Improving and Accelerating Drug Development for Nervous System Disorders
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TLDR
To accelerate nervous system drug development, the Institute of Medicine's Forum on Neuroscience and Nervous System Disorders has hosted a series of public workshops that brought together representatives of industry, government, academia, and patient groups to discuss these challenges and offer potential strategies to improve the translational neuroscience.About:
This article is published in Neuron.The article was published on 2014-11-05 and is currently open access. It has received 162 citations till now. The article focuses on the topics: Drug development.read more
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Resting-state connectivity biomarkers define neurophysiological subtypes of depression
Andrew T. Drysdale,Logan Grosenick,Logan Grosenick,Jonathan Downar,Katharine Dunlop,Farrokh Mansouri,Yue Meng,Robert N. Fetcho,Benjamin D. Zebley,Desmond J. Oathes,Amit Etkin,Alan F. Schatzberg,Keith Sudheimer,Jennifer Keller,Helen S. Mayberg,Faith M. Gunning,George S. Alexopoulos,Michael D. Fox,Alvaro Pascual-Leone,Henning U. Voss,B. J. Casey,Marc J. Dubin,Conor Liston +22 more
TL;DR: It is shown here that patients with depression can be subdivided into four neurophysiological subtypes defined by distinct patterns of dysfunctional connectivity in limbic and frontostriatal networks, which may be useful for identifying the individuals who are most likely to benefit from targeted neurostimulation therapies.
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IID 2018 update: context-specific physical protein-protein interactions in human, model organisms and domesticated species.
TL;DR: The Integrated Interactions Database (IID) provides one of the most comprehensive sets of context-specific human PPI networks, including networks for 133 tissues, 91 disease conditions, and many other contexts, and now supports topology and enrichment analyses of returned networks.
Journal ArticleDOI
The future of rodent models in depression research.
TL;DR: This Review examines the importance of sex as a biological variable and the controversial idea of intergenerational and transgenerational transmission of depressive-like traits, and discusses how genetic and circuit-dissection techniques might be used to refine existing models and generate new ones.
Journal ArticleDOI
The NIMH experimental medicine initiative.
TL;DR: The development of devices and psychosocial treatments in psychopharmacology over the past decade appears to have stalled after four decades of exuberant growth.
Journal ArticleDOI
Neuroethics Questions to Guide Ethical Research in the International Brain Initiatives
Global Neuroethics Summit Delegates,Karen S. Rommelfanger,Sung-Jin Jeong,Arisa Ema,Tamami Fukushi,Kiyoto Kasai,Khara M. Ramos,Arleen Salles,Ilina Singh +8 more
TL;DR: This Perspective article aims to prioritize and advance to the foreground a list of neuroethics questions for neuroscientists operating in the context of these international brain initiatives.
References
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Schwebel,James Scott,Maria Segui-Gomez,Saeid Shahraz,Donald S. Shepard,Hwashin Shin,Rupak Shivakoti,Donald H. Silberberg,David Singh,Gitanjali M Singh,Jasvinder A. Singh,Jessica Singleton,David A. Sleet,Karen Sliwa,Emma Smith,Jennifer L. Smith,Nicolas J. C. Stapelberg,Andrew C Steer,Timothy J. Steiner,Wilma A. Stolk,Lars Jacob Stovner,Christopher R. Sudfeld,Sana Syed,Giorgio Tamburlini,Mohammad Tavakkoli,Hugh R. Taylor,Jennifer A. Taylor,William J. Taylor,Bernadette Thomas,W. Murray Thomson,George D. Thurston,Imad M. Tleyjeh,Marcello Tonelli,Jeffrey A. Towbin,Thomas Truelsen,Miltiadis K. Tsilimbaris,Clotilde Ubeda,Eduardo A. Undurraga,Marieke J. van der Werf,Jim van Os,Monica S. Vavilala,Narayanaswamy Venketasubramanian,Mengru Wang,Wenzhi Wang,Kerrianne Watt,David Weatherall,Martin A. Weinstock,Robert G. Weintraub,Marc G. Weisskopf,Myrna M. Weissman,Richard A. White,Harvey Whiteford,Steven T. Wiersma,James D. Wilkinson,Hywel C Williams,Sean R.M. Williams,Emma Witt,Frederick Wolfe,Anthony D. Woolf,Sarah Wulf,Pon Hsiu Yeh,Anita K. M. Zaidi,Zhi Jie Zheng,David Zonies,Alan D. Lopez,Christopher J L Murray +363 more
TL;DR: Prevalence and severity of health loss were weakly correlated and age-specific prevalence of YLDs increased with age in all regions and has decreased slightly from 1990 to 2010, but population growth and ageing have increased YLD numbers and crude rates over the past two decades.
