“Semaphorin-Plexin Signaling: From Axonal Guidance to a New X-Linked Intellectual Disability Syndrome” (2022) Pediatric Neurology
Semaphorin-Plexin Signaling: From Axonal Guidance to a New X-Linked Intellectual Disability Syndrome(2022) Pediatric Neurology, 126, pp. 65-73.
Steele, J.L.a , Morrow, M.M.b , Sarnat, H.B.c , Alkhunaizi, E.d , Brandt, T.b , Chitayat, D.A.d , DeFilippo, C.P.e , Douglas, G.V.b , Dubbs, H.A.f , Elloumi, H.Z.b , Glassford, M.R.g , Hannibal, M.C.g , Héron, B.h , Kim, L.E.i , Marco, E.J.j , Mignot, C.k , Monaghan, K.G.b , Myers, K.A.l , Parikh, S.m , Quinonez, S.C.g , Rajabi, F.n , Shankar, S.P.e , Shinawi, M.S.o , van de Kamp, J.J.P.p , Veerapandiyan, A.q , Waldman, A.T.f , Graf, W.D.r
a University of Connecticut School of Medicine, Farmington, CT, United Statesb GeneDx, Inc., Gaithersburg, MD, United Statesc Departments of Paediatrics, Pathology (Neuropathology), and Clinical Neurosciences, University of Calgary Cumming School of Medicine and Alberta Children’s Hospital Research Institute, Calgary, AB, Canadad Department of Obstetrics and Gynecology, The Prenatal Diagnosis and Medical Genetics Program, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canadae Division of Genomic Medicine, Department of Pediatrics, MIND Institute, University of California-Davis, Sacramento, CA, United Statesf Division of Neurology, Children’s Hospital of Philadelphia, Philadelphia, PA, United Statesg Division of Pediatric Genetics, Metabolism and Genomic Medicine, Department of Pediatrics, C. S. Mott Children’s Hospital, University of Michigan, Ann Arbor, MI, United Statesh Hôpital Armand Trousseau, Service de Neurologie Pédiatrique, Paris, Francei Department of Laboratory Medicine and Genetics, Trillium Health Partners, Mississauga, ON, Canadaj Department of Neurodevelopmental Medicine, CorticaCare, San Diego, CA, United Statesk Clinical Genetic Department, Pitié Salpétrière University Hospital, Paris, Francel Division of Neurology, Department of Pediatrics, McGill University Health Centre, Montreal, Canadam Department of Mitochondrial Medicine & Genetics, Cleveland Clinic, Cleveland, OH, United Statesn Division of Genetics and Genomics, Boston Children’s Hospital; Department of Pediatrics, Harvard Medical School, Boston, MA, United Stateso Division of Genetics and Genomic Medicine, Department of Pediatrics, Washington University School of Medicine, St Louis, MO, United Statesp Clinical Genetics, Amsterdam University Medical Centers, Amsterdam, Netherlandsq Division of Neurology, Department of Pediatrics, Arkansas Children’s Hospital, Little Rock, AR, United Statesr Division of Neurology, Department of Pediatrics, Connecticut Children’s, University of Connecticut, Farmington, CT, United States
AbstractBackground: Semaphorins and plexins are ligands and cell surface receptors that regulate multiple neurodevelopmental processes such as axonal growth and guidance. PLXNA3 is a plexin gene located on the X chromosome that encodes the most widely expressed plexin receptor in fetal brain, plexin-A3. Plexin-A3 knockout mice demonstrate its role in semaphorin signaling in vivo. The clinical manifestations of semaphorin/plexin neurodevelopmental disorders have been less widely explored. This study describes the neurological and neurodevelopmental phenotypes of boys with maternally inherited hemizygous PLXNA3 variants. Methods: Data-sharing through GeneDx and GeneMatcher allowed identification of individuals with autism or intellectual disabilities (autism/ID) and hemizygous PLXNA3 variants in collaboration with their physicians and genetic counselors, who completed questionnaires about their patients. In silico analyses predicted pathogenicity for each PLXNA3 variant. Results: We assessed 14 boys (mean age, 10.7 [range 2 to 25] years) with maternally inherited hemizygous PLXNA3 variants and autism/ID ranging from mild to severe. Other findings included fine motor dyspraxia (92%), attention-deficit/hyperactivity traits, and aggressive behaviors (63%). Six patients (43%) had seizures. Thirteen boys (93%) with PLXNA3 variants showed novel or very low allele frequencies and probable damaging/disease-causing pathogenicity in one or more predictors. We found a genotype-phenotype correlation between PLXNA3 cytoplasmic domain variants (exons 22 to 32) and more severe neurodevelopmental disorder phenotypes (P < 0.05). Conclusions: We report 14 boys with maternally inherited, hemizygous PLXNA3 variants and a range of neurodevelopmental disorders suggesting a novel X-linked intellectual disability syndrome. Greater understanding of PLXNA3 variant pathogenicity in humans will require additional clinical, computational, and experimental validation. © 2021 The Author(s)
Author KeywordsAutism; Intellectual disability; Neurodevelopment; Plexin; PLXNA3; Semaphorin
Funding detailsCincinnati Children’s Hospital Medical CenterMcGill University Health CentreMUHCLiam M. Kinne FoundationSavoy Foundation
Document Type: ArticlePublication Stage: FinalSource: Scopus
“IL-4 expressing cells are recruited to nerve after injury and promote regeneration” (2022) Experimental Neurology
IL-4 expressing cells are recruited to nerve after injury and promote regeneration(2022) Experimental Neurology, 347, art. no. 113909, .
Pan, D., Schellhardt, L., Acevedo-Cintron, J.A., Hunter, D., Snyder-Warwick, A.K., Mackinnon, S.E., Wood, M.D.
Division of Plastic and Reconstructive Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, United States
AbstractInterleukin-4 (IL-4) has garnered interest as a cytokine that mediates regeneration across multiple tissues including peripheral nerve. Within nerve, we previously showed endogenous IL-4 was critical to regeneration across nerve gaps. Here, we determined a generalizable role of IL-4 in nerve injury and regeneration. In wild-type (WT) mice receiving a sciatic nerve crush, IL-4 expressing cells preferentially accumulated within the injured nerve compared to affected sites proximal, such as dorsal root ganglia (DRGs), or distal muscle. Immunohistochemistry and flow cytometry confirmed that eosinophils (CD45+, CD11b+, CD64−, Siglec-F+) were sources of IL-4 expression. Examination of targets for IL-4 within nerve revealed macrophages, as well as subsets of neurons expressed IL-4R, while Schwann cells expressed limited IL-4R. Dorsal root ganglia cultures were exposed to IL-4 and demonstrated an increased proportion of neurons that extended axons compared to cultures without IL-4 (control), as well as longer myelinated axons compared to cultures without IL-4. The role of endogenous IL-4 during nerve injury and regeneration in vivo was assessed following a sciatic nerve crush using IL-4 knockout (KO) mice. Loss of IL-4 affected macrophage accumulation within injured nerve compared to WT mice, as well as shifted macrophage phenotype towards a CD206- phenotype with altered gene expression. Furthermore, this loss of IL-4 delayed initial axon regeneration from the injury crush site and subsequently delayed functional recovery and re-innervation of neuromuscular junctions compared to wild-type mice. Given the role of endogenous IL-4 in nerve regeneration, exogenous IL-4 was administered daily to WT mice following a nerve crush to examine regeneration. Daily IL-4 administration increased early axonal extension and CD206+ macrophage accumulation but did not alter functional recovery compared to untreated mice. Our data demonstrate IL-4 promotes nerve regeneration and recovery after injury. © 2021 Elsevier Inc.
