NEUROBIOLOGICAL ISSUES IN AUTISM

Transcription

1 NEUROBIOLOGICAL ISSUES IN AUTISM

2 CURRENT ISSUES IN AUTISM Series Editors: Eric Schopler and Gary B. Mesibov University of North Carolina School of Medicine Chapel Hilf, North CaroJina AUTISM IN ADOLESCENTS AND ADULTS Edited by Eric Schopler and Gary B. Mesibov COMMUNICATION PROBLEMS IN AUTISM Edited by Eric Schop/er and Gary B. Mesibov THE EFFECTS OF AUTISM ON THE FAMILY Edited by Eric Schopler and Gary B. Mesibov NEUROBIOLOGICAL ISSUES IN AUTISM Edited by Eric Schopler and Gary B. Mesibov SOCIAL BEHAVIOR IN AUTISM Ed ited by Eric Schopler and Gary B. Mesibov

3 NEU ROBIOLOG ICAL ISSUES IN AUTISM Edited by Eric Schopler and Gary B. Mesibov University of North Carolina School of Medicine Chapel Hill, North Carolina Springer Science+Business Media, LLC

4 Neurobiological issues in autism. Library of Congress Cataloging in Publication Data. (Current issues in autism) Based on the 6th Annual TEACCH Conference held in Chapel Hill in Includes bibliographies and Index. I. Autism-Congresses. 2. Neurobiology-Congresses. I. Schopler, Erle. 11. Mesibov, Gary B TEACCH Conferenee (6th: 1985: Chapei Hili, N.C.) IV. Series, [ONLM: I. Autism-eongresses. 2. Neurobiology-eongresses. WM N ) RC553.A88N ' ISBN ISBN (ebook) DOI / Springer Scienee+Business Media New York Originally published by Plenum Press, New york in Softcover reprint ofthe hardcover 1st edition 1987 All rights reserved No part of this book may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanica1, photocopying, mierofilming, reeording, or otherwise, without written permission from the Publisher

5 To the North Carolina children and adults with autism and their families in the hope that the exciting new developments in this book will lead to new ways to assist in their struggle

6 Contributors MARGARET L. BAUMAN, Pediatric Neurology Unit, Massachusetts General Hospital, Boston, Massachusetts GEORGE R. BREESE, Departments of Psychiatry and Pharmacology, Child Development Institute and Mental Health Clinical Research Center, University of North Carolina, Chapei Hili, North Carolina MAGDA CAMPBELL, Department of Psychiatry, New York University Medical Center, New York, New York LARRY R. CHURCHILL, Departments ofsocial and Administrative Medicine and Religious Studies, University of North Carolina, ChapeI Hili, North Carolina ROLAND D. CIARANELLO, Division ofchild Psychiatry and Child Development, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, Califomia MARY COLEMAN, Children's Brain Research Clinic, Washington, DC 20008; and Georgetown University School of Medicine, Washington, DC ERIC COURCHESNE, Neuroseiences Department, School of Medicine, University of Califomia at San Diego, La Jolla, Califomia 92093; and Neuropsychology Research Laboratory, Children's Hospital Research Center, San Diego, California ALAN W. CROSS, Departments of Social and Administrative Medicine and Pediatrics, University of North Carolina, Chapel Hili, North Carolina GERALDINE DAWSON, Department of Psychology, University of Washington, Seattle, Washington G. ROBERT DeLONG, Pediatric Neurology Unit, Massachusetts General Hospital, Boston, Massachusetts MARTHA B. DENCKLA, Developmental Neurology Branch, National Institute of Neurological and Communicative Disorders and Stroke, Bethesda, Maryland GLEN R. ELLIOTT, Division of Child Psychiatry and Child Development, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, Califomia vii

