academy of Neurology.

Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access

“Functional and structural connectivity of the cerebellar nuclei with the striatum and cerebral cortex in first-episode psychosis” (2019) Journal of Neuropsychiatry and Clinical Neurosciences

Functional and structural connectivity of the cerebellar nuclei with the striatum and cerebral cortex in first-episode psychosis
(2019) Journal of Neuropsychiatry and Clinical Neurosciences, 31 (2), pp. 143-151. 

Lee, K.-H.a b , Oh, H.a , Suh, J.-H.S.a , Cho, K.I.K.a c , Yoon, Y.B.a e , Shin, W.-G.c , Lee, T.Y.d , Kwon, J.S.a b

a Department of Brain and Cognitive Sciences, College of Natural Sciences, Seoul National University, Seoul, South Korea
b Department of Psychiatry, Seoul National University College of Medicine, Seoul, South Korea
c Institute of Human Behavioral Medicine, SNU-MRC, Seoul, South Korea
d Center for Cognition and Sociality, Institute for Basic Science, Daejeon, South Korea
e Department of Psychiatry, Washington University, St. Louis, United States

Abstract
Objective: Evidence suggests that the cortico-striatalthalamo- cortical circuitry plays an important role in schizophrenia pathophysiology. Cerebellar contribution from deep cerebellar nuclei to the circuitry has not yet been examined. The authors investigated resting-state functional connectivity (RSFC) of cerebellar output nuclei with striatal-thalamiccortical regions in relation to white-matter integrity and regional gray-matter volumes in first-episode psychosis (FEP). Methods: Forty FEP patients and 40 age- and gendermatched healthy control subjects (HCs) participated. RSFC between cerebellar nuclei and striatal-thalamic-cortical regions was examined. Diffusion tensor imaging and volumetric scans were examined for possible structural constraints on RSFC. The authors also examined relationships between neuroimaging variables and cognitive and clinical measures. Results: FEP patients, compared with HCs, exhibited decreased RSFC between the left fastigial nucleus and right putamen, which was associated with poor letter fluency performance and lower global assessment of functioning scores. By contrast, patients showed widespread increased accumbens network connectivity in the left nucleus. The authors further observed both hypo- and hyper-RSFC between the cerebellar nuclei and fronto-parietal areas in patients, independent of striatal activity. Finally, the authors found impaired integrity of the left superior cerebellar peduncle and decreased bilateral putamen volume in patients, whereas structural-functional relationships found in HCs were absent in patients. Conclusions: This study provides evidence of disordered RSFC of cerebellar output nuclei to the striatum and neocortex at the early stage of schizophrenia. Furthermore, dysfunctional cerebellar influences on fronto-parietal areas that are independent of striatal dysfunction in patients with FEP were observed. The results suggest that cortico-striatal abnormalities in patients with FEP are produced by abnormal cerebellar influences. © 2019, American Psychiatric Association. All rights reserved.

Document Type: Article
Publication Stage: Final
Source: Scopus

“Standing enhances cognitive control and alters visual search” (2019) Attention, Perception, and Psychophysics

Standing enhances cognitive control and alters visual search
(2019) Attention, Perception, and Psychophysics, . 

Smith, K.C.a , Davoli, C.C.b , Knapp, W.H., IIIa , Abrams, R.A.a

a Department of Psychological and Brain Sciences, Washington University, St. Louis, MO, United States
b Department of Psychology, Central Michigan University, Mount Pleasant, MI, United States

Abstract
Postural changes and the maintenance of postural stability have been shown to affect many aspects of cognition. Here we examined the extent to which selective visual attention may differ between standing and seated postures in three tasks: the Stroop color-word task, a task-switching paradigm, and visual search. We found reduced Stroop interference, a reduction in switch costs, and slower search rates in the visual search task when participants stood compared to when they sat while performing the tasks. The results suggest that the postural demands associated with standing enhance cognitive control, revealing broad connections between body posture and cognitive mechanisms. © 2019, The Psychonomic Society, Inc.

Author Keywords
Attention and executive control;  Cognitive and attentional control;  Embodied perception

Document Type: Article
Publication Stage: Article in Press
Source: Scopus

“Diffusion weighted imaging evidence of extra-callosal pathways for interhemispheric communication after complete commissurotomy” (2019) Brain Structure and Function

Diffusion weighted imaging evidence of extra-callosal pathways for interhemispheric communication after complete commissurotomy
(2019) Brain Structure and Function, . 

Nomi, J.S.a , Marshall, E.a , Zaidel, E.b c , Biswal, B.d , Castellanos, F.X.e f , Dick, A.S.g , Uddin, L.Q.a h , Mooshagian, E.i

a Department of Psychology, University of Miami, P.O. Box 248185-0751, Coral Gables, FL 33124, United States
b Department of Psychology, University of California, Los Angeles, CA 90095, United States
c Brain Research Institute, University of California, Los Angeles, CA 90095, United States
d Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, NJ 07102, United States
e Department of Child and Adolescent Psychiatry, Hassenfeld Children’s Hospital at NYU Langone, New York, NY 10016, United States
f Nathan Kline Institute for Psychiatric Research, Orangeburg, NY 10962, United States
g Department of Psychology, Florida International University, Miami, FL 33199, United States
h Neuroscience Program, University of Miami Miller School of Medicine, Miami, FL 33136, United States
i Department of Neuroscience, Washington University School of Medicine, Saint Louis, MO 63110, United States

Abstract
The integrity of white matter architecture in the human brain is related to cognitive processing abilities. The corpus callosum is the largest white matter bundle interconnecting the two cerebral hemispheres. “Split-brain” patients in whom all cortical commissures have been severed to alleviate intractable epilepsy demonstrate remarkably intact cognitive abilities despite the lack of this important interhemispheric pathway. While it has often been speculated that there are compensatory alterations in the remaining interhemispheric fibers in split-brain patients several years post-commissurotomy, this has never been directly shown. Here we examined extra-callosal pathways for interhemispheric communication in the brain of a patient who underwent complete cerebral commissurotomy using diffusion weighted imaging tractography. We found that compared with a healthy age-matched comparison group, the split-brain patient exhibited increased fractional anisotropy (FA) of the dorsal and ventral pontine decussations of the cortico-cerebellar interhemispheric pathways. Few differences were observed between the patient and the comparison group with respect to FA of other long-range intrahemispheric fibers. These results point to specific cerebellar anatomical substrates that may account for the spared interhemispheric coordination and intact cognitive abilities that have been extensively documented in this unique patient. © 2019, Springer-Verlag GmbH Germany, part of Springer Nature.

