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Harris ST, Schieve LA, Drews-Botsch C, DiGuiseppi C, Tian LH, Soke GN, Bradley CB, Windham GC. Pregnancy Planning and its Association with Autism Spectrum Disorder: Findings from the Study to Explore Early Development. Matern Child Health J 2024; 28:949-958. [PMID: 38198102 PMCID: PMC11001519 DOI: 10.1007/s10995-023-03877-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/18/2023] [Indexed: 01/11/2024]
Abstract
OBJECTIVES To examine associations between pregnancy planning and autism spectrum disorder (ASD) in offspring. METHODS The Study to Explore Early Development (SEED), a multi-site case-control study, enrolled preschool-aged children with ASD, other DDs, and from the general population (POP). Some children with DDs had ASD symptoms but did not meet the ASD case definition. We examined associations between mother's report of trying to get pregnant (pregnancy planning) and (1) ASD and (2) ASD symptomatology (ASD group, plus DD with ASD symptoms group combined) (each vs. POP group). We computed odds ratios adjusted for demographic, maternal, health, and perinatal health factors (aORs) via logistic regression. Due to differential associations by race-ethnicity, final analyses were stratified by race-ethnicity. RESULTS Pregnancy planning was reported by 66.4%, 64.8%, and 76.6% of non-Hispanic White (NHW) mothers in the ASD, ASD symptomatology, and POP groups, respectively. Among NHW mother-child pairs, pregnancy planning was inversely associated with ASD (aOR = 0.71 [95% confidence interval 0.56-0.91]) and ASD symptomatology (aOR = 0.67 [0.54-0.84]). Pregnancy planning was much less common among non-Hispanic Black mothers (28-32% depending on study group) and Hispanic mothers (49-56%) and was not associated with ASD or ASD symptomatology in these two race-ethnicity groups. CONCLUSION Pregnancy planning was inversely associated with ASD and ASD symptomatology in NHW mother-child pairs. The findings were not explained by several adverse maternal or perinatal health factors. The associations observed in NHW mother-child pairs did not extend to other race-ethnicity groups, for whom pregnancy planning was lower overall.
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Affiliation(s)
- Shericka T Harris
- National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, 4770 Buford Hwy NE, Mailstop S106-4, Atlanta, GA, 30341, USA.
| | - Laura A Schieve
- National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, 4770 Buford Hwy NE, Mailstop S106-4, Atlanta, GA, 30341, USA
| | - Carolyn Drews-Botsch
- Department of Global and Community Health, College of Health and Human Services, George Mason University, 4400 University Drive, MS: 5B7, Fairfax, VA, 22030, USA
| | - Carolyn DiGuiseppi
- Colorado School of Public Health, University of Colorado Anschutz Medical Campus, 80045, Aurora, CO, USA
| | - Lin H Tian
- National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, 4770 Buford Hwy NE, Mailstop S106-4, Atlanta, GA, 30341, USA
| | - Gnakub N Soke
- Center for Global Health, Global Immunization Division, Centers for Disease Control and Prevention, Atlanta, GA, 30329, USA
| | - Chyrise B Bradley
- Gillings School of Global Public Health, The University of North Carolina, Chapel Hill, NC, 27599, USA
| | - Gayle C Windham
- California Department of Public Health, Environmental Health Investigations Branch, Richmond, CA, 94804, USA
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2
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Coutelle R, Coulon N, Schröder CM, Putois O. Investigating the borders of autism spectrum disorder: lessons from the former diagnosis of pervasive developmental disorder not otherwise specified. Front Psychiatry 2023; 14:1149580. [PMID: 38173703 PMCID: PMC10762794 DOI: 10.3389/fpsyt.2023.1149580] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2023] [Accepted: 11/29/2023] [Indexed: 01/05/2024] Open
Abstract
Introduction Autism Spectrum Disorder (ASD) diagnosis is relatively consensual in typical forms. The margins of the spectrum and their degree of extension, however, are controversial. This has far-reaching implications, which extend beyond theoretical considerations: first, peripheral forms of autism are more prevalent than central forms; second, we do not know how relevant typical-targeted recommendations are for atypical forms. In DSM-IV-TR, these margins of autism were studied within the category of Pervasive Developmental Disorder - Not Otherwise Specified (PDD-NOS). In spite of its low reliability, this former diagnosis was of particular interest to shed light on the gray area of margins. The aim of this systematic is therefore to investigate the clinical characteristics of PDD-NOS in comparison with Autistic Disorder. Method A stepwise systematic PRISMA literature review was conducted by searching PubMed and Web Of Science databases to select corresponding studies. Results The systematic review included 81 studies comprising 6,644 children with PDD-NOS. Cross-sectional and longitudinal studies comparing PDD-NOS and AD showed that PDD-NOS corresponds to milder form of autism with less impact and less associated disorder, with the exception of schizophrenia and mood disorder. Discussion Our review challenges initial views of PDD-NOS, and shows the clinical relevance of this diagnosis when dealing with the margins of autism, and the de facto diversity included in the spectrum. However, in view of the many limitations of PDD-NOS (low reliability, instability through time, low acceptability), we suggest taxonomic changes in DSM-5: we introduce a new category based on three main dimensions related to socialization impairment, emotional lability and psychotic symptoms. Conclusion Our review argues for a distinction between AD and PDD-NOS on clinical characteristics and thus highlights the need to study the margins of autism. While the limitations of the PDD-NOS category made it irrelevant to investigate these margins from a research perspective, we believe that a multidimensional approach for mental health professionals taping socialization, emotion lability and psychotic symptoms would be interesting. Our review therefore encourage future studies to test relevant criteria for a new category and possibly identify developmental trajectories, specific interventions and treatments.
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Affiliation(s)
- Romain Coutelle
- Hôpitaux Universitaires de Strasbourg, Department of Psychiatry, University of Strasbourg, Strasbourg, France
- INSERM 1114, Strasbourg, France
| | - Nathalie Coulon
- TSA-SDI Expert Center and Psychosocial Rehabilitation Reference Center, Alpes Isère Hospital (Saint-Egrève Psychiatric Hospital), Grenoble, France
| | - Carmen M. Schröder
- Hôpitaux Universitaires de Strasbourg, Department of Psychiatry, University of Strasbourg, Strasbourg, France
- CNRS UPR 3212, Strasbourg, France
| | - Olivier Putois
- Hôpitaux Universitaires de Strasbourg, Department of Psychiatry, University of Strasbourg, Strasbourg, France
- SuLiSoM UR 3071, Faculté de Psychologie, Université de Strasbourg, Strasbourg, France
- Institut d’Immunologie et d’Hématologie, Institut Thématique Interdisciplinaire TRANSPLANTEX NG, Université de Strasbourg, Strasbourg, France
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3
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Al-Beltagi M. Pre-autism: What a paediatrician should know about early diagnosis of autism. World J Clin Pediatr 2023; 12:273-294. [PMID: 38178935 PMCID: PMC10762597 DOI: 10.5409/wjcp.v12.i5.273] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Revised: 09/07/2023] [Accepted: 09/25/2023] [Indexed: 12/08/2023] Open
Abstract
Autism, also known as an autism spectrum disorder, is a complex neurodevelopmental disorder usually diagnosed in the first three years of a child's life. A range of symptoms characterizes it and can be diagnosed at any age, including adolescence and adulthood. However, early diagnosis is crucial for effective management, prognosis, and care. Unfortunately, there are no established fetal, prenatal, or newborn screening programs for autism, making early detection difficult. This review aims to shed light on the early detection of autism prenatally, natally, and early in life, during a stage we call as "pre-autism" when typical symptoms are not yet apparent. Some fetal, neonatal, and infant biomarkers may predict an increased risk of autism in the coming baby. By developing a biomarker array, we can create an objective diagnostic tool to diagnose and rank the severity of autism for each patient. These biomarkers could be genetic, immunological, hormonal, metabolic, amino acids, acute phase reactants, neonatal brainstem function biophysical activity, behavioral profile, body measurements, or radiological markers. However, every biomarker has its accuracy and limitations. Several factors can make early detection of autism a real challenge. To improve early detection, we need to overcome various challenges, such as raising community awareness of early signs of autism, improving access to diagnostic tools, reducing the stigma attached to the diagnosis of autism, and addressing various culturally sensitive concepts related to the disorder.
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Affiliation(s)
- Mohammed Al-Beltagi
- Department of Pediatric, Faculty of Medicine, Tanta University, Tanta 31511, Algahrbia, Egypt
- Department of Pediatric, University Medical Center, King Abdulla Medical City, Arabian Gulf University, Dr. Sulaiman Al Habib Medical Group, Manama 26671, Manama, Bahrain
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4
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Ayaz H, Baker WB, Blaney G, Boas DA, Bortfeld H, Brady K, Brake J, Brigadoi S, Buckley EM, Carp SA, Cooper RJ, Cowdrick KR, Culver JP, Dan I, Dehghani H, Devor A, Durduran T, Eggebrecht AT, Emberson LL, Fang Q, Fantini S, Franceschini MA, Fischer JB, Gervain J, Hirsch J, Hong KS, Horstmeyer R, Kainerstorfer JM, Ko TS, Licht DJ, Liebert A, Luke R, Lynch JM, Mesquida J, Mesquita RC, Naseer N, Novi SL, Orihuela-Espina F, O’Sullivan TD, Peterka DS, Pifferi A, Pollonini L, Sassaroli A, Sato JR, Scholkmann F, Spinelli L, Srinivasan VJ, St. Lawrence K, Tachtsidis I, Tong Y, Torricelli A, Urner T, Wabnitz H, Wolf M, Wolf U, Xu S, Yang C, Yodh AG, Yücel MA, Zhou W. Optical imaging and spectroscopy for the study of the human brain: status report. NEUROPHOTONICS 2022; 9:S24001. [PMID: 36052058 PMCID: PMC9424749 DOI: 10.1117/1.nph.9.s2.s24001] [Citation(s) in RCA: 67] [Impact Index Per Article: 22.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/14/2023]
Abstract
This report is the second part of a comprehensive two-part series aimed at reviewing an extensive and diverse toolkit of novel methods to explore brain health and function. While the first report focused on neurophotonic tools mostly applicable to animal studies, here, we highlight optical spectroscopy and imaging methods relevant to noninvasive human brain studies. We outline current state-of-the-art technologies and software advances, explore the most recent impact of these technologies on neuroscience and clinical applications, identify the areas where innovation is needed, and provide an outlook for the future directions.
