Arts & Sciences Brown School McKelvey School of Engineering School of Medicine Weekly Publications

WashU weekly Neuroscience publications

“Multi-scale semi-supervised clustering of brain images: Deriving disease subtypes” (2022) Medical Image Analysis

Multi-scale semi-supervised clustering of brain images: Deriving disease subtypes(2022) Medical Image Analysis, 75, art. no. 102304, . 

Wen, J.a , Varol, E.b , Sotiras, A.c , Yang, Z.a , Chand, G.B.d , Erus, G.a , Shou, H.a e , Abdulkadir, A.a , Hwang, G.a , Dwyer, D.B.f , Pigoni, A.g , Dazzan, P.h , Kahn, R.S.i , Schnack, H.G.j , Zanetti, M.V.k , Meisenzahl, E.l , Busatto, G.F.k , Crespo-Facorro, B.m , Rafael, R.-G.n , Pantelis, C.o , Wood, S.J.p , Zhuo, C.q , Shinohara, R.T.a e , Fan, Y.a , Gur, R.C.r , Gur, R.E.r , Satterthwaite, T.D.a r s , Koutsouleris, N.f , Wolf, D.H.a r s , Davatzikos, C.a , Alzheimer’s Disease Neuroimaging Initiativet

a Center for Biomedical Image Computing and Analytics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United Statesb Department of Statistics, Center for Theoretical Neuroscience, Zuckerman Institute, Columbia University, New York, United Statesc Department of Radiology and Institute for Informatics, Washington University School of Medicine, St. Louis, United Statesd Department of Radiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, United Statese Penn Statistics in Imaging and Visualization Center, Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United Statesf Department of Psychiatry and Psychotherapy, Ludwig-Maximilian University, Munich, Germanyg Department of Neurosciences and Mental Health, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italyh Institute of Psychiatry, King’s College London, London, UK, United Kingdomi Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, United Statesj Department of Psychiatry, University Medical Center UtrechtUtrecht, Netherlandsk Institute of Psychiatry, Faculty of Medicine, University of São Paulo, São Paulo, Brazill LVR-Klinikum Düsseldorf, Kliniken der Heinrich-Heine-Universität, Düsseldorf, Germanym Hospital Universitario Virgen del Rocio, University of Sevilla-IBIS, IDIVAL-CIBERSAM, Cantabria, Spainn Department of Medical Physiology and Biophysics, University of Seville, Instituto de Investigación Sanitaria de Sevilla, IBiS, CIBERSAM, Sevilla, Spaino Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne and Melbourne Health, Carlton South, Australiap Orygen, National Centre of Excellence for Youth Mental Health, Melbourne, Australiaq key Laboratory of Real Tine Tracing of Brain Circuits in Psychiatry and Neurology(RTBCPN-Lab), Nankai University Affiliated Tianjin Fourth Center Hospital, Department of Psychiatry, Tianjin Medical University, Tianjin, Chinar Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United Statess University Hospital of Old Age Psychiatry and Psychotherapy, University of Bern, Bern, Switzerland

AbstractDisease heterogeneity is a significant obstacle to understanding pathological processes and delivering precision diagnostics and treatment. Clustering methods have gained popularity for stratifying patients into subpopulations (i.e., subtypes) of brain diseases using imaging data. However, unsupervised clustering approaches are often confounded by anatomical and functional variations not related to a disease or pathology of interest. Semi-supervised clustering techniques have been proposed to overcome this and, therefore, capture disease-specific patterns more effectively. An additional limitation of both unsupervised and semi-supervised conventional machine learning methods is that they typically model, learn and infer from data using a basis of feature sets pre-defined at a fixed anatomical or functional scale (e.g., atlas-based regions of interest). Herein we propose a novel method, “Multi-scAle heteroGeneity analysIs and Clustering” (MAGIC), to depict the multi-scale presentation of disease heterogeneity, which builds on a previously proposed semi-supervised clustering method, HYDRA. It derives multi-scale and clinically interpretable feature representations and exploits a double-cyclic optimization procedure to effectively drive identification of inter-scale-consistent disease subtypes. More importantly, to understand the conditions under which the clustering model can estimate true heterogeneity related to diseases, we conducted extensive and systematic semi-simulated experiments to evaluate the proposed method on a sizeable healthy control sample from the UK Biobank (N = 4403). We then applied MAGIC to imaging data from Alzheimer’s disease (ADNI, N = 1728) and schizophrenia (PHENOM, N = 1166) patients to demonstrate its potential and challenges in dissecting the neuroanatomical heterogeneity of common brain diseases. Taken together, we aim to provide guidance regarding when such analyses can succeed or should be taken with caution. The code of the proposed method is publicly available at © 2021 Elsevier B.V.

Author KeywordsClustering;  Heterogeneity;  Multi-scale;  Semi-simulated;  Semi-supervised

Funding detailsNational Institutes of HealthNIH1RF1AG054409, 1U01AG068057, R01AG067103, R01EB022573, R01MH101111, R01MH112070, R01MH112847, R01MH113550, R01MH113565, S10OD023495, U01 AG024904U.S. Department of DefenseDODW81XWH-12-2-0012National Institute on AgingNIANational Institute of Biomedical Imaging and BioengineeringNIBIBGenentechJohnson and JohnsonJ&JMerckJanssen Research and DevelopmentJRDUniversity of Southern CaliforniaUSC35148GE HealthcareAlzheimer’s Disease Neuroimaging InitiativeADNINorthern California Institute for Research and EducationNCIRESeventh Framework ProgrammeFP7602152Fujirebio USH. Lundbeck A/SIXICO

Document Type: ArticlePublication Stage: FinalSource: Scopus

“Plasma phosphorylated-tau181 as a predictive biomarker for Alzheimer’s amyloid, tau and FDG PET status” (2021) Translational Psychiatry

Plasma phosphorylated-tau181 as a predictive biomarker for Alzheimer’s amyloid, tau and FDG PET status(2021) Translational Psychiatry, 11 (1), art. no. 585, . 