Author Keywords
Corpus callosum;  Epilepsy;  Hemispheric specialization;  Interhemispheric transfer;  Laterality;  Structural connectivity

Document Type: Article
Publication Stage: Article in Press
Source: Scopus

“The Experience of Chemotherapy-Induced Peripheral Neuropathy Among Childhood Cancer Survivors” (2019) Journal of Pediatric Oncology Nursing

The Experience of Chemotherapy-Induced Peripheral Neuropathy Among Childhood Cancer Survivors
(2019) Journal of Pediatric Oncology Nursing, . 

Mohrmann, C.

Washington University School of Medicine, St. Louis, MO, United States

Abstract
As the number of childhood cancer survivors (CCS) is increasing, it is imperative to understand the late effects of childhood cancer therapy to optimize their health and quality of life. Chemotherapy-induced peripheral neuropathy (CIPN) is an unpleasant effect of chemotherapy that affects the peripheral nervous system. This qualitative study uses narrative analysis with a phenomenological influence to understand the lived experience of CIPN among five CCS utilizing photo-elicitation. The lived experience of CIPN is characterized by “a condition of disconnection” with three subthemes: (1) disconnection between mind and body, (2) disconnection between anticipated potential and reality, and (3) disconnection between survivors and support. The condition of disconnection leads to a variety of negative physical and emotional performance outcomes. These findings support the need for refined clinical strategies for identifying this underappreciated condition and further development of interventions to “rebuild the connections” that CCS are lacking. © 2019 by Association of Pediatric Hematology/Oncology Nurses.

Author Keywords
adolescents and young adults;  AYA;  late effects of cancer;  survivorship;  symptom management

Document Type: Article
Publication Stage: Article in Press
Source: Scopus

“Transplantation of v2a interneurons and neural progenitors after cervical spinal cord injury” (2019) Transactions of the Annual Meeting of the Society for Biomaterials and the Annual International Biomaterials Symposium

Transplantation of v2a interneurons and neural progenitors after cervical spinal cord injury
(2019) Transactions of the Annual Meeting of the Society for Biomaterials and the Annual International Biomaterials Symposium, 40, p. 29. 

Sakiyama-Elbert, S.a , Thompson, R.a b , Zholudeva, L.V.c , Lane, M.c

a Department of Biomedical Engineering, University of Texas at Austin, United States
b Department of Biomedical Engineering, Washington University, St Louis, United States
c Department of Neurobiology and Anatomy, Spinal Cord Research Center, College of Medicine, Drexel University, United States

Abstract
Every year 17,000 Americans suffer a traumatic spinal cord injury (SCI) that leads to a significant, lifelong healthcare burden, which can cost from $1 to 4.5 million. One major reason for the high cost of SCI is the limited of regenerative capacity of the adult mammalian spinal cord. 1 This lack of regeneration is due, in part, to a highly organized, predominantly astrocytic glial scar that forms to limit the spread of secondary injury, but also represents a chemical and physical barrier to neuronal growth. Interestingly, it has been observed that astrocytes are also present where axons are able to cross the injury site. 2 This suggests that astrocytes are involved in both the formation of the glial scar and the creation of bridges across the scar and lesion environments. V2a interneurons are glutamatergic, ipsilaterally projecting cells that have been found to be important for local rewiring following SCI, particularly in the phrenic circuit. In this work, we used a novel hyaluronic acid (HA)-astrocyte extracellular matrix (ECM) hydrogel and demonstrate that this hydrogel can be used to deliver V2a interneurons into the injured spinal cord. © 2019 Omnipress – All rights reserved.

Document Type: Conference Paper
Publication Stage: Final
Source: Scopus

“Association of Patient Social, Cognitive, and Functional Risk Factors with Preventable Hospitalizations: Implications for Physician Value-Based Payment” (2019) Journal of General Internal Medicine

Association of Patient Social, Cognitive, and Functional Risk Factors with Preventable Hospitalizations: Implications for Physician Value-Based Payment
(2019) Journal of General Internal Medicine, . 

Johnston, K.J.a , Wen, H.b , Schootman, M.c , Joynt Maddox, K.E.d

a Department of Health Management and Policy and Center for Outcomes Research, College for Public Health and Social Justice, Saint Louis University, St. Louis, MO, United States
b Department of Health Management and Policy, University of Kentucky, Lexington, KY, United States
c Department of Clinical Analytics and Insights, Center for Clinical Excellence, SSM Health, St. Louis, MO, United States
d Cardiovascular Division, Washington University School of Medicine, St. Louis, MO, United States

Abstract
Background: Ambulatory care-sensitive condition (ACSC) hospitalizations are used to evaluate physicians’ performance in Medicare value-based payment programs. However, these measures may disadvantage physicians caring for vulnerable populations because they omit social, cognitive, and functional factors that may be important determinants of hospitalization. Objective: To determine whether social, cognitive, and functional risk factors are associated with ACSC hospitalization rates and whether adjusting for them changes outpatient safety-net providers’ performance. Design: Using data from the Medicare Current Beneficiary Survey, we conducted patient-level multivariable regression to estimate the association (as incidence rate ratios (IRRs)) between patient-reported social, cognitive, and functional risk factors and ACSC hospitalizations. We compared outpatient safety-net and non-safety-net providers’ performance after adjusting for clinical comorbidities alone and after additional adjustment for social, cognitive, and functional factors captured in survey data. Setting: Safety-net and non-safety-net clinics. Participants: Community-dwelling Medicare beneficiaries contributing 38,616 person-years from 2006 to 2013. Measurements: Acute and chronic ACSC hospitalizations. Results: After adjusting for clinical comorbidities, Alzheimer’s/dementia (IRR 1.30, 95% CI 1.02–1.65), difficulty with 3–6 activities of daily living (ADLs) (IRR 1.43, 95% CI 1.05–1.94), difficulty with 1–2 instrumental ADLs (IADLs, IRR 1.54, 95% CI 1.26–1.90), and 3–6 IADLs (IRR 1.90, 95% CI 1.49–2.43) were associated with acute ACSC hospitalization. Low income (IRR 1.28, 95% CI 1.03–1.58), lack of educational attainment (IRR 1.33, 95% CI 1.04–1.69), being unmarried (IRR 1.18, 95% CI 1.01–1.36), difficulty with 1–2 IADLs (IRR 1.30, 95% CI 1.05–1.60), and 3–6 IADLs (IRR 1.44, 95% CI 1.16–1.80) were associated with chronic ACSC hospitalization. Adding these factors to standard Medicare risk adjustment eliminated outpatient safety-net providers’ performance gap (p <.05) on ACSC hospitalization rates relative to non-safety-net providers. Conclusions: Social, cognitive, and functional risk factors are independently associated with ACSC hospitalizations. Failure to account for them may penalize outpatient safety-net providers for factors that are beyond their control. © 2019, Society of General Internal Medicine.

