WashU weekly Neuroscience publications

Visualizing the Heterogeneity of Retinal Microglia
(2019) Immunity, . 

Lin, J.B.^a , Apte, R.S.^{a b c}

^a Department of Ophthalmology & Visual Sciences, Washington University School of Medicine, St. Louis, MO, United States
^b Department of Medicine, Washington University School of Medicine, St. Louis, MO, United States
^c Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO, United States

Abstract
In this issue of Immunity, O’Koren et al. (2019) report that murine retinal microglia are long lived and are divided into two spatially and functionally distinct niches in the retina. In models of retinal neurodegeneration, retinal microglia migrate to the subretinal space, an inducible disease-associated niche, where they are neuroprotective. © 2019 Elsevier Inc.

In this issue of Immunity, O’Koren et al. (2019) report that murine retinal microglia are long lived and are divided into two spatially and functionally distinct niches in the retina. In models of retinal neurodegeneration, retinal microglia migrate to the subretinal space, an inducible disease-associated niche, where they are neuroprotective. © 2019 Elsevier Inc.

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

Identification of common genetic risk variants for autism spectrum disorder
(2019) Nature Genetics, . Cited 1 time.

Grove, J.^{a b c d} , Ripke, S.^{e f g} , Als, T.D.^{a b c} , Mattheisen, M.^{a b c h i} , Walters, R.K.^{e f} , Won, H.^{j k} , Pallesen, J.^{a b c} , Agerbo, E.^{a l m} , Andreassen, O.A.^{n o} , Anney, R.^p , Awashti, S.^g , Belliveau, R.^f , Bettella, F.^{n o} , Buxbaum, J.D.^{q r s t} , Bybjerg-Grauholm, J.^{a u} , Bækvad-Hansen, M.^{a u} , Cerrato, F.^f , Chambert, K.^f , Christensen, J.H.^{a b c} , Churchhouse, C.^{e f v} , Dellenvall, K.^w , Demontis, D.^{a b c} , De Rubeis, S.^{q r} , Devlin, B.^x , Djurovic, S.^{n y} , Dumont, A.L.^f , Goldstein, J.I.^{e f v} , Hansen, C.S.^{a u z} , Hauberg, M.E.^{a b c} , Hollegaard, M.V.^{a u} , Hope, S.^{n aa} , Howrigan, D.P.^{e f} , Huang, H.^{e f} , Hultman, C.M.^w , Klei, L.^x , Maller, J.^{f ab ac} , Martin, J.^{f p w} , Martin, A.R.^{e f v} , Moran, J.L.^f , Nyegaard, M.^{a b c} , Nærland, T.^{n ad} , Palmer, D.S.^{e f} , Palotie, A.^{e f v ae} , Pedersen, C.B.^{a l m} , Pedersen, M.G.^{a l m} , dPoterba, T.^{e f v} , Poulsen, J.B.^{a u} , Pourcain, B.S.