Shen, X.-N.a , Huang, Y.-Y.a , Chen, S.-D.a , Guo, Y.b , Tan, L.b , Dong, Q.a , Yu, J.-T.a , Weiner, M.W.c , Aisen, P.d , Petersen, R.e , Jack, C.R., Jre , Jagust, W.f , Trojanowki, J.Q.g , Toga, A.W.d , Beckett, L.h , Green, R.C.i , Saykin, A.J.j , Morris, J.C.k , Perrin, R.J.k , Shaw, L.M.g , Carrillo, M.l , Potter, W.m , Barnes, L.n , Bernard, M.o , González, H.p , Ho, C.q , Hsiao, J.K.r , Jackson, J.s , Masliah, E.o , Masterman, D.t , Okonkwo, O.u , Perrin, R.v , Ryan, L.o , Silverberg, N.o , Fleisher, A.w , Fockler, J.c , Conti, C.x , Veitch, D.x , Neuhaus, J.c , Jin, C.c , Nosheny, R.c , Ashford, M.x , Flenniken, D.x , Kormos, A.x , Jimenez, G.d , Donohue, M.d , Gessert, D.d , Salazar, J.d , Zimmerman, C.d , Cabrera, Y.d , Walter, S.d , Miller, G.d , Coker, G.d , Clanton, T.d , Hergesheimer, L.d , Smith, S.d , Adegoke, O.d , Mahboubi, P.d , Moore, S.d , Pizzola, J.d , Shaffer, E.d , Sloan, B.d , Harvey, D.h , Borowski, B.y , Ward, C.y , Schwarz, C.y , Jones, D.y , Gunter, J.y , Kantarci, K.y , Senjem, M.y , Vemuri, P.y , Reid, R.y , Fox, N.C.z , Malone, I.z , Thompson, P.aa , Thomopoulos, S.I.aa , Nir, T.M.aa , Jahanshad, N.aa , DeCarli, C.h , Knaack, A.h , Fletcher, E.h , Tosun-Turgut, D.c , Chen, S.R.x , Choe, M.x , Crawford, K.aa , Yushkevich, P.A.g , Das, S.g , Koeppe, R.A.ab , Reiman, , Chen, , Mathis, , Landau, S.f , Perrin, R.k , Cairns, N.J.k , Householder, E.k , Franklin, E.k , Bernhardt, H.k , Taylor-Reinwald, L.k , Shaw, , Trojanowki, , Korecka, , Figurski, , Crawford, K.d , Neu, S.d , Saykin, , Nho, , Risacher, , Apostolova, , Shen, , Foroud, T.M.ah , Nudelman, K.ah , Faber, K.ah , Wilmes, K.ah , Thal, L.p , Khachaturian, , Hsiao, J.K.aj , Silbert, L.C.ak , Lind, B.ak , Crissey, R.ak , Kaye, J.A.ak , Carter, R.ak , Dolen, S.ak , Quinn, J.ak , Schneider, L.S.d , Pawluczyk, S.d , Becerra, M.d , Teodoro, L.d , Dagerman, K.d , Spann, B.M.d , Brewer, J.p , Vanderswag, , Fleisher, , Ziolkowski, J.ab , Heidebrink, J.L.ab , Zbizek-Nulph, L.ab , Lord, J.L.ab , Albers, C.S.e , Knopman, D.e , Johnson, K.e , Villanueva-Meyer, , Pavlik, , Pacini, , Lamb, , Kass, , Doody, , Shibley, , Chowdhury, , Rountree, , Dang, , Stern, , Honig, , Mintz, , Ances, , Winkfield, , Carroll, , Stobbs-Cucchi, , Oliver, , Creech, , Mintun, , Schneider, , Geldmacher, D.ap , Love, M.N.ap , Griffith, R.ap , Clark, D.ap , Brockington, J.ap , Marson, D.ap , Grossman, , Goldstein, , Greenberg, , Mitsis, , Shah, , Lamar, , Samuels, , Duara, , Greig-Custo, , Rodriguez, , Albert, , Onyike, , Farrington, , Rudow, , Brichko, , Kielb, , Smith, , Raj, , Fargher, , Sadowski, M.av , Wisniewski, T.av , Shulman, M.av , Faustin, A.av , Rao, J.av , Castro, K.M.av , Ulysse, A.av , Chen, S.av , Sheikh, M.O.av , Singleton-Garvin, J.av , Doraiswamy, , Petrella, , James, , Wong, , Borges-Neto, , Karlawish, J.H.g , Wolk, D.A.g , Vaishnavi, S.g , Clark, C.M.g , Arnold, S.E.g , Smith, , Jicha, , El Khouli, , Raslau, , Lopez, , Oakley, , Simpson, , Porsteinsson, A.P.ay , Martin, K.ay , Kowalski, N.ay , Keltz, M.ay , Goldstein, B.S.ay , Makino, K.M.ay , Ismail, M.S.ay , Brand, C.ay , Thai, , Pierce, , Yanez, , Sosa, , Witbracht, , Kelley, , Nguyen, , Womack, , Mathews, , Quiceno, , Levey, , Lah, , Hajjar, , Cellar, , Burns, J.M.bc , Swerdlow, R.H.bc , Brooks, W.M.bc , Silverman, , Kremen, , Apostolova, , Tingus, , Lu, , Bartzokis, , Woo, , Teng, , Graff-Radford, , Parfitt, , Poki-Walker, , Farlow, M.R.j , Hake, A.M.j , Matthews, B.R.j , Brosch, J.R.j , Herring, S.j , van Dyck, , Mecca, , Good, , MacAvoy, , Carson, , Varma, , Chertkow, , Vaitekunis, , Hosein, , Black, , Stefanovic, , Heyn, , Hsiung, , Kim, , Mudge, , Sossi, , Feldman, , Assaly, , Finger, , Pasternak, , Rachinsky, , Kertesz, , Drost, , Rogers, , Grant, I.bk , Muse, B.bk , Rogalski, E.bk , Robson, J.bk , Mesulam, M.-M.bk , Kerwin, D.bk , Wu, C.-K.bk , Johnson, N.bk , Lipowski, K.bk , Weintraub, S.bk , Bonakdarpour, B.bk , Pomara, , Hernando, , Sarrael, , Rosen, H.J.c , Miller, B.L.c , Perry, D.c , Turner, , Johnson, , Reynolds, , MCCann, , Poe, , Sperling, , Johnson, , Marshall, , Belden, , Atri, , Spann, , Clark, K.A.g , Zamrini, , Sabbagh, , Killiany, R.bp , Stern, R.bp , Mez, J.bp , Kowall, N.bp , Budson, A.E.bp , Obisesan, , Ntekim, , Wolday, , Khan, , Nwulia, , Nadarajah, , Lerner, , Ogrocki, , Tatsuoka, , Fatica, , Fletcher, , Maillard, , Olichney, , DeCarli, , Carmichael, , Bates, , Capote, , Rainka, , Borrie, M.bu , Lee, T.-Y.bu , Bartha, R.bu , Johnson, , Asthana, , Carlsson, , Perrin, , Burke, , Scharre, , Kataki, , Tarawneh, , Kelley, , Hart, D.bx , Zimmerman, E.A.bx , Celmins, D.bx , Miller, , Boles Ponto, , Smith, , Koleva, , Shim, , Nam, , Schultz, S.K.h , Williamson, , Craft, , Cleveland, , Yang, , Sink, , Ott, , Drake, , Tremont, , Daiello, , Drake, , Sabbagh, M.cb , Ritter, A.cb , Bernick, C.cb , Munic, D.cb , Mintz, A.cb , O’Connelll, , Mintzer, , Wiliams, , Masdeu, , Shi, J.ce , Garcia, A.ce , Sabbagh, M.ce , Newhouse, , Potkin, , Salloway, , Malloy, , Correia, , Kittur, , Pearlson, G.D.cj , Blank, K.cj , Anderson, K.cj , Flashman, , Seltzer, , Hynes, , Santulli, , Relkin, , Chiang, , Lin, , Ravdin, , Lee, , Petersen, R.y , Neylan, T.c , Grafman, , Montine, , Danowski, S.d , Nguyen-Barrera, C.d , Finley, S.a , Harvey, D.f , Donohue, M.n , Bernstein, M.c , Foster, , Foroud, T.M.j , Potkin, S.cp , Shen, L.j , Faber, K.j , Kim, S.j , Nho, K.j , Wilmes, K.cq , Vanderswag, H.p , Fleisher, A.p , Sood, , Blanchard, , Fleischman, , Greig, , Goldstein, B.ay , Martin, K.S.ay , Thai, , Pierce, , Reist, , Yanez, , Sosa, , Witbracht, , Sadowsky, C.cs , Martinez, W.cs , Villena, T.cs , Rosen, H.c , Peskind, , Petrie, , Li, , Yesavage, J.ct , Taylor, J.L.ct , Chao, S.ct , Coleman, J.ct , White, J.D.ct , Lane, B.ct , Rosen, A.ct , Tinklenberg, J.ct , Jimenez-Maggiora, G.d , Drake, , Donohue, M.d , Nelson, C.c , Bickford, D.c , Butters, , Zmuda, , Borowski, B.e , Gunter, J.e , Senjem, M.e , Kantarci, K.e , Ward, C.e , Reyes, D.e , Faber, K.M.j , Nudelman, K.N.j , Au, Y.H.c , Scherer, K.c , Catalinotto, D.c , Stark, S.c , Ong, E.c , Fernandez, D.c , Zmuda, , Alzheimer’s Disease Neuroimaging Initiativecv

a Department of Neurology and Institute of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, Chinab Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, Chinac University of California, San Francisco, San Francisco, United Statesd University of Southern California, Los Angeles, United Statese Mayo Clinic, Rochester, Rochester, United Statesf University of California, Berkeley, Berkeley, United Statesg University of Pennsylvania, Philadelphia, United Statesh University of California, Davis, Davis, United Statesi BWH/HMS, Boston, United Statesj Indiana University, Bloomington, United Statesk Washington University St. Louis, St. Louis, United Statesl Alzheimer’s Association, Chicago, United Statesm National Institute of Mental Health, Rochville, United Statesn Rush University, Chicago, United Stateso NIA, Bethesda, United Statesp University of California, San Diego, San Diego, United Statesq Denali Therapeutics, South San Francisco, United Statesr NIH, Bethesda, United Statess Massachusetts General Hospital, Boston, United Statest Biogen, Cambridge, United Statesu University of Wisconsin, Madison, Madison, United Statesv Washington University, St. Louis, United Statesw Eli Lilly, Indianapolis, United Statesx NCIRE/The Vererans Health Research Institute, San Francisco, United Statesy Mayo Clinic, Scottsdale, United Statesz University College London, London, United Kingdomaa University of Southern California School of Medicine, Los Angeles, United Statesab University of Michigan, Ann Arbor, United Statesac Banner Alzheimer’s Institute, Phoenix, United Statesad University of Pittsburgh, Pittsburgh, United Statesae Perelman School of Medicine, University of Pennsylvania, Philadelphia, United Statesaf Indiana University School of Medicine, Indianapolis, United Statesag UPenn School of Medicine, Philadelphia, United Statesah NCRAD/Indiana University School of Medicine, Indianapolis, United Statesai Prevent Alzheimer’s Disease, Rockville, 2020, United Statesaj National Institute on Aging, Bethesda, United Statesak Oregon Health & Science University, Portland, United Statesal University of California – San Diego, San Diego, United Statesam Baylor College of Medicine, Houston, United Statesan Columbia University Medical Center, New York, United Statesao Washington University, St. Louis, St. Louis, United Statesap University of Alabama – Birmingham, Birmingham, United Statesaq Mount Sinai School of Medicine, New York, United Statesar Rush University Medical Center, Chicago, United Statesas Wien Center, Miami Beach, United Statesat Johns Hopkins University, Baltimore, United Statesau University of South Florida: USF Health Byrd Alzheimer’s Institute, Tampa, United Statesav New York University, New York, United Statesaw Duke University Medical Center, Durham, United Statesax University of Kentucky, Lexington, United Statesay University of Rochester Medical Center, New York, United Statesaz University of California Irvine IMIND, Irvine, United Statesba University of Texas Southwestern Medical School, Dallas, United Statesbb Emory University, Atlanta, United Statesbc University of Kansas, Medical Center, Kansas, United Statesbd University of California, Los Angeles, Los Angeles, United Statesbe Mayo Clinic, Jacksonville, Jacksonville, United Statesbf Yale University School of Medicine, New Haven, United Statesbg McGill Univ., Montreal-Jewish General Hospital, Montréal, Canadabh Sunnybrook Health Sciences, Ontario, Toronto, Canadabi U.B.C. Clinic for AD & Related Disorders, Vancouver, Canadabj St. Joseph’s Health Care, Petaluma, United Statesbk Northwestern University, Evanston, United Statesbl Nathan Kline Institute, Orangeburg, United Statesbm Georgetown University Medical Center, Washington, United Statesbn Brigham and Women’s Hospital, Boston, United Statesbo Banner Sun Health Research Institute, Sun City, United Statesbp Boston University, Boston, United Statesbq Howard University, Washington, United Statesbr Case Western Reserve University, Cleveland, United Statesbs University of California, Davis – Sacramento, Sacramento, United Statesbt Dent Neurologic Institute, Orchard Park, United Statesbu Parkwood Institute, London, Canadabv University of Wisconsin, Madison, United Statesbw Ohio State University, Columbus, United Statesbx Albany Medical College, Albany, United Statesby University of Iowa College of Medicine, Iowa City, United Statesbz Wake Forest University Health Sciences, Winston Salem, United Statesca Rhode Island Hospital, Providence, United Statescb Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, United Statescc Roper St. Francis Healthcare, Charleston, United Statescd Houston Methodist Neurological Institute, Houston, United Statesce Barrow Neurological Institute, Phoenix, United Statescf Vanderbilt University Medical Center, Nashville, United Statescg Long Beach VA Neuropsychiatric Research Program, Long Beach, United Statesch Butler Hospital Memory and Aging Program, Providence, United Statesci Neurological Care of CNY, East Syracuse, United Statescj Hartford Hospital, Olin Neuropsychiatry Research Center, Hartford, United Statesck Dartmouth-Hitchcock Medical Center, Lebanon, United Statescl Cornell University, Ithaca, United Statescm Rehabilitation Institute of Chicago, Feinberg School of Medicine, Northwestern University, Chicago, United Statescn University of Washington, Seattle, United Statesco University of Utah, Salt Lake City, United Statescp UC Irvine, Irvine, United Statescq NCRAD, Indianapolis, United Statescr University of California, Irvine, Irvine, United Statescs Premiere Research Inst (Palm Beach Neurology), West Palm Beach, United Statesct Stanford University, Stanford, United Statescu BWM/HMS, Boston, United States