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Affiliation(s)
- Hasan Ayaz
- Drexel University, School of Biomedical Engineering, Science, and Health Systems, Philadelphia, Pennsylvania, United States
- Drexel University, College of Arts and Sciences, Department of Psychological and Brain Sciences, Philadelphia, Pennsylvania, United States
| | - Wesley B. Baker
- Children’s Hospital of Philadelphia, Division of Neurology, Philadelphia, Pennsylvania, United States
- Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States
| | - Giles Blaney
- Tufts University, Department of Biomedical Engineering, Medford, Massachusetts, United States
| | - David A. Boas
- Boston University Neurophotonics Center, Boston, Massachusetts, United States
- Boston University, College of Engineering, Department of Biomedical Engineering, Boston, Massachusetts, United States
| | - Heather Bortfeld
- University of California, Merced, Departments of Psychological Sciences and Cognitive and Information Sciences, Merced, California, United States
| | - Kenneth Brady
- Lurie Children’s Hospital, Northwestern University Feinberg School of Medicine, Department of Anesthesiology, Chicago, Illinois, United States
| | - Joshua Brake
- Harvey Mudd College, Department of Engineering, Claremont, California, United States
| | - Sabrina Brigadoi
- University of Padua, Department of Developmental and Social Psychology, Padua, Italy
| | - Erin M. Buckley
- Georgia Institute of Technology, Wallace H. Coulter Department of Biomedical Engineering, Atlanta, Georgia, United States
- Emory University School of Medicine, Department of Pediatrics, Atlanta, Georgia, United States
| | - Stefan A. Carp
- Massachusetts General Hospital, Harvard Medical School, Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, Massachusetts, United States
| | - Robert J. Cooper
- University College London, Department of Medical Physics and Bioengineering, DOT-HUB, London, United Kingdom
| | - Kyle R. Cowdrick
- Georgia Institute of Technology, Wallace H. Coulter Department of Biomedical Engineering, Atlanta, Georgia, United States
| | - Joseph P. Culver
- Washington University School of Medicine, Department of Radiology, St. Louis, Missouri, United States
| | - Ippeita Dan
- Chuo University, Faculty of Science and Engineering, Tokyo, Japan
| | - Hamid Dehghani
- University of Birmingham, School of Computer Science, Birmingham, United Kingdom
| | - Anna Devor
- Boston University, College of Engineering, Department of Biomedical Engineering, Boston, Massachusetts, United States
| | - Turgut Durduran
- ICFO – The Institute of Photonic Sciences, The Barcelona Institute of Science and Technology, Castelldefels, Barcelona, Spain
- Institució Catalana de Recerca I Estudis Avançats (ICREA), Barcelona, Spain
| | - Adam T. Eggebrecht
- Washington University in St. Louis, Mallinckrodt Institute of Radiology, St. Louis, Missouri, United States
| | - Lauren L. Emberson
- University of British Columbia, Department of Psychology, Vancouver, British Columbia, Canada
| | - Qianqian Fang
- Northeastern University, Department of Bioengineering, Boston, Massachusetts, United States
| | - Sergio Fantini
- Tufts University, Department of Biomedical Engineering, Medford, Massachusetts, United States
| | - Maria Angela Franceschini
- Massachusetts General Hospital, Harvard Medical School, Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, Massachusetts, United States
| | - Jonas B. Fischer
- ICFO – The Institute of Photonic Sciences, The Barcelona Institute of Science and Technology, Castelldefels, Barcelona, Spain
| | - Judit Gervain
- University of Padua, Department of Developmental and Social Psychology, Padua, Italy
- Université Paris Cité, CNRS, Integrative Neuroscience and Cognition Center, Paris, France
| | - Joy Hirsch
- Yale School of Medicine, Department of Psychiatry, Neuroscience, and Comparative Medicine, New Haven, Connecticut, United States
- University College London, Department of Medical Physics and Biomedical Engineering, London, United Kingdom
| | - Keum-Shik Hong
- Pusan National University, School of Mechanical Engineering, Busan, Republic of Korea
- Qingdao University, School of Automation, Institute for Future, Qingdao, China
| | - Roarke Horstmeyer
- Duke University, Department of Biomedical Engineering, Durham, North Carolina, United States
- Duke University, Department of Electrical and Computer Engineering, Durham, North Carolina, United States
- Duke University, Department of Physics, Durham, North Carolina, United States
| | - Jana M. Kainerstorfer
- Carnegie Mellon University, Department of Biomedical Engineering, Pittsburgh, Pennsylvania, United States
- Carnegie Mellon University, Neuroscience Institute, Pittsburgh, Pennsylvania, United States
| | - Tiffany S. Ko
- Children’s Hospital of Philadelphia, Division of Cardiothoracic Anesthesiology, Philadelphia, Pennsylvania, United States
| | - Daniel J. Licht
- Children’s Hospital of Philadelphia, Division of Neurology, Philadelphia, Pennsylvania, United States
| | - Adam Liebert
- Polish Academy of Sciences, Nalecz Institute of Biocybernetics and Biomedical Engineering, Warsaw, Poland
| | - Robert Luke
- Macquarie University, Department of Linguistics, Sydney, New South Wales, Australia
- Macquarie University Hearing, Australia Hearing Hub, Sydney, New South Wales, Australia
| | - Jennifer M. Lynch
- Children’s Hospital of Philadelphia, Division of Cardiothoracic Anesthesiology, Philadelphia, Pennsylvania, United States
| | - Jaume Mesquida
- Parc Taulí Hospital Universitari, Critical Care Department, Sabadell, Spain
| | - Rickson C. Mesquita
- University of Campinas, Institute of Physics, Campinas, São Paulo, Brazil
- Brazilian Institute of Neuroscience and Neurotechnology, Campinas, São Paulo, Brazil
| | - Noman Naseer
- Air University, Department of Mechatronics and Biomedical Engineering, Islamabad, Pakistan
| | - Sergio L. Novi
- University of Campinas, Institute of Physics, Campinas, São Paulo, Brazil
- Western University, Department of Physiology and Pharmacology, London, Ontario, Canada
| | | | - Thomas D. O’Sullivan
- University of Notre Dame, Department of Electrical Engineering, Notre Dame, Indiana, United States
| | - Darcy S. Peterka
- Columbia University, Zuckerman Mind Brain Behaviour Institute, New York, United States
| | | | - Luca Pollonini
- University of Houston, Department of Engineering Technology, Houston, Texas, United States
| | - Angelo Sassaroli
- Tufts University, Department of Biomedical Engineering, Medford, Massachusetts, United States
| | - João Ricardo Sato
- Federal University of ABC, Center of Mathematics, Computing and Cognition, São Bernardo do Campo, São Paulo, Brazil
| | - Felix Scholkmann
- University of Bern, Institute of Complementary and Integrative Medicine, Bern, Switzerland
- University of Zurich, University Hospital Zurich, Department of Neonatology, Biomedical Optics Research Laboratory, Zürich, Switzerland
| | - Lorenzo Spinelli
- National Research Council (CNR), IFN – Institute for Photonics and Nanotechnologies, Milan, Italy
| | - Vivek J. Srinivasan
- University of California Davis, Department of Biomedical Engineering, Davis, California, United States
- NYU Langone Health, Department of Ophthalmology, New York, New York, United States
- NYU Langone Health, Department of Radiology, New York, New York, United States
| | - Keith St. Lawrence
- Lawson Health Research Institute, Imaging Program, London, Ontario, Canada
- Western University, Department of Medical Biophysics, London, Ontario, Canada
| | - Ilias Tachtsidis
- University College London, Department of Medical Physics and Biomedical Engineering, London, United Kingdom
| | - Yunjie Tong
- Purdue University, Weldon School of Biomedical Engineering, West Lafayette, Indiana, United States
| | - Alessandro Torricelli
- Politecnico di Milano, Dipartimento di Fisica, Milan, Italy
- National Research Council (CNR), IFN – Institute for Photonics and Nanotechnologies, Milan, Italy
| | - Tara Urner
- Georgia Institute of Technology, Wallace H. Coulter Department of Biomedical Engineering, Atlanta, Georgia, United States
| | - Heidrun Wabnitz
- Physikalisch-Technische Bundesanstalt (PTB), Berlin, Germany
| | - Martin Wolf
- University of Zurich, University Hospital Zurich, Department of Neonatology, Biomedical Optics Research Laboratory, Zürich, Switzerland
| | - Ursula Wolf
- University of Bern, Institute of Complementary and Integrative Medicine, Bern, Switzerland
| | - Shiqi Xu
- Duke University, Department of Biomedical Engineering, Durham, North Carolina, United States
| | - Changhuei Yang
- California Institute of Technology, Department of Electrical Engineering, Pasadena, California, United States
| | - Arjun G. Yodh
- University of Pennsylvania, Department of Physics and Astronomy, Philadelphia, Pennsylvania, United States
| | - Meryem A. Yücel
- Boston University Neurophotonics Center, Boston, Massachusetts, United States
- Boston University, College of Engineering, Department of Biomedical Engineering, Boston, Massachusetts, United States
| | - Wenjun Zhou
- University of California Davis, Department of Biomedical Engineering, Davis, California, United States
- China Jiliang University, College of Optical and Electronic Technology, Hangzhou, Zhejiang, China
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5
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Menashe I, Regev O, Hadar A, Meiri G, Michaelovski A, Dinstein I, Hershkovitz R. Reply: Methodological drawbacks in the alleged association between foetal sonographic anomalies and autism. Brain 2022; 145:e92-e94. [PMID: 35802504 DOI: 10.1093/brain/awac247] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2022] [Accepted: 07/03/2022] [Indexed: 11/13/2022] Open
Affiliation(s)
- Idan Menashe
- Department of Public Health, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.,Azrieli National Center for Autism and Neurodevelopment Research, Ben-Gurion University of the Negev, Beer Sheva, Israel
| | - Ohad Regev
- Azrieli National Center for Autism and Neurodevelopment Research, Ben-Gurion University of the Negev, Beer Sheva, Israel.,Joyce & Irving Goldman Medical School, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel
| | - Amnon Hadar
- Clalit Health Services, Beer Sheva, Israel.,Division of Obstetrics and Gynecology, Soroka University Medical Center, Beer Sheva, Israel
| | - Gal Meiri
- Azrieli National Center for Autism and Neurodevelopment Research, Ben-Gurion University of the Negev, Beer Sheva, Israel.,Preschool Psychiatric Unit, Soroka University Medical Center, Beer Sheva, Israel
| | - Analya Michaelovski
- Azrieli National Center for Autism and Neurodevelopment Research, Ben-Gurion University of the Negev, Beer Sheva, Israel.,Child Development Center, Soroka University Medical Center, Beer Sheva, Israel
| | - Ilan Dinstein
- Azrieli National Center for Autism and Neurodevelopment Research, Ben-Gurion University of the Negev, Beer Sheva, Israel.,Psychology and Brain and Cognition Departments, Ben-Gurion University of the Negev, Beer Sheva, Israel
| | - Reli Hershkovitz
- Division of Obstetrics and Gynecology, Soroka University Medical Center, Beer Sheva, Israel
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6
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Moreau MM, Pietropaolo S, Ezan J, Robert BJA, Miraux S, Maître M, Cho Y, Crusio WE, Montcouquiol M, Sans N. Scribble Controls Social Motivation Behavior through the Regulation of the ERK/Mnk1 Pathway. Cells 2022; 11:cells11101601. [PMID: 35626639 PMCID: PMC9139383 DOI: 10.3390/cells11101601] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2022] [Revised: 05/06/2022] [Accepted: 05/06/2022] [Indexed: 02/01/2023] Open
Abstract
Social behavior is a basic domain affected by several neurodevelopmental disorders, including ASD and a heterogeneous set of neuropsychiatric disorders. The SCRIB gene that codes for the polarity protein SCRIBBLE has been identified as a risk gene for spina bifida, the most common type of neural tube defect, found at high frequencies in autistic patients, as well as other congenital anomalies. The deletions and mutations of the 8q24.3 region encompassing SCRIB are also associated with multisyndromic and rare disorders. Nonetheless, the potential link between SCRIB and relevant social phenotypes has not been fully investigated. Hence, we show that Scribcrc/+ mice, carrying a mutated version of Scrib, displayed reduced social motivation behavior and social habituation, while other behavioral domains were unaltered. Social deficits were associated with the upregulation of ERK phosphorylation, together with increased c-Fos activity. Importantly, the social alterations were rescued by both direct and indirect pERK inhibition. These results support a link between polarity genes, social behaviors and hippocampal functionality and suggest a role for SCRIB in the etiopathology of neurodevelopmental disorders. Furthermore, our data demonstrate the crucial role of the MAPK/ERK signaling pathway in underlying social motivation behavior, thus supporting its relevance as a therapeutic target.