^{af ag ah} , Qvist, P.^{a b c} , Rehnström, K.^ai , Reichenberg, A.^{q r s} , Reichert, J.^{q r} , Robinson, E.B.^{e f aj} , Roeder, K.^{ak al} , Roussos, P.^{r am an ao} , Saemundsen, E.^ap , Sandin, S.^{q r w} , Satterstrom, F.K.^{e f v} , Davey Smith, G.^{ag aq} , Stefansson, H.^ar , Steinberg, S.^ar , Stevens, C.R.^f , Sullivan, P.F.^{j w as} , Turley, P.^{e f} , Walters, G.B.^{ar at} , Xu, X.^{q r} , Wray, N.R.^{ba bb} , Trzaskowski, M.^ba , Byrne, E.M.^ba , Abdellaoui, A.^bc , Adams, M.J.^bd , Air, T.M.^be , Andlauer, T.F.M.^{bf bg} , Bacanu, S.-A.^bh , Beekman, A.T.F.^bi , Bigdeli, T.B.^{bh bj} , Binder, E.B.^{bf bk} , Blackwood, D.H.R.^bd , Bryois, J.^w , Buttenschøn, H.N.^{a b bl} , Cai, N.^{bm bn} , Castelao, E.^bo , Clarke, T.-K.^bd , Coleman, J.R.I.^bp , Colodro-Conde, L.^bq , Couvy-Duchesne, B.^{br bs} , Craddock, N.^bt , Crawford, G.E.^{bu bv} , Davies, G.^bw , Deary, I.J.^bw , Degenhardt, F.^{bx by} , Derks, E.M.^bq , Direk, N.^{bz ca} , Dolan, C.V.^bc , Dunn, E.C.^{f cb cc} , Eley, T.C.^bp , Escott-Price, V.^cd , Kiadeh, F.F.H.^ce , Finucane, H.K.^{aj cf} , Forstner, A.J.^{bx by cg ch} , Frank, J.^ci , Gaspar, H.A.^bp , Gill, M.^cj , Goes, F.S.^ck , Gordon, S.D.^bq , Hall, L.S.^{bd cl} , Hansen, T.F.^{cm cn co} , Herms, S.^{bx by ch} , Hickie, I.B.^cp , Hoffmann, P.^{bx by ch} , Homuth, G.^cq , Horn, C.^cr , Hottenga, J.-J.^bc , Ising, M.^cs , Jansen, R.^bi , Jorgenson, E.^ct , Knowles, J.A.^cu , Kohane, I.S.^{cv cw cx} , Kraft, J.^cy , Kretzschmar, W.W.^cz , Krogh, J.^da , Kutalik, Z.^{db dc} , Li, Y.^cz , Lind, P.A.^bq , MacIntyre, D.J.^{dd de} , MacKinnon, D.F.^ck , Maier, R.M.^bb , Maier, W.^df , Marchini, J.^dg , Mbarek, H.^bc , McGrath, P.^dh , McGuffin, P.^bp , Medland, S.E.^bq , Mehta, D.^{bb di} , Middeldorp, C.M.^{bc dj dk} , Mihailov, E.^dl , Milaneschi, Y.^bi , Milani, L.^dl , Mondimore, F.M.^ck , Montgomery, G.W.^ba , Mostafavi, S.^{dm dn} , Mullins, N.^bp , Nauck, M.^{do dp} , Ng, B.^dn , Nivard, M.G.^bc , Nyholt, D.R.^dq , O’Reilly, P.F.^bp , Oskarsson, H.^dr , Owen, M.J.^p , Painter, J.N.^bq , Peterson, R.E.^{bh ds} , Pettersson, E.^w , Peyrot, W.J.^bi , Pistis, G.^bo , Posthuma, D.^{dt du} , Quiroz, J.A.^dv , Rice, J.P.^dw , Riley, B.P.^bh , Rivera, M.^{bp dx} , Mirza, S.S.^bz , Schoevers, R.^dy , Schulte, E.C.^{dz ea} , Shen, L.^ct , Shi, J.^eb , Shyn, S.I.^ec , Sigurdsson, E.^ed , Sinnamon, G.C.B.