Journal ArticleDOI
Biological insights from 108 schizophrenia-associated genetic loci
Stephan Ripke,Stephan Ripke,Benjamin M. Neale,Benjamin M. Neale,Aiden Corvin,James T.R. Walters,Kai-How Farh,Peter Holmans,Phil Lee,Phil Lee,Brendan Bulik-Sullivan,Brendan Bulik-Sullivan,David A. Collier,David A. Collier,Hailiang Huang,Hailiang Huang,Tune H. Pers,Tune H. Pers,Tune H. Pers,Ingrid Agartz,Ingrid Agartz,Esben Agerbo,Esben Agerbo,Margot Albus,Madeline Alexander,Farooq Amin,Silviu Alin Bacanu,Martin Begemann,Richard A. Belliveau,Judit Bene,Sarah E. Bergen,Sarah E. Bergen,Elizabeth Bevilacqua,Tim B. Bigdeli,Donald W. Black,Richard Bruggeman,Nancy G. Buccola,Randy L. Buckner,William Byerley,Wiepke Cahn,Guiqing Cai,Dominique Campion,Rita M. Cantor,Vaughan J. Carr,Noa Carrera,Stanley V. Catts,Kimberly Chambert,Raymond C.K. Chan,Ronald Y.L. Chen,Eric Y.H. Chen,Wei Cheng,Eric F.C. Cheung,Siow Ann Chong,C. Robert Cloninger,David Cohen,Nadine Cohen,Paul Cormican,Nicholas John Craddock,James J. Crowley,David Curtis,David Curtis,Michael Davidson,Kenneth L. Davis,Franziska Degenhardt,Jurgen Del Favero,Ditte Demontis,Ditte Demontis,Dimitris Dikeos,Timothy G. Dinan,Srdjan Djurovic,Gary Donohoe,Gary Donohoe,Elodie Drapeau,Jubao Duan,Frank Dudbridge,Naser Durmishi,Peter Eichhammer,Johan G. Eriksson,Johan G. Eriksson,Valentina Escott-Price,Laurent Essioux,Ayman H. Fanous,Martilias S. Farrell,Josef Frank,Lude Franke,Robert Freedman,Nelson B. Freimer,Marion Friedl,Joseph I. Friedman,Menachem Fromer,Menachem Fromer,Menachem Fromer,Giulio Genovese,Lyudmila Georgieva,Ina Giegling,Ina Giegling,Paola Giusti-Rodríguez,Stephanie Godard,Jacqueline I. Goldstein,Jacqueline I. Goldstein,Vera Golimbet,Srihari Gopal,Jacob Gratten,Lieuwe de Haan,Christian Hammer,Marian L. Hamshere,Mark Hansen,Thomas Hansen,Vahram Haroutunian,Vahram Haroutunian,Annette M. Hartmann,Frans Henskens,Stefan Herms,Stefan Herms,Joel N. Hirschhorn,Joel N. Hirschhorn,Per Hoffmann,Per Hoffmann,A. Hofman,Mads V. Hollegaard,David M. Hougaard,Masashi Ikeda,Inge Joa,Antonio Julià,René S. Kahn,Luba Kalaydjieva,Sena Karachanak-Yankova,Juha Karjalainen,David J. Kavanagh,Matthew C. Keller,James L. Kennedy,Andrey Khrunin,Yunjung Kim,Janis Klovins,James A. Knowles,Bettina Konte,Vaidutis Kučinskas,Zita Ausrele Kucinskiene,Hana Kuzelova-Ptackova,Anna K. Kähler,Claudine Laurent,Jimmy Lee Chee Keong,S. Hong Lee,Sophie E. Legge,Bernard Lerer,Miaoxin Li,Tao Li,Kung-Yee Liang,Jeffrey A. Lieberman,Svetlana A. Limborska,Carmel M. Loughland,Jan Lubinski,Jouko Lönnqvist,Milan Macek,Patrik K. E. Magnusson,Brion S. Maher,Wolfgang Maier,J. Mallet,Sara Marsal,Manuel Mattheisen,Manuel Mattheisen,Manuel Mattheisen,Morten