The neuropathology of autism: defects of neurogenesis and neuronal migration, and dysplastic changes
Jerzy Wegiel,Izabela Kuchna,Krzysztof Nowicki,Humi Imaki,Jarek Wegiel,Elaine Marchi,Shuang Yong Ma,Abha Chauhan,Ved Chauhan,Teresa Wierzba Bobrowicz,Mony J. de Leon,Mony J. de Leon,Leslie A. Saint Louis,Ira L. Cohen,Eric London,W. Ted Brown,Thomas Wisniewski +16 more
TLDR
Deterioration in the patterns of focal qualitative developmental defects in the brains of autistic subjects reflects multiregional dysregulation of neurogenesis, neuronal migration and maturation in autism, which may contribute to the heterogeneity of the clinical phenotype.Abstract:
Autism is characterized by a broad spectrum of clinical manifestations including qualitative impairments in social interactions and communication, and repetitive and stereotyped patterns of behavior. Abnormal acceleration of brain growth in early childhood, signs of slower growth of neurons, and minicolumn developmental abnormalities suggest multiregional alterations. The aim of this study was to detect the patterns of focal qualitative developmental defects and to identify brain regions that are prone to developmental alterations in autism. Formalin-fixed brain hemispheres of 13 autistic (4–60 years of age) and 14 age-matched control subjects were embedded in celloidin and cut into 200-μm-thick coronal sections, which were stained with cresyl violet and used for neuropathological evaluation. Thickening of the subependymal cell layer in two brains and subependymal nodular dysplasia in one brain is indicative of active neurogenesis in two autistic children. Subcortical, periventricular, hippocampal and cerebellar heterotopias detected in the brains of four autistic subjects (31%) reflect abnormal neuronal migration. Multifocal cerebral dysplasia resulted in local distortion of the cytoarchitecture of the neocortex in four brains (31%), of the entorhinal cortex in two brains (15%), of the cornu Ammonis in four brains and of the dentate gyrus in two brains. Cerebellar flocculonodular dysplasia detected in six subjects (46%), focal dysplasia in the vermis in one case, and hypoplasia in one subject indicate local failure of cerebellar development in 62% of autistic subjects. Detection of flocculonodular dysplasia in only one control subject and of a broad spectrum of focal qualitative neuropathological developmental changes in 12 of 13 examined brains of autistic subjects (92%) reflects multiregional dysregulation of neurogenesis, neuronal migration and maturation in autism, which may contribute to the heterogeneity of the clinical phenotype.read more
Citations
More filters
Journal ArticleDOI
Functional impact of global rare copy number variation in autism spectrum disorders