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Affiliation(s)
- Maïté M. Moreau
- Univ. Bordeaux, INSERM, Neurocentre Magendie, U1215, 33077 Bordeaux, France; (J.E.); (B.J.A.R.); (M.M.); (M.M.)
- Correspondence: (M.M.M.); (N.S.)
| | - Susanna Pietropaolo
- Univ. Bordeaux, CNRS, Aquitaine Institute for Cognitive and Integrative Neurosciences, UMR5287, 33405 Bordeaux, France; (S.P.); (Y.C.); (W.E.C.)
| | - Jérôme Ezan
- Univ. Bordeaux, INSERM, Neurocentre Magendie, U1215, 33077 Bordeaux, France; (J.E.); (B.J.A.R.); (M.M.); (M.M.)
| | - Benjamin J. A. Robert
- Univ. Bordeaux, INSERM, Neurocentre Magendie, U1215, 33077 Bordeaux, France; (J.E.); (B.J.A.R.); (M.M.); (M.M.)
| | - Sylvain Miraux
- Univ. Bordeaux, CNRS, Centre de Résonance Magnétique des Systèmes Biologiques UMR5536, 33077 Bordeaux, France;
| | - Marlène Maître
- Univ. Bordeaux, INSERM, Neurocentre Magendie, U1215, 33077 Bordeaux, France; (J.E.); (B.J.A.R.); (M.M.); (M.M.)
| | - Yoon Cho
- Univ. Bordeaux, CNRS, Aquitaine Institute for Cognitive and Integrative Neurosciences, UMR5287, 33405 Bordeaux, France; (S.P.); (Y.C.); (W.E.C.)
| | - Wim E. Crusio
- Univ. Bordeaux, CNRS, Aquitaine Institute for Cognitive and Integrative Neurosciences, UMR5287, 33405 Bordeaux, France; (S.P.); (Y.C.); (W.E.C.)
| | - Mireille Montcouquiol
- Univ. Bordeaux, INSERM, Neurocentre Magendie, U1215, 33077 Bordeaux, France; (J.E.); (B.J.A.R.); (M.M.); (M.M.)
| | - Nathalie Sans
- Univ. Bordeaux, INSERM, Neurocentre Magendie, U1215, 33077 Bordeaux, France; (J.E.); (B.J.A.R.); (M.M.); (M.M.)
- Correspondence: (M.M.M.); (N.S.)
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7
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Assimopoulos S, Hammill C, Fernandes DJ, Spencer Noakes TL, Zhou YQ, Nutter LMJ, Ellegood J, Anagnostou E, Sled JG, Lerch JP. Genetic mouse models of autism spectrum disorder present subtle heterogenous cardiac abnormalities. Autism Res 2022; 15:1189-1208. [PMID: 35445787 PMCID: PMC9325472 DOI: 10.1002/aur.2728] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Revised: 03/16/2022] [Accepted: 03/28/2022] [Indexed: 12/13/2022]
Abstract
Autism spectrum disorder (ASD) and congenital heart disease (CHD) are linked on a functional and genetic level. Most work has investigated CHD‐related neurodevelopmental abnormalities. Cardiac abnormalities in ASD have been less studied. We investigated the prevalence of cardiac comorbidities relative to ASD genetic contributors. Using high frequency ultrasound imaging, we screened 9 ASD‐related genetic mouse models (Arid1b(+/−), Chd8(+/−), 16p11.2 (deletion), Sgsh(+/−), Sgsh(−/−), Shank3 Δexon 4–9(+/−), Shank3 Δexon 4–9(−/−), Fmr1(−/−), Vps13b(+/−)), and pooled wild‐type littermates (WTs). We measured heart rate (HR), aorta diameter (AoD), thickness and thickening of the left‐ventricular (LV) anterior and posterior walls, LV chamber diameter, fractional shortening, stroke volume and cardiac output, mitral inflow Peak E and A velocity ratio, ascending aorta velocity time integral (VTI). Mutant groups presented small‐scale alterations in cardiac structure and function compared to WTs (LV anterior wall thickness and thickening, chamber diameter and fractional shortening, HR). A greater number of significant differences was observed among mutant groups than between mutant groups and WTs. Mutant groups differed primarily in structural measures (LV chamber diameter and anterior wall thickness, HR, AoD). The mutant groups with most differences to WTs were 16p11.2 (deletion), Fmr1(−/−), Arid1b(+/−). The mutant groups with most differences from other mutant groups were 16p11.2 (deletion), Sgsh(+/−), Fmr1(−/−). Our results recapitulate the associated clinical findings. The characteristic ASD heterogeneity was recapitulated in the cardiac phenotype. The type of abnormal measures (morphological, functional) can highlight common underlying mechanisms. Clinically, knowledge of cardiac abnormalities in ASD can be essential as even non‐lethal abnormalities impact normal development.
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Affiliation(s)
- Stephania Assimopoulos
- Mouse Imaging Centre, Hospital for Sick Children, Toronto, Ontario, Canada.,Sickkids Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada.,Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada
| | - Christopher Hammill
- Mouse Imaging Centre, Hospital for Sick Children, Toronto, Ontario, Canada.,Sickkids Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada
| | - Darren J Fernandes
- Mouse Imaging Centre, Hospital for Sick Children, Toronto, Ontario, Canada.,Sickkids Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada
| | - Tara Leigh Spencer Noakes
- Mouse Imaging Centre, Hospital for Sick Children, Toronto, Ontario, Canada.,Sickkids Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada
| | - Yu-Qing Zhou
- Mouse Imaging Centre, Hospital for Sick Children, Toronto, Ontario, Canada
| | - Lauryl M J Nutter
- Sickkids Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada.,The Centre for Phenogenomics, Toronto, Ontario, Canada
| | - Jacob Ellegood
- Mouse Imaging Centre, Hospital for Sick Children, Toronto, Ontario, Canada.,Sickkids Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada
| | - Evdokia Anagnostou
- Bloorview Research Institute, Holland Bloorview Kids Rehabilitation Hospital, Toronto, Ontario, Canada
| | - John G Sled
- Mouse Imaging Centre, Hospital for Sick Children, Toronto, Ontario, Canada.,Sickkids Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada.,Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada
| | - Jason P Lerch
- Mouse Imaging Centre, Hospital for Sick Children, Toronto, Ontario, Canada.,Sickkids Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada.,Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.,Wellcome Centre for Integrative Neuroimaging, The University of Oxford, Oxford, UK
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8
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Association of cumulative early medical factors with autism and autistic symptoms in a population-based twin sample. Transl Psychiatry 2022; 12:73. [PMID: 35194015 PMCID: PMC8863884 DOI: 10.1038/s41398-022-01833-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2021] [Revised: 02/01/2022] [Accepted: 02/02/2022] [Indexed: 12/03/2022] Open
Abstract
Although highly heritable, environment also contributes to the etiology of autism spectrum disorder (ASD), with several specific environmental factors previously suggested. A registry-linked population-based twin cohort of 15,701 pairs (586 individuals with an ASD diagnosis), was established within the Child and Adolescent Twin Study in Sweden. Participants were evaluated for autistic symptoms at age 9 using the Autism-Tics, ADHD and other Comorbidities parental interview. A series of binary cut-offs indicated whether participants scored over various ASD symptom percentiles. Three early medical factors previously associated with ASD, beyond familial confounding (low birth weight, congenital malformations and perinatal hypoxia), were summed up creating an individual cumulative exposure load. A series of unconditional logistic regressions between all individuals and conditional regressions within twin pairs were performed for each outcome and exposure level. Between all individuals increasing cumulative early exposure loads were associated with increasing risk of ASD diagnosis (OR 3.33 (95%CI 1.79-6.20) for three exposures) and autistic symptoms (ranging from OR 2.12 (1.57-2.86) for three exposures at the 55th symptom percentile cut-off to OR 3.39 (2.2-5.24) at the 95th). Within twin pairs, the association between three exposures and an ASD diagnosis remained similar, but not statistically significant (OR 2.39 (0.62-9.24)). Having a higher load of early cumulative exposure was consistently associated with autistic symptoms after adjusting for familial confounding and sex (OR 3.45 (1.66-7.15) to OR 7.36 (1.99-27.18)). This study gives support to the cumulative stress hypothesis of ASD, and the dimensional model regarding environmental exposures, after adjustment for familial confounding.