Author KeywordsFunctional recovery; IL-4; Interleukin; Macrophage; Nerve crush; Nerve regeneration; Peripheral nerve
Funding detailsNational Institutes of HealthNIHK08NS096232, R01 NS086773, R01 NS115960National Institute of Neurological Disorders and StrokeNINDS
Document Type: ArticlePublication Stage: FinalSource: Scopus
“Comparative connectomics of the primate social brain” (2021) NeuroImage
Comparative connectomics of the primate social brain(2021) NeuroImage, 245, art. no. 118693, .
Yokoyama, C.a , Autio, J.A.a , Ikeda, T.a , Sallet, J.b c , Mars, R.B.d e , Van Essen, D.C.f , Glasser, M.F.f j , Sadato, N.g h , Hayashi, T.a i
a Laboratory for Brain Connectomics Imaging, RIKEN Center for Biosystems Dynamics Research, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, 650-0047, Japanb Wellcome Centre for Integrative Neuroimaging, Department of Experimental Psychology, Oxford University, Oxford, United Kingdomc University of Lyon, Université Lyon 1, Inserm, Stem Cell and Brain Research Institute U1208, Bron, Franced Wellcome Centre for Integrative Neuroimaging, Centre for Functional MRI of the Brain (FMRIB), Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdome Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, Nijmegen, Netherlandsf Departments of Neuroscience and 7 Radiology, Washington University Medical School, St Louis, MO, United Statesg National Institute for Physiological Sciences, Okazaki, Japanh The Graduate University for Advanced Studies (SOKENDAI)Kanagawa, Japani School of Medicine, Kyoto University, Kyoto, Japanj Department of Radiology, Washington University Medical School, St Louis, MO, United States
AbstractSocial interaction is thought to provide a selection pressure for human intelligence, yet little is known about its neurobiological basis and evolution throughout the primate lineage. Recent advances in neuroimaging have enabled whole brain investigation of brain structure, function, and connectivity in humans and non-human primates (NHPs), leading to a nascent field of comparative connectomics. However, linking social behavior to brain organization across the primates remains challenging. Here, we review the current understanding of the macroscale neural mechanisms of social behaviors from the viewpoint of system neuroscience. We first demonstrate an association between the number of cortical neurons and the size of social groups across primates, suggesting a link between neural information-processing capacity and social capabilities. Moreover, by capitalizing on recent advances in species-harmonized functional MRI, we demonstrate that portions of the mirror neuron system and default-mode networks, which are thought to be important for representation of the other’s actions and sense of self, respectively, exhibit similarities in functional organization in macaque monkeys and humans, suggesting possible homologies. With respect to these two networks, we describe recent developments in the neurobiology of social perception, joint attention, personality and social complexity. Together, the Human Connectome Project (HCP)-style comparative neuroimaging, hyperscanning, behavioral, and other multi-modal investigations are expected to yield important insights into the evolutionary foundations of human social behavior. © 2021
Author KeywordsComparative connectomics; Cross-species; Neuroimaging; Primate; Social behavior
Funding detailsNational Institutes of HealthNIHANR-11-LABX-0042, R01MH118203Japan Agency for Medical Research and DevelopmentAMED21wm0525006, JP21dm0307005, JP21dm037006Wellcome TrustWT203139/Z/16/Z, R01MH060974Biotechnology and Biological Sciences Research CouncilBBSRCBB/N019814/1, IDEX/IMP/2020/14Japan Society for the Promotion of ScienceKAKEN16H01493, 18H05090, 18K06372, JP20K15945Université de LyonUDL
Document Type: ArticlePublication Stage: FinalSource: Scopus
“Synaptic Zn2+ potentiates the effects of cocaine on striatal dopamine neurotransmission and behavior” (2021) Translational Psychiatry
Synaptic Zn2+ potentiates the effects of cocaine on striatal dopamine neurotransmission and behavior(2021) Translational Psychiatry, 11 (1), art. no. 570, .
Gomez, J.L.a , Bonaventura, J.a , Keighron, J.b , Wright, K.M.a , Marable, D.L.a , Rodriguez, L.A.a , Lam, S.a , Carlton, M.L.a , Ellis, R.J.a , Jordan, C.J.c , Bi, G.-H.c , Solis, O.a , Pignatelli, M.d , Bannon, M.J.e , Xi, Z.-X.c , Tanda, G.b , Michaelides, M.a f
a Biobehavioral Imaging and Molecular Neuropsychopharmacology Unit, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD 21224, United Statesb Medication Development Program, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD 21224, United Statesc Addiction Biology Unit, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD 21224, United Statesd Department of Psychiatry and Taylor Family Institute for Innovative Psychiatric Research, Washington University School of Medicine, St Louis, MO 63110, United Statese Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI 48201, United Statesf Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States
AbstractCocaine binds to the dopamine (DA) transporter (DAT) to regulate cocaine reward and seeking behavior. Zinc (Zn2+) also binds to the DAT, but the in vivo relevance of this interaction is unknown. We found that Zn2+ concentrations in postmortem brain (caudate) tissue from humans who died of cocaine overdose were significantly lower than in control subjects. Moreover, the level of striatal Zn2+ content in these subjects negatively correlated with plasma levels of benzoylecgonine, a cocaine metabolite indicative of recent use. In mice, repeated cocaine exposure increased synaptic Zn2+ concentrations in the caudate putamen (CPu) and nucleus accumbens (NAc). Cocaine-induced increases in Zn2+ were dependent on the Zn2+ transporter 3 (ZnT3), a neuronal Zn2+ transporter localized to synaptic vesicle membranes, as ZnT3 knockout (KO) mice were insensitive to cocaine-induced increases in striatal Zn2+. ZnT3 KO mice showed significantly lower electrically evoked DA release and greater DA clearance when exposed to cocaine compared to controls. ZnT3 KO mice also displayed significant reductions in cocaine locomotor sensitization, conditioned place preference (CPP), self-administration, and reinstatement compared to control mice and were insensitive to cocaine-induced increases in striatal DAT binding. Finally, dietary Zn2+ deficiency in mice resulted in decreased striatal Zn2+ content, cocaine locomotor sensitization, CPP, and striatal DAT binding. These results indicate that cocaine increases synaptic Zn2+ release and turnover/metabolism in the striatum, and that synaptically released Zn2+ potentiates the effects of cocaine on striatal DA neurotransmission and behavior and is required for cocaine-primed reinstatement. In sum, these findings reveal new insights into cocaine’s pharmacological mechanism of action and suggest that Zn2+ may serve as an environmentally derived regulator of DA neurotransmission, cocaine pharmacodynamics, and vulnerability to cocaine use disorders. © 2021, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.