Author Keywords
Medicare;  physician value-based payment;  safety-net providers

Document Type: Article
Publication Stage: Article in Press
Source: Scopus

“Assessment of executive function declines in presymptomatic and mildly symptomatic familial frontotemporal dementia: NIH-EXAMINER as a potential clinical trial endpoint” (2019) Alzheimer’s and Dementia

Assessment of executive function declines in presymptomatic and mildly symptomatic familial frontotemporal dementia: NIH-EXAMINER as a potential clinical trial endpoint
(2019) Alzheimer’s and Dementia, . 

Staffaroni, A.M.a , Bajorek, L.a , Casaletto, K.B.a , Cobigo, Y.a , Goh, S.-Y.M.a , Wolf, A.a , Heuer, H.W.a , Elahi, F.M.a , Ljubenkov, P.A.a , Dever, R.a , Kornak, J.b , Appleby, B.c , Bove, J.d , Bordelon, Y.e , Brannelly, P.f , Brushaber, D.g , Caso, C.h , Coppola, G.e i , Dheel, C.j , Dickerson, B.C.k , Dickinson, S.l , Dominguez, S.d , Domoto-Reilly, K.h , Faber, K.m , Ferrall, J.n , Fields, J.A.o , Fishman, A.p , Fong, J.a , Foroud, T.m , Forsberg, L.K.j , Gavrilova, R.j , Gearhart, D.j , Ghazanfari, B.q r , Ghoshal, N.s , Goldman, J.t u , Graff-Radford, J.j , Graff-Radford, N.v , Grant, I.w , Grossman, M.d , Haley, D.v , Hsiung, G.-Y.x , Huey, E.D.t u , Irwin, D.J.d , Jones, D.T.j , Jones, L.y , Kantarci, K.z , Karydas, A.a , Kaufer, D.I.n , Kerwin, D.R.aa ab , Knopman, D.S.j , Kraft, R.j , Kremers, W.K.g , Kukull, W.A.ac , Litvan, I.ad , Lucente, D.k , Lungu, C.ae , Mackenzie, I.R.af , Maldonado, M.e , Manoochehri, M.t , McGinnis, S.M.k , McKinley, E.ag , Mendez, M.F.e i , Miller, B.L.a , Multani, N.q r , Onyike, C.ah , Padmanabhan, J.k , Pantelyat, A.ai , Pearlman, R.aj , Petrucelli, L.ak , Potter, M.m , Rademakers, R.ak , Ramos, E.M.i , Rankin, K.P.a , Rascovsky, K.d , Roberson, E.D.ag , Rogalski, E.al , Sengdy, P.x , Shaw, L.M.am , Syrjanen, J.g , Tartaglia, M.C.q r , Tatton, N.l , Taylor, J.a , Toga, A.an , Trojanowski, J.Q.am , Weintraub, S.w , Wang, P.a , Wong, B.k , Wszolek, Z.v , Boxer, A.L.a , Boeve, B.F.j , Kramer, J.H.a , Rosen, H.J.a , ARTFL/LEFFTDS consortiumao

a Department of Neurology, Memory and Aging Center, University of California, San Francisco, San Francisco, CA, United States
b Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, United States
c Department of Neurology, Case Western Reserve University, Cleveland, OH, United States
d Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
e Department of Neurology, University of California, Los Angeles, Los Angeles, CA, United States
f Tau Consortium, Rainwater Charitable Foundation, Fort Worth, TX, United States
g Department of Health Sciences Research, Mayo Clinic, Rochester, MN, United States
h Department of Neurology, University of Washington, Seattle, WA, United States
i Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, CA, United States
j Department of Neurology, Mayo Clinic, Rochester, MN, United States
k Department of Neurology, Frontotemporal Disorders Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
l Association for Frontotemporal Degeneration, Radnor, PA, United States
m National Cell Repository for Alzheimer’s Disease (NCRAD), Indiana University, Indianapolis, IN, United States
n Department of Neurology, University of North Carolina, Chapel Hill, NC, United States
o Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, United States
p School of Medicine, Department of Psychiatry, Johns Hopkins University, Baltimore, MD, United States
q Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada
r Division of Neurology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada
s Departments of Neurology and Psychiatry, Washington University School of Medicine, Washington University, St. Louis, MO, United States
t Department of Neurology, Columbia University, New York, NY, United States
u Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Columbia University, New York, NY, United States
v Department of Neurology, Mayo Clinic, Jacksonville, FL, United States
w Feinberg School of Medicine, Department of Neurology, Northwestern University, Chicago, IL, United States
x Division of Neurology, Deptartment of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
y Department of Radiology, Washington University School of Medicine, Washington University, St. Louis, MO, United States
z Department of Radiology, Mayo Clinic, Rochester, MN, United States
aa Department of Neurology and Neurotherapeutics, Center for Alzheimer’s and Neurodegenerative Diseases, The University of Texas, Southwestern Medical Center at Dallas, Dallas, TX, United States
ab Department of Internal Medicine, The University of Texas, Southwestern Medical Center at Dallas, Dallas, TX, United States
ac National Alzheimer Coordinating Center (NACC), University of Washington, Seattle, WA, United States
ad Department of Neurosciences, Parkinson and Other Movement Disorders Center, University of California, San Diego, San Diego, CA, United States
ae National Institute of Neurological Disorders and Stroke (NINDS), Bethesda, MD, United States
af Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada
ag Department of Neurology, Alzheimer’s Disease Center, University of Alabama at Birmingham, Birmingham, AL, United States
ah Department of Geriatric Psychiatry and Neuropsychiatry, Johns Hopkins University, Baltimore, MD, United States
ai School of Medicine, Department of Neurology, Johns Hopkins University, Baltimore, MD, United States
aj Bluefield Project, San Francisco, CA, United States
ak Department of Neurosciences, Mayo Clinic, Jacksonville, FL, United States
al Feinberg School of Medicine, Department of Psychiatry and Behavioral Sciences, Northwestern University, Chicago, IL, United States
am Perelman School of Medicine, Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, United States
an Departments of Ophthalmology, Neurology, Psychiatry and the Behavioral Sciences, Radiology and Engineering, Laboratory of Neuroimaging (LONI), USC, Los Angeles, CA, United States

