Scopus list of publications for June 18, 2023
Validation of the adolescent binge eating disorder measure (ADO-BED) among transgender youth and young adults
(2023) Journal of Eating Disorders, 11 (1), art. no. 91, .
Linsenmeyer, W.a , Stiles, D.a , Garwood, S.b , Giedinghagen, A.b , Lewis, C.b , Strand, G.b
a Saint Louis University, 3437 Caroline Street, St. Louis, MO 63104, United States
b Washington University School of Medicine in St. Louis, 660 South Euclid Ave, St. Louis, MO 63110, United States
Abstract
Background: Transgender youth and young adults are at increased risk for eating disorders, including binge eating disorder, yet few measures have been validated for screening purposes with the transgender population. Methods: The purpose of this study was to provide initial evidence for the internal consistency and convergent validity of the Adolescent Binge Eating Disorder questionnaire (ADO-BED) in a sample of transgender youth and young adults. 208 participants completed the ADO-BED as part of a routine nutrition screening protocol at a gender center. Exploratory factor analysis and confirmatory factor analysis was used to establish the factor structure of the ADO-BED. Relationships between the ADO-BED, Sick, Control, One Stone, Fat, Food (SCOFF), Nine Item Avoidant/restrictive Intake Disorder (NIAS), Patient Health Questionnaire 9 (PHQ-9), Generalized Anxiety Disorder 7 (GAD-7), and demographic characteristics were explored. Results: Analyses revealed a one-factor structure of the ADO-BED with good fit to the data in the present sample. The ADO-BED was shown to be significantly related to all convergent validity variables, except the NIAS. Conclusions: The ADO-BED is a valid measure to screen for BED among transgender youth and young adults. Healthcare professionals can screen all transgender patients for BED, regardless of body size, in order to effectively identify and manage binge eating concerns. © 2023, The Author(s).
Transgender individuals are at increased risk for eating disorders, including binge eating disorder. Different questionnaires are used to screen people for eating disorders to know if they need additional evaluation. However, few of the existing questionnaires commonly used to screen for eating disorders have been tested with the transgender population. Therefore, the purpose of this study was to determine if one questionnaire, the Adolescent Binge Eating Disorder questionnaire (ADO-BED), is an accurate measure to screen for binge eating disorder among transgender youth and young adults. The results of this study supported that the ADO-BED is indeed a valid measure to use with transgender patients. © 2023, The Author(s).
Author Keywords
Binge eating disorder; Eating disorder; Screening; Transgender
Document Type: Article
Publication Stage: Final
Source: Scopus
Sex-specific associations between plasma interleukin-6 and depression in persons with and without HIV
(2023) Brain, Behavior, and Immunity – Health, 30, art. no. 100644, .
Petersen, K.J.a , Yu, X.b , Masters, M.C.c , Lobo, J.D.d , Lu, T.a , Letendre, S.d e , Ellis, R.J.d , McCutchan, J.A.e , Sundermann, E.d
a Department of Neurology, Washington University in St. Louis, St. Louis, MO, United States
b Department of Biostatistics & Data Science, The University of Texas Medical Branch, Galveston, TX, United States
c Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, United States
d Department of Psychiatry, The University of California San Diego, San Diego, CA, United States
e Department of Medicine, The University of California San Diego, San Diego, CA, United States
Abstract
Background: Persons with HIV (PWH) have both more frequent depression and higher levels of plasma inflammatory biomarkers compared to persons without HIV (PWoH). Inflammation and depressive symptoms are linked, including in PWH; however, it is unclear whether these associations differ by HIV serostatus and biological sex. Methods: Six plasma inflammatory biomarkers were assessed using samples from PWH and PWoH who participated in six NIH-funded studies through the UCSD HIV Neurobehavioral Research Program (HNRP) from 2011 to 2019. Factor analysis was performed to identify intercorrelated groups of biomarkers. Factors and their components were then examined for relationships with Beck Depression Inventory-II (BDI-II) and modifying effects of sex or HIV serostatus using multivariable linear regression, adjusting for demographics, substance use diagnoses, and relevant co-morbidities. Results: Participants included 150 PWH (age = 48.3 ± 13.1 yr; 88% biologically male) and 138 PWoH (age = 46.3 ± 15.9; 56% male). Two inflammatory factors were identified: Factor 1 loaded on interleukin-6 (IL-6), C-reactive protein (CRP), and D-dimer; Factor 2 loaded on interleukin-8, chemokine C–C ligand 2 (CCL2), and chemokine C-X-C ligand 10 (CXCL10). Sex modified the effect of Factor 1 on BDI-II, with a more positive association for men than women (p = 0.04). No significant association between Factor 2 and BDI-II was found. Of the biomarkers in Factor 1, only IL-6 was significantly associated with BDI-II and was modified by sex (p = 0.003). In sex-stratified analysis, a positive association was found for men (β = 5.42; 95% confidence interval = [1.32, 9.52]) but not women (β = −3.88; 95% C.I. = [-11.02, 3.26]). No HIV-related interactions were detected. Interpretation: We identified a depression-associated inflammatory factor present in both PWH and PWoH, consistent with prior studies of PWH only. The association was driven by a correlation between IL-6 and depression exclusively in men, suggesting that the depression-inflammation link differs by sex. Future studies of depression etiology or treatment, including those on persons with HIV, should consider the impact of biological sex in both design and analysis. © 2023
Author Keywords
Depression; HIV infection; Inflammation; Sex differences
Funding details
National Institutes of HealthNIH
National Institute of Mental HealthNIMHF32 MH129151, HHSN271201000036C, N01 MH22005, P30MH062512, T32 AI007384, U24 MH100928
Document Type: Article
Publication Stage: Final
Source: Scopus
Standardized immunoprecipitation protocol for efficient isolation of native apolipoprotein E particles utilizing HJ15.4 monoclonal antibody
(2023) STAR Protocols, 4 (2), art. no. 102271, .