Funding detailsNational Institutes of HealthNIHU.S. Department of EnergyUSDOEDE-FG02-92ER14244National Institute on Drug AbuseNIDADA000069, DA000611
Document Type: ArticlePublication Stage: FinalSource: Scopus
“Competitive binding of E3 ligases TRIM26 and WWP2 controls SOX2 in glioblastoma” (2021) Nature Communications
Competitive binding of E3 ligases TRIM26 and WWP2 controls SOX2 in glioblastoma(2021) Nature Communications, 12 (1), art. no. 6321, .
Mahlokozera, T.a , Patel, B.a , Chen, H.a , Desouza, P.a , Qu, X.a , Mao, D.D.a , Hafez, D.a , Yang, W.b , Taiwo, R.a , Paturu, M.a , Salehi, A.a , Gujar, A.D.a , Dunn, G.P.a c d , Mosammaparast, N.c , Petti, A.A.a d e , Yano, H.a b d e , Kim, A.H.a b d e f
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 Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, United Statesd The Brain Tumor Center, Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, United Statese Department of Genetics, Washington University School of Medicine, St. Louis, MO, United Statesf Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO, United States
AbstractThe pluripotency transcription factor SOX2 is essential for the maintenance of glioblastoma stem cells (GSC), which are thought to underlie tumor growth, treatment resistance, and recurrence. To understand how SOX2 is regulated in GSCs, we utilized a proteomic approach and identified the E3 ubiquitin ligase TRIM26 as a direct SOX2-interacting protein. Unexpectedly, we found TRIM26 depletion decreased SOX2 protein levels and increased SOX2 polyubiquitination in patient-derived GSCs, suggesting TRIM26 promotes SOX2 protein stability. Accordingly, TRIM26 knockdown disrupted the SOX2 gene network and inhibited both self-renewal capacity as well as in vivo tumorigenicity in multiple GSC lines. Mechanistically, we found TRIM26, via its C-terminal PRYSPRY domain, but independent of its RING domain, stabilizes SOX2 protein by directly inhibiting the interaction of SOX2 with WWP2, which we identify as a bona fide SOX2 E3 ligase in GSCs. Our work identifies E3 ligase competition as a critical mechanism of SOX2 regulation, with functional consequences for GSC identity and maintenance. © 2021, The Author(s).
Funding detailsNational Institutes of HealthNIHP30 CA091842, R01 NS106612, R01 NS111014, R01NS051255, S10OD021629-01A1, S10OD027042National Institute of Neurological Disorders and StrokeNINDSR01 NS094670Foundation for Barnes-Jewish HospitalAlvin J. Siteman Cancer Center
Document Type: ArticlePublication Stage: FinalSource: Scopus
“Epilepsy and related challenges in children with COL4A1 and COL4A2 mutations: A Gould syndrome patient registry” (2021) Epilepsy and Behavior
Epilepsy and related challenges in children with COL4A1 and COL4A2 mutations: A Gould syndrome patient registry(2021) Epilepsy and Behavior, 125, art. no. 108365, .
Boyce, D.a , McGee, S.a , Shank, L.b c , Pathak, S.d , Gould, D.e
a Gould Syndrome Foundation, Cleveland, OH 44106, United Statesb Military Cardiovascular Outcomes Research (MiCOR) Program, Department of Medicine, Uniformed Services, University of the Health Sciences, Bethesda, MD 20814, United Statesc Metis Foundation, San Antonio, TX 78205, United Statesd Department of Neurology, Division of Pediatric and Developmental Neurology, Washington University School of Medicine, St. Louis, MO 63130, United Statese Departments of Ophthalmology and Anatomy, Institute for Human Genetics, University of California, San Francisco, School of Medicine, San Francisco, CA 94143, United States
AbstractRecently, patient advocacy groups started using the name Gould syndrome to describe clinical features of COL4A1 and COL4A2 mutations. Gould syndrome is increasingly identified in genetic screening panels, and because it is a rare disease, there is a disproportionate burden on families to understand the disease and chart the course for clinical care. Among the chief concerns for caregivers of children with Gould syndrome are the challenges faced because of epilepsy, including severe manifestations such as infantile spasms. To document the concerns of the patient population, the Gould Syndrome Foundation established the Gould Syndrome Global Registry (GSGR). Methods: The Gould Syndrome Foundation developed questions for the GSGR with iterative input from patients and caregivers. An institutional review board issued an exemption determination before data collection began. Participants were recruited through social media and clinician referrals. All participants consented electronically, and the data were collected and managed using REDCap electronic data capture tools. De-identified data representing responses received between October 2019 and February 2021 were exported and analyzed with IBM SPSS 27 using descriptive statistics (mean, standard deviation, frequency, range, and percent). Results: Seventy families from twelve countries provided data for the registry, representing 100 affected people (40 adults and 60 children). This analysis represents a subanalysis of the 35 out of 60 children <=18 years of age who reported a history of seizures. Nearly half of these participants were diagnosed with infantile spasms. Participants with epilepsy frequently reported developmental delays (88.6%), stroke (60.0%), cerebral palsy (65.7%), and constipation (57.1%). Ten (28.6%) children use a feeding tube. Despite the fact that more than half of respondents reported stroke, only 34.3% reported ever receiving education on stroke recognition. Conclusion: Here we describe the development and deployment of the first global registry for individuals and family members with Gould syndrome, caused by mutations in COL4A1 and COL4A2. It is important for pediatric neurologists to have access to resources to provide families upon diagnosis. Specifically, all families with Gould Syndrome must have access to infantile spasms awareness and stroke education materials. The Gould Syndrome Foundation is planning several improvements to this patient registry which will encourage collaboration and innovation for the benefit of people living with Gould syndrome. © 2021 Elsevier Inc.
Author KeywordsCOL4a1; COL4a2; Epilepsy; Genetic; Gould syndrome; Stroke
Document Type: ArticlePublication Stage: FinalSource: Scopus
“Demographic and mental health assessments in the adolescent brain and cognitive development study: Updates and age-related trajectories” (2021) Developmental Cognitive Neuroscience
Demographic and mental health assessments in the adolescent brain and cognitive development study: Updates and age-related trajectories(2021) Developmental Cognitive Neuroscience, 52, art. no. 101031, .