AbstractPlasma phosphorylated-tau181 (p-tau181) showed the potential for Alzheimer’s diagnosis and prognosis, but its role in detecting cerebral pathologies is unclear. We aimed to evaluate whether it could serve as a marker for Alzheimer’s pathology in the brain. A total of 1189 participants with plasma p-tau181 and PET data of amyloid, tau or FDG PET were included from ADNI. Cross-sectional relationships of plasma p-tau181 with PET biomarkers were tested. Longitudinally, we further investigated whether different p-tau181 levels at baseline predicted different progression of Alzheimer’s pathological changes in the brain. We found plasma p-tau181 significantly correlated with brain amyloid (Spearman ρ = 0.45, P < 0.0001), tau (0.25, P = 0.0003), and FDG PET uptakes (−0.37, P < 0.0001), and increased along the Alzheimer’s continuum. Individually, plasma p-tau181 could detect abnormal amyloid, tau pathologies and hypometabolism in the brain, similar with or even better than clinical indicators. The diagnostic accuracy of plasma p-tau181 elevated significantly when combined with clinical information (AUC = 0.814 for amyloid PET, 0.773 for tau PET, and 0.708 for FDG PET). Relationships of plasma p-tau181 with brain pathologies were partly or entirely mediated by the corresponding CSF biomarkers. Besides, individuals with abnormal plasma p-tau181 level (>18.85 pg/ml) at baseline had a higher risk of pathological progression in brain amyloid (HR: 2.32, 95%CI 1.32–4.08) and FDG PET (3.21, 95%CI 2.06–5.01) status. Plasma p-tau181 may be a sensitive screening test for detecting brain pathologies, and serve as a predictive biomarker for Alzheimer’s pathophysiology. © 2021, The Author(s).

Funding detailsNational Institutes of HealthNIHU01 AG024904U.S. Department of DefenseDODW81XWH-12-2-0012National Institute on AgingNIANational Institute of Biomedical Imaging and BioengineeringNIBIBAlzheimer’s Disease Neuroimaging InitiativeADNINational Outstanding Youth Science Fund Project of National Natural Science Foundation of ChinaIUSS81771148, 91849126National Natural Science Foundation of ChinaNSFC81571245, 9184910220Fudan UniversityScience and Technology Commission of Shanghai MunicipalitySTCSM2018SHZDZX01National Key Research and Development Program of ChinaNKRDPC2018YFC1314700

Document Type: ArticlePublication Stage: FinalSource: Scopus

“Stress, depression, sleep problems and unmet social needs: Baseline characteristics of low-income smokers in a randomized cessation trial” (2021) Contemporary Clinical Trials Communications

Stress, depression, sleep problems and unmet social needs: Baseline characteristics of low-income smokers in a randomized cessation trial(2021) Contemporary Clinical Trials Communications, 24, art. no. 100857, . 

Garg, R.a , McQueen, A.a b , Roberts, C.a , Butler, T.a , Grimes, L.M.a , Thompson, T.a , Caburnay, C.a , Wolff, J.a , Javed, I.a , Carpenter, K.M.c , Wartts, J.G.a , Charles, C.a , Howard, V.d , Kreuter, M.W.a

a Health Communication Research Laboratory, Brown School at Washington University in St. Louis, St. Louis, MO, United Statesb Division of General Medical Sciences, Washington University School of Medicine in St. Louis, St. Louis, MO, United Statesc Center for Wellbeing Research, OptumHealth, Seattle, WA, United Statesd Tobacco Prevention and Control Program, Missouri Department of Health and Senior Services, Jefferson City, MO, United States

AbstractBackground: Low-income Americans smoke cigarettes at higher rates and quit less than other groups. Methods: To increase their engagement in and success using evidence-based cessation methods, we tested two interventions using a 2×2 randomized factorial design: (1) telephone navigation to reduce financial strain and address social needs such as food, rent and utility payment; and (2) a specialized tobacco quitline designed for low-income smokers. From June 2017 to November 2020, we enrolled 1,944 low-income smokers in Missouri, USA, recruited through the Missouri 2-1-1 helpline, into the trial. This paper describes recruitment, key characteristics and life circumstances of this high-risk population. Results: After eligibility screening, 1,944 participants completed baseline and were randomized. Participants were racially diverse (58% African American), poor (51% < $10,000 annual pre-tax household income) and many reported less than high school education (30%). They reported a mean of 2.5 unmet social needs, especially childcare and paying bills, had high rates of stress, depressive symptoms and sleep problems, and most were in fair or poor health. There were few differences between these variables, and no differences between tobacco use and cessation variables, across the four study groups and between participants recruited pre and during the COVID-19 pandemic. Conclusions: Trial recruitment through the 2-1-1 helpline is feasible for reaching a population of low-income smokers. Low-income smokers face myriad daily challenges beyond quitting smoking. Cessation interventions need to account for and address these life circumstances. Trial registration: NCT03194958. © 2021 The Authors

Author KeywordsHealth disparities;  Minority health;  Randomized controlled trial;  Social needs;  Tobacco cessation;  Tobacco quit lines

Funding detailsNational Institutes of HealthNIHNational Cancer InstituteNCIR01CA201429

Document Type: ArticlePublication Stage: FinalSource: Scopus

“A model of tension-induced fiber growth predicts white matter organization during brain folding” (2021) Nature Communications

A model of tension-induced fiber growth predicts white matter organization during brain folding(2021) Nature Communications, 12 (1), art. no. 6681, . 

Garcia, K.E.a b , Wang, X.c d , Kroenke, C.D.c d

a Indiana University School of Medicine, Department of Radiology and Imaging Sciences, Evansville, IN 47715, United Statesb Washington University in St. Louis, Department of Mechanical Engineering and Materials Science, St. Louis, MO 63130, United Statesc Oregon Health and Science University, Division of Neuroscience, Oregon National Primate Research Center, Beaverton, OR 97006, United Statesd Advanced Imaging Research Center, Oregon Health and Science University, Portland, OR 97239, United States

AbstractThe past decade has experienced renewed interest in the physical processes that fold the developing cerebral cortex. Biomechanical models and experiments suggest that growth of the cortex, outpacing growth of underlying subcortical tissue (prospective white matter), is sufficient to induce folding. However, current models do not explain the well-established links between white matter organization and fold morphology, nor do they consider subcortical remodeling that occurs during the period of folding. Here we propose a framework by which cortical folding may induce subcortical fiber growth and organization. Simulations incorporating stress-induced fiber elongation indicate that subcortical stresses resulting from folding are sufficient to induce stereotyped fiber organization beneath gyri and sulci. Model predictions are supported by high-resolution ex vivo diffusion tensor imaging of the developing rhesus macaque brain. Together, results provide support for the theory of cortical growth-induced folding and indicate that mechanical feedback plays a significant role in brain connectivity. © 2021, The Author(s).

Funding detailsNational Science FoundationNSFDMS-2011274National Institutes of HealthNIHNS111948, R01 AA021981

Document Type: ArticlePublication Stage: FinalSource: Scopus

“Visual prototypes in the ventral stream are attuned to complexity and gaze behavior” (2021) Nature Communications

Visual prototypes in the ventral stream are attuned to complexity and gaze behavior(2021) Nature Communications, 12 (1), art. no. 6723, . 

Rose, O.a b , Johnson, J.a , Wang, B.a b , Ponce, C.R.a b

a Department of Neuroscience, Washington University School of Medicine, St. Louis, MO, United Statesb Department of Neurobiology, Harvard Medical School, Boston, MA, United States

AbstractEarly theories of efficient coding suggested the visual system could compress the world by learning to represent features where information was concentrated, such as contours. This view was validated by the discovery that neurons in posterior visual cortex respond to edges and curvature. Still, it remains unclear what other information-rich features are encoded by neurons in more anterior cortical regions (e.g., inferotemporal cortex). Here, we use a generative deep neural network to synthesize images guided by neuronal responses from across the visuocortical hierarchy, using floating microelectrode arrays in areas V1, V4 and inferotemporal cortex of two macaque monkeys. We hypothesize these images (“prototypes”) represent such predicted information-rich features. Prototypes vary across areas, show moderate complexity, and resemble salient visual attributes and semantic content of natural images, as indicated by the animals’ gaze behavior. This suggests the code for object recognition represents compressed features of behavioral relevance, an underexplored aspect of efficient coding. © 2021, The Author(s).

Funding detailsDavid and Lucile Packard FoundationDLPF, PF2020-71377

Document Type: ArticlePublication Stage: FinalSource: Scopus

“The hippocampus constructs narrative memories across distant events” (2021) Current Biology

The hippocampus constructs narrative memories across distant events(2021) Current Biology, 31 (22), pp. 4935-4945.e7. 