O’Leary, J.a , Raulin, A.-C.a , Li, Z.a , Martens, Y.a , Inoue, Y.a , Strickland, M.R.b , Han, X.c d , Holtzman, D.M.b , Bu, G.a , Zhao, N.a
a Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, United States
b Department of Neurology, Hope Center for Neurological Disorders, Knight Alzheimer’s Disease Research Center, Washington University in St. Louis, St. Louis, MO 63110, United States
c Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, United States
d Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, United States
Abstract
The apolipoprotein E protein (apoE) confers differential risk for Alzheimer’s disease depending on which isoforms are expressed. Here, we present a 2-day immunoprecipitation protocol using the HJ15.4 monoclonal apoE antibody for the pull-down of native apoE particles. We describe major steps for apoE production via immortalized astrocyte culture and HJ15.4 antibody bead coupling for apoE particle pull-down, elution, and characterization. This protocol could be used to isolate native apoE particles from multiple model systems or human biospecimens. © 2023 The Author(s)
Author Keywords
Cell Biology; Molecular Biology; Neuroscience
Funding details
National Institutes of HealthNIHRF1AG046205, RF1AG061872, U19AG069701
BrightFocus FoundationBFF
Document Type: Article
Publication Stage: Final
Source: Scopus
Fatigue and Quality of Life in Children with Hearing Loss or Obstructive Sleep Apnea
(2023) Laryngoscope, .
Zhang, A.L., Lin, R.Z., Landes, E.K., Ensing, A.E., Getahun, H., Lieu, J.E.C.
Department of Otolaryngology, Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO, United States
Abstract
Objective: To investigate the fatigue levels of children with hearing loss (HL) and obstructive sleep apnea (OSA), hypothesizing that the fatigue experienced by children with HL is under-recognized. Study Design: Cross-sectional survey. Methods: We identified children aged 2–18 with HL, OSA, sleep-disordered breathing (SDB), and controls from a pediatric otolaryngology clinic and sleep center. Children and/or parents completed the Pediatric Quality of Life Inventory Multidimensional Fatigue Scale (PedsQL MFS), Hearing Environments And Reflection on Quality of Life (HEAR-QL), and OSA-18. Results: Responses of 50 children with HL, 79 with OSA, and 18 with SDB were compared with those of 49 recruited controls (RC) and literature controls (LC). Children with HL or OSA had higher fatigue than controls in the PedsQL MFS self-reported (HL 65.4, OSA 54.7, RC 71.8, LC 80.5, p < 0.001) and parent-reported (HL 64.6, OSA 59.3, RC 75.2, LC 89.6, p < 0.001). Children with HL had Cognitive Fatigue similar to that of children with OSA (self 60.4 vs. 49.5, p = 0.170; parent 56.0 vs. 56.7, p = 0.998), though with decreased Sleep/Rest Fatigue (self 67.8 vs. 56.3, p = 0.033; parent 69.8 vs. 57.5, p = 0.001). Children with HL or OSA had lower disease-related quality of life (QOL) than controls in the HEAR-QL and OSA-18, respectively. Stratification with disease severity revealed no differences in fatigue. Conclusion: Children with HL or OSA experience higher fatigue and lower QOL than controls. Similar Cognitive Fatigue in both groups suggests under-recognized fatigue in children with HL. Level of Evidence: Level 3 Laryngoscope, 2023. © 2023 The American Laryngological, Rhinological and Otological Society, Inc.
Author Keywords
children; fatigue; hearing loss; obstructive sleep apnea; quality of life
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
Profiling baseline performance on the Longitudinal Early-Onset Alzheimer’s Disease Study (LEADS) cohort near the midpoint of data collection
(2023) Alzheimer’s and Dementia, .