Mattingsdal,Robert W. McCarley,Colm McDonald,Andrew M. McIntosh,Sandra Meier,Carin J. Meijer,Béla Melegh,Ingrid Melle,Raquelle I. Mesholam-Gately,Andres Metspalu,Patricia T. Michie,Lili Milani,Vihra Milanova,Younes Mokrab,Derek W. Morris,Derek W. Morris,Ole Mors,Ole Mors,Kieran C. Murphy,Robin M. Murray,Inez Myin-Germeys,Bertram Mueller-Myhsok,Mari Nelis,Igor Nenadic,Deborah A. Nertney,Gerald Nestadt,Kristin K. Nicodemus,Liene Nikitina-Zake,Laura Nisenbaum,Annelie Nordin,Eadbhard O'Callaghan,Colm O'Dushlaine,F. Anthony O'Neill,Sang-Yun Oh,Ann Olincy,Line Olsen,Jim van Os,Jim van Os,Christos Pantelis,George N. Papadimitriou,Sergi Papiol,Elena Parkhomenko,Michele T. Pato,Tiina Paunio,Tiina Paunio,Milica Pejovic-Milovancevic,Diana O. Perkins,Olli Pietiläinen,Olli Pietiläinen,Jonathan Pimm,Andrew Pocklington,John Powell,Alkes L. Price,Alkes L. Price,Ann E. Pulver,Shaun Purcell,Digby Quested,Henrik B. Rasmussen,Abraham Reichenberg,Mark Reimers,Alexander Richards,Joshua L. Roffman,Panos Roussos,Douglas M. Ruderfer,Douglas M. Ruderfer,Veikko Salomaa,Alan R. Sanders,Ulrich Schall,Christian R. Schubert,Thomas G. Schulze,Thomas G. Schulze,Sibylle G. Schwab,Edward M. Scolnick,Rodney J. Scott,Larry J. Seidman,Jianxin Shi,Engilbert Sigurdsson,Teimuraz Silagadze,Jeremy M. Silverman,Jeremy M. Silverman,Kang Sim,Petr Slominsky,Jordan W. Smoller,Jordan W. Smoller,Hon-Cheong So,Chris C. A. Spencer,Eli A. Stahl,Eli A. Stahl,Hreinn Stefansson,Stacy Steinberg,Elisabeth Stögmann,Richard E. Straub,Eric Strengman,Jana Strohmaier,T. Scott Stroup,Mythily Subramaniam,Jaana Suvisaari,Dragan M. Svrakic,Jin P. Szatkiewicz,Erik Söderman,Srinivas Thirumalai,Draga Toncheva,Sarah Tosato,Juha Veijola,John L. Waddington,Dermot Walsh,Dai Wang,Qiang Wang,Bradley T. Webb,Mark Weiser,Dieter B. Wildenauer,Nigel Williams,Stephanie Williams,Stephanie H. Witt,Aaron R. Wolen,Emily H. M. Wong,Brandon Wormley,Hualin Simon Xi,Clement C. Zai,Xuebin Zheng,Fritz Zimprich,Naomi R. Wray,Kari Stefansson,Peter M. Visscher,Rolf Adolfsson,Ole A. Andreassen,Douglas Blackwood,Elvira Bramon,Joseph D. Buxbaum,Anders D. Børglum,Anders D. Børglum,Sven Cichon,Sven Cichon,Ariel Darvasi,Enrico Domenici,Hannelore Ehrenreich,Tõnu Esko,Tõnu Esko,Tõnu Esko,Pablo V. Gejman,Michael Gill,Hugh Gurling,Christina M. Hultman,Nakao Iwata,Assen Jablensky,Erik G. Jönsson,Erik G. Jönsson,Kenneth S. Kendler,George Kirov,Jo Knight,Todd Lencz,Todd Lencz,Douglas F. Levinson,Qingqin S. Li,Jianjun Liu,Jianjun Liu,Anil K. Malhotra,Anil K. Malhotra,Steven A. McCarroll,Steven A. McCarroll,Andrew McQuillin,Jennifer L. Moran,Preben Bo Mortensen,Preben Bo Mortensen,Bryan J. Mowry,Markus M. Noethen,Roel A. Ophoff,Roel A. Ophoff,Michael