^ee , Smit, J.H.^bi , Smith, D.J.^ef , Streit, F.^ci , Strohmaier, J.^ci , Tansey, K.E.^eg , Teismann, H.^eh , Teumer, A.^ei , Thompson, W.^{a n o cn ej} , Thomson, P.A.^ek , Thorgeirsson, T.E.^el , Traylor, M.^em , Treutlein, J.^ci , Trubetskoy, V.^cy , Uitterlinden, A.G.^en , Umbricht, D.^eo , Van der Auwera, S.^ep , van Hemert, A.M.^eq , Viktorin, A.^w , Visscher, P.M.^{ba bb} , Wang, Y.^{a n o cn} , Webb, B.T.^ds , Weinsheimer, S.M.^{a cn} , Wellmann, J.^eh , Willemsen, G.^bc , Witt, S.H.^ci , Wu, Y.^ba , Xi, H.S.^er , Yang, J.^{bb es} , Zhang, F.^ba , Arolt, V.^et , Baune, B.T.^be , Berger, K.^eh , Boomsma, D.I.^bc , Cichon, S.^{bx ch eu ev} , Dannlowski, U.^et , de Geus, E.J.C.^{bc ew} , DePaulo, J.R.^ck , Domenici, E.^ex , Domschke, K.^ey , Esko, T.^{v dl} , Grabe, H.J.^ep , Hamilton, S.P.^ez , Hayward, C.^fa , Heath, A.C.^dw , Kendler, K.S.^bh , Kloiber, S.^{cs fb fc} , Lewis, G.^fd , Li, Q.S.^fe , Lucae, S.^cs , Madden, P.A.F.^dw , Magnusson, P.K.^w , Martin, N.G.^bq , McIntosh, A.M.^{bd bw} , Metspalu, A.^{dl ff} , Müller-Myhsok, B.^{bf bg fg} , Nöthen, M.M.^{bx by} , O’Donovan, M.C.^p , Paciga, S.A.^fh , Pedersen, N.L.^w , Penninx, B.W.J.H.^bi , Perlis, R.H.^{cb fi} , Porteous, D.J.^ek , Potash, J.B.^fj , Preisig, M.^bo , Rietschel, M.^ci , Schaefer, C.^ct , Schulze, T.G.^{ci ck ea fk fl} , Smoller, J.W.^{f cb cc} , Tiemeier, H.^{bz fm fn} , Uher, R.^fo , Völzke, H.^ei , Weissman, M.M.^{dh fp} , Lewis, C.M.^{bp fq} , Levinson, D.F.^fr , Breen, G.^{bp fs} , Agee, M.^ft , Alipanahi, B.^ft , Auton, A.^ft , Bell, R.K.^ft , Bryc, K.^ft , Elson, S.L.^ft , Fontanillas, P.^ft , Furlotte, N.A.^ft , Hromatka, B.S.^ft , Huber, K.E.^ft , Kleinman, A.^ft , Litterman, N.K.^ft , McIntyre, M.H.^ft , Mountain, J.L.^ft , Noblin, E.S.^ft , Northover, C.A.M.^ft , Pitts, S.J.^ft , Sathirapongsasuti, J.F.^ft , Sazonova, O.V.^ft , Shelton, J.F.^ft , Shringarpure, S.^ft , Tung, J.Y.^ft , Vacic, V.^ft , Wilson, C.H.^ft , Stefansson, K.^{ar at} , Geschwind, D.H.^{au av aw} , Nordentoft, M.^{a ax} , Hougaard, D.M.^{a u} , Werge, T.^{a z ay} , Mors, O.^{a az} , Mortensen, P.B.^{a b l m} , Neale, B.M.^{e f v} , Daly, M.J.^{e f v ae} , Børglum, A.D.^{a b c} , Autism Spectrum Disorder Working Group of the Psychiatric Genomics Consortium^fu , BUPGEN^fu , Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium^fv , 23andMe Research Team^fv