Hammers, D.B.a , Eloyan, A.b , Taurone, A.b , Thangarajah, M.b , Beckett, L.c , Gao, S.d , Kirby, K.a , Aisen, P.e , Dage, J.L.a , Foroud, T.f , Griffin, P.g , Grinberg, L.T.h i , Jack, C.R., Jr.j , Kramer, J.i , Koeppe, R.k , Kukull, W.A.l , Mundada, N.S.i , La Joie, R.i , Soleimani-Meigooni, D.N.i , Iaccarino, L.i , Murray, M.E.m , Nudelman, K.f , Polsinelli, A.J.a , Rumbaugh, M.f , Toga, A.n , Touroutoglou, A.o , Vemuri, P.j , Atri, A.p , Day, G.S.q , Duara, R.r , Graff-Radford, N.R.q , Honig, L.S.s , Jones, D.T.j t , Masdeu, J.u , Mendez, M.F.v , Womack, K.w , Musiek, E.w , Onyike, C.U.x , Riddle, M.y , Rogalski, E.z , Salloway, S.y , Sha, S.J.aa , Turner, R.S.ab , Wingo, T.S.ac , Wolk, D.A.ad , Carrillo, M.C.g , Dickerson, B.C.o , Rabinovici, G.D.i , Apostolova, L.G.a f ae , the LEADS Consortiumaf
a Department of Neurology, Indiana University School of Medicine, Indianapolis, IN, United States
b Department of Biostatistics, Center for Statistical Sciences, Brown University, Providence, RI, United States
c Department of Public Health Sciences, University of California – Davis, Davis, CA, United States
d Department of Biostatistics, Indiana University School of Medicine, Indianapolis, IN, United States
e Alzheimer’s Therapeutic Research Institute, University of Southern California, San Diego, CA, United States
f Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, United States
g Medical & Scientific Relations Division, Alzheimer’s Association, Chicago, IL, United States
h Department of Pathology, University of California – San Francisco, San Francisco, CA, United States
i Department of Neurology, University of California – San Francisco, San Francisco, CA, United States
j Department of Radiology, Mayo Clinic, Rochester, MN, United States
k Department of Radiology, University of Michigan, Ann Arbor, MI, United States
l Department of Epidemiology, University of Washington, Seattle, WA, United States
m Department of Neuroscience, Mayo Clinic, Jacksonville, FL, United States
n Laboratory of Neuro Imaging, USC Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of USC, Los Angeles, CA, United States
o Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States
p Banner Sun Health Research Institute, Sun City, AZ, United States
q Department of Neurology, Mayo Clinic, Jacksonville, FL, United States
r Wien Center for Alzheimer’s Disease and Memory Disorders, Mount Sinai Medical Center, Miami, FL, United States
s Taub Institute and Department of Neurology, Columbia University Irving Medical Center, New York, NY, United States
t Department of Neurology, Mayo Clinic, Rochester, MN, United States
u Nantz National Alzheimer Center, Houston Methodist and Weill Cornell Medicine, Houston, TX, United States
v Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States
w Department of Neurology, Washington University in St. Louis, St. Louis, MO, United States
x Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, United States
y Department of Neurology, Alpert Medical School, Brown University, Providence, RI, United States
z Department of Psychiatry and Behavioral Sciences, Mesulam Center for Cognitive Neurology and Alzheimer’s Disease, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States
aa Department of Neurology & Neurological Sciences, Stanford University, Palo Alto, CA, United States
ab Department of Neurology, Georgetown University, Washington, DC, United States
ac Department of Neurology and Human Genetics, Emory University School of Medicine, Atlanta, GA, United States
ad Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
ae Department of Radiology and Imaging Sciences, Center for Neuroimaging, Indiana University School of Medicine Indianapolis, Indianapolis, IN, United States
Abstract
Objective: The Longitudinal Early-Onset Alzheimer’s Disease Study (LEADS) seeks to provide comprehensive understanding of early-onset Alzheimer’s disease (EOAD; onset <65 years), with the current study profiling baseline clinical, cognitive, biomarker, and genetic characteristics of the cohort nearing the data-collection mid-point. Methods: Data from 371 LEADS participants were compared based on diagnostic group classification (cognitively normal [n = 89], amyloid-positive EOAD [n = 212], and amyloid-negative early-onset non-Alzheimer’s disease [EOnonAD; n = 70]). Results: Cognitive performance was worse for EOAD than other groups, and EOAD participants were apolipoprotein E (APOE) ε4 homozygotes at higher rates. An amnestic presentation was common among impaired participants (81%), with several clinical phenotypes present. LEADS participants generally consented at high rates to optional trial procedures. Conclusions: We present the most comprehensive baseline characterization of sporadic EOAD in the United States to date. EOAD presents with widespread cognitive impairment within and across clinical phenotypes, with differences in APOE ε4 allele carrier status appearing to be relevant. HIGHLIGHTS: Findings represent the most comprehensive baseline characterization of sporadic early-onset Alzheimer’s disease (EOAD) to date. Cognitive impairment was widespread for EOAD participants and more severe than other groups. EOAD participants were homozygous apolipoprotein E (APOE) ε4 carriers at higher rates than the EOnonAD group. Amnestic presentation predominated in EOAD and EOnonAD participants, but other clinical phenotypes were present. © 2023 the Alzheimer’s Association.
Author Keywords
Alzheimer’s disease; amnestic; atypical variant; early-onset; memory
Funding details
National Institute on AgingNIAR56 AG057195, U01AG6057195, U24AG021886
Alzheimer’s AssociationAALEADS GENETICS‐19‐639372, P30 AG010124, P30 AG010133, P30 AG013854, P30 AG062421, P30 AG062422, P30AG066506, P50 AG005146, P50 AG005681, P50 AG008702, P50 AG023501, P50 AG025688, P50AG047366, U01 AG016976
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
Eye-related quality of life and activities of daily living in pediatric retinoblastoma patients: A single-center, non-controlled, cross-sectional analysis
(2023) Pediatric Blood and Cancer, .
Wise, J., Hayashi, R., Wu, T., Malone, S., Badawi, A.A., King, A., Gordon, M., Kimera, L., Lueder, G., Reynolds, M.