Cohn-Sheehy, B.I.a b c , Delarazan, A.I.e , Reagh, Z.M.e , Crivelli-Decker, J.E.c d , Kim, K.c , Barnett, A.J.c , Zacks, J.M.e , Ranganath, C.b c d

a M.D./Ph.D. Program, University of California, Davis, Sacramento, CA, United Statesb Neuroscience Graduate Group, University of California, Davis, Davis, CA, United Statesc Center for Neuroscience, University of California, Davis, Davis, CA, United Statesd Department of Psychology, University of California, Davis, Davis, CA, United Statese Department of Psychological and Brain Sciences, Washington University, 1 Brookings Drive, St. Louis, MO, United States

AbstractLife’s events are scattered throughout time, yet we often recall different events in the context of an integrated narrative. Prior research suggests that the hippocampus, which supports memory for past events, can support the integration of overlapping associations or separate events in memory. However, the conditions that lead to hippocampus-dependent memory integration are unclear. We used functional brain imaging to test whether the opportunity to form a larger narrative (narrative coherence) drives hippocampal memory integration. During encoding of fictional stories, patterns of hippocampal activity, including activity at boundaries between events, were more similar between distant events that formed one coherent narrative, compared with overlapping events taken from unrelated narratives. One day later, the hippocampus preferentially supported detailed recall of coherent narrative events, through reinstatement of hippocampal activity patterns from encoding. These findings demonstrate a key function of the hippocampus: the integration of events into a narrative structure for memory. © 2021 Elsevier Inc.

Author Keywordsepisodic memory;  event cognition;  fMRI;  hippocampus;  narratives;  naturalistic stimuli;  pattern similarity

Funding detailsN00014-17-1-2961F30AG062053U.S. Department of DefenseDODOffice of Naval ResearchONRNational Institute on AgingNIAUniversity of California, DavisUCD

Document Type: ArticlePublication Stage: FinalSource: Scopus

“Gene regulatory networks controlling temporal patterning, neurogenesis, and cell-fate specification in mammalian retina” (2021) Cell Report

Gene regulatory networks controlling temporal patterning, neurogenesis, and cell-fate specification in mammalian retina(2021) Cell Reports, 37 (7), art. no. 109994, . 

Lyu, P.a , Hoang, T.b , Santiago, C.P.b , Thomas, E.D.f , Timms, A.E.f , Appel, H.b , Gimmen, M.b , Le, N.b , Jiang, L.b , Kim, D.W.b , Chen, S.b , Espinoza, D.F.b , Telger, A.E.g , Weir, K.b , Clark, B.S.g h i , Cherry, T.J.f h j , Qian, J.a , Blackshaw, S.a b c d e

a Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United Statesb Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United Statesc Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United Statesd Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United Statese Kavli Neuroscience Discovery Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United Statesf Center for Developmental Biology and Regenerative Medicine, Seattle Children’s Research Institute, Seattle, WA 98101, United Statesg Department of Ophthalmology and Visual Sciences, Brotman Baty Institute, Seattle, WA 98195, United Statesh Brotman Baty Institute, Seattle, WA 98195, United Statesi Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110, United Statesj Department of Pediatrics, University of Washington School of Medicine, Seattle, WA 98195, United States

AbstractGene regulatory networks (GRNs), consisting of transcription factors and their target sites, control neurogenesis and cell-fate specification in the developing central nervous system. In this study, we use integrated single-cell RNA and single-cell ATAC sequencing (scATAC-seq) analysis in developing mouse and human retina to identify multiple interconnected, evolutionarily conserved GRNs composed of cell-type-specific transcription factors that both activate genes within their own network and inhibit genes in other networks. These GRNs control temporal patterning in primary progenitors, regulate transition from primary to neurogenic progenitors, and drive specification of each major retinal cell type. We confirm that NFI transcription factors selectively activate expression of genes promoting late-stage temporal identity in primary retinal progenitors and identify other transcription factors that regulate rod photoreceptor specification in postnatal retina. This study inventories cis- and trans-acting factors that control retinal development and can guide cell-based therapies aimed at replacing retinal neurons lost to disease. © 2021 The Authors

Author Keywordsdevelopment;  gene regulatory network;  neurogenesis;  NFI;  progenitor;  retina;  single-cell ATAC-seq;  single-cell RNA-seq;  temporal patterning;  transcription factor

Funding detailsNational Eye InstituteNEI2T32EY007143, P30 EY002687, P30EY001765, R00EY027844, R01EY020560, R01EY028584, R01EY029548, U01EY027267Research to Prevent BlindnessRPB

Document Type: ArticlePublication Stage: FinalSource: Scopus

“Cognitive deficits and impaired hippocampal long-term potentiation in KATPinduced DEND syndrome” (2021) Proceedings of the National Academy of Sciences of the United States of America

Cognitive deficits and impaired hippocampal long-term potentiation in KATPinduced DEND syndrome(2021) Proceedings of the National Academy of Sciences of the United States of America, 118 (45), art. no. e2109721118, . 

Yahil, S.a , Wozniak, D.F.b c , Yan, Z.a , Mennerick, S.b c , Remedi, M.S.a d

a Division of Endocrinology, Metabolism, and Lipid Research, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, United Statesb Department of Psychiatry, Washington University, School of Medicine, St. Louis, MO 63110, United Statesc Taylor Family Institute for Innovative Psychiatric Research, Washington University School of Medicine, St. Louis, MO 63110, United Statesd Department of Cell Biology and Physiology, Washington University, School of Medicine, St. Louis, MO 63110, United States

AbstractATP-sensitive potassium (KATP) gain-of-function (GOF) mutations cause neonatal diabetes, with some individuals exhibiting developmental delay, epilepsy, and neonatal diabetes (DEND) syndrome. Mice expressing KATP-GOF mutations pan-neuronally (nKATP-GOF) demonstrated sensorimotor and cognitive deficits, whereas hippocampus-specific hKATP-GOF mice exhibited mostly learning and memory deficiencies. Both nKATP-GOF and hKATP-GOF mice showed altered neuronal excitability and reduced hippocampal long-term potentiation (LTP). Sulfonylurea therapy, which inhibits KATP, mildly improved sensorimotor but not cognitive deficits in KATP-GOF mice. Mice expressing KATP-GOF mutations in pancreatic β-cells developed severe diabetes but did not show learning and memory deficits, suggesting neuronal KATP-GOF as promoting these features. These findings suggest a possible origin of cognitive dysfunction in DEND and the need for novel drugs to treat neurological features induced by neuronal KATP-GOF. © 2021 National Academy of Sciences. All rights reserved.

Author KeywordsBehavior;  Cognition;  DEND;  Electrophysiology;  KATP

Funding detailsNational Institutes of HealthNIHR01DK098584, R01DK123163, R01MH123748National Institute of Child Health and Human DevelopmentNICHDU54HD087011/ P50HD103425

Document Type: ArticlePublication Stage: FinalSource: Scopus

“Evaluation of Kratom Opioid Derivatives as Potential Treatment Option for Alcohol Use Disorder” (2021) Frontiers in Pharmacology

Evaluation of Kratom Opioid Derivatives as Potential Treatment Option for Alcohol Use Disorder(2021) Frontiers in Pharmacology, 12, art. no. 764885, . 

Gutridge, A.M.a , Chakraborty, S.b , Varga, B.R.b , Rhoda, E.S.a , French, A.R.a c , Blaine, A.T.a , Royer, Q.H.a , Cui, H.a , Yuan, J.a , Cassell, R.J.a d , Szabó, M.e , Majumdar, S.b , van Rijn, R.M.a c d

a Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN, United Statesb Center for Clinical Pharmacology, University of Heath Sciences and Pharmacy at St. Louis, Washington University School of Medicine, St. Louis, MO, United Statesc Purdue Institute for Integrative Neuroscience, West Lafayette, IN, United Statesd Purdue Institute for Drug Discovery, West Lafayette, IN, United Statese XiMo Hungary Ltd, Budapest, Hungary

AbstractBackground and Purpose: Mitragyna speciosa extract and kratom alkaloids decrease alcohol consumption in mice at least in part through actions at the δ-opioid receptor (δOR). However, the most potent opioidergic kratom alkaloid, 7-hydroxymitragynine, exhibits rewarding properties and hyperlocomotion presumably due to preferred affinity for the mu opioid receptor (µOR). We hypothesized that opioidergic kratom alkaloids like paynantheine and speciogynine with reduced µOR potency could provide a starting point for developing opioids with an improved therapeutic window to treat alcohol use disorder. Experimental Approach: We characterized paynantheine, speciociliatine, and four novel kratom-derived analogs for their ability to bind and activate δOR, µOR, and κOR. Select opioids were assessed in behavioral assays in male C57BL/6N WT and δOR knockout mice. Key Results: Paynantheine (10 mg∙kg−1, i.p.) produced aversion in a limited conditioned place preference (CPP) paradigm but did not produce CPP with additional conditioning sessions. Paynantheine did not produce robust antinociception but did block morphine-induced antinociception and hyperlocomotion. Yet, at 10 and 30 mg∙kg−1 doses (i.p.), paynantheine did not counteract morphine CPP. 7-hydroxypaynantheine and 7-hydroxyspeciogynine displayed potency at δOR but limited µOR potency relative to 7-hydroxymitragynine in vitro, and dose-dependently decreased voluntary alcohol consumption in WT but not δOR in KO mice. 7-hydroxyspeciogynine has a maximally tolerated dose of at least 10 mg∙kg−1 (s.c.) at which it did not produce significant CPP neither alter general locomotion nor induce noticeable seizures. Conclusion and Implications: Derivatizing kratom alkaloids with the goal of enhancing δOR potency and reducing off-target effects could provide a pathway to develop novel lead compounds to treat alcohol use disorder with an improved therapeutic window. Copyright © 2021 Gutridge, Chakraborty, Varga, Rhoda, French, Blaine, Royer, Cui, Yuan, Cassell, Szabó, Majumdar and van Rijn.