Dalila Pinto,Alistair T. Pagnamenta,Lambertus Klei,Richard Anney,Daniele Merico,Regina Regan,Judith Conroy,Tiago R. Magalhaes,Tiago R. Magalhaes,Catarina Correia,Catarina Correia,Brett S. Abrahams,Joana Almeida,Elena Bacchelli,Gary D. Bader,Anthony J. Bailey,Gillian Baird,Agatino Battaglia,Tom Berney,Nadia Bolshakova,Sven Bölte,Patrick Bolton,Thomas Bourgeron,Sean Brennan,Jessica Brian,Susan E. Bryson,Andrew R. Carson,Guillermo Casallo,Jillian P. Casey,Brian H.Y. Chung,Lynne E Cochrane,Christina Corsello,Emily L. Crawford,Andrew Crossett,Cheryl Cytrynbaum,Geraldine Dawson,Maretha de Jonge,Richard Delorme,Irene Drmic,Eftichia Duketis,Frederico Duque,Annette Estes,Penny Farrar,Bridget A. Fernandez,Susan E. Folstein,Eric Fombonne,Christine M. Freitag,John Gilbert,Christopher Gillberg,Joseph T. Glessner,Jeremy Goldberg,Andrew Green,Jonathan Green,Stephen J. Guter,Hakon Hakonarson,Elizabeth A. Heron,Matthew Hill,Richard Holt,Jennifer L. Howe,Gillian Hughes,Vanessa Hus,Roberta Igliozzi,Cecilia Kim,Sabine M. Klauck,Alexander Kolevzon,Olena Korvatska,Vlad Kustanovich,Clara Lajonchere,Janine A. Lamb,Magdalena Laskawiec,Marion Leboyer,Ann Le Couteur,Bennett L. Leventhal,Anath C. Lionel,Anath C. Lionel,Xiao-Qing Liu,Catherine Lord,Linda Lotspeich,Sabata C. Lund,Elena Maestrini,William M. Mahoney,Carine Mantoulan,Christian R. Marshall,Helen McConachie,Christopher J. McDougle,Jane McGrath,William M. McMahon,Alison K. Merikangas,Ohsuke Migita,Nancy J. Minshew,Ghazala Mirza,Jeff Munson,Stanley F. Nelson,Carolyn Noakes,Abdul Noor,Gudrun Nygren,Guiomar Oliveira,Katerina Papanikolaou,Jeremy R. Parr,Barbara Parrini,Tara Paton,Andrew Pickles,Marion Pilorge,Joseph Piven,Chris P. Ponting,David J. Posey,Annemarie Poustka,Fritz Poustka,Aparna Prasad,Jiannis Ragoussis,Katy Renshaw,Jessica Rickaby,Wendy Roberts,Kathryn Roeder,Bernadette Rogé,Michael Rutter,Laura J. Bierut,John P. Rice,Jeff Salt,Katherine Sansom,Daisuke Sato,Ricardo Segurado,Ana Filipa Sequeira,Lili Senman,Lili Senman,Naisha Shah,Val C. Sheffield,Latha Soorya,Inês Sousa,Olaf Stein,Nuala Sykes,Vera Stoppioni,Christina Strawbridge,Raffaella Tancredi,Katherine E. Tansey,Bhooma Thiruvahindrapduram,Ann P. Thompson,Susanne Thomson,Ana Tryfon,John Tsiantis,Herman Van Engeland,John B. Vincent,Fred R. Volkmar,Simon Wallace,Kai Wang,Zhouzhi Wang,Thomas H. Wassink,Caleb Webber,Rosanna Weksberg,Kirsty Wing,Kerstin Wittemeyer,Shawn Wood,Jing Wu,Brian L. Yaspan,Danielle Zurawiecki,Lonnie Zwaigenbaum,Joseph D. Buxbaum,Rita M. Cantor,Edwin H. Cook,Hilary Coon,Michael L. Cuccaro,Bernie Devlin,Sean Ennis,Louise Gallagher,Daniel H. Geschwind,Michael Gill,Jonathan L. Haines,Joachim Hallmayer,Judith Miller,Anthony P. Monaco,John I. Nurnberger,Andrew D. Paterson,Margaret A. Pericak-Vance,Gerard D. Schellenberg,Peter Szatmari,Astrid M. Vicente,Veronica J. Vieland,Veronica J. Vieland,Ellen M. Wijsman,Stephen W. Scherer,James S. Sutcliffe,Catalina Betancur +181 more
TL;DR: The genome-wide characteristics of rare (<1% frequency) copy number variation in ASD are analysed using dense genotyping arrays to reveal many new genetic and functional targets in ASD that may lead to final connected pathways.
Journal ArticleDOI
Patches of Disorganization in the Neocortex of Children with Autism
Rich Stoner,Maggie Chow,Maureen P. Boyle,Susan M. Sunkin,Peter R. Mouton,Subhojit Roy,Anthony Wynshaw-Boris,Sophia A. Colamarino,Ed S. Lein,Eric Courchesne +9 more
TL;DR: Focal disruption of cortical laminar architecture in the cortexes of a majority of young children with autism is found, suggesting a probable dysregulation of layer formation and layer-specific neuronal differentiation at prenatal developmental stages.