Abstract
Introduction: Identifying clinical measures that track disease in the earliest stages of frontotemporal lobar degeneration (FTLD)is important for clinical trials. Familial FTLD provides a unique paradigm to study early FTLD. Executive dysfunction is a clinically relevant hallmark of FTLD and may be a marker of disease progression. Methods: Ninety-three mutation carriers with no symptoms or minimal/questionable symptoms (MAPT, n = 31; GRN, n = 28; C9orf72, n = 34; Clinical Dementia Rating scale plus NACC FTLD Module < 1)and 78 noncarriers enrolled through Advancing Research and Treatment in Frontotemporal Lobar Degeneration/Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects studies completed the Executive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research (NIH-EXAMINER)and the UDS neuropsychological battery. Linear mixed-effects models were used to identify group differences in cognition at baseline and longitudinally. We examined associations between cognition, clinical functioning, and magnetic resonance imaging volumes. Results: NIH-EXAMINER scores detected baseline and differences in slopes between carriers and noncarriers, even in carriers with a baseline Clinical Dementia Rating scale plus NACC FTLD Module = 0. NIH-EXAMINER declines were associated with worsening clinical symptoms and brain volume loss. Discussion: The NIH-EXAMINER is sensitive to cognitive changes in presymptomatic familial FTLD and is a promising surrogate endpoint. © 2019 The Authors

Author Keywords
Behavioral variant;  Cognition;  Corticobasal syndrome;  Fluency;  Genetic;  Inhibition;  Neuropsychology;  Nonfluent variant;  Primary progressive aphasia;  Progranulin;  Progressive supranuclear palsy;  Semantic variant;  Set-shifting;  Tau;  Working memory

Document Type: Article
Publication Stage: Article in Press
Source: Scopus
Access Type: Open Access

“Simultaneous patient presentation for endovascular thrombectomy in acute ischemic stroke” (2019) Journal of NeuroInterventional Surgery

Simultaneous patient presentation for endovascular thrombectomy in acute ischemic stroke
(2019) Journal of NeuroInterventional Surgery, . 

Dalsania, A.K.a , Kansagra, A.P.b c d

a Rutgers New Jersey Medical School, Newark, NJ, United States
b Mallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, MO 63110, United States
c Department of Neurological Surgery, Washington University School of Medicine, St Louis, MO, United States
d Department of Neurology, Washington University School of Medicine, St Louis, MO, United States

Abstract
Background: Increased demand for endovascular thrombectomy has increased the likelihood of simultaneous patient presentation leading to competing demand for time-critical treatment that could adversely impact patient outcomes. We aimed to quantify the occurrence of simultaneous patient presentation at different patient volumes. Methods: Empirical distributions for time of patient presentation and case duration were used to probabilistically generate arrival time and case duration for a set annual patient volume, ranging from 1 to 500 cases per year, for 16 000 independent trials at each volume. Time series were generated for each trial to represent the number of cases being performed at each minute of the year. Time series were used to calculate daily thrombectomy demand, annual concurrent demand, and hourly excess demand. Results: The patient volumes at which at least one annual occurrence of concurrent demand by two patients was 50% and 97.5% likely were 45 and 101, respectively. The volumes at which at least one annual occurrence of concurrent demand by three patients was 50% and 97.5% likely were 216 and 387, respectively. There was dramatic variation in the occurrence of excess demand by two or more patients throughout the day. Conclusions: The occurrence of simultaneous presentation by multiple patients for endovascular thrombectomy varies with annual patient volume and time of day. Understanding these trends and the associated patient impact can inform intelligent strategies at regional and national levels for optimizing patient care within real-world financial and operational constraints. © Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.

Author Keywords
brain;  economics;  intervention;  stroke;  thrombectomy

Document Type: Article
Publication Stage: Article in Press
Source: Scopus

“Patient Stakeholder Versus Physician Preferences Regarding Amyloid PET Testing” (2019) Alzheimer Disease and Associated Disorders

Patient Stakeholder Versus Physician Preferences Regarding Amyloid PET Testing
(2019) Alzheimer Disease and Associated Disorders, . 

Armstrong, M.J.a , Gronseth, G.S.b , Day, G.S.c , Rheaume, C.d , Alliance, S.a , Mullins, C.D.e

a Department of Neurology, McKnight Brain Institute, University of Florida, College of Medicine, Gainesville, FL, United States
b Department of Neurology, University of Kansas Medical Center, Kansas City, KS, United States
c Department of Neurology, Charles F and Joanne Knight Alzheimer Disease Research Center, Washington University School of Medicine, St Louis, MO, United States
d American Academy of Neurology, Minneapolis, MN, United States
e Pharmaceutical Health Research Department, University of Maryland School of Pharmacy, Baltimore, MD, United States

Author Keywords
amyloid PET imaging;  dementia;  guidelines as topic;  mild cognitive impairment;  patient participation;  preclinical Alzheimer disease

Document Type: Review
Publication Stage: Article in Press
Source: Scopus

“Differential Relationships of Child Anxiety and Depression to Child Report and Parent Report of Electronic Media Use” (2019) Child Psychiatry and Human Development

Differential Relationships of Child Anxiety and Depression to Child Report and Parent Report of Electronic Media Use
(2019) Child Psychiatry and Human Development, . 

Fors, P.Q.a , Barch, D.M.a b c

a Department of Psychological & Brain Sciences, Washington University, Campus Box 1125, 1 Brookings Drive, St. Louis, MO 63130, United States
b Department of Psychiatry, Washington University, St. Louis, MO, United States
c Department of Radiology, Washington University, St. Louis, MO, United States

Abstract
Child depression and anxiety have been associated with electronic media use, but the comorbidity between the two has rarely been accounted for in analyses. We examined both child and parent reports of electronic media use in relation to parent-reported child depression and anxiety. Using survey and interview data collected for 9- to 11-year-olds from the 21-site adolescent brain cognitive development study, we conducted generalized linear mixed models. Our results demonstrated that electronic media use was more strongly associated with depression than anxiety, and that accounting for depression significantly reduced the relationship between electronic media use and anxiety. Different categories of electronic media showed differential relationships to anxiety and depression, with video gaming and video chatting related to anxiety, but video watching related to depression. These findings provide important data to ground theories of the mechanisms that contribute to these associations. © 2019, The Author(s).

Author Keywords
Anxiety;  Children;  Depression;  Electronic media use;  Technology

Document Type: Article
Publication Stage: Article in Press
Source: Scopus
Access Type: Open Access

“A pathogenic CtBP1 missense mutation causes altered cofactor binding and transcriptional activity” (2019) Neurogenetics

A pathogenic CtBP1 missense mutation causes altered cofactor binding and transcriptional activity
(2019) Neurogenetics, . 