Author Keywordsalcohol use disorder;  biased signaling;  delta opioid receptor;  kratom;  nociception;  reward;  seizures

Funding detailsNational Institute on Drug AbuseNIDANational Institute on Alcohol Abuse and AlcoholismNIAAA

Document Type: ArticlePublication Stage: FinalSource: Scopus

“Sirtuin 1 mediates protection against delayed cerebral ischemia in subarachnoid hemorrhage in response to hypoxic postconditioning” (2021) Journal of the American Heart Association

Sirtuin 1 mediates protection against delayed cerebral ischemia in subarachnoid hemorrhage in response to hypoxic postconditioning(2021) Journal of the American Heart Association, 10 (20), art. no. e021113, . 

Diwan, D.a , Vellimana, A.K.a , Aum, D.J.a , Clarke, J.a , Nelson, J.W.a , Lawrence, M.a , Han, B.H.c , Gidday, J.M.d , Zipfel, G.J.a b

a Department of Neurological Surgery, Washington University School of Medicine, St. Louis, MO, United Statesb Department of Neurology, Washington University School of Medicine, St. Louis, MO, United Statesc Department of Pharmacology, A.T. Still, University of Health Sciences, Kirksville College of Osteopathic Medicine, Kirksville, MO, United Statesd Departments of Ophthalmology, Physiology, Biochemistry, and Neuroscience, Louisiana State University, New Orleans, LA, United States

AbstractBACKGROUND: Many therapies designed to prevent delayed cerebral ischemia (DCI) and improve neurological outcome in an-eurysmal subarachnoid hemorrhage (SAH) have failed, likely because of targeting only one element of what has proven to be a multifactorial disease. We previously demonstrated that initiating hypoxic conditioning before SAH (hypoxic preconditioning) provides powerful protection against DCI. Here, we expanded upon these findings to determine whether hypoxic conditioning delivered at clinically relevant time points after SAH (hypoxic postconditioning) provides similarly robust DCI protection. METHODS AND RESULTS: In this study, we found that hypoxic postconditioning (8% O2 for 2 hours) initiated 3 hours after SAH provides strong protection against cerebral vasospasm, microvessel thrombi, and neurological deficits. By pharmacologic and genetic inhibition of SIRT1 (sirtuin 1) using EX527 and global Sirt1−/− mice, respectively, we demonstrated that this mul-tifaceted DCI protection is SIRT1 mediated. Moreover, genetic overexpression of SIRT1 using Sirt1-Tg mice, mimicked the DCI protection afforded by hypoxic postconditioning. Finally, we found that post-SAH administration of resveratrol attenuated cerebral vasospasm, microvessel thrombi, and neurological deficits, and did so in a SIRT1-dependent fashion. CONCLUSIONS: The present study indicates that hypoxic postconditioning provides powerful DCI protection when initiated at clinically relevant time points, and that pharmacologic augmentation of SIRT1 activity after SAH can mimic this beneficial ef-fect. We conclude that conditioning-based therapies administered after SAH hold translational promise for patients with SAH and warrant further investigation. © 2021 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Author KeywordsDelayed cerebral ischemia;  Microvessel thrombi;  Postconditioning;  Resveratrol;  Sirt1;  Subarachnoid hemorrhage;  Vasospasm

Funding detailsNational Institutes of HealthNIHR01 NS091603, R25 NS090978Neurosurgery Research and Education FoundationNREF

Document Type: ArticlePublication Stage: FinalSource: Scopus

“Vocabulary Acquisition as a By-Product of Meaning-Oriented Auditory Training for Children Who Are Deaf or Hard of Hearing” (2021) Language, Speech, and Hearing Services in Schools

Vocabulary Acquisition as a By-Product of Meaning-Oriented Auditory Training for Children Who Are Deaf or Hard of Hearing(2021) Language, Speech, and Hearing Services in Schools, 52 (4), pp. 1049-1060. 

Barcroft, J.a , Grantham, H.b , Mauzé, E.b , Spehar, B.b , Sommers, M.S.c , Spehar, C.b , Tye-Murray, N.b

a Department of Romance Languages and Literatures, Washington University in St. Louis, MO, Norwayb Department of Otolaryngology-Head & Neck Surgery, Washington University School of Medicine in St. Louis, MO, Norwayc Department of Psychological & Brain Sciences, Washington University in St. Louis, MO, Norway

AbstractPurpose A meaning-oriented auditory training program for children who are deaf or hard of hearing (d/hh) was assessed with regard to its efficacy in promoting novel word learning. Method While administering the auditory training program, one of the authors (Elizabeth Mauzé) observed that children were learning words they previously did not know. Therefore, we systematically assessed vocabulary gains among 16 children. Most completed pretest, posttest, and retention versions of a picture-naming task in which they attempted to verbally identify 199 color pictures of words that would appear during training. Posttest and retention versions included both pictures used and not used during training in order to test generalization of associations between words and their referents. Importantly, each training session involved meaning-oriented, albeit simple, activities/games on a computer. Results At posttest, the percentage of word gain was 27.3% (SD = 12.5; confidence interval [CI] of the mean: 24.2-30.4) using trained pictures as cues and 25.9% (CI of the mean: 22.9-29.0) using untrained pictures as cues. An analysis of retention scores (for 13 of the participants who completed it weeks later) indicated strikingly high levels of retention for the words that had been learned. Conclusions These findings favor auditory training that is meaning oriented when it comes to the acquisition of different linguistic subsystems, lexis in this case. We also expand the discussion to include other evidence-based recommendations regarding how vocabulary is presented (input-based effects) and what learners are asked to do (task-based effects) as part of an overall effort to help children who are d/hh increase their vocabulary knowledge.

Document Type: ArticlePublication Stage: FinalSource: Scopus

“Neuroimaging in the term newborn with neonatal encephalopathy” (2021) Seminars in Fetal and Neonatal Medicine

Neuroimaging in the term newborn with neonatal encephalopathy(2021) Seminars in Fetal and Neonatal Medicine, 26 (5), art. no. 101304, . 

Wisnowski, J.L.a , Wintermark, P.b , Bonifacio, S.L.c , Smyser, C.D.d , Barkovich, A.J.e , Edwards, A.D.f , de Vries, L.S.g , Inder, T.E.h , Chau, V.i , Newborn Brain Society Guidelines and Publications Committeej

a Departments of Radiology and Pediatrics (Neonatology), Children’s Hospital Los Angeles, 4650 Sunset Blvd. MS #81, Los Angeles, CA 90027, United Statesb Department of Pediatrics (Neonatology), McGill University/Montreal Children’s Hospital, Division of Newborn Medicine, Research Institute of the McGill University Health Centre, 1001 boul. Décarie, Site Glen Block E, EM0.3244, Montréal, QC H4A 3J1, Canadac Division of Neonatal and Developmental Medicine, Department of Pediatrics (Neonatology), Lucile Packard Children’s Hospital, Stanford University School of Medicine, 750 Welch Road, Suite 315, Palo Alto, CA 94304, United Statesd Departments of Neurology, Radiology, and Pediatrics, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8111, St. Louis, MO 63110-1093, United Statese Department of Radiology, UCSF Benioff Children’s Hospital, University of California San Francisco, 505 Parnassus Avenue, M-391, San Francisco, CA 94143-0628, United Statesf Evelina London Children’s Hospital, Centre for Developing Brain, King’s College London, Westminster Bridge Road, London, SE1 7EH, United Kingdomg Department of Neonatology, University Medical Center Utrecht, Utrecht University, Lundlaan 6, Utrecht, 3584 EA, Netherlandsh Department of Pediatric Newborn Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, United Statesi Department of Pediatrics (Neurology), The Hospital for Sick Children, University of Toronto, 555 University Avenue, Room 6513, Toronto, ON M5G 1X8, Canada

AbstractNeuroimaging is widely used to aid in the diagnosis and clinical management of neonates with neonatal encephalopathy (NE). Yet, despite widespread use clinically, there are few published guidelines on neuroimaging for neonates with NE. This review outlines the primary patterns of brain injury associated with hypoxic-ischemic injury in neonates with NE and their frequency, associated neuropathological features, and risk factors. In addition, it provides an overview of neuroimaging methods, including the most widely used scoring systems used to characterize brain injury in these neonates and their utility as predictive biomarkers. Last, recommendations for neuroimaging in neonates with NE are presented. © 2021

Author KeywordsAdvanced MRI techniques;  Asphyxia;  Diffusion-tensor imaging;  Diffusion-weighted imaging;  Hypoxic-ischemic brain injury;  Magnetic resonance spectroscopy imaging;  Neonatal encephalopathy;  Neonates;  Outcome prediction;  Predictive values

Funding detailsNational Institutes of HealthNIHK23HD099309, U01NS092764Canadian Institutes of Health ResearchIRSC

Document Type: ArticlePublication Stage: FinalSource: Scopus

“Sleep and longitudinal cognitive performance in preclinical and early symptomatic Alzheimer’s disease” (2021) Brain

Sleep and longitudinal cognitive performance in preclinical and early symptomatic Alzheimer’s disease(2021) Brain, 144 (9), pp. 2852-2862. Cited 1 time.