Barch, D.M.a , Albaugh, M.D.b , Baskin-Sommers, A.c , Bryant, B.E.d , Clark, D.B.e , Dick, A.S.f , Feczko, E.g , Foxe, J.J.h , Gee, D.G.i , Giedd, J.j , Glantz, M.D.k , Hudziak, J.J.l , Karcher, N.R.m , LeBlanc, K.n , Maddox, M.o , McGlade, E.C.o , Mulford, C.k , Nagel, B.J.p , Neigh, G.q , Palmer, C.E.j , Potter, A.S.r , Sher, K.J.s , Tapert, S.F.j , Thompson, W.K.t , Xie, L.j
a Departments of Psychological & Brain Sciences, Psychiatry, & Radiology, Washington University, Box 1125, One Brookings Drive, St. Louis, MO 63130, United Statesb Department of Psychiatry, University of Vermont College of Medicine, Mail Stop 446 AR6, 1 South Prospect Street, Burlington, VT 05401, United Statesc Department of Psychology, Yale University, P.O. Box 208205, New Haven, CT 06520, United Statesd Department of Psychiatry and Behavioral Science, Medical University of South Carolina, 171 Ashley Avenue, Charleston, SC 29425, United Statese Department of Psychiatry, University of Pittsburgh, 3811O’Hara Street, Pittsburgh, PA 15215, United Statesf Department of Psychology, Florida International University, 11200 SW 8th Street, DM 256, Miami, FL 33199, United Statesg Masonic Institute for the Developing Brain, University of Minnesota, 717 Delaware SE St, Minneapolis, MN 55414, United Statesh The Del Monte Institute for Neuroscience, Department of Neuroscience, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, United Statesi Department of Psychology, Yale University, 216 Kirtland Hall, New Haven, CT 06520, United Statesj Department of Psychiatry, University of California at San Diego, 9500 Gilman Drive (0603), La Jolla, CA 92093-0603, United Statesk Department of Epidemiology, Services, and Prevention Research, National Institute on Drug Abuse, National Institutes of Health, Bethesda, MD 20892, United Statesl Department of Psychiatry, University of Vermont College of Medicine, St. Joe’s Room 3213, Box 364SJ, 1 South Prospect, Burlington, VT 05401, United Statesm Department of Psychiatry, Washington University, 660 South Euclid Avenue, St. Louis, MO 63110, United Statesn Division of Extramural Research, National Institute on Drug Abuse, Kimberly, United Stateso Department of Psychiatry, University of Utah School of Medicine, 501 Chipeta Way, Salt Lake City, UT 84108, United Statesp Departments of Psychiatry and Behavioral Neuroscience, Oregon Health & Science University, 3181 SW Sam Jackson Park Road UHN-80R1, Portland, OR 97239, United Statesq Department of Anatomy and Neurobiology, Virginia Commonwealth University, 1101 East Marschall Street, Box 980709, Richmond, VA 23298, United Statesr Department of Psychiatry, University of Vermont College of Medicine, 1 South Prospect Street Arnold 6, Burlington, VT 05401, United Statess Department of Psychological Sciences, University of Missouri, 200 South Seventh Street, Columbia, MO 65211, United Statest Population Neuroscience and Genetics Lab, Herbert Wertheim School of Public Health, University of California at San Diego, 9500 Gilman Drive (0603), La Jolla, CA 92093-0603, United States
AbstractThe Adolescent Brain Cognitive Development (ABCD) Study of 11,880 youth incorporates a comprehensive range of measures assessing predictors and outcomes related to mental health across childhood and adolescence in participating youth, as well as information about family mental health history. We have previously described the logic and content of the mental health assessment battery at Baseline and 1-year follow-up. Here, we describe changes to that battery and issues and clarifications that have emerged, as well as additions to the mental health battery at the 2-, 3-, 4-, and 5-year follow-ups. We capitalize on the recent release of longitudinal data for caregiver and youth report of mental health data to evaluate trajectories of dimensions of psychopathology as a function of demographic factors. For both caregiver and self-reported mental health symptoms, males showed age-related decreases in internalizing and externalizing symptoms, while females showed an increase in internalizing symptoms with age. Multiple indicators of socioeconomic status (caregiver education, family income, financial adversity, neighborhood poverty) accounted for unique variance in both caregiver and youth-reported externalizing and internalizing symptoms. These data highlight the importance of examining developmental trajectories of mental health as a function of key factors such as sex and socioeconomic environment. © 2021 The Authors
Author KeywordsAssessment; Longitudinal assessment; Mental health; Psychopathology
Funding detailsNational Institutes of HealthNIH1RF1MH120025, K05AA017242, U01DA041022, U01DA041028, U01DA041048, U01DA041089, U01DA041106, U01DA041117, U01DA041120, U01DA041134, U01DA041148, U01DA041156, U01DA041174, U01DA050988, U24DA041123, U24DA041147U.S. Department of Health and Human ServicesHHSNational Institute of Mental HealthNIMH
Document Type: ArticlePublication Stage: FinalSource: Scopus
“TSC1 loss increases risk for tauopathy by inducing tau acetylation and preventing tau clearance via chaperone-mediated autophagy” (2021) Science Advances
TSC1 loss increases risk for tauopathy by inducing tau acetylation and preventing tau clearance via chaperone-mediated autophagy(2021) Science Advances, 7 (45), art. no. eabg3897, .
Alquezar, C.a , Schoch, K.M.b , Geier, E.G.c , Ramos, E.M.d , Scrivo, A.e , Li, K.H.f , Argouarch, A.R.a , Mlynarski, E.E.g , Dombroski, B.g , DeTure, M.h , Dickson, D.W.h , Yokoyama, J.S.c , Cuervo, A.M.e , Burlingame, A.L.f , Schellenberg, G.D.g , Miller, T.M.b , Miller, B.L.a , Kao, A.W.a
a UCSF Memory and Aging Center, Department of Neurology, University of California San Francisco, San Francisco, CA 94158, United Statesb Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, United Statesc Depart-ment of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA 94143, United Statesd Department of Neurology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, United Statese Institute for Aging Research, Albert Einstein College of Medicine, New York, NY 10461, United Statesf Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA 94158, United Statesg Department of Pathology and Laboratory Medicine, Penn Neurodegeneration Genomics Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-4238, United Statesh Depart-ment of Neuroscience, The Mayo Clinic Florida, 4500 San Pablo Road, Jacksonville, FL 32224, United States
AbstractAge-associated neurodegenerative disorders demonstrating tau-laden intracellular inclusions are known as tauopathies. We previously linked a loss-of-function mutation in the TSC1 gene to tau accumulation and frontotemporal lobar degeneration. Now, we have identified genetic variants in TSC1 that decrease TSC1/hamartin levels and predispose to tauopathies such as Alzheimer’s disease and progressive supranuclear palsy. Cellular and murine models of TSC1 haploinsufficiency, as well as human brains carrying a TSC1 risk variant, accumulated tau protein that exhibited aberrant acetylation. This acetylation hindered tau degradation via chaperone-mediated autophagy, thereby leading to its accumulation. Aberrant tau acetylation in TSC1 haploinsufficiency resulted from the dysregulation of both p300 acetyltransferase and SIRT1 deacetylase. Pharmacological modulation of either enzyme restored tau levels. This study substantiates TSC1 as a novel tauopathy risk gene and includes TSC1 haploinsufficiency as a genetic model for tauopathies. In addition, these findings promote tau acetylation as a rational target for tauopathy therapeutics and diagnostic. Copyright © 2021 The Authors, some rights reserved;
Document Type: ArticlePublication Stage: FinalSource: Scopus
“Neuronal activity in dorsal anterior cingulate cortex during economic choices under variable action costs” (2021) eLife
Neuronal activity in dorsal anterior cingulate cortex during economic choices under variable action costs(2021) eLife, 10, art. no. e71695, .