Beck, D.B.a , Subramanian, T.b , Vijayalingam, S.b , Ezekiel, U.R.c , Donkervoort, S.d , Yang, M.L.e , Dubbs, H.A.f , Ortiz-Gonzalez, X.R.g , Lakhani, S.h , Segal, D.i , Au, M.j , Graham, J.M., Jr.j , Verma, S.k , Waggoner, D.l , Shinawi, M.m , Bönnemann, C.G.d , Chung, W.K.n , Chinnadurai, G.b

a National Human Genome Research Institute, National Institutes of Health, 10 Center Drive, Room B3-4129, Bethesda, MD 20892, United States
b Institute for Molecular Virology, Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, E. A. Doisy Research Center, 6th Floor, St. Louis, MO 63104, United States
c Clinical Health Sciences, Saint Louis University, 3437 Caroline Street, Allied Health Building, Suite 3025, Saint Louis, MO 63104, United States
d National Institute of Neurological Disorders and Stroke Neurogenetics Branch, National Institutes of Health, 10 Center Drive Room 2B39, MSC 1477, Bethesda, MD 20892, United States
e University of Colorado Denver, 13123 E. 16th Ave; Box B155, Aurora, CO 80238, United States
f Division of Neurology, The Children’s Hospital of Philadelphia, Philadelphia, PA 19104, United States
g Department of Neurology, Pereleman School of Medicine, University of Pennsylvania; Division of Neurology, The Children’s Hospital of Philadelphia, Philadelphia, PA 19104, United States
h Center for Neurogenetics, Brain and Mind Research Institute, Weill Cornell Medicine, 413 E 69th Street, New York, NY 10021, United States
i Department of Pediatrics, Division of Child Neurology, Weill Cornell Medicine, 525 E. 68th St, Box 91, New York, NY 10065, United States
j Medical Genetics, Department of Pediatrics, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA 90068, United States
k Division of Pediatric Neurology, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, United States
l Department of Human Genetics, University of Chicago, Chicago, IL 60637, United States
m Department of Pediatrics, Division of Genetics and Genomic Medicine, Washington University School of Medicine, St. Louis, MO 63110, United States
n Departments of Pediatrics and Medicine, Columbia University Medical Center, New York, NY, United States

Abstract
We previously reported a pathogenic de novo p.R342W mutation in the transcriptional corepressor CTBP1 in four independent patients with neurodevelopmental disabilities [1]. Here, we report the clinical phenotypes of seven additional individuals with the same recurrent de novo CTBP1 mutation. Within this cohort, we identified consistent CtBP1-related phenotypes of intellectual disability, ataxia, hypotonia, and tooth enamel defects present in most patients. The R342W mutation in CtBP1 is located within a region implicated in a high affinity-binding cleft for CtBP-interacting proteins. Unbiased proteomic analysis demonstrated reduced interaction of several chromatin-modifying factors with the CtBP1 W342 mutant. Genome-wide transcriptome analysis in human glioblastoma cell lines expressing -CtBP1 R342 (wt) or W342 mutation revealed changes in the expression profiles of genes controlling multiple cellular processes. Patient-derived dermal fibroblasts were found to be more sensitive to apoptosis during acute glucose deprivation compared to controls. Glucose deprivation strongly activated the BH3-only pro-apoptotic gene NOXA, suggesting a link between enhanced cell death and NOXA expression in patient fibroblasts. Our results suggest that context-dependent relief of transcriptional repression of the CtBP1 mutant W342 allele may contribute to deregulation of apoptosis in target tissues of patients leading to neurodevelopmental phenotypes. © 2019, Springer-Verlag GmbH Germany, part of Springer Nature.

Author Keywords
C-terminal binding protein;  Chromatin modifying complex;  CtBP1;  Neurodevelopmental disease;  p.R342W mutation

Document Type: Article
Publication Stage: Article in Press
Source: Scopus

“PCH1 regulates light, temperature, and circadian signaling as a structural component of phytochrome B-photobodies in Arabidopsis” (2019) Proceedings of the National Academy of Sciences of the United States of America

PCH1 regulates light, temperature, and circadian signaling as a structural component of phytochrome B-photobodies in Arabidopsis
(2019) Proceedings of the National Academy of Sciences of the United States of America, 116 (17), pp. 8603-8608. 

Huang, H.a , McLoughlin, K.E.b , Sorkin, M.L.a c , Sethe Burgie, E.b , Bindbeutel, R.K.a , Vierstra, R.D.b , Nusinow, D.A.a

a Donald Danforth Plant Science Center, St. Louis, MO 63132, United States
b Department of Biology, Washington University in St. Louis, St. Louis, MO 63130, United States
c Division of Biology and Biomedical Sciences, Washington University in St. Louis, St. Louis, MO 63130, United States

Abstract
The members of the phytochrome (phy) family of bilin-containing photoreceptors are major regulators of plant photomorphogenesis through their unique ability to photointerconvert between a biologically inactive red light-absorbing Pr state and an active far-red light-absorbing Pfr state. While the initial steps in Pfr signaling are unclear, an early event for the phyB isoform after photoconversion is its redistribution from the cytoplasm into subnuclear foci known as photobodies (PBs), which dissipate after Pfr reverts back to Pr by far-red irradiation or by temperature-dependent nonphotochemical reversion. Here we present evidence that PHOTOPERIODIC CONTROL OF HYPOCOTYL 1 (PCH1) functions both as an essential structural component of phyB-containing PBs and as a direct regulator of thermal reversion that is sufficient to stabilize phyB as Pfr in vitro. By examining the genetic interaction between a constitutively active phyB Y276H -YFP allele (YHB-YFP) and PCH1, we show that the loss of PCH1 prevents YHB from coalescing into PBs without affecting its nuclear localization, whereas overexpression of PCH1 dramatically increases PB levels. Loss of PCH1, presumably by impacting phyB-PB assembly, compromises a number of events elicited in YHB-YFP plants, including their constitutive photomorphogenic phenotype, red light-regulated thermomorphogenesis, and input of phyB into the circadian clock. Conversely, elevated levels of both phyB and PCH1 generate stable, yet far-red light–reversible PBs that persisted for days. Collectively, our data demonstrate that the assembly of PCH1-containing PBs is critical for phyB signaling to multiple outputs and suggest that altering PB dynamics could be exploited to modulate plant responses to light and temperature. © 2019 National Academy of Sciences. All rights reserved.