Lucey, B.P.a b , Wisch, J.a , Boerwinkle, A.H.a , Landsness, E.C.a , Toedebusch, C.D.a , McLeland, J.S.a , Butt, O.H.a , Hassenstab, J.a b c , Morris, J.C.a b c , Ances, B.M.a b , Holtzman, D.M.a b c

a Department of Neurology, Washington University School of Medicine, St Louis, MO 63110, United Statesb Hope Center for Neurological Disorders, Washington University School of Medicine, St Louis, MO 63110, United Statesc Knight Alzheimer Disease Research Center, Washington University School of Medicine, St Louis, MO 63110, United States

AbstractSleep monitoring may provide markers for future Alzheimer’s disease; however, the relationship between sleep and cognitive function in preclinical and early symptomatic Alzheimer’s disease is not well understood. Multiple studies have associated short and long sleep times with future cognitive impairment. Since sleep and the risk of Alzheimer’s disease change with age, a greater understanding of how the relationship between sleep and cognition changes over time is needed. In this study, we hypothesized that longitudinal changes in cognitive function will have a non-linear relationship with total sleep time, time spent in non-REM and REM sleep, sleep efficiency and non-REM slow wave activity. To test this hypothesis, we monitored sleep-wake activity over 4-6 nights in 100 participants who underwent standardized cognitive testing longitudinally, APOE genotyping, and measurement of Alzheimer’s disease biomarkers, total tau and amyloid-β42 in the CSF. To assess cognitive function, individuals completed a neuropsychological testing battery at each clinical visit that included the Free and Cued Selective Reminding test, the Logical Memory Delayed Recall assessment, the Digit Symbol Substitution test and the Mini-Mental State Examination. Performance on each of these four tests was Z-scored within the cohort and averaged to calculate a preclinical Alzheimer cognitive composite score. We estimated the effect of cross-sectional sleep parameters on longitudinal cognitive performance using generalized additive mixed effects models. Generalized additive models allow for non-parametric and non-linear model fitting and are simply generalized linear mixed effects models; however, the linear predictors are not constant values but rather a sum of spline fits. We found that longitudinal changes in cognitive function measured by the cognitive composite decreased at low and high values of total sleep time (P < 0.001), time in non-REM (P < 0.001) and REM sleep (P < 0.001), sleep efficiency (P < 0.01) and <1 Hz and 1-4.5 Hz non-REM slow wave activity (P < 0.001) even after adjusting for age, CSF total tau/amyloid-β42 ratio, APOE ϵ4 carrier status, years of education and sex. Cognitive function was stable over time within a middle range of total sleep time, time in non-REM and REM sleep and <1 Hz slow wave activity, suggesting that certain levels of sleep are important for maintaining cognitive function. Although longitudinal and interventional studies are needed, diagnosing and treating sleep disturbances to optimize sleep time and slow wave activity may have a stabilizing effect on cognition in preclinical or early symptomatic Alzheimer’s disease. © 2021 The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved.

Author KeywordsAlzheimer’s disease;  biomarkers;  EEG;  memory;  mild cognitive impairment

Document Type: ArticlePublication Stage: FinalSource: Scopus



Constantino, J.N.a , Baumel, W.T.b

a Washington University School of Medicine, St. Louis, MO, United Statesb Anxiety Disorders Research Program, University of Cincinnati College of Medicine, Cincinnati, OH, United States

AbstractSteady advances in neuroscience have shaped understanding of brain and mind, in ways that challenge spiritual belief and can amplify misconceptions about biological determinism. The inability to reconcile spirituality and science risks faith being construed as “out of touch” with reality, and in worst-case scenarios engendering clinical-level crises of hope. The latter typically involve three central issues: the free will problem, desperate perceptions about mortality, and the constraint of individual identity. Here, we synthesize contemporary scientific and philosophical understanding to propose a reconciliation of faith and science of particular relevance to preservation of hope. In this approach, we review the compatibility of natural causation and human freedom, parameterize “meaning” on the basis of specific opportunities for decision-making within the timeframe of a lifetime, and articulate a model of self-transcendence predicated on these principles and on observed characteristics of human love. This model resides within “common ground” for faith and science by avoiding unnecessary dichotomization of the material and the Divine. © 2021 by the Joint Publication Board of Zygon.

Author Keywordscompatibilism;  determinism;  existential conflict;  free will;  identity;  meaning;  neuroscience;  psychiatry;  self-transcendence;  theology

Document Type: ArticlePublication Stage: Article in PressSource: Scopus

“Dopaminergic and other genes related to reward induced overeating, Bulimia, Anorexia Nervosa, and Binge eating” (2021) Expert Review of Precision Medicine and Drug Development

Dopaminergic and other genes related to reward induced overeating, Bulimia, Anorexia Nervosa, and Binge eating(2021) Expert Review of Precision Medicine and Drug Development, . 

Blum, K.a b c d e f , Thanos, P.K.g , Wang, G.-J.h , Bowirrat, A.i , Gomez, L.L.b , Baron, D.a , Jalali, R.b , Gondré-Lewis, M.C.j , Gold, M.S.k

a Division of Addiction Research Education, Center for Psychiatry, Medicine Primary Care (Office of the Provost), Western University Health Sciences Graduate School of Biomedical Sciences, Pomona, CA, United Statesb Department of Precision Behavioral Management, The Kenneth Blum Behavioral Neurogenetic Institute (Division of Ivitalize Inc.), Austin, TX, United Statesc Institute of Psychology, ELTE Eötvös Loránd University, Budapest, Hungaryd Department of Psychiatry, University of Vermont, Burlington, VM, United Statese Centre for Genomics and Applied Gene Technology, Institute of Integrative Omics and Applied Biotechnology, Nonakuri, Indiaf Department of Psychiatry, Wright State University Boonshoft School of Medicine, Dayton Va Medical Centre, Dayton, OH, United Statesg Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions, Research Institute on Addictions, University at Buffalo, Buffalo, NY, United Statesh Laboratory of Neuroimaging, National Institute of Alcohol Abuse and Alcoholism, Bethesda, MD, United Statesi Department of Molecular Biology and Adelson School of Medicine, Ariel University, Ariel, Israelj Neuropsychopharmacology Laboratory, Department of Anatomy, Howard University College of Medicine, Washington, Washington, DC, United Statesk Department of Psychiatry, School of Medicine, Washington University, St. Louis, MO, United States

AbstractIntroduction: Eating Disorders and Obesity are a primary global public health concern. Areas Covered: This article aims to trace the neurochemical mechanisms of unwanted eating disorders and target specific loci, within the Brain Reward Cascade (BRC) for therapeutic interventions. Changes due to BRC polymorphisms in functional connectivity and neurotransmission can manifest as overeating, Bulimia Nervosa, and Anorexia Nervosa, and other related eating disorders. Expert opinion: Variations in dopamine function within the Ventral Tegmental Area (VTA), Nucleus Accumbens (NAc), and Ventral Striatum of individuals result in different outcomes related to maladaptive eating behaviors. The goal is to reduce maladaptive eating behaviors by implementing novel strategies that induce Dopamine Homeostasis within the BRC. Clinicians determine genetic risk severity and identify polymorphic targets for either pharmaceutical or nutraceutical interventions. Precision neuro-nutrient formulations of KB220 (Research ID Code) matched precisely to deficient neurotransmitter systems may promote the long-term development of ‘dopamine homeostasis’ to treat and prevent overeating, Bulimia, and Anorexia Nervosa. © 2021 Informa UK Limited, trading as Taylor & Francis Group.

Author KeywordsAnorexia Nervosa;  binging;  Bulimia Nervosa;  dopamine homeostasis;  Eating disorders;  Genetic Addiction Risk Severity (GARS);  hypodopaminergia;  neurogenetics;  overeating;  polymorphic genetic antecedents;  undereating

Document Type: ReviewPublication Stage: Article in PressSource: Scopus

“Persistent and distressing psychotic-like experiences using adolescent brain cognitive development℠ study data” (2021) Molecular Psychiatry

Persistent and distressing psychotic-like experiences using adolescent brain cognitive development study data(2021) Molecular Psychiatry, . 

Karcher, N.R.a , Loewy, R.L.b , Savill, M.b , Avenevoli, S.c , Huber, R.S.d , Makowski, C.e , Sher, K.J.f , Barch, D.M.a g

a Washington University School of Medicine, Dept. of Psychiatry, St. Louis, MO, United Statesb University of California, San Francisco, Dept. of Psychiatry, San Francisco, CA, United Statesc National Institute of Mental Health, Bethesda, MD, United Statesd University of Utah, Dept. of Psychiatry, Salt Lake City, UT, United Statese University of California San Diego, Dept. of Radiology, San Diego, CA, United Statesf University of Missouri, Dept. of Psychological Sciences, Columbia, MO, United Statesg Washington University in St. Louis, Dept. of Psychological and Brain Sciences, St. Louis, MO, United States

AbstractChildhood psychotic-like experiences (PLEs) are associated with a range of impairments; a subset of children experiencing PLEs will develop psychiatric disorders, including psychotic disorders. A potential distinguishing factor between benign PLEs versus PLEs that are clinically relevant is whether PLEs are distressing and/or persistent. The current study used three waves of Adolescent Brain Cognitive Development (ABCD) study PLEs assessments to examine the extent to which persistent and/or distressing PLEs were associated with relevant baseline risk factors (e.g., cognition) and functioning/mental health service utilization domains. Four groups varying in PLE persistence and distress endorsement were created based on all available data in ABCD Release 3.0, with group membership not contingent on complete data: persistent distressing PLEs (n = 272), transient distressing PLEs (n = 298), persistent non-distressing PLEs (n = 221), and transient non-distressing PLEs (n = 536) groups. Using hierarchical linear models, results indicated youth with distressing PLEs, whether transient or persistent, showed delayed developmental milestones (β = 0.074, 95%CI:0.013,0.134) and altered structural MRI metrics (β = −0.0525, 95%CI:−0.100,−0.005). Importantly, distress interacted with PLEs persistence for the domains of functioning/mental health service utilization (β = 0.079, 95%CI:0.016,0.141), other reported psychopathology (β = 0.101, 95%CI:0.030,0.170), cognition (β = −0.052, 95%CI:0.−0.099,−0.002), and environmental adversity (β = 0.045, 95%CI:0.003,0.0.86; although no family history effects), with the interaction characterized by greatest impairment in the persistent distressing PLEs group. These results have implications for disentangling the importance of distress and persistence for PLEs with regards to impairments, including functional, pathophysiological, and environmental outcomes. These novel longitudinal data underscore that it is often only in the context of distress that persistent PLEs were related to impairments. © 2021, The Author(s), under exclusive licence to Springer Nature Limited.