Cai, X.a b c d , Padoa-Schioppa, C.a e f
a Department of Neuroscience, Washington University in St Louis, Saint Louis, United Statesb NYU Shanghai, Shanghai, Chinac Shanghai Key Laboratory of Brain Functional Genomics (Ministry of Education), School of Psychology and Cognitive Science, East China Normal University, Shanghai, Chinad NYU-ECNU Institute of Brain and Cognitive Science, NYU Shanghai, Shanghai, Chinae Departments of Economics, Washington University in St Louis, St Louis, Chinaf Biomedical Engineering, Washington University in St Louis, St Louis, China
AbstractThe role of the dorsal anterior cingulate cortex (ACCd) in decision making has often been discussed but remains somewhat unclear. On the one hand, numerous studies implicated this area in decisions driven by effort or action cost. On the other hand, work on economic choices between goods (under fixed action costs) found that neurons in ACCd encoded only post-decision variables. To advance our understanding of the role played by this area in decision making, we trained monkeys to choose between different goods (juice types) offered in variable amounts and with different action costs. Importantly, the task design dissociated computation of the action cost from planning of any particular action. Neurons in ACCd encoded the chosen value and the binary choice outcome in several reference frames (chosen juice, chosen cost, chosen action). Thus, this area provided a rich representation of post-decision variables. In contrast to the OFC, neurons in ACCd did not represent pre-decision variables such as individual offer values in any reference frame. Hence, ongoing decisions are unlikely guided by ACCd. Conversely, neuronal activity in this area might inform subsequent actions. © Cai and Padoa-Schioppa.
Funding detailsNational Natural Science Foundation of ChinaNSFC
Document Type: ArticlePublication Stage: FinalSource: Scopus
“Mechanical overstimulation causes acute injury and synapse loss followed by fast recovery in lateral-line neuromasts of larval zebrafish” (2021) eLife
Mechanical overstimulation causes acute injury and synapse loss followed by fast recovery in lateral-line neuromasts of larval zebrafish(2021) eLife, 10, art. no. e69264, .
Holmgren, M.a , Ravicz, M.E.b c , Hancock, K.E.b c , Strelkova, O.b c , Kallogjeri, D.a , Indzhykulian, A.A.b c , Warchol, M.E.a d , Sheets, L.a e
a Department of Otolaryngology, Washington University School of Medicine, St Louis, United Statesb Eaton-Peabody Laboratory, Massachusetts Eye and Ear, Boston, United Statesc Department of Otolaryngology-Head and Neck Surgery, Harvard Medical School, Boston, United Statesd Department of Neuroscience, Washington University School of Medicine, St Louis, United Statese Department of Developmental Biology, Washington University School of Medicine, St. Louis, United States
AbstractExcess noise damages sensory hair cells, resulting in loss of synaptic connections with auditory nerves and, in some cases, hair-cell death. The cellular mechanisms underlying mechani¬cally induced hair-cell damage and subsequent repair are not completely understood. Hair cells in neuromasts of larval zebrafish are structurally and functionally comparable to mammalian hair cells but undergo robust regeneration following ototoxic damage. We therefore developed a model for mechanically induced hair-cell damage in this highly tractable system. Free swimming larvae exposed to strong water wave stimulus for 2 hr displayed mechanical injury to neuromasts, including afferent neurite retraction, damaged hair bundles, and reduced mechanotransduction. Synapse loss was observed in apparently intact exposed neuromasts, and this loss was exacerbated by inhibiting glutamate uptake. Mechanical damage also elicited an inflammatory response and macrophage recruitment. Remarkably, neuromast hair-cell morphology and mechanotransduction recovered within hours following exposure, suggesting severely damaged neuromasts undergo repair. Our results indicate functional changes and synapse loss in mechanically damaged lateral-line neuro¬masts that share key features of damage observed in noise-exposed mammalian ear. Yet, unlike the mammalian ear, mechanical damage to neuromasts is rapidly reversible. © Holmgren et al.
Funding detailsNational Institute on Deafness and Other Communication DisordersNIDCDR01DC006283, R01DC016066, R01DC017166Amelia Peabody Charitable FundAPCFWashington University in St. LouisWUSTLMassachusetts Eye and EarMEE
Document Type: ArticlePublication Stage: FinalSource: Scopus
“Predicting audiovisual word recognition in noisy situations: Toward precision audiology” (2021) Ear and Hearing
Predicting audiovisual word recognition in noisy situations: Toward precision audiology(2021) Ear and Hearing, pp. 1656-1667.
Myerson, J.a , Tye-Murray, N.b , Spehar, B.b , Hale, S.a , Sommers, M.a
a Department of Psychological and Brain Sciences, Washington University, Saint Louis, MO, United Statesb Department of Otolaryngology, Washington University, School of Medicine, Saint Louis, MO, United States
AbstractObjective: Spoken communication is better when one can see as well as hear the talker. Although age-related deficits in speech perception were observed, Tye-Murray and colleagues found that even when age-related deficits in audiovisual (AV) speech perception were observed, AV performance could be accurately predicted from auditory-only (A-only) and visual-only (V-only) performance, and that knowing individuals’ ages did not increase the accuracy of prediction. This finding contradicts conventional wisdom, according to which age-related differences in AV speech perception are due to deficits in the integration of auditory and visual information, and our primary goal was to determine whether Tye-Murray et al.’s finding with a closed-set test generalizes to situations more like those in everyday life. A second goal was to test a new predictive model that has important implications for audiological assessment. Design: Participants (N = 109; ages 22-93 years), previously studied by Tye-Murray et al., were administered our new, open-set Lex-List test to assess their auditory, visual, and audiovisual perception of individual words. All testing was conducted in six-talker babble (three males and three females) presented at approximately 62 dB SPL. The level of the audio for the Lex-List items, when presented, was approximately 59 dB SPL because pilot testing suggested that this signal-to-noise ratio would avoid ceiling performance under the AV condition. Results: Multiple linear regression analyses revealed that A-only and V-only performance accounted for 87.9% of the variance in AV speech perception, and that the contribution of age failed to reach significance. Our new parabolic model accounted for even more (92.8%) of the variance in AV performance, and again, the contribution of age was not significant. Bayesian analyses revealed that for both linear and parabolic models, the present data were almost 10 times as likely to occur with a reduced model (without age) than with a full model (with age as a predictor). Furthermore, comparison of the two reduced models revealed that the data were more than 100 times as likely to occur with the parabolic model than with the linear regression model. Conclusions: The present results strongly support Tye-Murray et al.’s hypothesis that AV performance can be accurately predicted from unimodal performance and that knowing individuals’ ages does not increase the accuracy of that prediction. Our results represent an important initial step in extending Tye-Murray et al.’s findings to situations more like those encountered in everyday communication. The accuracy with which speech perception was predicted in this study foreshadows a form of precision audiology in which determining individual strengths and weaknesses in unimodal and multimodal speech perception facilitates identification of targets for rehabilitative efforts aimed at recovering and maintaining speech perception abilities critical to the quality of an older adult’s life. © 2021 Wolters Kluwer Health, Inc.