Author Keywords
Circadian clock;  Photobodies;  Photomorphogenesis;  Phytochrome;  Thermomorphogenesis

Document Type: Article
Publication Stage: Final
Source: Scopus

“Gambling in Emerging Adulthood: the Role of Adolescent Depressive Symptoms, Antisocial Behaviors, and Alcohol Use” (2019) International Journal of Mental Health and Addiction

Gambling in Emerging Adulthood: the Role of Adolescent Depressive Symptoms, Antisocial Behaviors, and Alcohol Use
(2019) International Journal of Mental Health and Addiction, . 

Jun, H.-J.a , Sacco, P.a , Cunningham-Williams, R.M.b

a University of Maryland School of Social Work, 525 W. Redwood Street, Baltimore, MD 21201, United States
b Brown School, Washington University in St. Louis, One Brookings Drive, St. Louis, MO 63130, United States

Abstract
Emerging adults (ages 18–29) display higher prevalence of gambling participation and problem gambling as well as co-occurrence with other risk behaviors compared to other age groups. Consequences of these co-occurring conditions may lead to psychological symptoms, behavioral problems, and socioeconomic and medical costs. Depressive symptoms, antisocial behaviors, and alcohol use are known risk factors for gambling participation and problem gambling. However, scarce research has examined the co-occurrence of those adolescent risk factors and later gambling behaviors in emerging adulthood longitudinally. Using multiple waves of National Longitudinal Study of Adolescent to Adult Health (Add Health) data, we examined the relationship between earlier depressive symptoms, antisocial behaviors, alcohol use, and gambling behaviors at wave III, and later gambling participation and problem gambling (wave IV) in emerging adults ages 18–29, using multinomial logistic regression. Our findings suggest that earlier antisocial behaviors and gambling behaviors increased later risk for gambling participation and problem gambling. Past-year alcohol use and heavy drinking were associated with the increased risk of gambling participation but not problem gambling. Earlier depressive symptoms decreased the risk of gambling participation later among those who endorsed antisocial behaviors. Emerging adulthood may be a critical developmental period in the development of comorbid conditions of gambling and other risk behaviors. The results contribute evidence supporting the importance of early prevention and intervention for the co-occurrence of gambling and other risk behaviors in emerging adulthood. © 2019, Springer Science+Business Media, LLC, part of Springer Nature.

Author Keywords
Alcohol use;  Emerging adults;  Externalizing behaviors;  Gambling;  Internalizing behaviors

Document Type: Article
Publication Stage: Article in Press
Source: Scopus

“Frequency and Risk Factors for Prolonged Opioid Prescriptions After Surgery for Brachial Plexus Injury” (2019) Journal of Hand Surgery

Frequency and Risk Factors for Prolonged Opioid Prescriptions After Surgery for Brachial Plexus Injury
(2019) Journal of Hand Surgery, . 

Dy, C.J.a b , Peacock, K.c , Olsen, M.A.b c , Ray, W.Z.d , Brogan, D.M.a

a Department of Orthopaedic Surgery, Division of Hand and Microsurgery, United States
b Department of Surgery, Division of Public Health Sciences, United States
c Department of Medicine, Center for Administrative Data Research, United States
d Department of Neurological Surgery, Washington University School of Medicine, St. Louis, MO, United States

Abstract
Purpose: We hypothesized that patients with preoperative opioid prescriptions and diagnoses of depression and anxiety would be at increased risk for prolonged opioid prescriptions after surgery for brachial plexus injury (BPI). Methods: Using an administrative database of privately insured patients, we assembled a cohort of BPI surgery patients and a control group of non-BPI patients, matching for age, sex, and year. Pharmacy claims for prescriptions filled for opioids and neuropathic pain medications were examined 12 months before surgery to 180 days after surgery. The primary outcome was prolonged opioid prescription, defined as receiving a prescription 90 to 180 days after the index (BPI surgery or randomly selected date of service for controls). Multivariable regression was used to examine risk factors for postoperative opioid use, including diagnoses of depression, anxiety, drug abuse, tobacco use, and preoperative use of opioids and neuropathic pain medications. A subgroup analysis was performed for opioid-naive BPI patients between 30 days to 1 year before surgery. Results: Among BPI surgery patients (n = 1,936), 27.7% had prolonged opioid prescriptions. Among opioid-naive BPI patients (n = 911), 10.8% had prolonged opioid prescriptions. In controls (n = 19,360), frequency of prolonged opioid prescriptions was 0.11%. Among all BPI patients, after adjustment for age and sex, predictors of prolonged postoperative opioid prescriptions in BPI patients were preoperative opioids, preoperative neuropathic pain medication use, histories of drug abuse, tobacco use, and anxiety. Conclusions: Prolonged postoperative opioids prescriptions after BPI reconstruction are higher than previous estimates among other surgical patients. In addition to establishing normative data among this population, our findings serve to increase awareness of risk factors for prolonged opioids after BPI reconstruction and encourage coordinated multidisciplinary care. Type of study/level of evidence: Prognostic II. © 2019 American Society for Surgery of the Hand

Author Keywords
Brachial plexus;  chronic pain;  nerve injury;  neuropathic pain;  opioids

Document Type: Article
Publication Stage: Article in Press
Source: Scopus

“Research Review: Outcomes of 24- to 36-month-old children with autism spectrum disorder vary by ascertainment strategy: a systematic review and meta-analysis” (2019) Journal of Child Psychology and Psychiatry and Allied Disciplines

Research Review: Outcomes of 24- to 36-month-old children with autism spectrum disorder vary by ascertainment strategy: a systematic review and meta-analysis
(2019) Journal of Child Psychology and Psychiatry and Allied Disciplines, . 