John Owen,Aarno Palotie,Aarno Palotie,Aarno Palotie,Carlos N. Pato,Tracey L. Petryshen,Tracey L. Petryshen,Danielle Posthuma,Danielle Posthuma,Marcella Rietschel,Brien P. Riley,Dan Rujescu,Dan Rujescu,Pak C. Sham,Pamela Sklar,David St Clair,Daniel R. Weinberger,Jens R. Wendland,Thomas Werge,Thomas Werge,Mark J. Daly,Mark J. Daly,Patrick F. Sullivan,Patrick F. Sullivan,Michael Conlon O'Donovan +354 more
TL;DR: Associations at DRD2 and several genes involved in glutamatergic neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia, and are consistent with leading pathophysiological hypotheses.
Journal ArticleDOI
Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease
Jean-Charles Lambert,Jean-Charles Lambert,Jean-Charles Lambert,Carla A. Ibrahim-Verbaas,Denise Harold,Adam C. Naj,Rebecca Sims,Céline Bellenguez,Céline Bellenguez,Céline Bellenguez,Gyungah Jun,Anita L. DeStefano,Joshua C. Bis,Gary W. Beecham,Benjamin Grenier-Boley,Benjamin Grenier-Boley,Benjamin Grenier-Boley,Giancarlo Russo,Tricia A. Thornton-Wells,Nicola Jones,Albert V. Smith,Vincent Chouraki,Vincent Chouraki,Vincent Chouraki,Charlene Thomas,M. Arfan Ikram,Diana Zelenika,Badri N. Vardarajan,Yoichiro Kamatani,Chiao-Feng Lin,Amy Gerrish,Helena Schmidt,Brian W. Kunkle,Melanie L. Dunstan,Agustín Ruiz,Marie-Thérèse Bihoreau,Seung Hoan Choi,Christiane Reitz,Florence Pasquier,Paul Hollingworth,Alfredo Ramirez,Olivier Hanon,Annette L. Fitzpatrick,Joseph D. Buxbaum,Dominique Campion,Paul K. Crane,Clinton T. Baldwin,Tim Becker,Tim Becker,Vilmundur Gudnason,Carlos Cruchaga,David Craig,Najaf Amin,Claudine Berr,Oscar L. Lopez,Philip L. De Jager,Philip L. De Jager,Vincent Deramecourt,Janet A. Johnston,Denis A. Evans,Simon Lovestone,Luc Letenneur,Francisco J. Morón,David C. Rubinsztein,Gudny Eiriksdottir,Kristel Sleegers,Kristel Sleegers,Alison Goate,Nathalie Fievet,Nathalie Fievet,Matthew J. Huentelman,Michael Gill,Kristelle Brown,M. Ilyas Kamboh,Lina Keller,Pascale Barberger-Gateau,Bernadette McGuinness,Eric B. Larson,Eric B. Larson,Robert C. Green,Amanda J. Myers,Carole Dufouil,Stephen Todd,David Wallon,Seth Love,Ekaterina Rogaeva,John Gallacher,Peter St George-Hyslop,Peter St George-Hyslop,Jordi Clarimón,Alberto Lleó,Anthony Bayer,Debby W. Tsuang,Lei Yu,Magda Tsolaki,Paola Bossù,Gianfranco Spalletta,Petroula Proitsi,John Collinge,Sandro Sorbi,Florentino Sanchez-Garcia,Nick C. Fox,John Hardy,Maria Candida Deniz Naranjo,Paolo Bosco,Robert Clarke,Carol Brayne,Daniela Galimberti,Michelangelo Mancuso,Fiona E. Matthews,Genetic,Environmental Risk in Alzheimer's Disease,Environmental Risk in Alzheimer's Disease,Cohorts for Heart,Cohorts for Heart,Susanne Moebus,Patrizia Mecocci,Maria Del