Author KeywordsAging and speech perception; Audiovisual speech perception; Speech perception modeling
Funding detailsNational Institutes of HealthNIH
Document Type: ArticlePublication Stage: Article in PressSource: Scopus
“The addiction risk factor: A unitary genetic vulnerability characterizes substance use disorders and their associations with common correlates” (2021) Neuropsychopharmacology
The addiction risk factor: A unitary genetic vulnerability characterizes substance use disorders and their associations with common correlates(2021) Neuropsychopharmacology, .
Hatoum, A.S.a , Johnson, E.C.a , Colbert, S.M.C.a , Polimanti, R.b c , Zhou, H.b c , Walters, R.K.d e , Gelernter, J.b c f g , Edenberg, H.J.h i , Bogdan, R.j , Agrawal, A.a
a Washington University School of Medicine, Department of Psychiatry, Saint Louis, MO, United Statesb Department of Psychiatry, Division of Human Genetics, Yale School of Medicine, New Haven, CT, United Statesc Veterans Affairs Connecticut Healthcare System, West Haven, CT, United Statesd Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United Statese Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, United Statesf Department of Genetics, Yale School of Medicine, New Haven, CT, United Statesg Department of Neuroscience, Yale School of Medicine, New Haven, CT, United Statesh Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, United Statesi Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, United Statesj Department of Psychological & Brain Sciences, Washington University in St. Louis, St. Louis, MO, United States
AbstractSubstance use disorders commonly co-occur with one another and with other psychiatric disorders. They share common features including high impulsivity, negative affect, and lower executive function. We tested whether a common genetic factor undergirds liability to problematic alcohol use (PAU), problematic tobacco use (PTU), cannabis use disorder (CUD), and opioid use disorder (OUD) by applying genomic structural equation modeling to genome-wide association study summary statistics for individuals of European ancestry (Total N = 1,019,521; substance-specific Ns range: 82,707–435,563) while adjusting for the genetics of substance use (Ns = 184,765−632,802). We also tested whether shared liability across SUDs is associated with behavioral constructs (risk-taking, executive function, neuroticism; Ns = 328,339−427,037) and non-substance use psychopathology (psychotic, compulsive, and early neurodevelopmental disorders). Shared genetic liability to PAU, PTU, CUD, and OUD was characterized by a unidimensional addiction risk factor (termed The Addiction-Risk-Factor, independent of substance use. OUD and CUD demonstrated the largest loadings, while problematic tobacco use showed the lowest loading. The Addiction-Risk-Factor was associated with risk-taking, neuroticism, executive function, and non-substance psychopathology, but retained specific variance before and after accounting for the genetics of substance use. Thus, a common genetic factor partly explains susceptibility for alcohol, tobacco, cannabis, and opioid use disorder. The Addiction-Risk-Factor has a unique genetic architecture that is not shared with normative substance use or non-substance psychopathology, suggesting that addiction is not the linear combination of substance use and psychopathology. © 2021, The Author(s), under exclusive licence to American College of Neuropsychopharmacology.
Funding detailsNational Institute of Mental HealthNIMHNational Institute on Drug AbuseNIDAU.S. Department of Veterans AffairsVAOffice of Research and DevelopmentORDHealth Services Research and DevelopmentHSR&D
Document Type: ArticlePublication Stage: Article in PressSource: Scopus
“Genome-wide association study of problematic opioid prescription use in 132,113 23andMe research participants of European ancestry” (2021) Molecular Psychiatry
Genome-wide association study of problematic opioid prescription use in 132,113 23andMe research participants of European ancestry(2021) Molecular Psychiatry, .
Sanchez-Roige, S.a b , Fontanillas, P.c , Jennings, M.V.a , Bianchi, S.B.a , Huang, Y.a , Hatoum, A.S.d , Sealock, J.b , Davis, L.K.b e f , Elson, S.L.c , Agee, M.c , Alipanahi, B.c , Auton, A.c , Bell, R.K.c , Bryc, K.c , Furlotte, N.A.c , Hinds, D.A.c , Huber, K.E.c , Kleinman, A.c , Litterman, N.K.c , McCreight, J.C.c , McIntyre, M.H.c , Mountain, J.L.c , Noblin, E.S.c , Northover, C.A.M.c , Pitts, S.J.c , Sathirapongsasuti, J.F.c , Sazonova, O.V.c , Shelton, J.F.c , Shringarpure, S.c , Tian, C.c , Tung, J.Y.c , Vacic, V.c , Wilson, C.H.c , Palmer, A.A.a g , 23andMe Research Teamh
a Department of Psychiatry, University of California San Diego, San Diego, CA, United Statesb Department of Medicine, Division of Genetic Medicine, Vanderbilt University, Nashville, TN, United Statesc 23andMe, Inc., Sunnyvale, CA, United Statesd Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United Statese Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, TN, United Statesf Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, United Statesg Institute for Genomic Medicine, University of California San Diego, San Diego, CA, United States
AbstractThe growing prevalence of opioid use disorder (OUD) constitutes an urgent health crisis. Ample evidence indicates that risk for OUD is heritable. As a surrogate (or proxy) for OUD, we explored the genetic basis of using prescription opioids ‘not as prescribed’. We hypothesized that misuse of opiates might be a heritable risk factor for OUD. To test this hypothesis, we performed a genome-wide association study (GWAS) of problematic opioid use (POU) in 23andMe research participants of European ancestry (N = 132,113; 21% cases). We identified two genome-wide significant loci (rs3791033, an intronic variant of KDM4A; rs640561, an intergenic variant near LRRIQ3). POU showed positive genetic correlations with the two largest available GWAS of OUD and opioid dependence (rg = 0.64, 0.80, respectively). We also identified numerous additional genetic correlations with POU, including alcohol dependence (rg = 0.74), smoking initiation (rg = 0.63), pain relief medication intake (rg = 0.49), major depressive disorder (rg = 0.44), chronic pain (rg = 0.42), insomnia (rg = 0.39), and loneliness (rg = 0.28). Although POU was positively genetically correlated with risk-taking (rg = 0.38), conditioning POU on risk-taking did not substantially alter the magnitude or direction of these genetic correlations, suggesting that POU does not simply reflect a genetic tendency towards risky behavior. Lastly, we performed phenome- and lab-wide association analyses, which uncovered additional phenotypes that were associated with POU, including respiratory failure, insomnia, ischemic heart disease, and metabolic and blood-related biomarkers. We conclude that opioid misuse can be measured in population-based cohorts and provides a cost-effective complementary strategy for understanding the genetic basis of OUD. © 2021, The Author(s).