Funding detailsNational Institutes of HealthNIHU01DA041022, U01DA041025, U01DA041028, U01DA041048, U01DA041089, U01DA041093, U01DA041106, U01DA041117, U01DA041134, U01DA041148, U01DA041156, U01DA041174, U24DA041123, U24DA041147National Institute of Mental HealthNIMHK23MH121792-01, L30 MH120574-01, MH018261-31National Institute on Drug AbuseNIDAU01DA041120National Institute on Alcohol Abuse and AlcoholismNIAAAK05-AA017242Canadian Institutes of Health ResearchIRSCFonds de Recherche du Québec – SantéFRQS

Document Type: ArticlePublication Stage: Article in PressSource: Scopus

“Correlates of real-world goal-directed behavior in schizophrenia” (2021) Psychological Medicine

Correlates of real-world goal-directed behavior in schizophrenia(2021) Psychological Medicine, . 

Merchant, J.T.a , Moran, E.K.a b , Strube, M.J.a , Barch, D.M.a b c

a Department of Psychological and Brain Sciences, Washington University in St. Louis, St. Louis, MO 63130, United Statesb Department of Psychiatry, Washington University, School of Medicine, St. Louis, MO 63110, United Statesc Department of Radiology, Mallinckrodt Institute of Radiology, Washington University, School of Medicine, St. Louis, MO 63110, United States

AbstractBackground Deficits in goal-directed behavior (i.e. behavior conducted to achieve a specific goal or outcome) are core to schizophrenia, difficult to treat, and associated with poor functional outcomes. Factors such as negative symptoms, effort-cost decision-making, cognition, and functional skills have all been associated with goal-directed behavior in schizophrenia as indexed by clinical interviews or laboratory-based tasks. However, little work has examined whether these factors relate to the real-world pursuit of goal-directed activities in this population. Methods This study aimed to fill this gap by using Ecological Momentary Assessment (four survey prompts per day for 1 week) to test hypotheses about symptom, effort allocation, cognitive, and functional measures associated with planned and completed goal-directed behavior in the daily lives of 63 individuals with schizophrenia. Results Individuals with schizophrenia completed more goal-directed activities than they planned [t(62) = -4.01, p < 0.001]. Motivation and pleasure (i.e. experiential) negative symptoms, controlling for depressive symptoms, negatively related to planned goal-directed behavior [odds ratio (OR) 0.92, p = 0.005]. Increased effort expenditure for high probability rewards (planned: OR 1.01, p = 0.034, completed: OR 1.01, p = 0.034) along with performance on a daily functional skills task (planned: OR 1.04, p = 0.002, completed: OR 1.03, p = 0.047) negatively related to both planned and completed goal-directed activity. Conclusions Our results present correlates of real-world goal-directed behavior that largely align with impaired ability to make future estimations in schizophrenia. This insight could help identify targeted treatments for the elusive motivated behavior deficits in this population. © The Author(s), 2021. Published by Cambridge University Press.

Author KeywordsAnticipation;  cognitive function;  ecological momentary assessment;  effort-cost decision-making;  goal-directed behavior;  motivation;  negative symptoms;  schizophrenia;  working memory

Funding detailsNational Institute of Mental HealthNIMHR01-MH066031

Document Type: ArticlePublication Stage: Article in PressSource: Scopus

“Understanding Indecisiveness: Dimensionality of Two Self-Report Questionnaires and Associations With Depression and Indecision” (2021) Psychological Assessment

Understanding Indecisiveness: Dimensionality of Two Self-Report Questionnaires and Associations With Depression and Indecision(2021) Psychological Assessment, . 

Hallenbeck, H.W., Rodebaugh, T.L., Thompson, R.J.

Department of Psychological and Brain Sciences, Washington University in St. Louis, United States

AbstractIndecisiveness is a prevalent and impairing symptom among individuals with major depressive disorder (MDD). However, the use of different self-report questionnaires and factor analysis methods in past researc has been a barrier to understanding the nature of indecisiveness in depression. Addressing these barriers could help to elucidate the dimensionality and validity of indecisiveness questionnaires, which in turn would clarify the relation of indecisiveness to depression. In our study of an online sample of adults (N = 602), we administered two commonly used indecisiveness questionnaires, a depressive symptom questionnaire, and a behavioral task assessing indecision. Through confirmatory factor analysis, we found that the combinedindecisiveness questionnaires were best characterized by a two-factor model, with one factor corresponding to straightforwardly worded items and the other corresponding to reverse-scored items. Based on post hoc analyses involving tests of discriminant validity, we think that these two factors represent indecisiveness and decision-making confidence, respectively. Indecisiveness, but not decision-making confidence, was strongly associated with depressive symptoms. Indecisiveness was also strongly associated with behavioral indecision, a finding that helps to validate indecisiveness as a construct. We posit that the assessment of indecisiveness could be enhanced by excluding the reverse-scored items because they appear to represent decision-making confidence, a distinct construct from indecisiveness. Excluding the reverse-scored items revealed a robust link between indecisiveness and depressive symptoms, highlighting the importance o targeting this symptom in depression research © 2021 American Psychological Association

Author Keywordsconfirmatory factor analysis;  decision-making;  depression;  indecision;  indecisiveness

Document Type: ArticlePublication Stage: Article in PressSource: Scopus

“Distinct epilepsy phenotypes and response to drugs in KCNA1 gain- and loss-of function variants” (2021) Epilepsia

Distinct epilepsy phenotypes and response to drugs in KCNA1 gain- and loss-of function variants(2021) Epilepsia, . 

Miceli, F.a , Guerrini, R.b , Nappi, M.a , Soldovieri, M.V.c , Cellini, E.b , Gurnett, C.A.d , Parmeggiani, L.e , Mei, D.b , Taglialatela, M.a

a Department of Neuroscience, University of Naples “Federico II”, Naples, Italyb Neuroscience Department, A. Meyer Children’s Hospital, University of Florence, Florence, Italyc Department of Medicine and Health Science “V. Tiberio”, University of Molise, Campobasso, Italyd Department of Neurology, Washington University in St. Louis, St. Louis, MO, United Statese Department of Pediatric Neurology, Bolzano Hospital, Bolzano, Italy

AbstractA wide phenotypic spectrum of neurological diseases is associated with KCNA1 (Kv1.1) variants. To investigate the molecular basis of such a heterogeneous clinical presentation and identify the possible correlation with in vitro phenotypes, we compared the functional consequences of three heterozygous de novo variants (p.P403S, p.P405L, and p.P405S) in Kv1.1 pore region found in four patients with severe developmental and epileptic encephalopathy (DEE), with those of a de novo variant in the voltage sensor (p.A261T) identified in two patients with mild, carbamazepine-responsive, focal epilepsy. Patch-clamp electrophysiology was used to investigate the functional properties of mutant Kv1.1 subunits, both expressed as homomers and heteromers with wild-type Kv1.1 subunits. KCNA1 pore mutations markedly decreased (p. P405S) or fully suppressed (p. P403S, p. P405L) Kv1.1-mediated currents, exerting loss-of-function (LoF) effects. By contrast, channels carrying the p.A261T variant exhibited a hyperpolarizing shift of the activation process, consistent with a gain-of-function (GoF) effect. The present results unveil a novel correlation between in vitro phenotype (GoF vs LoF) and clinical course (mild vs severe) in KCNA1-related phenotypes. The excellent clinical response to carbamazepine observed in the patients carrying the A261T variant suggests an exquisite sensitivity of KCNA1 GoF to sodium channel inhibition that should be further explored. © 2021 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.

Author Keywordsdevelopmental encephalopathies;  epilepsy;  gain-of-function variants;  KCNA1;  loss-of-function variants;  potassium channels

Funding detailsDECODEEESeventh Framework ProgrammeFP7N602531European CommissionECUNICOM – 875299Ministero della SaluteRF201912370491Ministero dell’Istruzione, dell’Università e della RicercaMIURPRIN 2017ALCR7C, PRIN 2017YH3SXK

Document Type: ArticlePublication Stage: Article in PressSource: Scopus

“Priming of Movie Content Is Modulated by Event Boundaries” (2021) Journal of Experimental Psychology: Learning Memory and Cognition

Priming of Movie Content Is Modulated by Event Boundaries(2021) Journal of Experimental Psychology: Learning Memory and Cognition, . 

Kurby, C.A.a , Zacks, J.M.b

a Department of Psychology, Grand Valley State University, United Statesb Department of Psychological and Brain Sciences, Washington University in St. Louis, United States

AbstractPerceivers spontaneously segment ongoing activity into discrete events. This segmentation is important for the moment-by-moment understanding of events, but may also be critical for how events are encoded into episodic memory. In 3 experiments, we used priming to test the possibility that perceptual event boundaries organize memory for everyday activity into episodic units. Viewers watched movies of everyday activities, such as someone washing a car, and then performed a yes-no recognition task using pictures taken from the movies. Some target pictures were preceded by a prime picture taken from 5 s previously in the movie. This produced priming, reducing response times for the target picture. Priming was greater when the prime was part of the same perceptual event as the target than when it was part of a different event, suggesting that event structure organizes episodic memory. This effect persisted when the sequence of activity was scrambled during encoding, which suggests that it reflects, in part, knowledge about event types and not just the specifics of a given episode. © 2021 American Psychological Association

Author Keywordsepisodic memory;  event schemata;  event segmentation

Funding detailsNational Institutes of HealthNIHR01 AG031150, T32 AG000030-31

Document Type: ArticlePublication Stage: Article in PressSource: Scopus

“Future Time Perspective and Personality Trait Change During the Retirement Transition: Insights From a Six-Wave Longitudinal Study in Sweden” (2021) Psychology and Aging

Future Time Perspective and Personality Trait Change During the Retirement Transition: Insights From a Six-Wave Longitudinal Study in Sweden(2021) Psychology and Aging, . 