7 viii CONTRIBUTORS RANDALL W. EVANS. Biological Seiences Research Center, University ofnorth Carolina, Chapei Hili. North Carolina DEBORAH FEIN, Laboratory of Neuropsychology, Boston University Medical Center, Boston. Massachusetts SUSAN E. FOLSTEIN, Division of Psychiatrie Genetics, Department of Psychiatry, Johns Hopkins University, Baltirnore, Maryland DANIEL X. FREEDMAN. Department of Psychiatry, University of Califomia at Los Angeles, Los Angeles, Califomia WAYNE H. GREEN, Department of Psychiatry, New York University Medical Center, New York, New York THOMAS GUALTIERI, Department of Psychiatry, University of North Carolina, ChapeI Hili, North Carolina NANCY M. P. KING. Department of Social and Administrative Medicine, University of North Carolina, Chapel Hili, North Carolina MARCEL KINSBOURNE, Eunice Kennedy Shriver Center for Mental Retardation, Waltham, Massachusetts 02254; and Harvard Medical School, Boston. Massachusetts EUGENE M. C. LEE, Child at Risk Project, Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Harborview Medical Center, Seattle, Washington CATHERINE LORD, Department of Pediatrics, University of Alberta, and Department of Psychology, Glenrose Hospital. Edmonton, Alberta T5G OB7, Canada GARY B. MESIBOV. Division TEACCH, University of North Carolina, Chapel Hill, North Carolina ROBERT A. MUELLER, Departments of Anesthesiology and Pharrnacology, University of North Carolina, Chapel Hill, North Carolina JAAK PANKSEPP, Department of Psychology, Bowling Green State University, Bowling Green, Ohio DEBRA R. PAITERSON. Biological Seiences Research Center, University of North Carolina, Chapel Hili, North Carolina BRUCE PENNINGTON, University ofcolorado Health Seiences Center, Denver, Colorado RICHARD PERRY, Department of Psychiatry, New York University Medical Center. New York, New York DANIEL J. RAITEN, Department of Behavioral Medicine, Children's Hospital, National Medical Center, Washington, DC ROBERT JAY REICHLER. Child at Risk Project, Department of Psychiatry and Behaviora1 Seiences. University of Washington School of Medicine, Harborview Medical Center, Seattle, Washington 98104

8 CONTRIBUTORS ix BERNARD RIMLAND, Institute for Child Behavior Research, San Diego, Califomia JUDITH M. RUMSEY, Child Psychiatry Branch, National Institute of Mental Health, Bethesda, Maryland MICHAEL L. RUTTER, M. R. C. Child Psychiatry Unit, Department of Child and Adolescent Psychiatry, Institute of Psychiatry, University of London, De Crespigny Park, Denmark Hili, London SE5 8AF, England TONY L. SAHLEY, Coleman Memorial Laboratory, Department of Otolaryngology, University of California, San Francisco, Califomia ERIC SCHOPLER, Division TEACCH, University of North Carolina, Chapel Hili, North Carolina STEPHEN R. SCHROEDER, Department of Psychiatry, Child Development Institute, University of North Carolina, Chapel Hili, North Carolina MICHAEL C. SHARP, Department of Pediatrics, University of North Carolina, Chapel Hili, North Carolina ARTHUR M. SMALL, Department of Psychiatry, New York University Medical Center, New York, New York LUKE Y. TSAI, Department of Psychiatry, University of Kansas, Kansas City, Kansas LYNN WATERHOUSE, Child Behavior Study, Trenton State College, Trenton, New Jersey ARTHUR YUWILER, Neurobiochemistry Research, Veterans Administration, Los Angeles, California 90073; and Department of Psychiatry, University of Califomia at Los Angeles, Los Angeles, Califomia 90024

9 Preface As a division of the School of Medicine at the University of North Carolina at ChapeI Hili, TEACCH has always been involved in the latest biological research on autism and related developmental disabilities. However, until now there has not been sufficient information to justify aseparate volume on this most important topic. Recent advances both in our understanding of the brain and in the technology to facilitate the measurement of neurological functioning have stimulated significant growth, which is reflected in this volume. As with the preceding books in this series, Current Issues in Autism, this volume is based on one of the annual TEACCH conferences held in ChapeI Hili each May. The books are not simply published proceedings of the conference papers, however. lnstead, conference participants are asked to develop chapters around their presentations, and other international experts whose work is beyond the scope of the conference, but related to the major theme, are asked to contribute as weil. These volumes are intended to provide the most current knowledge and professional practice available to us concerning major issues in autism. In this volume, recent advances in our understanding of causes and neurological mechanisms are described by the leading scientists and c1inicians in the field. The latest genetic and pharmacological research is also cited, along with speculations about future advances in the field. We believe that the infonnation in this volume is the most current report of the state of the art in this rapidly expanding area and will be most useful to professionals and parents concerned with understanding and helping people with autism. ERIC SCHOPLER GARY B. MESIBOV xi

10 Acknowledgments We are, of course, indebted to many people for their cooperation and assistance, and it is our great pleasure to acknowledge each of them. First, our thanks to Helen Garrison, who organized the conference that was the starting point for this book. Her thoroughness, attention to detail, and organizational ability have been impressive throughout this project. John Swetnam provided valuable editorial assistance in strengthening individual chapters and managing the overall product. Our secretarial staff, including Judy Carter, Deana Betterton, and Vickie Weaver, provided competent typing and secretarial assistance. We also thank our TEACCH colleagues for their thoughtful and stimulating suggestions. As with all of the efforts in the TEACCH program, this book would not have been possible without the assistance of the families of autistic people in North Carolina, the state legislature, and the University of North Carolina School of Medicine. The ability of these three groups to cooperate in their ongoing efforts gives us all hope and optimism as we struggle to help those with this most difficult handicap. E.S. G.B.M. xiii