Journal ArticleDOI
The Cerebellum, Sensitive Periods, and Autism
TL;DR: Evidence that the cerebellum may guide the maturation of remote nonmotor neural circuitry and influence cognitive development and it is proposed that sensitive-period disruption of such internal brain communication can account for autism's key features is reviewed.
Journal ArticleDOI
Identification, Evaluation, and Management of Children With Autism Spectrum Disorder.
TL;DR: This single clinical report updates the 2007 American Academy of Pediatrics clinical reports on the evaluation and treatment of ASD in one publication with an online table of contents and section view available to help the reader identify topic areas within the report.
Journal ArticleDOI
Brain Growth Across the Life Span in Autism: Age-Specific Changes in Anatomical Pathology
TL;DR: Age-related changes in brain size in autistic and typical subjects from 12 months to 50 years of age is reported based on analyses of 586 longitudinal and cross-sectional MRI scans, several times larger than the largest autism study to date.
References
More filters
Journal ArticleDOI
The autism diagnostic observation schedule-generic: a standard measure of social and communication deficits associated with the spectrum of autism.
Catherine Lord,Susan Risi,Linda Lambrecht,Edwin H. Cook,Bennett L. Leventhal,Pamela C. DiLavore,Andrew Pickles,Michael Rutter +7 more
TL;DR: Algorithm sensitivities and specificities for autism and PD DNOS relative to nonspectrum disorders were excellent, with moderate differentiation of autism from PDDNOS.
Reference EntryDOI
Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR)
TL;DR: The Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision (DSM-IV-TR) (American Psychiatric Association], 2000) is a compendium of mental disorders, a listing of the criteria used to diagnose them, and a detailed system for their definition, organization, and classification.
Journal ArticleDOI
Neurogenesis in the adult human hippocampus
Peter S. Eriksson,Ekaterina Perfilieva,Thomas Björk-Eriksson,Ann Marie Alborn,Claes Nordborg,Daniel A. Peterson,Fred H. Gage +6 more
TL;DR: It is demonstrated that new neurons, as defined by these markers, are generated from dividing progenitor cells in the dentate gyrus of adult humans, indicating that the human hippocampus retains its ability to generate neurons throughout life.
Journal ArticleDOI
Chronic Antidepressant Treatment Increases Neurogenesis in Adult Rat Hippocampus
TL;DR: Investigation of the effect of antidepressants on hippocampal neurogenesis in the adult rat using the thymidine analog bromodeoxyuridine (BrdU) as a marker for dividing cells demonstrates that chronic antidepressant treatment significantly increases the number of BrdU-labeled cells in the dentate gyrus and hilus of the hippocampus.
Journal ArticleDOI
Structural variation of chromosomes in autism spectrum disorder.
Christian R. Marshall,Abdul Noor,John B. Vincent,Anath C. Lionel,Lars Feuk,Jennifer Skaug,Mary Shago,Rainald Moessner,Dalila Pinto,Yan Ren,Bhooma Thiruvahindrapduram,Andreas Fiebig,Stefan Schreiber,Jan M. Friedman,Cees E.J. Ketelaars,Yvonne J. Vos,Can Ficicioglu,Susan J. Kirkpatrick,Rob Nicolson,Leon Sloman,Anne Summers,Clare A. Gibbons,Ahmad S. Teebi,David Chitayat,Rosanna Weksberg,Ann Thompson,Cathy Vardy,Vicki Crosbie,Sandra Luscombe,Rebecca Baatjes,Lonnie Zwaigenbaum,Wendy Roberts,Bridget A. Fernandez,Peter Szatmari,Stephen W. Scherer +34 more
TL;DR: The results further implicate the SHANK3-NLGN4-NRXN1 postsynaptic density genes and also identify novel loci at DPP6-DPP10-PCDH9 (synapse complex), ANKRD11, DPYD, PTCHD1, 15q24, among others, for a role in ASD susceptibility.