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9
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Regev O, Hadar A, Meiri G, Flusser H, Michaelovski A, Dinstein I, Hershkovitz R, Menashe I. OUP accepted manuscript. Brain 2022; 145:4519-4530. [PMID: 35037687 PMCID: PMC9762947 DOI: 10.1093/brain/awac008] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Revised: 11/30/2021] [Accepted: 12/20/2021] [Indexed: 11/13/2022] Open
Abstract
Multiple pieces of evidence support the prenatal predisposition of autism spectrum disorder (ASD). Nevertheless, robust data about abnormalities in foetuses later developing into children diagnosed with ASD are lacking. Prenatal ultrasound is an excellent tool to study abnormal foetal development as it is frequently used to monitor foetal growth and identify foetal anomalies throughout pregnancy. We conducted a retrospective case-sibling-control study of children diagnosed with ASD (cases); their own typically developing, closest-in-age siblings (TDS); and typically developing children from the general population (TDP), matched by year of birth, sex and ethnicity to investigate the association between ultrasonography foetal anomalies and ASD. The case group was drawn from all children diagnosed with ASD enrolled at the National Autism Research Center of Israel. Foetal ultrasound data from the foetal anatomy survey were obtained from prenatal ultrasound clinics of Clalit Health Services in southern Israel. The study comprised 659 children: 229 ASD, 201 TDS and 229 TDP. Ultrasonography foetal anomalies were found in 29.3% of ASD cases versus only 15.9% and 9.6% in the TDS and TDP groups [adjusted odds ratio (aOR) = 2.23, 95% confidence interval (CI) = 1.32-3.78, and aOR = 3.50, 95%CI = 2.07-5.91, respectively]. Multiple co-occurring ultrasonography foetal anomalies were significantly more prevalent among ASD cases. Ultrasonography foetal anomalies in the urinary system, heart, and head and brain were the most significantly associated with ASD diagnosis (aORUrinary = 2.08, 95%CI = 0.96-4.50 and aORUrinary = 2.90, 95%CI = 1.41-5.95; aORHeart = 3.72, 95%CI = 1.50-9.24 and aORHeart = 8.67, 95%CI = 2.62-28.63; and aORHead&Brain = 1.96, 95%CI = 0.72-5.30 and aORHead&Brain = 4.67, 95%CI = 1.34-16.24; versus TDS and TDP, respectively). ASD females had significantly more ultrasonography foetal anomalies than ASD males (43.1% versus 25.3%, P = 0.013) and a higher prevalence of multiple co-occurring ultrasonography foetal anomalies (15.7% versus 4.5%, P = 0.011). No sex differences were seen among TDS and TDP controls. ASD foetuses were characterized by a narrower head and a relatively wider ocular-distance versus TDP foetuses (ORBPD = 0.81, 95%CI = 0.70-0.94, and aOROcular distance = 1.29, 95%CI = 1.06-1.57). Ultrasonography foetal anomalies were associated with more severe ASD symptoms. Our findings shed important light on the multiorgan foetal anomalies associated with ASD.
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Affiliation(s)
- Ohad Regev
- Joyce and Irving Goldman Medical School, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel
- Department of Public Health, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel
| | - Amnon Hadar
- Clalit Health Services, Beer Sheva, Israel
- Division of Obstetrics and Gynecology, Soroka University Medical Center, Beer Sheva, Israel
| | - Gal Meiri
- Preschool Psychiatric Unit, Soroka University Medical Center, Beer Sheva, Israel
- Azrieli National Center for Autism and Neurodevelopment Research, Ben-Gurion University of the Negev, Beer Sheva, Israel
| | - Hagit Flusser
- Child Development Center, Soroka University Medical Center, Beer Sheva, Israel
| | - Analya Michaelovski
- Azrieli National Center for Autism and Neurodevelopment Research, Ben-Gurion University of the Negev, Beer Sheva, Israel
- Child Development Center, Soroka University Medical Center, Beer Sheva, Israel
| | - Ilan Dinstein
- Azrieli National Center for Autism and Neurodevelopment Research, Ben-Gurion University of the Negev, Beer Sheva, Israel
- Psychology and Brain and Cognition Departments, Ben-Gurion University of the Negev, Beer Sheva, Israel
| | - Reli Hershkovitz
- Division of Obstetrics and Gynecology, Soroka University Medical Center, Beer Sheva, Israel
| | - Idan Menashe
- Correspondence to: Idan Menashe, PhD Department of Public Health, Faculty of Health Sciences Ben-Gurion University of the Negev Beer Sheva 8410501, Israel E-mail:
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10
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Association between craniofacial anomalies, intellectual disability and autism spectrum disorder: Western Australian population-based study. Pediatr Res 2022; 92:1795-1804. [PMID: 35352007 PMCID: PMC9771801 DOI: 10.1038/s41390-022-02024-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2021] [Revised: 02/14/2022] [Accepted: 03/06/2022] [Indexed: 12/30/2022]
Abstract
BACKGROUND Accurate knowledge of the relationship between craniofacial anomalies (CFA), intellectual disability (ID) and autism spectrum disorder (ASD) is essential to improve services and outcomes. The aim is to describe the association between CFA, ID and ASD using linked population data. METHODS All births (1983-2005; n = 566,225) including CFA births (comprising orofacial clefts, craniosynostosis, craniofacial microsomia and mandibulofacial dysostosis) surviving to 5 years were identified from the birth, death, birth defects and midwives population data sets. Linked data from these data sets were followed for a minimum of 5 years from birth until 2010 in the intellectual disability database to identify ID and ASD. These associations were examined using a modified Poisson regression. RESULTS Prevalence of ID and ASD was higher among CFA (especially with additional anomalies) than those without [prevalence ratio 5.27, 95% CI 4.44, 6.25]. It was higher among CFA than those with other gastrointestinal and urogenital anomalies but lower than nervous system and chromosomal anomalies. Children with CFA and severe ID had a higher proportion of nervous system anomalies. CONCLUSIONS Findings indicate increased ID and ASD among CFA but lower than nervous system and chromosomal anomalies. This population evidence can improve early identification of ID/ASD among CFA and support service planning. IMPACT Our study found about one in ten children born with craniofacial anomalies (CFA) are later identified with intellectual disability (ID). Prevalence of ID among CFA was higher than those with other gastrointestinal, urogenital, and musculoskeletal birth defects but lower than those with the nervous system and chromosomal abnormalities. Most children with craniofacial anomalies have a mild-to-moderate intellectual disability with an unknown aetiology. On average, intellectual disability is identified 2 years later for children born with non-syndromic craniofacial anomalies than those with syndromic conditions. Our findings can improve the early identification of ID/ASD among CFA and support service planning.
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11
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Abstract
Neurodevelopmental impairments have been recognised as a major association of paediatric kidney disease and bladder dysfunction, presenting challenges to clinicians and families to provide reasonable adjustments in order to allow access to investigations and treatments. Autism spectrum disorder (ASD) is a common neurodevelopmental disorder characterised by impairments in social interaction/communication and repetitive sensory-motor behaviours. Mental health, learning and physical co-morbidities are common. There is emerging evidence that ASD and kidney disease have some overlaps with genetic copy number variants and environmental factors contributing to shared pathogenesis. Prevalence rates of ASD in kidney disease are currently not known. A high index of suspicion of underlying ASD is required when a young person presents with communication difficulties, anxiety or behaviour that challenges, which should then trigger referral for a neurodevelopmental and behavioural assessment. We discuss practical approaches for providing care, which include understanding methods of communication and sensory, behavioural and environmental adaptations.
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12
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Hirayama A, Wakusawa K, Fujioka T, Iwata K, Usui N, Kurita D, Kameno Y, Wakuda T, Takagai S, Hirai T, Nara T, Ito H, Nagano Y, Oowada S, Tsujii M, Tsuchiya KJ, Matsuzaki H. Simultaneous evaluation of antioxidative serum profiles facilitates the diagnostic screening of autism spectrum disorder in under-6-year-old children. Sci Rep 2020; 10:20602. [PMID: 33244118 PMCID: PMC7691362 DOI: 10.1038/s41598-020-77328-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2020] [Accepted: 11/05/2020] [Indexed: 11/10/2022] Open
Abstract
This case–control study aimed to assess oxidative stress alterations in autism spectrum disorder (ASD). We used the MULTIS method, an electron spin resonance-based technique measuring multiple free radical scavenging activities simultaneously, in combination with conventional oxidative stress markers to investigate the ability of this MULTIS approach as a non-behavioural diagnostic tool for children with ASD. Serum samples of 39 children with ASD and 58 age-matched children with typical development were analysed. The ASD group showed decreased hydroxyl radical (·OH) and singlet oxygen scavenging activity with increased serum coenzyme Q10 oxidation rate, indicating a prooxidative tendency in ASD. By contrast, scavenging activities against superoxide (O2·−) and alkoxyl radical (RO·) were increased in the ASD group suggesting antioxidative shifts. In the subgroup analysis of 6-year-olds or younger, the combination of ·OH, O2·−, and RO· scavenging activities predicted ASD with high odds ratio (50.4), positive likelihood (12.6), and percentage of correct classification (87.0%). Our results indicate that oxidative stress in children with ASD is not simply elevated but rather shows a compensatory shift. MULTIS measurements may serve as a very powerful non-behavioural tool for the diagnosis of ASD in children.
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Affiliation(s)
- Aki Hirayama
- Center for Integrative Medicine, Tsukuba University of Technology, Tsukuba, Japan
| | - Keisuke Wakusawa
- Department of Developmental Neuropsychiatry, Miyagi Children's Hospital, Sendai, Japan
| | - Toru Fujioka
- Research Center for Child Mental Development, University of Fukui, Fukui, Japan.,United Graduate School of Child Development, Osaka University, Osaka, Japan
| | - Keiko Iwata
- Research Center for Child Mental Development, University of Fukui, Fukui, Japan.,United Graduate School of Child Development, Osaka University, Osaka, Japan.,Life Science Innovation Center, University of Fukui, Fukui, Japan
| | - Noriyoshi Usui
- Research Center for Child Mental Development, University of Fukui, Fukui, Japan.,United Graduate School of Child Development, Osaka University, Osaka, Japan.,Life Science Innovation Center, University of Fukui, Fukui, Japan.,Center for Medical Research and Education, Department of Neuroscience and Cell Biology, Graduate School of Medicine, Osaka University, Osaka, Japan.,Department of Neuroscience and Cell Biology, Graduate School of Medicine, Osaka University, Osaka, Japan.,Global Center for Medical Engineering and Informatics, Osaka University, Osaka, Japan.,Addiction Research Unit, Osaka Psychiatric Research Center, Osaka Psychiatric Medical Center, Osaka, Japan
| | - Daisuke Kurita
- Department of Psychiatry, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Yosuke Kameno
- Department of Psychiatry, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Tomoyasu Wakuda
- Department of Psychiatry, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Shu Takagai
- United Graduate School of Child Development, Osaka University, Osaka, Japan.,Department of Child and Adolescent Psychiatry, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Takaharu Hirai
- Research Center for Child Mental Development, University of Fukui, Fukui, Japan.,United Graduate School of Child Development, Osaka University, Osaka, Japan.,Department of Community Health Nursing, School of Medical Sciences, University of Fukui, Fukui, Japan
| | - Takahiro Nara
- Department of Developmental Neuropsychiatry, Miyagi Children's Hospital, Sendai, Japan
| | - Hiromu Ito
- Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
| | - Yumiko Nagano
- Center for Integrative Medicine, Tsukuba University of Technology, Tsukuba, Japan
| | | | - Masatsugu Tsujii
- School of Contemporary Sociology, Chukyo University, Toyota, Japan
| | - Kenji J Tsuchiya
- United Graduate School of Child Development, Osaka University, Osaka, Japan.,Research Center for Child Mental Development, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Hideo Matsuzaki
- Research Center for Child Mental Development, University of Fukui, Fukui, Japan. .,United Graduate School of Child Development, Osaka University, Osaka, Japan. .,Life Science Innovation Center, University of Fukui, Fukui, Japan.