11 Contents Part I: Introduction and Overview Chapter 1 INTRODUGION TO NEUROBIOLOGICAL ISSUES IN AUTISM Eric Schopler and Gary B. Mesibov Tensions between Basic and Applied Research 3 Overview of the Book 5 Summary References Chapter 2 OVERVIEW OF BIOMEDICAL ISSUES IN AUTISM Robert Jay Reichler and Eugene M. C. Lee Specificity Model 14 Etiological Specificity Biological Mechanisms and Models 16 Neurologicall Anatomical Approach 16 Brain Anatomy and Autistic Symptoms 21 Neurochemistry Genetics Critique of Localization Approaches and Models Developmental Approach 34 Summary and Conclusions References xv

12 xvi CONTENTS Chapter 3 NEUROBIOLOGICAL RESEARCH PRIORITIES IN AUTISM Iud ith M. Rumsey and Martha B. Denckla Characterization and Classification of Behavioral Pathology 44 Localization Research Neurochemistry Conclusion 53 Glossary 54 References Chapter 4 ETHICAL ISSUES IN THE HEALTH CARE OF CHILDREN WITH DEVELOPMENTAL HANDICAPS Alan W. Cross, Larry R. Churchill, Michael C. Sha rp, and Nancy M. P. King The RoJe of Ethical Reflection in Medicine 63 The Case Approach to Ethical Analysis 65 Case 1: Leonard 66 Case 2: Monica Case 3: Charlie 70 Case 4: Robert 72 Case 5: Susan 74 Case 6: Samantha 75 Summary References Part 11: Neurological and Genetic Issues: Theory Based Chapter 5 AUTISM: FAMILIAL AGGREGATION AND GENETIC IMPLICATIONS Susan E. Folste in and Michael L. Rutter Introduction Characteristics of Autism 84

13 CONTENTS xvii Evidence for Genetic Factors in Autism Derived from Family and Twin Studies of Cases of Unknown Etiology Single Gene Disorders Associated with Autism ", Genetic Evaluation and Counseling for Families with an Autistic Child 96 Conclusions References Chapter 6 CEREBRAL-BRAINSTEM RELATIONS IN INFANTILE AUTISM Marcel Kinsbourne Overactivation in Autism : Behavioral Observations 107 Overactivation in Autism : Psychopathological Observations 109 The Varieties of Hemispheric Dysfunction 110 Activational Pathology 111 Neurological Findings in Autism Peripheral Laterality 112 Evidence on Peripheral Laterality in Infantile Autism 113 Hemisphere Dysfunction: Less Is More? 114 Evidence on Central Laterality in Infantile Autism 115 Ascending Activation and Laterality 117 Overactivation and Autistic Symptomatology 117 Approach versus Withdrawal and the Balance of Hemispheric Activation 119 References Chapter 7 IMPLICATIONS OF SOCIAL DEFICITS IN AUTISM FOR NEUROLOGICAL DYSFUNCTION Deborah Fein, Bruce Pennington, and Lynn Waterhouse Introduction Social Deficits in Autism 127 Neurological Basis of Social Behavior 131 Neurological Involvement in Autism

14 xviii CONTENTS Conclusions Referenees Chapter 8 THE NEUROCHEMICAL BASIS OF SYMPTOMS IN THE LESCH-NYHAN SYNDROME : RELATIONSHIP TO CENTRAL SYMPTOMS IN OTHER DEVELOPMENTAL DISORDERS George R. Breese, Robert A. Mueller, and Stephen R. Schroeder Introduetion Neurological Symptoms 146 Neurochemieal Assessment 146 Comparison with Parkinsonism and Huntington Chorea 148 Modeling the Neurochemieal Deficit 149 Age-Dependent Responses: Neurobiologieal Considerations 150 Investigation of Dopamine Reeeptor Supersensitivity 152 Purinergie Mechanisms Associated with Self-Biting 153 Possible Treatment Strategies 153 Relevanee of Neurochemical Findings to Other Developmental Disorders Summary Referenees Part III: Neurological and Genetic Issues: Empirical Basis Chapter 9 THE SEARCH FOR NEUROLOGICAL SUBGROUPS IN AUTISM Mary Coleman Introduetion Genetie Disorders 164 Infeetious Disorders 166 Birth Injury 167 Metabolie Diseases 167 Struetural Changes in the Brain Associated with Autistic Symptoms 170 Other DiseaseEntities 171 B1indness and Deafness 173