^a The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark
^b Centre for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, Denmark
^c Department of Biomedicine–Human Genetics, Aarhus University, Aarhus, Denmark
^d Bioinformatics Research Centre, Aarhus University, Aarhus, Denmark
^e Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States
^f Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, United States
^g Department of Psychiatry and Psychotherapy, Charité-Universitätsmedizin, Berlin, Germany
^h Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany
ⁱ Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
^j Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States
^k UNC Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States
^l National Centre for Register-Based Research, Aarhus University, Aarhus, Denmark
^m Centre for Integrated Register-based Research, Aarhus University, Aarhus, Denmark
ⁿ NORMENT-KG Jebsen Centre for Psychosis Research, University of Oslo, Oslo, Norway
^o Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
^p MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, United Kingdom
^q Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY, United States
^r Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, United States
^s Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States
^t Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States
^u Center for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark
^v Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, United States
^w Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
^x Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States
^y Department of Medical Genetics, Oslo University Hospital, Oslo, Norway
^z Institute of Biological Psychiatry, MHC SctHans, Mental Health Services, Copenhagen, Denmark
^aa Department of Neurohabilitation, Oslo University Hospital, Oslo, Norway
^ab Genomics plc, Oxford, United Kingdom
^ac Vertex Pharmaceuticals, Abingdon, United Kingdom
^ad NevSom, Department of Rare Disorders and Disabilities, , Oslo University Hospital, Oslo, Norway
^ae Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland
^af Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, Netherlands
^ag MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom
^ah Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, Netherlands
^ai Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom
^aj Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States
^ak Computational Biology Department, Carnegie Mellon University, Pittsburgh, PA, United States
^al Department of Statistics and Data Science, Carnegie Mellon University, Pittsburgh, PA, United States
^am Institute for Genomics and Multiscale Biology, Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, United States
^an Friedman Brain Institute, Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, United States
^ao Mental Illness Research Education and Clinical Center (MIRECC), James J. Peters VA Medical Center, Bronx, NY, United States
^ap The State Diagnostic and Counselling Centre, Kópavogur, Iceland
^aq Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom
^ar deCODE genetics/Amgen, Reykjavík, Iceland
^as Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States
^at Faculty of Medicine, University of Iceland, Reykjavik, Iceland
^au Program in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States
^av Center for Autism Research and Treatment and Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA, United States
^aw Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States
^ax Mental Health Services in the Capital Region of Denmark, Mental Health Center Copenhagen, University of Copenhagen, Copenhagen, Denmark
^ay Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
^az Psychosis Research Unit, Aarhus University Hospital, Risskov, Denmark
^ba Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD, Australia
^bb Queensland Brain Institute, University of Queensland, Brisbane, QLD, Australia
^bc Department of Biological Psychology & EMGO+ Institute for Health and Care Research, Vrije Universiteit, Amsterdam, Amsterdam, Netherlands
^bd Division of Psychiatry, University of Edinburgh, Edinburgh, United Kingdom
^be Discipline of Psychiatry, University of Adelaide, Adelaide, SA, Australia
^bf Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany
^bg Munich Cluster for Systems Neurology (SyNergy), Munich, Germany
^bh Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, United States
^bi Department of Psychiatry, Vrije Universiteit Medical Center and GGZ inGeest, Amsterdam, Netherlands
^bj Virginia Institute for Psychiatric and Behavior Genetics, Richmond, VA, United States
^bk Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, United States
^bl Department of Clinical Medicine, Translational Neuropsychiatry Unit, Aarhus University, Aarhus, Denmark