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13
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Usui N, Iwata K, Miyachi T, Takagai S, Wakusawa K, Nara T, Tsuchiya KJ, Matsumoto K, Kurita D, Kameno Y, Wakuda T, Takebayashi K, Iwata Y, Fujioka T, Hirai T, Toyoshima M, Ohnishi T, Toyota T, Maekawa M, Yoshikawa T, Maekawa M, Nakamura K, Tsujii M, Sugiyama T, Mori N, Matsuzaki H. VLDL-specific increases of fatty acids in autism spectrum disorder correlate with social interaction. EBioMedicine 2020; 58:102917. [PMID: 32739868 PMCID: PMC7393524 DOI: 10.1016/j.ebiom.2020.102917] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2020] [Revised: 07/08/2020] [Accepted: 07/10/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Abnormalities of lipid metabolism contributing to the autism spectrum disorder (ASD) pathogenesis have been suggested, but the mechanisms are not fully understood. We aimed to characterize the lipid metabolism in ASD and to explore a biomarker for clinical evaluation. METHODS An age-matched case-control study was designed. Lipidomics was conducted using the plasma samples from 30 children with ASD compared to 30 typical developmental control (TD) children. Large-scale lipoprotein analyses were also conducted using the serum samples from 152 children with ASD compared to 122 TD children. Data comparing ASD to TD subjects were evaluated using univariate (Mann-Whitney test) and multivariate analyses (conditional logistic regression analysis) for main analyses using cofounders (diagnosis, sex, age, height, weight, and BMI), Spearman rank correlation coefficient, and discriminant analyses. FINDINGS Forty-eight significant metabolites involved in lipid biosynthesis and metabolism, oxidative stress, and synaptic function were identified in the plasma of ASD children by lipidomics. Among these, increased fatty acids (FAs), such as omega-3 (n-3) and omega-6 (n-6), showed correlations with clinical social interaction score and ASD diagnosis. Specific reductions of very-low-density lipoprotein (VLDL) and apoprotein B (APOB) in serum of ASD children also were found by large-scale lipoprotein analysis. VLDL-specific reduction in ASD was correlated with APOB, indicating VLDL-specific dyslipidaemia associated with APOB in ASD children. INTERPRETATION Our results demonstrated that the increases in FAs correlated positively with social interaction are due to VLDL-specific degradation, providing novel insights into the lipid metabolism underlying ASD pathophysiology. FUNDING This study was supported mainly by MEXT, Japan.
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Affiliation(s)
- Noriyoshi Usui
- Research Center for Child Mental Development, University of Fukui, 23-3, Matsuokashimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui 910-1193, Japan; Department of Child Development, United Graduate School of Child Development, Osaka University, Osaka 565-0871, Japan; Life Science Innovation Center, University of Fukui, Fukui 910-1193, Japan; Center for Medical Research and Education, and Department of Neuroscience and Cell Biology, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan; Department of Neuroscience and Cell Biology, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan; Global Center for Medical Engineering and Informatics, Osaka University, Osaka 565-0871, Japan; Addiction Research Unit, Osaka Psychiatric Research Center, Osaka Psychiatric Medical Center, Osaka 541-8567, Japan
| | - Keiko Iwata
- Research Center for Child Mental Development, University of Fukui, 23-3, Matsuokashimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui 910-1193, Japan; Department of Child Development, United Graduate School of Child Development, Osaka University, Osaka 565-0871, Japan; Life Science Innovation Center, University of Fukui, Fukui 910-1193, Japan
| | - Taishi Miyachi
- Department of Pediatrics, Nagoya City University Medical School, Aichi 467-8601, Japan
| | - Shu Takagai
- Department of Child and Adolescent Psychiatry, Hamamatsu University School of Medicine, Shizuoka 431-3192, Japan
| | - Keisuke Wakusawa
- Department of Rehabilitation, Miyagi Children's Hospital, Miyagi 989-3126, Japan
| | - Takahiro Nara
- Department of Rehabilitation, Miyagi Children's Hospital, Miyagi 989-3126, Japan
| | - Kenji J Tsuchiya
- Research Center for Child Mental Development, Hamamatsu University School of Medicine, Shizuoka 431-3192, Japan
| | - Kaori Matsumoto
- Graduate School of Psychology, Kanazawa Institute of Technology, Ishikawa 921-8054, Japan
| | - Daisuke Kurita
- Department of Psychiatry, Hamamatsu University School of Medicine, Shizuoka 431-3192, Japan
| | - Yosuke Kameno
- Department of Psychiatry, Hamamatsu University School of Medicine, Shizuoka 431-3192, Japan
| | - Tomoyasu Wakuda
- Department of Psychiatry, Hamamatsu University School of Medicine, Shizuoka 431-3192, Japan
| | - Kiyokazu Takebayashi
- Department of Psychiatry, Hamamatsu University School of Medicine, Shizuoka 431-3192, Japan
| | - Yasuhide Iwata
- Department of Psychiatry and Neurology, Fukude Nishi Hospital, Shizuoka 437-1216, Japan
| | - Toru Fujioka
- Research Center for Child Mental Development, University of Fukui, 23-3, Matsuokashimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui 910-1193, Japan; Department of Child Development, United Graduate School of Child Development, Osaka University, Osaka 565-0871, Japan
| | - Takaharu Hirai
- Department of Child Development, United Graduate School of Child Development, Osaka University, Osaka 565-0871, Japan; Department of Community Health Nursing, School of Medical Sciences, University of Fukui, Fukui 910-1193, Japan
| | - Manabu Toyoshima
- Laboratory for Molecular Psychiatry, RIKEN Center for Brain Science, Saitama 351-0198, Japan
| | - Tetsuo Ohnishi
- Laboratory for Molecular Psychiatry, RIKEN Center for Brain Science, Saitama 351-0198, Japan
| | - Tomoko Toyota
- Laboratory for Molecular Psychiatry, RIKEN Center for Brain Science, Saitama 351-0198, Japan
| | - Motoko Maekawa
- Laboratory for Molecular Psychiatry, RIKEN Center for Brain Science, Saitama 351-0198, Japan
| | - Takeo Yoshikawa
- Laboratory for Molecular Psychiatry, RIKEN Center for Brain Science, Saitama 351-0198, Japan
| | - Masato Maekawa
- Department of Laboratory Medicine, Hamamatsu University School of Medicine, Shizuoka 431-3192, Japan
| | - Kazuhiko Nakamura
- Department of Psychiatry, Hirosaki University School of Medicine, Aomori 036-8562, Japan
| | - Masatsugu Tsujii
- School of Contemporary Sociology, Chukyo University, Aichi 470-0393, Japan
| | - Toshiro Sugiyama
- Research Center for Child Mental Development, University of Fukui, 23-3, Matsuokashimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui 910-1193, Japan
| | - Norio Mori
- Department of Psychiatry and Neurology, Fukude Nishi Hospital, Shizuoka 437-1216, Japan
| | - Hideo Matsuzaki
- Research Center for Child Mental Development, University of Fukui, 23-3, Matsuokashimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui 910-1193, Japan; Department of Child Development, United Graduate School of Child Development, Osaka University, Osaka 565-0871, Japan; Life Science Innovation Center, University of Fukui, Fukui 910-1193, Japan.
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14
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Early environmental risk factors for neurodevelopmental disorders - a systematic review of twin and sibling studies. Dev Psychopathol 2020; 33:1448-1495. [PMID: 32703331 PMCID: PMC8564717 DOI: 10.1017/s0954579420000620] [Citation(s) in RCA: 75] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
While neurodevelopmental disorders (NDDs) are highly heritable, several environmental risk factors have also been suggested. However, the role of familial confounding is unclear. To shed more light on this, we reviewed the evidence from twin and sibling studies. A systematic review was performed on case control and cohort studies including a twin or sibling within-pair comparison of neurodevelopmental outcomes, with environmental exposures until the sixth birthday. From 7,315 screened abstracts, 140 eligible articles were identified. After adjustment for familial confounding advanced paternal age, low birth weight, birth defects, and perinatal hypoxia and respiratory stress were associated with autism spectrum disorder (ASD), and low birth weight, gestational age and family income were associated with attention-deficit/hyperactivity disorder (ADHD), categorically and dimensionally. Several previously suspected factors, including pregnancy-related factors, were deemed due to familial confounding. Most studies were conducted in North America and Scandinavia, pointing to a global research bias. Moreover, most studies focused on ASD and ADHD. This genetically informed review showed evidence for a range of environmental factors of potential casual significance in NDDs, but also points to a critical need of more genetically informed studies of good quality in the quest of the environmental causes of NDDs.
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15
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Abstract
Atypical responses to sound are common in individuals with autism spectrum disorder (ASD), and growing evidence suggests an underlying auditory brainstem pathology. This review of the literature provides a comprehensive account of the structural and functional evidence for auditory brainstem abnormalities in ASD. The studies reviewed were published between 1975 and 2016 and were sourced from multiple online databases. Indices of both the quantity and quality of the studies reviewed are considered. Findings show converging evidence for auditory brainstem pathology in ASD, although the specific functions and anatomical structures involved remain equivocal. Two main trends emerge from the literature: (1) abnormalities occur mainly at higher levels of the auditory brainstem, according to structural imaging and electrophysiology studies; and (2) brainstem abnormalities appear to be more common in younger than older children with ASD. These findings suggest delayed maturation of neural transmission pathways between lower and higher levels of the brainstem and are consistent with the auditory disorders commonly observed in ASD, including atypical sound sensitivity, poor sound localization, and difficulty listening in background noise. Limitations of existing studies are discussed, and recommendations for future research are offered.