Micheletti, M.a b c , McCracken, C.b c , Constantino, J.N.d , Mandell, D.e , Jones, W.a b c f , Klin, A.a b c f

a Marcus Autism Center, Atlanta, GA, United States
b Children’s Healthcare of Atlanta, Atlanta, GA, United States
c Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, United States
d Departments of Psychiatry and Pediatrics, Intellectual and Developmental Disabilities Research Center, Washington University School of Medicine, St Louis, MO, United States
e Center for Mental Health Policy and Services Research, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
f Emory Center for Translational Social Neuroscience, Atlanta, GA, United States

Abstract
Background: Despite widespread recommendations for early surveillance of risk for autism spectrum disorder (ASD), no research to date has shown that early surveillance leads to better clinical outcomes. Preliminary research has suggested that children with ASD ascertained via prospective follow-up have better outcomes than those ascertained via community referral. Because prospective studies include early surveillance, by comparing outcomes of children with ASD across ascertainment strategies, we may gain insight into the effects of early surveillance relative to its absence. Methods: A systematic review was conducted to identify studies reporting outcomes of 24- to 36-month-olds with ASD ascertained via prospective follow-up, community referral, or universal screening. A meta-analysis using a random effects model was used to calculate overall effect size estimates for developmental level and symptom severity across ascertainment cohorts. Results: Eleven prospective, ten community referral, and eight universal screening studies were identified, reporting on 1,658 toddlers with ASD. We found no differences in outcomes between community referral and universal screening studies. Relative to both, prospective studies reported significantly higher developmental levels and lower symptom severities. Conclusions: Outcomes of young children with ASD ascertained via prospective follow-up are better than those of children with ASD recruited via community referral or universal screening. Although we discuss why sampling bias is not likely the driving force behind these findings, we cannot rule out the possibility that sampling bias contributes to the observed differences; future studies should probe the effects of sociodemographic variables on clinical outcomes as a function of ascertainment strategy. This limitation notwithstanding, our results raise the possibility that prospective follow-up may confer a ‘surveillance effect’ that contributes to improved developmental and diagnostic outcomes in children with ASD. Future research should test this hypothesis and determine the specific mechanism by which surveillance may improve outcomes. © 2019 Association for Child and Adolescent Mental Health

Author Keywords
Autism spectrum disorder;  meta-analysis;  outcomes;  sampling bias;  surveillance;  systematic review;  toddlers

Document Type: Review
Publication Stage: Article in Press
Source: Scopus

“Positive Affect and Well-Being in Huntington’s Disease Moderates the Association between Functional Impairment and HRQOL Outcomes” (2019) Journal of Huntington’s Disease

Positive Affect and Well-Being in Huntington’s Disease Moderates the Association between Functional Impairment and HRQOL Outcomes
(2019) Journal of Huntington’s Disease, 8 (2), pp. 221-232. 

Ready, R.E.a , Boileau, N.R.b , Barton, S.K.c , Lai, J.-S.d , McCormack, M.K.e f , Cella, D.d , Fritz, N.E.g , Paulsen, J.S.h , Carlozzi, N.E.b

a Department of Psychological and Brain Sciences, University of Massachusetts, Amherst, MA, United States
b Department of Physical Medicine and Rehabilitation, University of Michigan, North Campus Research Complex, Building NCRC B14, 2800 Plymouth Road, Ann Arbor, MI 48109-2800, United States
c Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
d Department of Medical Social Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL, United States
e Department of Psychiatry, Rutgers-Robert Wood Johnson Medical School, Piscataway, NJ, United States
f Department of Pathology, Rowan-SOM, Stratford, NJ, United States
g Physical Therapy Program, Wayne State University, Detroit, MI, United States
h Departments of Neurology, Psychiatry, and Psychological and Brain Sciences, University of Iowa, Iowa City, IA, United States

Abstract
Background: Positive affect is associated with resiliency and beneficial health outcomes, but little is known about associations between positive affect and health-related quality of life (HRQOL) in Huntington’s disease (HD). Objective: This longitudinal study determined the association between positive affect and several HRQOL outcomes in persons with HD. Functional status was examined as a moderator of the association between positive affect and HRQOL. Methods: Participants, with premanifest (i.e., genetically at risk but no clinical diagnosis, n = 50) and manifest HD (earlystage n = 171; late-stage n = 101), completed a measure of positive affect and well-being and several HRQOL measures at baseline, 12-, and 24-month follow-ups. UHDRS Functional Assessment scale indicated functional status. Results: Positive affect was associated with better HRQOL for persons with premanifest and manifest HD over the 24-month time frame. These associations were moderated by functional status. For persons with higher functional status, positive affect was associated with better HRQOL, including less depression, lower anxiety, less anger, better social role satisfaction, better executive functions, greater upper extremity function, less dyscontrol, and less concern with death and dying. For persons with lower functional status, positive affect was not associated with HRQOL. Conclusions: Positive affect predicted better self-reported HRQOL over a 24-month period in persons with premanifest and manifest HD, particularly when participnats had better functional status. Interventions to enhance positive affect in HD may have beneficial effects on HRQOL. © 2019-IOS Press and the authors. All rights reserved.

Author Keywords
Functional assessment;  Huntington’s disease;  Longitudinal;  Positive affect;  Quality of life

Document Type: Article
Publication Stage: Final
Source: Scopus

“Emotional response inhibition is greater in older than younger adults” (2019) Frontiers in Psychology

Emotional response inhibition is greater in older than younger adults
(2019) Frontiers in Psychology, 10 (APR), art. no. 961, . 

Waring, J.D.a , Greif, T.R.a , Lenze, E.J.b

a Saint Louis University, United States
b Washington University School of Medicine in St. Louis, United States

Abstract
Emotional information rapidly captures our attention and also often invokes automatic response tendencies, whereby positive information motivates approach, while negative information encourages avoidance. However, many circumstances require the need to override or inhibit these automatic responses. Control over responses to emotional information remains largely intact in late life, in spite of age-related declines in cognitive control and inhibition of responses to non-emotional information. The goal of this behavioral study was to understand how the aging process influences emotional response inhibition for positive and negative information in older adults. We examined emotional response inhibition in 36 healthy older adults (ages 60-89) and 44 younger adults (ages 18-22) using an emotional Go/No-Go task presenting happy (positive), fearful (negative), and neutral faces. In both younger and older adults, happy faces produced more approach-related behavior (i.e., fewer misses), while fearful faces produced more avoidance-related behavior, in keeping with theories of approach/avoidance-motivated responses. Calculation of speed/accuracy trade-offs between response times and false alarm rates revealed that younger and older adults both favored speed at the expense of accuracy, most robustly within blocks with fearful faces. However, there was no indication that the strength of the speed/accuracy trade-off differed between younger and older adults. Although younger adults were faster to respond to all types of faces, older adults had greater emotional response inhibition (i.e., fewer false alarms). This is the first study to directly test effects of aging on emotional response inhibition. Complementing previous literature in the domains of attention and memory, these results provide new evidence that in the domain of response inhibition older adults may more effectively employ emotion regulatory ability, albeit on a slower time course, compared to younger adults. The present study extends the literature of emotional response inhibition in younger adulthood into late life, and in doing so further elucidates how cognitive aging interacts with affective control processes. © 2019 Waring, Greif and Lenze.