15 CONTENTS xix Conclusion 173 References Chapter 10 PRE-, PERI-, AND NEONATAl FACTORS IN AUTISM luke Y. Tsai Prenatal Factors 180 Perinatal Factors 184 Neonatal Factors 186 Conclusions References Chapter 11 NEUROBIOlOGICAllMPlICATIONS OF SEX DIFFERENCES IN AUTISM Catherine lord and Eric Schopler Sex Differences in Incidence 192 Sex Ratios, Autism, and Mental Retardation 194 Genetic Implications of Differences in Sex Ratios 196 Relevance of Sex Differences in Normal Development to Autism 202 Sex Differences in Identification, Diagnosis, and Referral 206 Conclusion 207 References Chapter 12 THE ROlE OF ABNORMAL HEMISPHERIC SPECIAlIZATION IN AUTISM Geraldine Dawson Introduction Review of the Evidence 213 Theories Regarding the Role of Abnormal Hemispheric Specialization in Autism 215 A Test of Some Predictions 219 The Possible Role of Abnormal Hemispheric Specialization in the Affective and Social Deficits of Autistic Children 221 Conclusion 223 References

16 xx CONTENTS Chapter 13 BRAIN LESIONS IN AUTISM G. Robert DeLong and Margaret L. Bauman Introduction The Significance of Drain Lesions : Neurologieal versus Nonneurologieal Autism 229 Clinical Studies 230 Epidemiological Factors Associated with Encephalopathy Neuroradiological Studies 231 Cases with Discrete Medial Temporal Lobe Lesions 235 Neuroanatomie Studies Discussion References, 240 Part IV: Neurochemieal, Biochemieal, and NutritionaI Issues Chapter 14 NEUROCHEMICAL HYPOTHESES OF CHILDHOOD PSYCHOSES Gien R. Elliott and Roland D. Ciaranello Introduction Evidence of Central Nervous System Abnormalities 246 Evidence of Abnormalities in Drain Neuroregulators 249 Future Directions for Research 254 References Chapter 15 NEUROTRANSMITTER RESEARCH IN AUTISM Arthur Yuwiler and Daniel X. Freedman General Introduction Transmitters 264

17 CONTENTS xxi Conclusion 276 References Chapter 16 A NEUROPHYSIOlOGICAl VIEW OF AUTISM Eric Courchesne Introduction An Introduction to ERPs 287 ERP Research Requirements and Studies of Autism 292 ERP Studies in Autism ERP Findings: Summary and ConcIuding Remarks 310 A Conjecture about the Pathophysiology of Autism 312 References Chapter 17 NUTRITION AND DEVElOPMENTAl DISABllITlES : ISSUES IN CHRONIC CARE Daniel ]. Raiten Introduction Dietary Adequacy 327 Nutrition and Behavior Pharmacology and Nutrition 330 References Part V: Medication Issues Chapter 18 OVERVIEW OF DRUG TREATMENT IN AUTISM Magda Campbell, Richard Perry, Arthur M. SmalI, and Wayne H. Green Introduction Historical Background 346 Recent Studies 348 Conclusion 352 References

18 xxii CONTENTS Chapter 19 POSSIBlE BRAIN OPIOIO INVOlVEMENT IN OISRUPTED SOCIAl INTENT ANO LANGUAGE DEVElOPMENT OF AUTISM laak Panksepp and Tony l. Sahley Background Information Possible Neurochemical Oysfunctions in Autism 36I Concluding Remarks 366 References Chapter 20 THE MEDICAl TREATMENT OF AUTISTIC PEOPLE: PROBLEMS ANO SIOE EFFECTS Thomas Gualtieri, Randall W. Evans, and Oebra R. Patterson Neuroleptic Drugs Fenfluramine 377 "Megavitamin" Therapy 378 Anticonvulsant Drugs 384 References Chapter 21 MEGAVITAMIN B6 ANO MAGNESIUM IN THE TREATMENT OF AUTISTIC CHILOREN ANO AOULTS Bernard Rimland The First Institute for Child Behavior Research Vitamin Study 390 The Institute for Child Behavior ResearchJUniversity of Califomia Medical School Vitamin B6 Study 394 Additional Studies in the United States of Vitamin B6 with Autistic Individuals The French Studies of Vitamin B6 and Magnesium 396 Criticismsof Vitamin B6 Therapy with Autism Oiscussion References INDEX