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16
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Yuen T, Carter MT, Szatmari P, Ungar WJ. Cost-effectiveness of Genome and Exome Sequencing in Children Diagnosed with Autism Spectrum Disorder. APPLIED HEALTH ECONOMICS AND HEALTH POLICY 2018; 16:481-493. [PMID: 29651777 DOI: 10.1007/s40258-018-0390-x] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/08/2023]
Abstract
BACKGROUND Genome (GS) and exome sequencing (ES) could potentially identify pathogenic variants with greater sensitivity than chromosomal microarray (CMA) in autism spectrum disorder (ASD) but are costlier and result interpretation can be uncertain. Study objective was to compare the costs and outcomes of four genetic testing strategies in children with ASD. METHODS A microsimulation model estimated the outcomes and costs (in societal and public payer perspectives in Ontario, Canada) of four genetic testing strategies: CMA for all, CMA for all followed by ES for those with negative CMA and syndromic features (CMA+ES), ES or GS for all. RESULTS Compared to CMA, the incremental cost-effectiveness ratio (ICER) per additional child identified with rare pathogenic variants within 18 months of ASD diagnosis was $CAN5997.8 for CMA+ES, $CAN13,504.2 for ES and $CAN10,784.5 for GS in the societal perspective. ICERs were sensitive to changes in ES or GS diagnostic yields, wait times for test results or pre-test genetic counselling, but were robust to changes in the ES or GS costs. CONCLUSION Strategic integration of ES into ASD care could be a cost-effective strategy. Long wait times for genetic services and uncertain utility, both clinical and personal, of sequencing results could limit broader clinical implementation.
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Affiliation(s)
- Tracy Yuen
- Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada
- Child Health Evaluative Sciences, The Hospital for Sick Children Peter Gilgan Centre for Research and Learning, 11/F, 686 Bay St, Toronto, M5G 0A4, Canada
| | - Melissa T Carter
- Regional Genetics Program, Children's Hospital of Eastern Ontario, Ottawa, Canada
| | - Peter Szatmari
- Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada
- Child Health Evaluative Sciences, The Hospital for Sick Children Peter Gilgan Centre for Research and Learning, 11/F, 686 Bay St, Toronto, M5G 0A4, Canada
- Centre for Addiction and Mental Health, Hospital for Sick Children, University of Toronto, Toronto, Canada
| | - Wendy J Ungar
- Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada.
- Child Health Evaluative Sciences, The Hospital for Sick Children Peter Gilgan Centre for Research and Learning, 11/F, 686 Bay St, Toronto, M5G 0A4, Canada.
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17
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Ruhela RK, Sarma P, Soni S, Prakash A, Medhi B. Congenital malformation and autism spectrum disorder: Insight from a rat model of autism spectrum disorder. Indian J Pharmacol 2018; 49:243-249. [PMID: 29033484 PMCID: PMC5637135 DOI: 10.4103/ijp.ijp_183_17] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023] Open
Abstract
AIMS AND OBJECTIVES: The primary aim was an evaluation of the pattern of gross congenital malformations in a rat model of autism spectrum disorder (ASD) and the secondary aim was characterization of the most common gross malformation observed. MATERIALS AND METHODS: In females, the late pro-oestrous phase was identified by vaginal smear cytology, and then, they were allowed to mate at 1:3 ratio (male: female). Pregnancy was confirmed by the presence of sperm plug in the vagina and presence of sperm in the vaginal smear. In the ASD group, ASD was induced by injecting valproic acid 600 mg/kg (i.p.) to pregnant female rats (n = 18) on day 12.5 (single injection). Only vehicle (normal saline) was given in the control group (n = 12). After delivery, pups were grossly observed for congenital malformations until the time of sacrifice (3 months) and different types of malformations and their frequency were noted and characterized. RESULTS: In the ASD group, congenital malformation was present in 69.9% of the pups, whereas in the control group, it was 0%. Male pups were most commonly affected (90% in males vs. only 39.72% in female pups). The tail deformity was the most common malformation found affecting 61.2% pups in the ASD group. Other malformations observed were dental malformation (3.82%), genital malformation (3.28%) and paw malformation (1.1%). Hind limb paralysis was observed in one pup. The tail anomalies were characterized as per gross appearance and location of the malformation. CONCLUSION: In this well-validated rat model of ASD, congenital malformation was quite common. It seems screening of congenital malformations should be an integral part of the management of ASD, or the case may be vice versa, i.e., in the case of a baby born with a congenital deformity, they should be screened for ASD.
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Affiliation(s)
| | - Phulen Sarma
- Department of Pharmacology, PGIMER, Chandigarh, India
| | | | - Ajay Prakash
- Department of Pharmacology, PGIMER, Chandigarh, India
| | - Bikash Medhi
- Department of Pharmacology, PGIMER, Chandigarh, India
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Schieve LA, Shapira SK. Invited Commentary: Male Reproductive System Congenital Malformations and the Risk of Autism Spectrum Disorder. Am J Epidemiol 2018; 187:664-667. [PMID: 29452336 PMCID: PMC5884740 DOI: 10.1093/aje/kwx369] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2017] [Accepted: 10/24/2017] [Indexed: 11/14/2022] Open
Abstract
Autism spectrum disorder (ASD) is a prevalent developmental disorder. Studies indicate that while ASD etiology has a genetic component, the risk is polygenic, with gene-environment interactions being likely. The prenatal period is a critical exposure window for nongenetic risk factors. Previous studies have found positive associations between congenital malformations (all types) and ASD; a few also found specific associations between genitourinary system malformations and ASD; and one study found an association between hypospadias and ASD. In the accompanying article, Rotem et al. (Am J Epidemiol. 2018;187(4):656-663) describe how they conducted a comprehensive analysis focusing on the shared risk of ASD with hypospadias or cryptorchidism, using existing data from a large Israeli health services system, which afforded several advantages because of the large sample size and low attrition of the patient population. The authors conducted a careful analysis, including sensitivity analyses, to account for risk factor and case misclassifications that might have occurred had they relied solely on preexisting diagnostic codes to define exposures and outcome. They observed positive associations between both hypospadias and cryptorchidism and ASD that were independent of numerous sociodemographic and pregnancy health factors. This study advances our understanding of ASD etiology and illustrates how existing data might be used to assess some ASD risk factors.
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Affiliation(s)
- Laura A. Schieve
- National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia (Laura A. Schieve, Stuart K. Shapira)
| | - Stuart K. Shapira
- National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia (Laura A. Schieve, Stuart K. Shapira)
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Myers L, Anderlid BM, Nordgren A, Willfors C, Kuja-Halkola R, Tammimies K, Bölte S. Minor physical anomalies in neurodevelopmental disorders: a twin study. Child Adolesc Psychiatry Ment Health 2017; 11:57. [PMID: 29209412 PMCID: PMC5706157 DOI: 10.1186/s13034-017-0195-y] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2017] [Accepted: 11/19/2017] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Minor physical anomalies (MPAs) are subtle anatomical deviations in one's appearance and may suggest altered embryogenesis. MPAs have been shown to be more common in neurodevelopmental disorders (NDDs) compared with typical development. Still, further studies are needed on MPAs in NDDs, especially using twins to adjust for confounding familial factors. METHODS Clinical assessments were conducted on 116 twins (61 NDD, 55 controls) from 51 monozygotic and 7 dizygotic pairs to examine MPAs and their association with DSM-5 defined NDDs. Additionally, the relationship between the number of MPAs within twins by zygosity was investigated. RESULTS Within the cohort sample, a specific association was found between MPAs and autism spectrum disorder (ASD) diagnosis (crude odds ratio = 1.29, p = .047; adjusted odds ratios = 1.26-1.33, adjusted p values = .032-.073) and autistic traits (crude β = 3.02, p = .002; adjusted β = 2.28, p = .019), but not NDDs in general or ADHD, nor within-pairs. Identified MPAs in ASD included overweight, hypermobility, pes planus, straight eyebrows, vision impairment, arachnodactyly/long toes, long eyelashes, and microtia. The number of MPAs within all monozygotic pairs was highly correlated (r = .88, p < .001). CONCLUSION MPAs are more frequent in participants with ASD and may be influenced by genetics. The value of MPAs for (early) detection should be further explored, as they might index individuals at increased risk for ASD in particular.
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Affiliation(s)
- Lynnea Myers
- 0000 0001 2326 2191grid.425979.4Department of Women’s and Children’s Health, Center of Neurodevelopmental Disorders (KIND), Karolinska Institutet & Center for Psychiatry Research, Stockholm County Council, Stockholm, Sweden
| | - Britt-Marie Anderlid
- 0000 0004 1937 0626grid.4714.6Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden ,0000 0000 9241 5705grid.24381.3cDepartment of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden
| | - Ann Nordgren
- 0000 0004 1937 0626grid.4714.6Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden ,0000 0000 9241 5705grid.24381.3cDepartment of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden
| | - Charlotte Willfors
- 0000 0001 2326 2191grid.425979.4Department of Women’s and Children’s Health, Center of Neurodevelopmental Disorders (KIND), Karolinska Institutet & Center for Psychiatry Research, Stockholm County Council, Stockholm, Sweden
| | - Ralf Kuja-Halkola
- 0000 0004 1937 0626grid.4714.6Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Kristiina Tammimies
- 0000 0001 2326 2191grid.425979.4Department of Women’s and Children’s Health, Center of Neurodevelopmental Disorders (KIND), Karolinska Institutet & Center for Psychiatry Research, Stockholm County Council, Stockholm, Sweden
| | - Sven Bölte
- 0000 0001 2326 2191grid.425979.4Department of Women’s and Children’s Health, Center of Neurodevelopmental Disorders (KIND), Karolinska Institutet & Child and Adolescent Psychiatry, Center for Psychiatry Research, Stockholm County Council, Gävlegatan 22B, 113 30 Stockholm, Sweden
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Abstract
BACKGROUND The aim of this meta-analysis was to investigate the prenatal, perinatal, and postnatal risk factors for children autism. METHODS PubMed, Embase, Web of Science were used to search for studies that examined the prenatal, perinatal, and postnatal risk factors for children autism. A fixed-effects model or random-effects model was used to pool the overall effect estimates. RESULTS Data from 37,634 autistic children and 12,081,416 nonautistic children enrolled in 17 studies were collated. During the prenatal period, the factors associated with autism risk were maternal and paternal age≥35 years, mother's and father's race: White and Asian, gestational hypertension, gestational diabetes, maternal and paternal education college graduate+, threatened abortion, and antepartum hemorrhage. During perinatal period, the factors associated with autism risk were caesarian delivery, gestational age≤36 weeks, parity≥4, spontaneous labor, induced labor, no labor, breech presentation, preeclampsia, and fetal distress. During the postnatal period, the factors associated with autism risk were low birth weight, postpartum hemorrhage, male gender, and brain anomaly. Parity≥4 and female were associated with a decreased risk of autism. In addition, exposure to cigarette smoking, urinary infection, mother's and father's race: Black and Hispanic, mother's country of birth outside Europe and North America, umbilical cord around neck, premature membrane rupture, 5-minutes Apgar score<7, and respiratory infection were not associated with increased risk of autism. CONCLUSION The present meta-analysis confirmed the relation between some prenatal, perinatal, and postnatal factors with autism. All these factors were examined individually, thus it was still unclear that whether these factors are causal or play a secondary role in the development of autism. Further studies are needed to verify our findings, and investigate the effects of multiple factors on autism, rather than the single factor.