Funding detailsNational Institutes of HealthNIHS10RR025141, UL1RR024975, UL1TR000445, UL1TR002243National Institute on Drug AbuseNIDA1F31MH124306–01A1, DP1DA054394, K02AA018755, P50AA022537, R01DA050721, T32DA007261, U10AA008401National Institute on Alcohol Abuse and AlcoholismNIAAAR01AA015416Tobacco-Related Disease Research ProgramTRDRP28IR-0070, P50DA037844, T29KT0526Vanderbilt University Medical CenterVUMCEuropean Research CouncilERC647648 EdGe
Document Type: ArticlePublication Stage: Article in PressSource: Scopus
“Motivation and Cognitive Abilities as Mediators Between Polygenic Scores and Psychopathology in Children” (2021) Journal of the American Academy of Child and Adolescent Psychiatry
Motivation and Cognitive Abilities as Mediators Between Polygenic Scores and Psychopathology in Children(2021) Journal of the American Academy of Child and Adolescent Psychiatry, .
Pat, N.a , Riglin, L.b , Anney, R.b , Wang, Y.a , Barch, D.M.c , Thapar, A.b , Stringaris, A.d
a University of Otago, Dunedin, New Zealandb Cardiff University, Wales, United Kingdomc Washington University in St. LouisMO, United Statesd National Institute of Mental Health, Bethesda, MD, United States
AbstractObjective: Fundamental questions in biological psychiatry concern the mechanisms that mediate between genetic liability and psychiatric symptoms. Genetic liability for many common psychiatric disorders often confers transdiagnostic risk to develop a wide variety of psychopathological symptoms through yet unknown pathways. This study examined the psychological and cognitive pathways that might mediate the relationship between genetic liability (indexed by polygenic scores; PS) and broad psychopathology (indexed by p factor and its underlying dimensions). Method: First, which of the common psychiatric PSs (major depressive disorder [MDD], attention-deficit/hyperactivity disorder [ADHD], anxiety, bipolar disorder, schizophrenia, autism) that were associated with p factor were identified. Then focused was shifted to 3 pathways: punishment sensitivity (reflected by behavioral inhibition system), reward sensitivity (reflected by behavioral activation system), and cognitive abilities (reflected by g factor based on 10 neurocognitive tasks). We applied structural equation modeling on the Adolescent Brain Cognitive Development (ABCD) Study dataset (n = 4,814; 2,263 girls; 9–10 years old). Results: MDD and ADHD PSs were associated with p factor. The association between MDD PS and psychopathology was partially mediated by punishment sensitivity and cognitive abilities (proportion mediated = 22.35%). Conversely, the influence of ADHD PS on psychopathology was partially mediated by reward sensitivity and cognitive abilities (proportion mediated = 30.04%). The mediating role of punishment sensitivity was specific to emotional/internalizing. The mediating role of both reward sensitivity and cognitive abilities was specific to behavioral/externalizing and neurodevelopmental dimensions of psychopathology. Conclusion: This study provides a better understanding of how genetic risks for MDD and ADHD confer risks for psychopathology and suggests potential prevention/intervention targets for children at risk. © 2021 American Academy of Child and Adolescent Psychiatry
Author KeywordsADHD; Adolescent Brain Cognitive Development; MDD; polygenic score; transdiagnostic psychopathology
Funding detailsNational Institutes of HealthNIHU01DA041022, U01DA041025, U01DA041028, U01DA041048, U01DA041089, U01DA041093, U01DA041106, U01DA041117, U01DA041120, U01DA041134, U01DA041148, U01DA041156, U01DA041174, U24DA041123, U24DA041147National Institute of Mental HealthNIMHOtago Medical Research FoundationOMRF
Document Type: ArticlePublication Stage: Article in PressSource: Scopus
“Calibrating temper loss severity in the transition to toddlerhood: Implications for developmental science” (2021) Applied Developmental Science
Calibrating temper loss severity in the transition to toddlerhood: Implications for developmental science(2021) Applied Developmental Science, .
Krogh-Jespersen, S.a , Kaat, A.J.a , Petitclerc, A.b , Perlman, S.B.c , Briggs-Gowan, M.J.d , Burns, J.L.a , Adam, H.a , Nili, A.a , Gray, L.a e , Wakschlag, L.S.a
a Northwestern University, United Statesb Universite Laval, Canadac Washington University School of Medicine, United Statesd University of Connecticut Health Center, United Statese Ann and Robert H. Lurie Children’s Hospital of Chicago, United States
AbstractThe integration of neurodevelopmental perspectives into clinical science has identified irritability as an early dimensional marker of lifespan mental health risk. Elucidating the developmental patterning of irritable behavior is key to differentiating normative variation from risk markers. Accounting for dysregulation and contextual features of irritability is useful for differentiation at preschool age, laying the groundwork for even earlier characterization. We provide initial evidence for the validity of the Multidimensional Assessment Profile of Disruptive Behavior Temper Loss Scale, Infant-Toddler version in two independent samples of 12-18-month-olds from the US. We calibrated the measure using item response theory in a large representative sample, then validated within an independent sample. We characterized the developmental patterning of irritable behaviors and their dimensional spectrum, and demonstrated test-retest reliability, and convergent validity. The MAP-DB-IT is a standardized, dimensional survey assessing irritability that serves as a tool for characterizing the developmental expression of early mental health risk. © 2021 Taylor & Francis Group, LLC.
Document Type: ArticlePublication Stage: Article in PressSource: Scopus
“Evaluating chronotypically tailored light therapy for breast cancer survivors: Preliminary findings on fatigue and disrupted sleep” (2021) Chronobiology International
Evaluating chronotypically tailored light therapy for breast cancer survivors: Preliminary findings on fatigue and disrupted sleep(2021) Chronobiology International, .