^bm Human Genetics, Wellcome Trust Sanger Institute, Cambridge, United Kingdom
^bn Statistical genomics and systems genetics, European Bioinformatics Institute (EMBL-EBI), Cambridge, United Kingdom
^bo Department of Psychiatry, University Hospital of Lausanne, Prilly, Switzerland
^bp MRC Social Genetic and Developmental Psychiatry Centre, King’s College London, London, United Kingdom
^bq Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
^br Centre for Advanced Imaging, University of Queensland, Saint Lucia, QLD, Australia
^bs Queensland Brain Institute, University of Queensland, Saint Lucia, QLD, Australia
^bt Psychological Medicine, Cardiff University, Cardiff, United Kingdom
^bu Center for Genomic and Computational Biology, Duke University, Durham, NC, United States
^bv Department of Pediatrics, Division of Medical Genetics, Duke University, Durham, NC, United States
^bw Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, United Kingdom
^bx Institute of Human Genetics, University of Bonn, Bonn, Germany
^by Life&Brain Center, Department of Genomics, University of Bonn, Bonn, Germany
^bz Epidemiology, Erasmus MC, Rotterdam, Netherlands
^ca Psychiatry, Dokuz Eylul University School Of Medicine, Izmir, Turkey
^cb Department of Psychiatry, Massachusetts General Hospital, Boston, MA, United States
^cc Psychiatric and Neurodevelopmental Genetics Unit (PNGU), Massachusetts General Hospital, Boston, MA, United States
^cd Neuroscience and Mental Health, Cardiff University, Cardiff, United Kingdom
^ce Bioinformatics, University of British Columbia, Vancouver, BC, Canada
^cf Department of Mathematics, Massachusetts Institute of Technology, Cambridge, MA, United States
^cg Department of Psychiatry (UPK), University of Basel, Basel, Switzerland
^ch Human Genomics Research Group, Department of Biomedicine, University of Basel, Basel, Switzerland
^ci Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty, Mannheim, Heidelberg University, Mannheim, Baden-Württemberg, Germany
^cj Department of Psychiatry, Trinity College Dublin, Dublin, Ireland
^ck Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, United States
^cl Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom
^cm Danish Headache Centre, Department of Neurology, Rigshospitalet, Glostrup, Denmark
^cn Institute of Biological Psychiatry, Mental Health Center SctHans, Mental Health Services Capital Region of Denmark, Copenhagen, Denmark
^co iPSYCH, Lundbeck Foundation Initiative for Psychiatric Research, Copenhagen, Denmark
^cp Brain and Mind Centre, University of Sydney, Sydney, NSW, Australia
^cq Interfaculty Institute for Genetics and Functional Genomics, Department of Functional Genomics, University Medicine and Ernst Moritz Arndt University Greifswald, Greifswald, Mecklenburg-Vorpommern, Germany
^cr Roche Pharmaceutical Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, FHoffmann-La Roche Ltd, Basel, Switzerland
^cs Max Planck Institute of Psychiatry, Munich, Germany
^ct Division of Research, Kaiser Permanente Northern California, Oakland, CA, United States
^cu Psychiatry & The Behavioral Sciences, University of Southern California, Los Angeles, CA, United States
^cv Department of Biomedical Informatics, Harvard Medical School, Boston, MA, United States
^cw Department of Medicine, Brigham and Women’s Hospital, Boston, MA, United States
^cx Informatics Program, Boston Children’s Hospital, Boston, MA, United States
^cy Department of Psychiatry and Psychotherapy, Universitätsmedizin Berlin Campus Charité Mitte, Berlin, Germany
^cz Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom
^da Department of Endocrinology at Herlev University Hospital, University of Copenhagen, Copenhagen, Denmark
^db Institute of Social and Preventive Medicine (IUMSP), University Hospital of Lausanne, Lausanne, Switzerland
^dc Swiss Institute of Bioinformatics, Lausanne, Switzerland
^dd Division of Psychiatry, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom
^de Mental Health, NHS 24, Glasgow, United Kingdom
^df Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany
^dg Statistics, University of Oxford, Oxford, United Kingdom
^dh Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY, United States
^di School of Psychology and Counseling, Queensland University of Technology, Brisbane, QLD, Australia
^dj Child and Youth Mental Health Service, Children’s Health Queensland Hospital and Health Service, South Brisbane, QLD, Australia
^dk Child Health Research Centre, University of Queensland, Brisbane, QLD, Australia
^dl Estonian Genome Center, University of Tartu, Tartu, Estonia
^dm Medical Genetics, University of British Columbia, Vancouver, BC, Canada
^dn Statistics, University of British Columbia, Vancouver, BC, Canada
^do DZHK (German Centre for Cardiovascular Research), Partner Site Greifswald, University Medicine, University Medicine Greifswald, Greifswald, Germany