Zompo,Wolfgang Maier,Wolfgang Maier,Harald Hampel,Harald Hampel,Alberto Pilotto,María J. Bullido,María J. Bullido,Francesco Panza,Paolo Caffarra,Paolo Caffarra,Benedetta Nacmias,John R. Gilbert,Manuel Mayhaus,Lars Lannfelt,Hakon Hakonarson,Sabrina Pichler,Minerva M. Carrasquillo,Martin Ingelsson,Duane Beekly,Victoria Alvarez,Fanggeng Zou,Otto Valladares,Steven G. Younkin,Eliecer Coto,Kara L. Hamilton-Nelson,Wei Gu,Cristina Razquin,Pau Pastor,Ignacio Mateo,Michael John Owen,Kelley Faber,Palmi V. Jonsson,Onofre Combarros,Michael Conlon O'Donovan,Laura B. Cantwell,Hilkka Soininen,Deborah Blacker,Simon Mead,Thomas H. Mosley,David A. Bennett,Tamara B. Harris,Laura Fratiglioni,Laura Fratiglioni,Clive Holmes,Renée F.A.G. de Bruijn,Peter Passmore,Thomas J. Montine,Karolien Bettens,Karolien Bettens,Jerome I. Rotter,Alexis Brice,Alexis Brice,Kevin Morgan,Tatiana Foroud,Walter A. Kukull,Didier Hannequin,John Powell,Mike A. Nalls,Karen Ritchie,Kathryn L. Lunetta,John S. K. Kauwe,Eric Boerwinkle,Eric Boerwinkle,Matthias Riemenschneider,Mercè Boada,Mikko Hiltunen,Eden R. Martin,Reinhold Schmidt,Dan Rujescu,Li-San Wang,Jean-François Dartigues,Jean-François Dartigues,Richard Mayeux,Christophe Tzourio,Albert Hofman,Markus M. Nöthen,Caroline Graff,Caroline Graff,Bruce M. Psaty,Bruce M. Psaty,Lesley Jones,Jonathan L. Haines,Peter Holmans,Mark Lathrop,Mark Lathrop,Margaret A. Pericak-Vance,Lenore J. Launer,Lindsay A. Farrer,Cornelia M. van Duijn,Christine Van Broeckhoven,Christine Van Broeckhoven,Valentina Moskvina,Sudha Seshadri,Julie Williams,Gerard D. Schellenberg,Philippe Amouyel,Philippe Amouyel,Philippe Amouyel +215 more
TL;DR: In addition to the APOE locus (encoding apolipoprotein E), 19 loci reached genome-wide significance (P < 5 × 10−8) in the combined stage 1 and stage 2 analysis, of which 11 are newly associated with Alzheimer's disease.
Journal ArticleDOI
How to improve R&D productivity: the pharmaceutical industry's grand challenge
Steven M. Paul,Daniel S. Mytelka,Dunwiddie Christopher T,Charles C. Persinger,Bernard H. Munos,Stacy R. Lindborg,Aaron Leigh Schacht +6 more
TL;DR: A detailed analysis based on comprehensive, recent, industry-wide data is presented to identify the relative contributions of each of the steps in the drug discovery and development process to overall R&D productivity and propose specific strategies that could have the most substantial impact in improving R &D productivity.
Journal ArticleDOI
Alzheimer disease in the United States (2010-2050) estimated using the 2010 census.
TL;DR: The number of people in the United States with AD dementia will increase dramatically in the next 40 years unless preventive measures are developed.