Washington University Saint Louis/Saint Louis Children’s Hospital, Saint Louis, MO, United States
Abstract
Introduction: Childhood retinoblastoma (RB) survivors are known to experience long-term morbidity; however, eye-related quality of life (QoL), which may significantly impact activities of daily living (ADL), has not been extensively studied in this population. The purpose of this cross-sectional study was to assess QoL and ADL morbidity among school-age RB survivors. Methods: The Pediatric Eye Questionnaire (PedEyeQ) and Roll Evaluation Activities of Life (REAL) were administered to childhood RB survivors between ages 5 and 17 followed at St. Louis Children’s Hospital. Visual outcomes and demographic predictors of ADL and QoL were examined. Results: Total 23 patients (mean age 9.6 years) consented for participation in this study. All children experienced at least one domain on the PedEyeQ ≤ 80%. Subjects and parents marked functional vision to be the most impacted domain with a median score of 82.5 and 83.4, respectively. Only 10.5% of participants scored above 75% on the ADL percentile rank. On multivariable analysis, decreased visual acuity (VA) was associated with worse “Child Functional” (odds ratio [OR] −59.2, p =.004) and “Parent Worry Function” (OR −66.5, p =.03) metrics. Decreased contrast sensitivity was associated with worse “Parent Impact” (OR 21.0, p =.02) and “Parent Worry Function” (OR 3.70, p =.04) metrics. Longer saccade horizontal latency was associated with a worse “Parent Worry Function” metric (OR 43.0, p =.009). On multivariable analysis, no variable was significantly associated with ADL. Conclusion: RB survivors have impaired QoL and ADL. Screening for such difficulties should strongly be considered for all RB patients. Additional studies may help predict morbidity based on visual metrics and demographic data. © 2023 Wiley Periodicals LLC.
Author Keywords
activities of daily living; contrast sensitivity; quality of life; retinoblastoma; visual acuity
Funding details
Research to Prevent BlindnessRPB
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
Social media’s influence on momentary emotion based on people’s initial mood: an experimental design
(2023) Cognition and Emotion, .
Tuck, A.B., Long, K.A., Thompson, R.J.
Department of Psychological & Brain Sciences, Washington University, St. Louis, MO, United States
Abstract
Can you think of a meme that made you laugh or a political post that made you angry? These examples illustrate how social media use (SMU) impacts how people feel. Similarly, how people feel when they initiate SMU may impact the emotional effects of SMU. Someone feeling happy may feel more positively during SMU, whereas someone feeling sad may feel more negatively. Using an experimental design, we examined whether following SMU, those in a happy mood would experience increases in positive affect (PA) and those in a sad mood would experience increases in negative affect (NA). A large sample of college students (N = 703) were randomly assigned to a happy, sad, or neutral mood induction before SMU. PA and NA were assessed at baseline, post-mood induction, and after SMU. Contrary to hypotheses, after SMU, people in happy moods experienced decreases in PA, and those in sad moods experienced decreases in NA, reflecting SMU having a dampening effect on emotions. PA and NA were significantly lower after SMU compared to baseline and did not vary by condition. How young adults feel when they log onto SMU matters in understanding how SMU impacts PA and NA, but on average, emotional experiences are dampened. © 2023 Informa UK Limited, trading as Taylor & Francis Group.
Author Keywords
attentional bias; Emotion; mood induction; social media; social networking sites
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
Gaps in clinical research in frontotemporal dementia: A call for diversity and disparities–focused research
(2023) Alzheimer’s and Dementia, .
Franzen, S.a , Nuytemans, K.b , Bourdage, R.a c , Caramelli, P.d , Ellajosyula, R.e f , Finger, E.g h i , Illán-Gala, I.j k , Loi, S.M.l m , Morhardt, D.n , Pijnenburg, Y.o p , Rascovsky, K.q , Williams, M.M.r , Yokoyama, J.S.s t , Alladi, S.u , Ayhan, Y.v , Broce, I.s w , Castro-Suarez, S.x y , Coleman, K.g , de Souza, L.C.z , Dacks, P.A.aa , de Boer, S.C.M.o p , de Leon, J.s , Dodge, S.aa , Grasso, S.ab , Gupta, V.ac , Gupta, V.ad , Ghoshal, N.ae , Kamath, V.af , Kumfor, F.ag , Matias-Guiu, J.A.ah , Narme, P.c , Nielsen, T.R.ai , Okhuevbie, D.aj ak , Piña-Escudero, S.D.s y , Garcia, R.R.g i al , Scarioni, M.o am , Slachevsky, A.an ao ap aq , Suarez-Gonzalez, A.ar , Tee, B.L.s y as , Tsoy, E.s y , Ulugut, H.o p s , Babulal, G.M.at au av aw , Onyike, C.U.af , for the ISTAART FTD PIA and ISTAART Diversity and Disparities PIAax
a Department of Neurology and Alzheimer Center, Erasmus MC University Medical Center, Rotterdam, Netherlands
b John P. Hussman Institute for Human Genomics and Dr. John T. Macdonald Department of Human Genetics, University of Miami, Miller School of Medicine, Miami, FL, United States
c Laboratoire Mémoire Cerveau et Cognition (UR 7536), Institut de Psychologie, Université Paris Cité, Boulogne-Billancourt, France
d Behavioral and Cognitive Neurology Research Group, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte (MG), Brazil
e Manipal Hospitals, Bangalore and Annasawmy Mudaliar Hospital, Bangalore, India
f Manipal Academy of Higher Education (MAHE), Manipal, India
g Parkwood Institute Research, London, ON, Canada
h Robarts Research Institute, University of Western Ontario, London, ON, Canada