Author Keywords
Aging;  Emotion;  Emotion Regulation;  Executive Function;  Facial expressions;  Go/No Go;  Older adult;  Response inhibition

Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access

“A comparison of resting state functional magnetic resonance imaging to invasive electrocortical stimulation for sensorimotor mapping in pediatric patients” (2019) NeuroImage: Clinica

A comparison of resting state functional magnetic resonance imaging to invasive electrocortical stimulation for sensorimotor mapping in pediatric patients
(2019) NeuroImage: Clinical, 23, art. no. 101850, . 

Roland, J.L.a , Hacker, C.D.a , Snyder, A.Z.b c , Shimony, J.S.b , Zempel, J.M.c , Limbrick, D.D.a , Smyth, M.D.a , Leuthardt, E.C.a d e f g h

a Department of Neurological Surgery, Washington University in St. Louis, St. Louis, MO, United States
b Mallinckrodt Institute Radiology, Washington University in St. Louis, St. Louis, MO, United States
c Neurology, Washington University in St. Louis, St. Louis, MO, United States
d Biomedical Engineering, Washington University in St. Louis, St. Louis, MO, United States
e Neuroscience, Washington University in St. Louis, St. Louis, MO, United States
f Mechanical Engineering and Materials Science, Washington University in St. Louis, St. Louis, MO, United States
g Center for Innovation in Neuroscience and Technology, Washington University in St. Louis, St. Louis, MO, United States
h Brain Laser Center, Washington University in St. Louis, St. Louis, MO, United States

Abstract
Localizing neurologic function within the brain remains a significant challenge in clinical neurosurgery. Invasive mapping with direct electrocortical stimulation currently is the clinical gold standard but is impractical in young or cognitively delayed patients who are unable to reliably perform tasks. Resting state functional magnetic resonance imaging non-invasively identifies resting state networks without the need for task performance, hence, is well suited to pediatric patients. We compared sensorimotor network localization by resting state fMRI to cortical stimulation sensory and motor mapping in 16 pediatric patients aged 3.1 to 18.6 years. All had medically refractory epilepsy that required invasive electrographic monitoring and stimulation mapping. The resting state fMRI data were analyzed using a previously trained machine learning classifier that has previously been evaluated in adults. We report comparable functional localization by resting state fMRI compared to stimulation mapping. These results provide strong evidence for the utility of resting state functional imaging in the localization of sensorimotor cortex across a wide range of pediatric patients. © 2019 The Author(s)

Author Keywords
Functional MRI;  Mapping;  Neurosurgery;  Pediatric;  Resting state

Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access

“Additive effects of item-specific and congruency sequence effects in the vocal stroop task” (2019) Frontiers in Psychology

Additive effects of item-specific and congruency sequence effects in the vocal stroop task
(2019) Frontiers in Psychology, 10 (APR), art. no. 860, . 

Aschenbrenner, A., Balota, D.

Washington University in St. Louis, United States

Abstract
There is a growing interest in assessing how cognitive processes fluidly adjust across trials within a task. Dynamic adjustments of control are typically measured using the congruency sequence effect (CSE), which refers to the reduction in interference following an incongruent trial, relative to a congruent trial. However, it is unclear if this effect stems from a general control mechanism or a distinct process tied to cross-trial reengagement of the task set. We examine the relationship of the CSE with another measure of control referred to as the item-specific proportion congruency effect (ISPC), the finding that frequently occurring congruent items exhibit greater interference than items that are often incongruent. If the two effects reflect the same control mechanism, one should find interactive effects of CSE and ISPC. We report results from three experiments utilizing a vocal Stroop task that manipulated these two effects while controlling for variables that are often confounded in the literature. Across three experiments, we observed large CSE and ISPC effects. Importantly, these effects were robustly additive with one another (Bayes Factor for the null approaching 9). This finding indicates that the CSE and ISPC arise from independent mechanisms and suggests the CSE in Stroop may reflect a more general response adjustment process that is not directly tied to trial-by-trial changes in attentional control. © 2019 Aschenbrenner and Balota.

Author Keywords
Attention;  Attentional control;  Cognitive control;  Congruency sequence effect (CSE);  Item-specific proportion congruency

Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access

“Detection of TAR DNA-binding protein 43 (TDP-43) oligomers as initial intermediate species during aggregate formation” (2019) Journal of Biological Chemistry

Detection of TAR DNA-binding protein 43 (TDP-43) oligomers as initial intermediate species during aggregate formation
(2019) Journal of Biological Chemistry, 294 (17), pp. 6696-6709. 

French, R.L.a , Grese, Z.R.a , Aligireddy, H.a , Dhavale, D.D.b , Reeb, A.N.a d , Kedia, N.c , Kotzbauer, P.T.b , Bieschke, J.c , Ayala, Y.M.a

a Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University, St. Louis, MO 63103, United States
b Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, United States
c MRC Prion Unit, University College London, London, W1W7FF, United Kingdom
d Dept. of Otolaryngology, Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO 63110, United States

Abstract
Aggregates of the RNA-binding protein TDP-43 (TAR DNA-binding protein) are a hallmark of the overlapping neurode-generative disorders amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. The process of TDP-43 aggregation remains poorly understood, and whether it includes formation of intermediate complexes is unknown. Here, we analyzed aggregates derived from purified TDP-43 under semidenaturing conditions, identifying distinct oligomeric complexes at the initial time points before the formation of large aggregates. We found that this early oligomerization stageisprimarily driven by TDP-43’s RNA-binding region. Specific binding to GU-rich RNA strongly inhibited both TDP-43 oligomerization and aggregation, suggesting that RNA interactions are critical for maintaining TDP-43 solubility. Moreover, we analyzed TDP-43 liquid-liquid phase separation and detected similar detergent-resistant oligomers upon maturation of liquid droplets into solid-like fibrils. These results strongly suggest that the oligomers form during the early steps of TDP-43 misfolding. Importantly, the ALS-linked TDP-43 mutations A315T and M337V significantly accelerate aggregation, rapidly decreasing the monomeric population and shortening the oligomeric phase. We also show that aggregates generated from purified TDP-43 seed intracellular aggregation detected by established TDP-43 pathology markers. Remarkably, cytoplasmic aggregate seeding was detected earlier for the A315T and M337V variants and was 50% more widespread than for WT TDP-43 aggregates. We provide evidence for an initial step of TDP-43 self-assembly into intermediate oligomeric complexes, whereby these complexes may provide a scaffold for aggregation. This process is altered by ALS-linked mutations, underscoring the role of perturbations in TDP-43 homeostasis in protein aggregation and ALS-FTD pathogenesis. © 2019 French et al.

Document Type: Article
Publication Stage: Final
Source: Scopus