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Karimi P, Kamali E, Mousavi SM, Karahmadi M. Environmental factors influencing the risk of autism. JOURNAL OF RESEARCH IN MEDICAL SCIENCES : THE OFFICIAL JOURNAL OF ISFAHAN UNIVERSITY OF MEDICAL SCIENCES 2017; 22:27. [PMID: 28413424 PMCID: PMC5377970 DOI: 10.4103/1735-1995.200272] [Citation(s) in RCA: 124] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/06/2016] [Revised: 11/06/2016] [Accepted: 11/30/2016] [Indexed: 12/16/2022]
Abstract
Autism is a developmental disability with age of onset in childhood (under 3 years old), which is characterized by definite impairments in social interactions, abnormalities in speech, and stereotyped pattern of behaviors. Due to the progress of autism in recent decades, a wide range of studies have been done to identify the etiological factors of autism. It has been found that genetic and environmental factors are both involved in autism pathogenesis. Hence, in this review article, a set of environmental factors involved in the occurrence of autism has been collected, and finally, some practical recommendations for reduction of the risk of this devastating disease in children are represented.
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Affiliation(s)
- Padideh Karimi
- Division of Genetics, Department of Biology, Faculty of Science, Tarbiat Modares University, Tehran, Iran
| | - Elahe Kamali
- Division of Genetics, Department of Biology, Faculty of Science, Isfahan University, Isfahan, Iran
| | - Seyyed Mohammad Mousavi
- Cellular and Molecular Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran
- Genetic and Identification Lab, Legal Medicine Center, Isfahan, Iran
| | - Mojgan Karahmadi
- Department of Psychiatry, School of Medicine, Isfahan University of Medical Sciences, Noor Hospital, Isfahan, Iran
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Huang F, Long Z, Chen Z, Li J, Hu Z, Qiu R, Zhuang W, Tang B, Xia K, Jiang H. Investigation of Gene Regulatory Networks Associated with Autism Spectrum Disorder Based on MiRNA Expression in China. PLoS One 2015; 10:e0129052. [PMID: 26061495 PMCID: PMC4462583 DOI: 10.1371/journal.pone.0129052] [Citation(s) in RCA: 45] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2015] [Accepted: 05/03/2015] [Indexed: 11/25/2022] Open
Abstract
Autism spectrum disorder (ASD) comprise a group of neurodevelopmental disorders characterized by deficits in social and communication capacities and repetitive behaviors. Increasing neuroscientific evidence indicates that the neuropathology of ASD is widespread and involves epigenetic regulation in the brain. Differentially expressed miRNAs in the peripheral blood from autism patients were identified by high-throughput miRNA microarray analyses. Five of these miRNAs were confirmed through quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis. A search for candidate target genes of the five confirmed miRNAs was performed through a Kyoto encyclopedia of genes and genomes (KEGG) biological pathways and Gene Ontology enrichment analysis of gene function to identify gene regulatory networks. To the best of our knowledge, this study provides the first global miRNA expression profile of ASD in China. The differentially expressed miR-34b may potentially explain the higher percentage of male ASD patients, and the aberrantly expressed miR-103a-3p may contribute to the abnormal ubiquitin-mediated proteolysis observed in ASD.
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Affiliation(s)
- Fengzhen Huang
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, P. R. China
- Department of Neurology at University of South China, The First People’s Hospital of Chenzhou, Chenzhou, Hunan, 423000, P. R. China
- Institute of Translational Medicine at University of South China, The First People’s Hospital of Chenzhou, Chenzhou, Hunan, 423000, P. R. China
| | - Zhe Long
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, P. R. China
| | - Zhao Chen
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, P. R. China
| | - Jiada Li
- State Key Laboratory of Medical Genetics of China, Central South University, Changsha, Hunan,410078, P. R. China
| | - Zhengmao Hu
- State Key Laboratory of Medical Genetics of China, Central South University, Changsha, Hunan,410078, P. R. China
| | - Rong Qiu
- School of Information Science and Engineering, Central South University, Hunan, 410083, P. R. China
- Hunan Engineering Laboratory for Advanced Control and Intelligent Automation, Hunan, 410083, P. R. China
| | - Wei Zhuang
- Department of Thoracic surgery, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, P. R. China
| | - Beisha Tang
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, P. R. China
- State Key Laboratory of Medical Genetics of China, Central South University, Changsha, Hunan,410078, P. R. China
- Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, Hunan, 410008, P. R. China
| | - Kun Xia
- State Key Laboratory of Medical Genetics of China, Central South University, Changsha, Hunan,410078, P. R. China
| | - Hong Jiang
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, P. R. China
- State Key Laboratory of Medical Genetics of China, Central South University, Changsha, Hunan,410078, P. R. China
- Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, Hunan, 410008, P. R. China
- * E-mail:
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The Association Between Autism Spectrum Disorders and Congenital Anomalies by Organ Systems in a Finnish National Birth Cohort. J Autism Dev Disord 2015; 45:3195-203. [DOI: 10.1007/s10803-015-2477-7] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
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TIMONEN-SOIVIO LAURA, VANHALA RAIJA, MALM HELI, LEIVONEN SUSANNA, JOKIRANTA ELINA, HINKKA-YLI-SALOMÄKI SUSANNA, GISSLER MIKA, BROWN ALANS, SOURANDER ANDRE. The association between congenital anomalies and autism spectrum disorders in a Finnish national birth cohort. Dev Med Child Neurol 2015; 57:75-80. [PMID: 25200584 PMCID: PMC4267988 DOI: 10.1111/dmcn.12581] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/08/2014] [Indexed: 11/26/2022]
Abstract
AIM The first aim of this study was to evaluate the association between different subgroups of autism spectrum disorders (ASDs) (childhood autism, Asperger syndrome, and pervasive developmental disorder/pervasive developmental disorder - not otherwise specified [PDD/PDD-NOS]) and congenital anomalies. Second, we assessed the association among intellectually disabled children with ASDs in the subgroups of childhood autism and PDD/PDD-NOS. METHOD Nationwide population-based register data for children with a diagnosis of ASD (n=4449; 3548 males, 901 females) were collected during years 1987-2000 from the Finnish Hospital Discharge Register. Data on congenital anomalies were derived from the National Register of Congenital Malformations. Conditional logistic regression models were used as a statistical method. The association between ASD subgroups and congenital anomalies was stratified by the presence or absence of intellectual disability. RESULTS Congenital anomalies occurred more frequently in all subgroups of ASD than in comparison participants (adjusted odds ratio [OR] for major congenital anomalies 1.8, 95% confidence interval [CI] 1.5-2.2, p<0.001). The association between congenital anomalies and childhood autism (OR 2.4, 95% CI 1.6-3.6, p<0.001) and between congenital anomalies and PDD/PDD-NOS (OR 3.7, 95% CI 2.4-5.7, p<0.001) among children with an intellectual disability was strong but remained significant also without intellectual disability (childhood autism: OR 1.7, 95% CI 1.3-2.3, p<0.001; PDD/PDD-NOS: OR 2.3, 95% CI 1.9-2.8, p<0.001). INTERPRETATION The results suggest a significant association between ASDs and congenital anomalies regardless of the ASD subgroup. The association between childhood autism and PDD/PDD-NOS and congenital anomalies is stronger among children with intellectual disability is stronger than among those without intellectual disability. These results may have relevance in examining early risk factors in autism during fetal neurodevelopment.
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Affiliation(s)
- LAURA TIMONEN-SOIVIO
- Department of Child Psychiatry, Turku University and Turku University Central Hospital, Turku
| | - RAIJA VANHALA
- Department of Child Neurology, Helsinki University and Helsinki University Central Hospital, Helsinki
| | - HELI MALM
- Teratology Information Service, Helsinki University Central Hospital, Helsinki
| | - SUSANNA LEIVONEN
- Department of Child Psychiatry, Turku University and Turku University Central Hospital, Turku
| | - ELINA JOKIRANTA
- Department of Child Psychiatry, Turku University and Turku University Central Hospital, Turku
| | | | - MIKA GISSLER
- National Institute of Health and Welfare, Helsinki, Finland
| | - ALAN S BROWN
- Department of Psychiatry, College of Physicians and Surgeons of Columbia University, New York State Psychiatric Institute, New York, NY, USA
| | - ANDRE SOURANDER
- Department of Child Psychiatry, Turku University and Turku University Central Hospital, Turku
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25
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Abstract
The fifth edition of the diagnostic and statistical manual of mental disorders (DSM-5) (APA in diagnostic and statistical manual of mental disorders, Author, Washington, 2013) has decided to merge the subtypes of pervasive developmental disorders into a single category of autism spectrum disorder (ASD) on the assumption that they cannot be reliably differentiated from one another. The purpose of this review is to analyze the basis of this assumption by examining the comparative studies between Asperger's disorder (AsD) and autistic disorder (AD), and between pervasive developmental disorder not otherwise specified (PDDNOS) and AD. In all, 125 studies compared AsD with AD. Of these, 30 studies concluded that AsD and AD were similar conditions while 95 studies found quantitative and qualitative differences between them. Likewise, 37 studies compared PDDNOS with AD. Nine of these concluded that PDDNOS did not differ significantly from AD while 28 reported quantitative and qualitative differences between them. Taken together, these findings do not support the conceptualization of AD, AsD and PDDNOS as a single category of ASD. Irrespective of the changes proposed by the DSM-5, future research and clinical practice will continue to find ways to meaningfully subtype the ASD.