i Department of Clinical Neurological Sciences, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada
j Sant Pau Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain
k Centro de Investigación en Red-Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain
l Neuropsychiatry, Royal Melbourne Hospital, Parkville, VIC, Australia
m Department of Psychiatry, University of Melbourne, Parkville, VIC, Australia
n Mesulam Center for Cognitive Neurology and Alzheimer’s Disease and Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, United States
o Alzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc, Amsterdam, Netherlands
p Amsterdam Neuroscience, Neurodegeneration, Amsterdam, Netherlands
q Department of Neurology and Penn Frontotemporal Degeneration Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States
r St. Louis Oak Street Health, St. Louis, MO, United States
s Memory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, CA, United States
t Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, United States
u National Institute of Mental Health and Neurosciences, Bangalore, India
v Faculty of Medicine, Department of Psychiatry, Hacettepe University, Ankara, Turkey
w Department of Neurosciences, University of California, San Diego, La JollaCA, United States
x CBI en Demencias y Enfermedades Desmielinizantes del Sistema Nervioso, Instituto Nacional de Ciencias Neurológicas, Lima, Peru
y Global Brain Health Institute, University of California San Francisco, San Francisco, California, USA and Trinity College, Dublin, Ireland
z Department of Internal Medicine, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
aa The Association for Frontotemporal Degeneration, King of Prussia, PA, United States
ab Speech, Language and Hearing Sciences, The University of Texas at Austin, Austin, TX, United States
ac IMPACT—The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, Geelong, VIC, Australia
ad Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW, Australia
ae Departments of Neurology and Psychiatry, Knight Alzheimer Disease Research Center, Washington University School of Medicine, St. Louis, MO, United States
af Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD, United States
ag Brain & Mind Centre and the School of Psychology, The University of Sydney, Sydney, NSW, Australia
ah Department of Neurology, Hospital Clinico San Carlos, San Carlos Institute for Health Research (IdiSSC), Universidad Complutense, Madrid, Spain
ai Danish Dementia Research Center, Department of Neurology, Copenhagen University Hospital – Rigshospitalet, Copenhagen, Denmark
aj Department of Cell Biology and Genetics, University of Lagos, Lagos, Nigeria
ak Department of Comparative Biosciences, University of Wisconsin–Madison, Madison, WI, United States
al National Institute of Neurology and Neurosurgery, Mexico City, Mexico
am Department of Neurology, Ghent University Hospital, Ghent, Belgium
an Geroscience Center for Brain Health and Metabolism (GERO), Santiago, Chile
ao Neuropsychology and Clinical Neuroscience Laboratory (LANNEC), Physiopathology Department – Intitute of Biomedical Sciences (ICBM), Neuroscience and East Neuroscience Departments, Faculty of Medicine, University of Chile, Santiago, Chile
ap Memory and Neuropsychiatric Center (CMYN), Memory Unit, Neurology Department, Hospital del Salvador and Faculty of Medicine, University of Chile, Santiago, Chile
aq Servicio de Neurología, Departamento de Medicina, Clínica Alemana-Universidad del Desarrollo, Santiago, Chile
ar Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom
as Department of Neurology, Dyslexia Center, University of California, San Francisco, CA, United States
at Department of Neurology, Washington University in St. Louis, St. Louis, MO, United States
au Institute of Public Health, Washington University in St. Louis, St. Louis, MO, United States
av Department of Psychology, Faculty of Humanities, University of Johannesburg, Johannesburg, South Africa
aw Department of Clinical Research and Leadership, The George Washington University School of Medicine and Health Sciences, Washington, District of Columbia, United States
Abstract
Frontotemporal dementia (FTD) is one of the leading causes of dementia before age 65 and often manifests as abnormal behavior (in behavioral variant FTD) or language impairment (in primary progressive aphasia). FTD’s exact clinical presentation varies by culture, language, education, social norms, and other socioeconomic factors; current research and clinical practice, however, is mainly based on studies conducted in North America and Western Europe. Changes in diagnostic criteria and procedures as well as new or adapted cognitive tests are likely needed to take into consideration global diversity. This perspective paper by two professional interest areas of the Alzheimer’s Association International Society to Advance Alzheimer’s Research and Treatment examines how increasing global diversity impacts the clinical presentation, screening, assessment, and diagnosis of FTD and its treatment and care. It subsequently provides recommendations to address immediate needs to advance global FTD research and clinical practice. © 2023 The Authors. Alzheimer’s & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer’s Association.
Author Keywords
cultural diversity; diagnosis; ethnicity; frontotemporal dementia; language; literacy; neuropsychological tests; primary progressive aphasia
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
Large-scale encoding of emotion concepts becomes increasingly similar between individuals from childhood to adolescence
(2023) Nature Neuroscience, .