^dp Institute of Clinical Chemistry and Laboratory Medicine, University Medicine, Greifswald, Germany
^dq Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia
^dr Humus, Reykjavik, Iceland
^ds Virginia Institute for Psychiatric & Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, United States
^dt Clinical Genetics, Vrije Universiteit Medical Center, Amsterdam, Netherlands
^du Complex Trait Genetics, Vrije Universiteit Amsterdam, Amsterdam, Netherlands
^dv Solid Biosciences, Boston, MA, United States
^dw Department of Psychiatry, Washington University in Saint Louis School of Medicine, Saint Louis, MO, United States
^dx Department of Biochemistry and Molecular Biology II, Institute of Neurosciences, Center for Biomedical Research, University of Granada, Granada, Spain
^dy Department of Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
^dz Department of Psychiatry and Psychotherapy, Medical Center of the University of Munich, Campus Innenstadt, Munich, Germany
^ea Institute of Psychiatric Phenomics and Genomics (IPPG), Medical Center of the University of Munich, Campus Innenstadt, Munich, Germany
^eb Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, United States
^ec Behavioral Health Services, Kaiser Permanente Washington, Seattle, WA, United States
^ed Faculty of Medicine, Department of Psychiatry, University of Iceland, Reykjavik, Iceland
^ee School of Medicine and Dentistry, James Cook University, Townsville, QLD, Australia
^ef Institute of Health and Wellbeing, University of Glasgow, Glasgow, United Kingdom
^eg College of Biomedical and Life Sciences, Cardiff University, Cardiff, United Kingdom
^eh Institute of Epidemiology and Social Medicine, University of Münster, Münster, Germany
^ei Institute for Community Medicine, University Medicine, Greifswald, Germany
^ej Department of Psychiatry, University of California, San Diego, San Diego, CA, United States
^ek Medical Genetics Section, CGEM, IGMM, University of Edinburgh, Edinburgh, United Kingdom
^el deCODE Genetics/Amgen, Reykjavik, Iceland
^em Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom
^en Internal Medicine, Erasmus MC, Rotterdam, Netherlands
^eo Roche Pharmaceutical Research and Early Development, Neuroscience, Ophthalmology and Rare Diseases Discovery & Translational Medicine Area, Roche Innovation Center Basel, FHoffmann-La Roche Ltd, Basel, Switzerland
^ep Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany
^eq Department of Psychiatry, Leiden University Medical Center, Leiden, Netherlands
^er Computational Sciences Center of Emphasis, Pfizer Global Research and Development, Cambridge, MA, United States
^es Institute for Molecular Bioscience, Queensland Brain Institute, University of Queensland, Brisbane, QLD, Australia
^et Department of Psychiatry, University of Münster, Münster, Germany
^eu Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Basel, Switzerland
^ev Institute of Neuroscience and Medicine (INM-1), Research Center Juelich, Juelich, Germany
^ew Amsterdam Public Health Institute, Vrije Universiteit Medical Center, Amsterdam, Netherlands
^ex Centre for Integrative Biology, Università degli Studi di Trento, Trento, Trentino-Alto Adige, Italy
^ey Department of Psychiatry and Psychotherapy, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany
^ez Psychiatry, Kaiser Permanente Northern California, San Francisco, CA, United States
^fa Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom
^fb Department of Psychiatry, University of Toronto, Toronto, ON, Canada
^fc Centre for Addiction and Mental Health, Toronto, ON, Canada
^fd Division of Psychiatry, University College London, London, United Kingdom
^fe Neuroscience Therapeutic Area, Janssen Research and Development, LLC, Titusville, NJ, United States
^ff Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia
^fg University of Liverpool, Liverpool, United Kingdom
^fh Human Genetics and Computational Biomedicine, Pfizer Global Research and Development, Groton, CT, United States
^fi Psychiatry, Harvard Medical School, Boston, MA, United States
^fj Psychiatry, University of Iowa, Iowa City, IA, United States
^fk Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Göttingen, Germany
^fl Human Genetics Branch, NIMH Division of Intramural Research Programs, Bethesda, MD, United States
^fm Child and Adolescent Psychiatry, Erasmus MC, Rotterdam, Netherlands
^fn Psychiatry, Erasmus MC, Rotterdam, Netherlands
^fo Psychiatry, Dalhousie University, Halifax, NS, Canada
^fp Division of Epidemiology, New York State Psychiatric Institute, New York, NY, United States
^fq Department of Medical & Molecular Genetics, King’s College London, London, United Kingdom
^fr Psychiatry & Behavioral Sciences, Stanford University, Stanford, CA, United States
^fs NIHR BRC for Mental Health, King’s College London, London, United Kingdom
^ft 23andMe, Inc., Mountain View, CA, United States