Hill, P.L.a , Kivi, M.b , Hansson, I.b , Thorvaldsson, V.b , Allemand, M.c

a Department of Psychological and Brain Sciences, Washington University in St. Louis, United Statesb Department of Psychology and Center for Ageing and Health (AgeCap), University of Gothenburg, Swedenc Department of Psychology and University Research Priority Program Dynamics of Healthy Aging, University of Zurich, Switzerland

AbstractThe present study examined associations between two future time perspective (FTP) dimensions (perceived opportunities and perceived time) and the Big Five personality traits during older adulthood, a developmental period that has received limited attention in personality development. Specifically, it tested whether FTP dimensions were cross-sectionally associated with personality traits, as well as if they predicted changes on those traits during a time when participants were transitioning to retirement. Participants from the Health, Ageing and Retirement Transitions in Sweden (HEARTS) study (N = 5,913, Mage = 63.09 years) reported on their FTP at the initial assessment and on their Big Five personality traits on six assessments 1 year apart. Latent growth curve models were fit to examine FTP as a predictor of level and change in the Big Five traits over time, with perceived time and opportunities included as unique predictors. Results found that broader FTP was associated with higher extraversion, agreeableness, openness to experience, and conscientiousness, but lower neuroticism initially. However, results indicated associations were stronger and sometimes only significant for perceived opportunities not time. Regarding FTP as a predictor of personality trait change, modest evidence was found that perceived opportunities predicted changes in neuroticism and openness over time. The present study extends past work by showing the importance of capturing different components of FTP when examining personality traits during older adulthood. Research needs to further explore the longitudinal predictive effects of FTP, focusing on more proximal assessments and how FTP changes during retirement © 2021 American Psychological Association

Author Keywordsfuture time perspective;  longitudinal change;  personality;  retirement

Funding detailsGöteborgs UniversitetForskningsrådet om Hälsa, Arbetsliv och VälfärdFORTE2013-2291, 2013-2300

Document Type: ArticlePublication Stage: Article in PressSource: Scopus

“Awe is Associated With Creative Personality, Convergent Creativity, and Everyday Creativity” (2021) Psychology of Aesthetics, Creativity, and the Arts

Awe is Associated With Creative Personality, Convergent Creativity, and Everyday Creativity(2021) Psychology of Aesthetics, Creativity, and the Arts, . 

Zhang, J.W.a , Howell, R.T.b , Razavi, P.c , Shaban-Azad, H.d , Chai, W.J.e , Ramis, T.f , Mello, Z.b , Anderson, C.L.g , Keltner, D.h

a Department of Psychology, University of Memphis, United Statesb Department of Psychology, San Francisco State University, United Statesc Department of Psychology, University of Oregon, United Statesd Department of Psychology, University of Tehran, Irane Department of Neuroscience, Universiti Sains Malaysia, Malaysiaf Department of Psychology, Sunway University, Malaysiag Department of Marketing, Washington University, St. Louis, United Statesh Department of Psychology, University of California, Berkeley, United States

AbstractCreativity has many benefits, such as workplace performance and life satisfaction. Three studies extended a small body of work to examine whether awe was associated with creative personality, convergent creativity, and everyday creative behaviors (N = 1,844). Study 1 demonstrated that trait awe was associated with a more creative personality among adolescents and adults in the U.S., Iran, and Malaysia. Study 2 showed that trait awe was associated with an increased likelihood of solving the Duncker’s Candle Problem. Finally, Study 3 found that on days when participants felt more daily awe than they typically do, they reported having done more everyday creative activities. The effects of awe were independent of amusement (Studies 1–3) and Big Five personality (Study 3). Moreover, we found that daily curiosity explained the link between daily awe and daily creativity in Study 3. These results are the first to demonstrate a consistent link between awe and complementary measures of creativity. The discussion focuses on the limitations of the present work as well as implications of the present results for future research on awe and creativity © 2021 American Psychological Association

Author Keywordsawe;  convergent creativity;  creative personality;  curiosity;  everyday creativity

Document Type: ArticlePublication Stage: Article in PressSource: Scopus

“Unusually High Prevalence of Stroke and Cerebral Vasculopathy in Hemoglobin SC Disease: A Retrospective Single Institution Study” (2021) Acta Haematologica

Unusually High Prevalence of Stroke and Cerebral Vasculopathy in Hemoglobin SC Disease: A Retrospective Single Institution Study(2021) Acta Haematologica, . 

Sathi, B.K.a b , Yoshida, Y.c , Weaver, M.R.b d , Nolan, L.S.b e , Gruner, B.b , Balasa, V.a , Altes, T.b f , Leiva-Salinas, C.f

a Pediatric Hematology Oncology, Valley Children’s Hospital, University of San Francisco-Fresno Program, Madera, CA, United Statesb Department of Child Health, University of Missouri, Columbia, SC, United Statesc Department of Internal Medicine, Tulane University, New Orleans, LA, United Statesd University of South Florida, Tampa, FL, United Statese Department of Pediatrics, Washington University, St. Louis, MO, United Statesf Department of Radiology, University of Missouri, Columbia, SC, United States

AbstractIntroduction: Unlike homozygous hemoglobin SS (HbSS) disease, stroke is a rare complication in hemoglobin SC (HbSC) disease. However, recent studies have demonstrated a high prevalence of silent stroke in HbSC disease. The factors associated with stroke and cerebral vasculopathy in the HbSC population are unknown. Methods: We conducted a retrospective study of all patients with sickle cell disease treated at the University of Missouri, Columbia, over an 18-year period (2000-2018). The goal of the study was to characterize the silent, overt stroke, and cerebral vasculopathy in HbSC patients and compare them to patients with HbSS and HbS/β thalassemia1 (thal) in this cohort. We also analyzed the laboratory and clinical factors associated with stroke and cerebral vasculopathy in the HbSC population. Results: Of the 34 HbSC individuals, we found that the overall prevalence of stroke and cerebral vasculopathy was 17.7%. Only females had evidence of stroke or cerebral vasculopathy in our HbSC cohort (33.3%, p = 0.019). Time-averaged means of maximum velocities were lower in the HbSC group than the HbSS group and did not correlate with stroke outcome. Among HbSC individuals, those with stroke and cerebral vasculopathy had a marginally higher serum creatinine than those without these complications (0.77 mg/dL vs. 0.88 mg/dL, p = 0.08). Stroke outcome was associated with recurrent vaso-occlusive pain crises (Rec VOCs) (75 vs. 25%, p = 0.003) in HbSC patients. The predominant cerebrovascular lesions in HbSC included microhemorrhages and leukoencephalopathy. Conclusion: There is a distinct subset of individuals with HbSC who developed overt, silent stroke, and cerebral vasculopathy. A female predominance and association with Rec VOCs were identified in our cohort; however, larger clinical trials are needed to identify and confirm specific clinical and laboratory markers associated with stroke and vasculopathy in HbSC disease. © 2021 The Author(s). Published by S. Karger AG, Basel.

Author KeywordsCerebral vasculopathy;  Hemoglobin SC disease;  Silent cerebral infarction;  Stroke

Document Type: ArticlePublication Stage: Article in PressSource: Scopus

“Socioeconomic disadvantage and parental mood/affective problems links negative parenting and executive dysfunction in children born very preterm” (2021) Development and Psychopathology

Socioeconomic disadvantage and parental mood/affective problems links negative parenting and executive dysfunction in children born very preterm(2021) Development and Psychopathology, . 

Lean, R.E.a , Gerstein, E.D.b , Smyser, T.A.a , Smyser, C.D.c d e , Rogers, C.E.a e

a Psychiatry, Washington University, School of Medicine, St. Louis, United Statesb Psychological Sciences, University Missouri-St. Louis, St. Louis, United Statesc Neurology, Washington University, School of Medicine, St. Louis, United Statesd Radiology, Washington University, School of Medicine, St. Louis, United Statese Pediatrics, Washington University, School of Medicine, St. Louis, United States

AbstractPoverty increases the risk of poorer executive function (EF) in children born full-term (FT). Stressors associated with poverty, including variability in parenting behavior, may explain links between poverty and poorer EF, but this remains unclear for children born very preterm (VPT). We examine socioeconomic and parental psychosocial adversity on parenting behavior, and whether these factors independently or jointly influence EF in children born VPT. At age five years, 154 children (VPT = 88, FT = 66) completed parent-child interaction and EF tasks. Parental sensitivity, intrusiveness, cognitive stimulation, and positive and negative regard were coded with the Parent-Child Interaction Rating Scale. Socioeconomic adversity spanned maternal demographic stressors, Income-to-Needs ratio, and Area Deprivation Index. Parents completed measures of depression, anxiety, inattention/hyperactivity, parenting stress, and social-communication interaction (SCI) problems. Parental SCI problems were associated with parenting behavior in parents of children born VPT, whereas socioeconomic adversity was significant in parents of FT children. Negative parenting behaviors, but not positive parenting behaviors, were related to child EF. This association was explained by parental depression/anxiety symptoms and socioeconomic adversity. Results persisted after adjustment for parent and child IQ. Findings may inform research on dyadic interventions that embed treatment for parental mood/affective symptoms and SCI problems to improve childhood EF. © The Author(s), 2021. Published by Cambridge University Press.

Author Keywordsexecutive function;  parenting;  poverty;  prematurity

Funding detailsU54-HD087011National Institutes of HealthNIHK01-MH122735, K02-NS089852, K23-MH105179, R01-HD057098, R01-MH113570, R01-MH113883, UL1-TR000448Doris Duke Charitable FoundationDDCFBrain and Behavior Research FoundationBBRFMarch of Dimes FoundationDana FoundationCerebral Palsy International Research FoundationCPIRFChild Neurology FoundationCNFNational Alliance for Research on Schizophrenia and DepressionNARSAD28521

Document Type: ArticlePublication Stage: Article in PressSource: Scopus