Camacho, M.C.a , Nielsen, A.N.b , Balser, D.c , Furtado, E.b , Steinberger, D.C.c , Fruchtman, L.c , Culver, J.P.a d e f g , Sylvester, C.M.a b , Barch, D.M.a b c
a Division of Biology and Biomedical Sciences, Washington University School of Medicine, St. Louis, MO, United States
b Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
c Department of Psychological and Brain Sciences, Washington University in St. Louis, St. Louis, MO, United States
d Department of Radiology, Washington University School of Medicine, St. Louis, MO, United States
e Department of Physics, Washington University in St. Louis, St. Louis, MO, United States
f Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO, United States
g Department of Electrical and Systems Engineering, Washington University in St. Louis, St. Louis, MO, United States
Abstract
Humans require a shared conceptualization of others’ emotions for adaptive social functioning. A concept is a mental blueprint that gives our brains parameters for predicting what will happen next. Emotion concepts undergo refinement with development, but it is not known whether their neural representations change in parallel. Here, in a sample of 5–15-year-old children (n = 823), we show that the brain represents different emotion concepts distinctly throughout the cortex, cerebellum and caudate. Patterns of activation to each emotion changed little across development. Using a model-free approach, we show that activation patterns were more similar between older children than between younger children. Moreover, scenes that required inferring negative emotional states elicited higher default mode network activation similarity in older children than younger children. These results suggest that representations of emotion concepts are relatively stable by mid to late childhood and synchronize between individuals during adolescence. © 2023, The Author(s), under exclusive licence to Springer Nature America, Inc.
Funding details
National Science FoundationNSFDGE-1745038
National Institutes of HealthNIHHD102156, MH109589
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
COURAGE-ALS: a randomized, double-blind phase 3 study designed to improve participant experience and increase the probability of success
(2023) Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, .
Shefner, J.M.a , Al-Chalabi, A.b , Andrews, J.A.c , Chio, A.d , De Carvalho, M.e , Cockroft, B.M.f , Corcia, P.g , Couratier, P.h , Cudkowicz, M.E.i , Genge, A.j , Hardiman, O.k , Heiman-Patterson, T.l , Henderson, R.D.m , Ingre, C.n , Jackson, C.E.o , Johnston, W.p , Lechtzin, N.q , Ludolph, A.r , Maragakis, N.J.s , Miller, T.M.t , Mora Pardina, J.S.u , Petri, S.v , Simmons, Z.w , Van Den Berg, L.H.x , Zinman, L.y , Kupfer, S.z , Malik, F.I.z , Meng, L.z , Simkins, T.J.z , Wei, J.z , Wolff, A.A.z , Rudnicki, S.A.z
a Barrow Neurological Institute, University of Arizona, and Creighton University, Phoenix, AZ, United States
b King’s College London, London, United Kingdom
c The Neurological Institute of New York, Columbia University Irving Medical Center, New York, NY, United States
d Rita Levi Montalcini’ Department of Neuroscience, University of Turin, Turin, Italy
e Department of Neurosciences of Centro Hospitalar Universitário Lisboa-Norte, Faculty of Medicine, Centro de Estudos Egas Moniz, Institute of Molecular Medicine, Universidade de Lisboa, Lisbon, Portugal
f Sangamo Therapeutics, Inc, Brisbane, CA, United States
g Centre de Réference SLA, CHU Bretonneau, Tours, France
h Neurology Department, LS Centre CHU Dupuytren, Limoges, France
i Neurological Clinical Research Institute, Massachusetts General Hospital, Boston, MA, United States
j Montreal Neurological Institute, Montreal, QC, Canada
k Academic Unit of Neurology, Trinity Biomedical Sciences Institute, Trinity College, Dublin, Ireland
l Neurology Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United States
m UQ Centre for Clinical Research, The University of Queensland, Brisbane, Australia
n Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden
o University of Texas Health Science Center at San Antonio, San Antonio, TX, United States
p University of Alberta, Edmonton, AB, Canada
q Johns Hopkins University School of Medicine, Baltimore, MD, United States
r UULM Clinic of Neurology, Ulm University, Ulm, Germany
s Johns Hopkins ALS Clinical Trials Unit, Johns Hopkins University, Baltimore, MD, United States
t Washington University School of Medicine, St. Louis, MO, United States
u ALS Unit, Hospital Universitario San Rafael, Madrid, Spain
v Department of Neurology, Hannover Medical School, Hannover, Germany
w Penn State Health Milton S Hershey Medical Center, Hershey, PA, United States
x Department of Neurology, UMC Utrecht Brain Center, Netherlands ALS Centre, University Medical Center Utrecht, Utrecht, Netherlands
y Sunnybrook Health Sciences Centre, Toronto, ON, Canada
z Cytokinetics, Incorporated, South San Francisco, CA, United States
Abstract
Objective: To determine the target population and optimize the study design of the phase 3 clinical trial evaluating reldesemtiv in participants with amyotrophic lateral sclerosis (ALS). Methods: We evaluated the phase 2 study of reldesemtiv, FORTITUDE-ALS, to inform eligibility criteria and design features that would increase trial efficiency and reduce participant burden of the phase 3 trial. Results: In FORTITUDE-ALS, the effect of reldesemtiv was particularly evident among participants in the intermediate- and fast-progressing tertiles for pre-study disease progression. These participants most often had symptom onset ≤24 months and an ALS Functional Rating Scale-Revised (ALSFRS-R) total score ≤44 at baseline. Compared with the overall FORTITUDE-ALS population, the subgroup meeting these criteria declined by fewer ALSFRS-R points at 12 weeks (difference of least-squares mean [SE] versus placebo 1.84 [0.49] and 0.87 [0.35] for the overall population). These inclusion criteria will be used for the phase 3 clinical trial, COURAGE-ALS, in which the primary outcome is the change in ALSFRS-R total score at week 24. We also measure durable medical equipment use and evaluate strength in muscles expected to change rapidly. To reduce participant burden, study visits are often remote, and strength evaluation is simplified to reduce time and effort. Conclusions: In COURAGE-ALS, the phase 3 clinical trial to evaluate reldesemtiv, the sensitivity of detecting a potential treatment effect may be increased by defining eligibility criteria that limit the proportion of participants who have slower disease progression. Implementing remote visits and simplifying strength measurements will reduce both site and participant burden. ClinicalTrials.gov identifiers: NCT03160898 (FORTITUDE-ALS) and NCT04944784 (COURAGE-ALS). © 2023 World Federation of Neurology on behalf of the Research Group on Motor Neuron Diseases.