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Abstract
This review focuses on identifying up-to-date number of publications that compared DSM-IV/ICD-10 Asperger's disorder (AspD) to Autistic Disorder/High-functioning Autism (AD/HFA). One hundred and twenty-eight publications were identified through an extensive search of major electronic databases and journals. Based on more than 90 clinical variables been investigated, 94 publications concluded that there were statistically significant or near significant level of quantitative and/or qualitative differences between AspD and AD/HFA groups; 4 publications found both similarities and differences between the two groups; 30 publications concluded with no differences between the two groups. Although DSM-5 ASD will eliminate Asperger's disorder. However, it is plausible to predict that the field of ASD would run full circle during the next decade or two and that AspD will be back in the next edition of DSM.
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Affiliation(s)
- Luke Y Tsai
- Department of Psychiatry, University of Michigan Medical School, 2385 Placid Way, Ann Arbor, MI, 48105, USA,
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27
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Neggers YH. Increasing prevalence, changes in diagnostic criteria, and nutritional risk factors for autism spectrum disorders. ISRN NUTRITION 2014; 2014:514026. [PMID: 24967269 PMCID: PMC4045304 DOI: 10.1155/2014/514026] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 10/27/2013] [Accepted: 12/09/2013] [Indexed: 12/31/2022]
Abstract
The frequency of autism spectrum disorders (ASD) diagnoses has been increasing for decades, but researchers cannot agree on whether the trend is a result of increased awareness, improved detection, expanding definition, or an actual increase in incidence or a combination of these factors. Though both genetic and multiple environmental risk factors have been studied extensively, many potentially modifiable risk factors including nutritional and immune function related risk factors such as vitamin D, folic acid, and metabolic syndrome have not received sufficient attention. Several recent studies have put forward hypotheses to explain the mechanism of association between both folic acid and vitamin D and autism. A continuous rise in the prevalence of autism in the USA has coincided with a significant enhancement of maternal folate status with FDA mandated folic acid fortification of certain foods starting in 1998. There is also a growing body of research that suggests that vitamin D status either in utero or early in life may be a risk for autism. In this communication, controversies regarding increase in estimate of prevalence, implications of changes in definition, and possible association between some modifiable nutritional risk factors such as folic acid and vitamin D and ASD will be discussed.
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Affiliation(s)
- Yasmin H. Neggers
- Department of Human Nutrition, University of Alabama, P.O. Box 870311, Tuscaloosa, AL 35487, USA
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Abstract
AbstractThe results of conducted research studies suggest that heredity and early fetal and neonatal development play a causal role in autism. The objective was to determine a relationship between pre-, peri-, and neonatal factors and autism. The relationship between genders and individual risk factors for autism was also examined. A case-control study was conducted among 288 children (96 cases with childhood or atypical autism and 192 controls individually matched to cases by the year of birth, sex, and general practitioners). Data on autism diagnosis and other medical conditions were acquired from physicians. All other information on potential autism risk factors were collected from mothers. Autism risk was significantly higher when mothers were taking medications (OR=2.72, 95%CI: 1.47-5.04) and smoked during pregnancy (OR=3.32, 95%CI: 1.12-9.82). It was also significantly associated with neonatal dyspnea (OR=3.20, 95%CI: 1.29-8.01) and congenital anomalies (OR=7.17, 95%CI: 2.23-23.1). In gender analysis only congenital anomalies were significantly associated with autism for girls but all of mentioned factors stayed independent risk factors for boys.
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Guinchat V, Thorsen P, Laurent C, Cans C, Bodeau N, Cohen D. Pre-, peri- and neonatal risk factors for autism. Acta Obstet Gynecol Scand 2012; 91:287-300. [PMID: 22085436 DOI: 10.1111/j.1600-0412.2011.01325.x] [Citation(s) in RCA: 157] [Impact Index Per Article: 12.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
OBJECTIVE To identify pre-, peri- and neonatal risk factors for pervasive developmental disorders (PDD). METHODS We searched the Medline database through March 2011 for relevant case-control and population-based studies on pre-, peri- and neonatal hazards related to PDD, including autism. We identified 85 studies for this review. Data were extracted systematically and organized according to risk factors related to family history, pregnancy, gestational age, delivery, birth milestones and the neonate's condition at birth. RESULTS During the prenatal period, risk factors for PDD were advanced maternal or paternal ages, being firstborn vs. third or later, maternal prenatal medication use and mother's status as foreign born. During the perinatal and neonatal periods, the risk factors for PDD were preterm birth, breech presentation, planned cesarean section, low Apgar scores, hyperbilirubinemia, birth defect and a birthweight small for gestational age. The influence of maternal pre-eclampsia, diabetes, vomiting, infections and stress during pregnancy requires further study in order to determine risk for PDD. DISCUSSION Despite evidence for the association of some pre-, peri- and neonatal risk factors associated with PDD, it remains unclear whether these risks are causal or play a secondary role in shaping clinical expression in individuals with genetic vulnerability. A plausible hypothsesis is that improvements in obstetric and neonatal management have led to an increased rate of survivors with pre-existing brain damage. Given the variety of risk factors, we propose that future studies should investigate combinations of multiple factors, rather than focusing on a single factor.
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Affiliation(s)
- Vincent Guinchat
- Department of Child and Adolescent Psychiatry, Pitié-Salpêtrière Universitary Hospital, Paris, France.
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Matson ML, Matson JL, Beighley JS. Comorbidity of physical and motor problems in children with autism. RESEARCH IN DEVELOPMENTAL DISABILITIES 2011; 32:2304-2308. [PMID: 21890317 DOI: 10.1016/j.ridd.2011.07.036] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/22/2011] [Accepted: 07/19/2011] [Indexed: 05/31/2023]
Abstract
Autism and the related pervasive developmental disorders are a heavily researched group of neurodevelopmental conditions. In addition to core symptoms, there are a number of other physical and motor conditions that co-occur at high rates. This paper provides a review of factors and behaviors that correlate highly with disorders on the autism spectrum. Among these conditions are premature birth, birth defects, gross and fine motor skills, and obesity. Each of these topics is addressed, and what researchers have found are presented. These data have important implications for the types of collateral behaviors that should be assessed and treated, along with the core symptoms of autism.
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Ploeger A, Galis F. Evo Devo and cognitive science. WILEY INTERDISCIPLINARY REVIEWS. COGNITIVE SCIENCE 2011; 2:429-440. [PMID: 26302202 DOI: 10.1002/wcs.137] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Evo Devo (evolutionary developmental) biology forges a synthesis of evolutionary and developmental processes. Evo Devo is the result of collaborative work of evolutionary and developmental biologists after the discovery of regulatory genes that human beings share with many other animals, including fruit flies, frogs, and rats. Compared to traditional evolutionary biologists, Evo Devo biologists focus on processes underlying the generation of evolutionary novelties, rather than on how natural selection changes gene frequencies in populations and how organisms are adapted to their environment. Evo Devo biologists try to answer questions such as: How do novel structures arise? Which mechanisms facilitate or constrain evolutionary change? In this article we argue that insights from Evo Devo research can contribute to the understanding of the evolution and development of cognition, and of the origin of neurocognitive disorders. We discuss three major Evo Devo topics: modularity, evolvability, and developmental constraints. We argue that each of these topics are relevant for research in cognitive science, and we argue that interdisciplinary research is necessary in order to unravel the evolutionary and developmental mechanisms of cognitive traits and disorders. WIREs Cogni Sci 2011 2 429-440 DOI: 10.1002/wcs.137 For further resources related to this article, please visit the WIREs website.
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Affiliation(s)
- Annemie Ploeger
- Department of Psychology, University of Amsterdam, Amsterdam, The Netherlands
| | - Frietson Galis
- Department of Biology, Leiden University, Leiden, The Netherlands
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Kim EK, Neggers YH, Shin CS, Kim E, Kim EM. Alterations in lipid profile of autistic boys: a case control study. Nutr Res 2010; 30:255-60. [PMID: 20534328 DOI: 10.1016/j.nutres.2010.04.002] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2010] [Revised: 04/06/2010] [Accepted: 04/07/2010] [Indexed: 12/21/2022]
Abstract
We hypothesize that autism is associated with alterations in the plasma lipid profile and that some lipid fractions in autistic boys may be significantly different than those of healthy boys. A matched case control study was conducted with 29 autistic boys (mean age, 10.1 +/- 1.3 years) recruited from a school for disabled children and 29 comparable healthy boys from a neighboring elementary school in South Korea. Fasting plasma total cholesterol (T-Chol), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), the LDL/HDL ratio, and 1-day food intakes were measured. Multiple regression analyses were performed to assess the association between autism and various lipid fractions. The mean TG level (102.4 +/- 52.4 vs 70.6 +/- 36.3; P = .01) was significantly higher, whereas the mean HDL-C level (48.8 +/- 11.9 vs 60.5 +/- 10.9 mg/dL; P = .003) was significantly lower in cases as compared to controls. There was no significant difference in T-Chol and LDL-C levels between cases and controls. The LDL/HDL ratio was significantly higher in cases as compared to controls. Multiple regression analyses indicated that autism was significantly associated with plasma TG (beta = 31.7 +/- 11.9; P = .01), HDL (beta = -11.6 +/- 2.1; P = .0003), and the LDL/HDL ratio (beta = 0.40 +/- 0.18; P = .04). There was a significant interaction between autism and TG level in relation to plasma HDL level (P = .02). Fifty-three percent of variation in the plasma HDL was explained by autism, plasma TG, LDL/HDL ratio, and the interaction between autism and plasma TG level. These results indicate the presence of dyslipidemia in boys with autism and suggest a possibility that dyslipidemia might be a marker of association between lipid metabolism and autism.
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Affiliation(s)
- Eun-Kyung Kim
- Department of Food Science, Gangneung-Wonju National University, Gangwon-do, Korea
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Current world literature. Curr Opin Pediatr 2010; 22:246-55. [PMID: 20299870 DOI: 10.1097/mop.0b013e32833846de] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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34
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Current World Literature. Curr Opin Neurol 2010; 23:194-201. [DOI: 10.1097/wco.0b013e328338cade] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Msall ME. Central nervous system connectivity after extreme prematurity: understanding autistic spectrum disorder. J Pediatr 2010; 156:519-21. [PMID: 20303436 DOI: 10.1016/j.jpeds.2009.12.035] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2009] [Accepted: 12/17/2009] [Indexed: 11/17/2022]
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