Abstract
Autism spectrum disorder (ASD) is a highly heritable and heterogeneous group of neurodevelopmental phenotypes diagnosed in more than 1% of children. Common genetic variants contribute substantially to ASD susceptibility, but to date no individual variants have been robustly associated with ASD. With a marked sample-size increase from a unique Danish population resource, we report a genome-wide association meta-analysis of 18,381 individuals with ASD and 27,969 controls that identified five genome-wide-significant loci. Leveraging GWAS results from three phenotypes with significantly overlapping genetic architectures (schizophrenia, major depression, and educational attainment), we identified seven additional loci shared with other traits at equally strict significance levels. Dissecting the polygenic architecture, we found both quantitative and qualitative polygenic heterogeneity across ASD subtypes. These results highlight biological insights, particularly relating to neuronal function and corticogenesis, and establish that GWAS performed at scale will be much more productive in the near term in ASD. © 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.

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

Novel neurosteroid hypnotic blocks T-type calcium channel-dependent rebound burst firing and suppresses long-term potentiation in the rat subiculum
(2019) British Journal of Anaesthesia, . 

Joksimovic, S.M.^a , Izumi, Y.^{b c} , Joksimovic, S.L.^a , Tesic, V.^a , Krishnan, K.^d , Asnake, B.^e , Jevtovic-Todorovic, V.^a , Covey, D.F.^{c d} , Zorumski, C.F.^{b c} , Todorovic, S.M.^a

^a Department of Anesthesiology, University of Colorado, School of Medicine, Aurora, CO, United States
^b Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
^c Taylor Family Institute for Innovative Psychiatric Research, Washington University School of Medicine, St. Louis, MO, United States
^d Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO, United States
^e Department of Anesthesiology and Pain Medicine, University of California, Davis, CA, United States

Abstract
Background: Hypnotics and general anaesthetics impair memory by altering hippocampal synaptic plasticity. We recently reported on a neurosteroid analogue with potent hypnotic activity [(3β,5β,17β)-3-hydroxyandrostane-17-carbonitrile; 3β-OH], which does not cause developmental neurotoxicity in rat pups. Here, we investigated the effects of 3β-OH on neuronal excitability in the subiculum, the major output structure of the hippocampal formation, and synaptic plasticity at two key hippocampal synapses in juvenile rats. Methods: Biophysical properties of isolated T-type calcium currents (T-currents) in the rat subiculum were investigated using acute slice preparations. Subicular T-type calcium channel (T-channel) subtype mRNA expression was compared using qRT–PCR. Using electrophysiological recordings, we examined the effects of 3β-OH and an endogenous neuroactive steroid, allopregnanolone (Allo), on T-currents and burst firing properties of subicular neurones, and on the long-term potentiation (LTP) in CA3-CA1 and CA1-subiculum pathways. Results: Biophysical and molecular studies confirmed that Ca V 3.1 channels represent the dominant T-channel isoform in the subiculum of juvenile rats. 3β-OH and Allo inhibited rebound burst firing by decreasing the amplitude of T-currents in a voltage-dependent manner with similar potency, with 30–80% inhibition. Both neurosteroids suppressed LTP at the CA1-subiculum, but not at the CA3-CA1 Schaffer collateral synapse. Conclusions: Neurosteroid effects on T-channels modulate hippocampal output and provide possible molecular mechanisms for the amnestic action of the novel hypnotic 3β-OH. Effects on T-channels in the subiculum provide a novel target for amnestic effects of hypnotics. © 2019 British Journal of Anaesthesia

Author Keywords
amnesia;  general anaesthetic;  hippocampus;  neurosteroid;  subiculum;  synaptic plasticity;  T-type calcium channels

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