Author Keywords
ALSFRS-R; Amyotrophic lateral sclerosis; randomized clinical trial; reldesemtiv
Funding details
CytokineticsCYTK
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
Survival Modeling of Suicide Risk with Rare and Uncertain Diagnoses
(2023) Statistics in Biosciences, .
Wang, W.a , Luo, C.b , Aseltine, R.H.c e , Wang, F.d , Yan, J.a c , Chen, K.a c
a Department of Statistics, University of Connecticut, Storrs, United States
b Division of Public Health Sciences, Washington University School of Medicine in St. Louis, St. Louis, United States
c Center for Population Health, University of Connecticut Health Center, Farmington, United States
d Weill Cornell Medical College, Cornell University, New York, United States
e Division of Behavioral Sciences and Community Health, University of Connecticut Health Center, Farmington, United States
Abstract
Motivated by the pressing need for suicide prevention through improving behavioral healthcare, we use medical claims data to study the risk of subsequent suicide attempts (SA) for patients who were hospitalized due to suicide attempts and later discharged. Understanding the risk behaviors of such patients at elevated suicide risk is an important step towards the goal of “Zero Suicide”. An immediate and unconventional challenge is that the identification of SA from medical claims contains substantial uncertainty: almost 20% of “suspected” SA are identified from diagnosis codes indicating external causes of injury and poisoning with undermined intent. It is thus of great interest to learn which of these undetermined events are more likely actual SA and how to properly utilize them in survival analysis with severe censoring. To tackle these interrelated problems, we develop an integrative Cox cure model with regularization to perform survival regression with uncertain events and a latent cure fraction. We apply the proposed approach to study the risk of subsequent SA after suicide-related hospitalization for the adolescent and young adult population, using medical claims data from Connecticut. The identified risk factors are highly interpretable; more intriguingly, our method distinguishes the risk factors that are most helpful in assessing either susceptibility or timing of subsequent attempts. The predicted statuses of the uncertain attempts are further investigated, leading to several new insights on suicide event identification. © 2023, The Author(s) under exclusive licence to International Chinese Statistical Association.
Author Keywords
Integrative learning; Medical claims data; Mental health; Missing censoring indicator; Rare event; Uncertainty quantification
Funding details
National Science FoundationNSFDMS-1613295, IIS-1718798
National Institutes of HealthNIHR01-MH124740
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
Early-Life and Family Risk Factors for Tic Disorder Persistence into Adulthood
(2023) Movement Disorders, .
Mataix-Cols, D.a b , Isomura, K.a b , Brander, G.c d , Brikell, I.e , Lichtenstein, P.e , Chang, Z.e , Larsson, H.e f , Kuja-Halkola, R.e , Black, K.J.g , Sidorchuk, A.a b , Fernández de la Cruz, L.a b
a Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
b Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden
c Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden
d Broad Institute of MIT and Harvard, Cambridge, MA, United States
e Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
f School of Medical Sciences, Örebro University, Örebro, Sweden
g Departments of Psychiatry, Neurology, Radiology, and Neuroscience, Washington University in St. Louis, St. Louis, MO, United States
Abstract
Background: Many children with tic disorders outgrow their tics, but little is known about the proportion of individuals who will continue to require specialist services in adulthood and which variables are associated with tic persistence. Objectives: The aims were to estimate the proportion of individuals first diagnosed with tic disorders in childhood who continued to receive tic disorder diagnoses after age 18 years and to identify risk factors for persistence. Methods: In this Swedish nationwide cohort study including 3761 individuals diagnosed with tic disorders in childhood, we calculated the proportion of individuals whose diagnoses persisted into adulthood. Minimally adjusted logistic regression models examined the associations between sociodemographic, clinical, and family variables and tic disorder persistence. A multivariable model was then fitted, including only variables that were statistically significant in the minimally adjusted models. Results: Seven hundred and fifty-four (20%) children with tic disorders received a diagnosis of a chronic tic disorder in adulthood. Psychiatric comorbidity in childhood (particularly attention-deficit hyperactivity disorder, obsessive-compulsive disorder, pervasive developmental disorders, and anxiety disorders) and psychiatric disorders in first-degree relatives (particularly tic and anxiety disorders) were the strongest risk factors for persistence. We did not observe statistically significant associations with socioeconomic variables, perinatal complications, comorbid autoimmune diseases, or family history of autoimmune diseases. All statistically significant variables combined explained approximately 10% of the variance in tic disorder persistence (P < 0.0001). Conclusions: Childhood psychiatric comorbidities and family history of psychiatric disorders were the strongest risk factors associated with tic disorder persistence into adulthood. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Author Keywords
adults; children; risk factors; tic disorders; Tourette syndrome
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
Anesthetics inhibit phosphorylation of the ribosomal protein S6 in mouse cultured cortical cells and developing brain
(2023) Frontiers in Aging Neuroscience, 15, art. no. 1060186, .