Wu, H.-S.a , Gao, F.b , Yan, L.c , Given, C.a
a College of Nursing, Michigan State University, East Lansing, MI, United Statesb Division of Public Health Sciences, Washington University School of Medicine, St. Louis, MO, United Statesc Department of Psychology, Michigan State University, East Lansing, MI, United States
AbstractMore than one-third of cancer survivors experience significant residual symptoms after treatment completion. Fatigue and sleep disruption often co-occur and exacerbate each other. The purpose of this preliminary analysis was to examine the effect of a chronotypically tailored light therapy on fatigue and sleep disruption in female survivors 1–3 years post-completion of chemotherapy and/or radiation for stage I to III breast cancer. The data for this analysis were collected as part of an ongoing two-group randomized controlled trial (NCT03304587). Participants were randomized to receive either bright blue-green light (experimental) or dim red light (control). Light therapy was self-administered using a light visor cap at home. Both groups received 30-min daily light therapy for 14 consecutive days either between 19:00 and 20:00 h (for morning chronotypes) or within 30 min of waking in the morning (for evening chronotypes). Fatigue and sleep quality were self-reported using the Patient-Reported Outcomes Measurement Information System (PROMIS)-Fatigue, PROMIS-Sleep Disturbance, Pittsburgh Sleep Quality Index, and a daily log before (pre-test) and following the light intervention (post-test). Linear mixed model analysis or generalized estimating equations examined group difference overtime adjusting for pre-test scores. No between-group differences were found. However, after adjusting for the baseline fatigue, the experimental group reported significant decreases in fatigue (p < .001) and sleep disturbance (p = .024) overtime. The experimental group also reported significantly better subjective sleep quality after 14 d of light therapy (p = .017). Positive trends in sleep latency, sleep duration, night-time awakenings, and early morning awakenings were also observed. Unexpectedly, sleep disturbance significantly decreased in the control group (p = .030). Those who received dim light control reported significantly shorter sleep latency (p = .002), longer total sleep time (p = .042), and greater habitual sleep efficiency (p = .042). These findings suggest that bright light therapy significantly improved post-treatment fatigue and subjective sleep quality in breast cancer survivors. Although it remains to be confirmed, the findings additionally show unexpected benefits of dim light on sleep. Properly timed light exposure may optimize the therapeutic effect and can be the key for successful light therapy. How the administration timing coupled with wavelengths (short vs. long) and intensity of light affecting fatigue and disrupted sleep requires further investigation. © 2021 Taylor & Francis Group, LLC.
Author Keywordscancer survivors; chronotype; fatigue; Light therapy; sleep quality
Document Type: ArticlePublication Stage: Article in PressSource: Scopus
“Depression and Inflammatory Markers in Veterans With Multiple Sclerosis” (2021) Biological Research for Nursing
Depression and Inflammatory Markers in Veterans With Multiple Sclerosis(2021) Biological Research for Nursing, .
Newland, P.a , Basan, Y.a , Chen, L.b , Wu, G.b
a Goldfarb School of Nursing at Barnes-Jewish College, Saint Louis, MO, United Statesb Washington University in St Louis, Saint Louis, MO, United States
AbstractMultiple sclerosis (MS), an inflammatory neurodegenerative disease of the central nervous system (CNS), afflicts over one per thousand people in the United States. The pathology of MS typically involves lesions in several regions, including the brain and spinal cord. The manifestation of MS is variable and carries great potential to negatively impact quality of life (QOL). Evidence that inflammatory markers are related to depression in MS is accumulating. However, there are barriers in precisely identifying the biological mechanisms underlying depression and inflammation. Analysis of cytokines provides one promising approach for understanding the mechanisms that may contribute to MS symptoms. Methods: In this pilot study, we measured salivary levels of interleukin (IL)-6, IL-1beta (β), and IL-10 in 24 veterans with MS. Descriptive statistics were reported and Pearson correlation coefficients were obtained between cytokines and depression. Results: The anti-inflammatory cytokine IL-10 was significantly negatively associated with depression in veterans with MS (r = −0.47, p =.024). Conclusion: Cytokines may be useful for elucidating biological mechanisms associated with the depression and a measure for nurses caring for veterans with MS. © The Author(s) 2021.
Author Keywordsdepression; inflammatory markers; multiple sclerosis; veterans
Funding detailsUniversity of WashingtonUW
Document Type: ArticlePublication Stage: Article in PressSource: Scopus
“Infant vocalizing and phenotypic outcomes in autism: Evidence from the first 2 years” (2021) Child Development
Infant vocalizing and phenotypic outcomes in autism: Evidence from the first 2 years(2021) Child Development, .
Plate, S.a b , Yankowitz, L.a c , Resorla, L.d , Swanson, M.R.e , Meera, S.S.f , Estes, A.g , Marrus, N.h , Cola, M.a , Petrulla, V.a , Faggen, A.a , Pandey, J.a i , Paterson, S.j , Pruett, J.R., Jr.h , Hazlett, H.k , Dager, S.g , St. John, T.g , Botteron, K.h , Zwaigenbaum, L.l , Piven, J.k , Schultz, R.T.a i , Parish-Morris, J.a i , IBIS Networkm
a Center for Autism Research, Children’s Hospital of Philadelphia, Philadelphia, PA, United Statesb Department of Psychology, University of Pittsburgh, Pittsburgh, PA, United Statesc Department of Psychology, University of Pennsylvania, Philadelphia, PA, United Statesd Bryn Mawr College, Bryn Mawr, PA, United Statese University of Texas at Dallas, Richardson, TX, United Statesf National Institute of Mental Health and Neurosciences, Bangalore, Indiag Department of Speech and Hearing Sciences, University of Washington, Seattle, WA, United Statesh Department of Psychiatry, Washington University School of Medicine, Saint Louis, MO, United Statesi Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United Statesj The James S. McDonnel Foundation, Saint Louis, MO, United Statesk University of North Carolina, Chapel Hill, NC, United Statesl Department of Pediatrics, University of Alberta, Edmonton, AB, Canada
AbstractInfant vocalizations are early-emerging communicative markers shown to be atypical in autism spectrum disorder (ASD), but few longitudinal, prospective studies exist. In this study, 23,850 infant vocalizations from infants at low (LR)- and high (HR)-risk for ASD (HR-ASD = 23, female = 3; HR-Neg = 35, female = 13; LR = 32, female = 10; 80% White; collected from 2007 to 2017 near Philadelphia) were analyzed at 6, 12, and 24 months. At 12 months, HR-ASD infants produced fewer vocalizations than HR-Neg infants. From 6 to 24 months, HR-Neg infants demonstrated steeper vocalization growth compared to HR-ASD and LR infants. Finally, among HR infants, vocalizing at 12 months was associated with language, social phenotype, and diagnosis at age 2. Infant vocalizing is an objective behavioral marker that could facilitate earlier detection of ASD. © 2021 The Authors. Child Development © 2021 Society for Research in Child Development
Funding detailsNational Institute of Mental HealthNIMH1R01MH118362‐01National Institute on Deafness and Other Communication DisordersNIDCD1R03DC017944National Institute of Child Health and Human DevelopmentNICHD5R01HD055741‐14, U54HD086984Simons FoundationSFAutism Science FoundationASF19‐006Allen Foundation
Document Type: ArticlePublication Stage: Article in PressSource: Scopus