Friese, M.B.a c d e f g , Gujral, T.S.b g c d e f g , Palanisamy, A.a g c d e f g , Hemmer, B.a g c d e f g , Culley, D.J.a g c d e f g , Crosby, G.a
a Laboratory for Aging Neuroscience, Department of Anesthesiology, Perioperative and Pain Medicine, Harvard Medical School and Brigham and Women’s Hospital, Boston, MA, United States
b Department of Systems Biology, Harvard Medical School, Boston, MA, United States
c Sanofi US, Boston, MA, United States
d Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA, United States
e Department of Anesthesiology, Washington University, St. Louis, MO, United States
f Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, United States
g Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
Abstract
Introduction: The development and maintenance of neural circuits is highly sensitive to neural activity. General anesthetics have profound effects on neural activity and, as such, there is concern that these agents may alter cellular integrity and interfere with brain wiring, such as when exposure occurs during the vulnerable period of brain development. Under those conditions, exposure to anesthetics in clinical use today causes changes in synaptic strength and number, widespread apoptosis, and long-lasting cognitive impairment in a variety of animal models. Remarkably, most anesthetics produce these effects despite having differing receptor mechanisms of action. We hypothesized that anesthetic agents mediate these effects by inducing a shared signaling pathway. Methods: We exposed cultured cortical cells to propofol, etomidate, or dexmedetomidine and assessed the protein levels of dozens of signaling molecules and post-translational modifications using reverse phase protein arrays. To probe the role of neural activity, we performed separate control experiments to alter neural activity with non-anesthetics. Having identified anesthetic-induced changes in vitro, we investigated expression of the target proteins in the cortex of sevoflurane anesthetized postnatal day 7 mice by Western blotting. Results: All the anesthetic agents tested in vitro reduced phosphorylation of the ribosomal protein S6, an important member of the mTOR signaling pathway. We found a comparable decrease in cortical S6 phosphorylation by Western blotting in sevoflurane anesthetized neonatal mice. Using a systems approach, we determined that propofol, etomidate, dexmedetomidine, and APV/TTX all similarly modulate a signaling module that includes pS6 and other cell mediators of the mTOR-signaling pathway. Discussion: Reduction in S6 phosphorylation and subsequent suppression of the mTOR pathway may be a common and novel signaling event that mediates the impact of general anesthetics on neural circuit development. Copyright © 2023 Friese, Gujral, Palanisamy, Hemmer, Culley and Crosby.
Author Keywords
activity dependent cell signaling; anesthetic neurotoxicity; developmental neurotoxicity; mTOR; reverse phase protein array
Funding details
GM007592
National Institute on AgingNIAAG048522, AG051812, AG053280
Foundation for Anesthesia Education and ResearchFAER
Document Type: Article
Publication Stage: Final
Source: Scopus
Sleep deprivation, sleep fragmentation, and social jet lag increase temperature preference in Drosophila
(2023) Frontiers in Neuroscience, 17, art. no. 1175478, .
Roach, S.T.a b , Ford, M.C.b , Simhambhatla, V.b , Loutrianakis, V.b , Farah, H.b , Li, Z.b , Periandri, E.M.b , Abdalla, D.b , Huang, I.b , Kalra, A.b , Shaw, P.J.b
a Department of Physiology and Biophysics, University of Illinois at Chicago, Chicago, IL, United States
b Department of Neuroscience, Washington University School of Medicine, St. Louis, MO, United States
Abstract
Despite the fact that sleep deprivation substantially affects the way animals regulate their body temperature, the specific mechanisms behind this phenomenon are not well understood. In both mammals and flies, neural circuits regulating sleep and thermoregulation overlap, suggesting an interdependence that may be relevant for sleep function. To investigate this relationship further, we exposed flies to 12 h of sleep deprivation, or 48 h of sleep fragmentation and evaluated temperature preference in a thermal gradient. Flies exposed to 12 h of sleep deprivation chose warmer temperatures after sleep deprivation. Importantly, sleep fragmentation, which prevents flies from entering deeper stages of sleep, but does not activate sleep homeostatic mechanisms nor induce impairments in short-term memory also resulted in flies choosing warmer temperatures. To identify the underlying neuronal circuits, we used RNAi to knock down the receptor for Pigment dispersing factor, a peptide that influences circadian rhythms, temperature preference and sleep. Expressing UAS-PdfrRNAi in subsets of clock neurons prevented sleep fragmentation from increasing temperature preference. Finally, we evaluated temperature preference after flies had undergone a social jet lag protocol which is known to disrupt clock neurons. In this protocol, flies experience a 3 h light phase delay on Friday followed by a 3 h light advance on Sunday evening. Flies exposed to social jet lag exhibited an increase in temperature preference which persisted for several days. Our findings identify specific clock neurons that are modulated by sleep disruption to increase temperature preference. Moreover, our data indicate that temperature preference may be a more sensitive indicator of sleep disruption than learning and memory. Copyright © 2023 Roach, Ford, Simhambhatla, Loutrianakis, Farah, Li, Periandri, Abdalla, Huang, Kalra and Shaw.
Author Keywords
Drosophila; sleep; sleep deprivation; sleep fragmentation; temperature preference behavior
Funding details
National Institutes of HealthNIH5R01NS051305-14, 5R01NS076980-08, S1OD21629-01A1
Document Type: Article
Publication Stage: Final
Source: Scopus