Autism and Environmental Factors

Autism and Environmental Factors Autism and Environmental Factors Omar Bagasra Claflin University, Orangeburg, South Carolina, USA and Cherilyn Heggen Immunologist, Florida, USA Illustrations by Muhammad I. Hossain Orangeburg, South Carolina, USA This edition first published 2018 © 2018 John Wiley & Sons, Inc. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, except as permitted by law. Advice on how to obtain permission to reuse material from this title is available at http://www.wiley.com/go/permissions. The right of Omar Bagasra and Cherilyn Heggen to be identified as the author(s) of this work has been asserted in accordance with law. Registered Offices John Wiley & Sons, Inc., 111 River Street, Hoboken, NJ 07030, USA Editorial Office 111 River Street, Hoboken, NJ 07030, USA For details of our global editorial offices, customer services, and more information about Wiley products visit us at www.wiley.com. Wiley also publishes its books in a variety of electronic formats and by print‐on‐demand. Some content that appears in standard print versions of this book may not be available in other formats. Limit of Liability/Disclaimer of Warranty The publisher and the authors make no representations or warranties with respect to the accuracy or completeness of the contents of this work and specifically disclaim all warranties; including without limitation any implied warranties of fitness for a particular purpose. This work is sold with the understanding that the publisher is not engaged in rendering professional services. The advice and strategies contained herein may not be suitable for every situation. 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Neither the publisher nor the author shall be liable for any damages arising here from. Library of Congress Cataloging‐in‐Publication Data Names: Bagasra, Omar, 1948– author. | Heggen, Cherilyn, 1973– author. Title: Autism and environmental factors / by Omar Bagasra, Cherilyn Heggen ; illustrations by Muhammad I. Hossain. Description: Hoboken, NJ : Wiley, 2018. | Includes bibliographical references and index. | Identifiers: LCCN 2017056771 (print) | LCCN 2017059203 (ebook) | ISBN 9781119042266 (pdf) | ISBN 9781119042273 (epub) | ISBN 9781119042259 (hardback) Subjects: | MESH: Autism Spectrum Disorder–etiology | Environmental Exposure–adverse effects | Gene-Environment Interaction Classification: LCC RC553.A88 (ebook) | LCC RC553.A88 (print) | NLM WS 350.8.P4 | DDC 616.85/882–dc23 LC record available at https://lccn.loc.gov/2017056771 Cover Design: Wiley Cover Image: Courtesy of Muhammad Hossain Set in 10/12pt Warnock by SPi Global, Pondicherry, India 10 9 8 7 6 5 4 3 2 1 v Contents Acknowledgments xi Prologue xiii 1 Introduction to Autism Spectrum Disorders 1 Smell of Autism 5 The Roundup™ Conundrum 7 Testosterone and Male Gender Bias 9 Connecting the Dots 12 Why Is There a “Spectrum” in Autism? 20 Are Genetic Mutations the Cause of Autism? 23 ASD Parent and Affected Child Exome Sequencing Display De Novo Mutation 23 More Than 1,000 Genetic and Genomic Disorders and Still Counting 24 Why Do Certain Chemicals Induce Specific Depletions of Certain Brain Compartments? 30 Genesis of an ASD Brain 31 Pinpointing Critical Steps Where the Autistic Brain Emerges 32 Is Finding Mutations the Path to Discovering the Genesis of ASD? 34 Does Brain Size Matter? 36 How Autism Develops in a Fetal Brain 36 Why Is There a “Spectrum” in ASD? 39 ASD and Vaccines 41 Thimerosal Containing Mercury Stays in the Body and Is Very Toxic 42 Summary 43 References 43 2 What is Autism? 51 Legacy of Autism 51 A Short History of Autism 53 DSM‐5 and the ASD Spectrum 60 vi Contents Changes in ASD diagnosis approved by the APA 61 The impact of the Recent DSM‐5 Changes on Diagnosis and Support Practices 61 A New ASD Diagnosis Category: Social Communication Disorder 62 ASD or a Giant Spectrum of Socioneuropsychological Disorders 62 Asperger Syndrome 63 Pervasive Developmental Disorder Not Otherwise Specified 63 Autistic Disorder 64 Rett Syndrome 64 Childhood Disintegrative Disorder 64 Is Autism a Genetic Disease? 65 Synthetic Chemicals Lack Coevolutionary Adaptation 66 Myth of the Genetic Origin of Autism 67 Phenotypic Heterogeneity in Autism 67 Why Fragile X Syndrome or Tuberous Sclerosis Should Not Be Included in ASD 70 Tuberous Sclerosis 71 Is Finding Mutation the Path to Discovering the Origin of ASD? 72 How Quickly Does Human DNA Mutate? 73 What is the Mutation Rate in the Whole Human Genome? 74 Does Brain Size Matter? 74 Genetics versus Environment 75 References 77 3 Olfaction and Autism 83 How Do We Smell? 87 Summary and Conclusions 92 References 92 4 Oxytocin, Arginine Vasopressin and Autism Spectrum Disorder 97 Oxytocin 97 Why Oxytocin Therapy May be Important for ASD? 99 Hormones, Neuropeptide Arginine Vasopressin and Oxytocin in ASD 102 Development of Oxytocin and AVP Neurons in Various Animals and in Man 103 Oxytocin and Social Experience in Development 104 Oxytocin and Developmental Neurological Disorders 106 Exogenous Oxytocin Treatments in Humans 108 Intranasal and Intravenous Oxytocin Studies in ASD 109 Oxytocin Trials in ASD: Beyond the Hype and Hope 110 Summary and Conclusions 112 References 113 Contents vii 5 Male Gender Bias and Levels of Male Hormones During Fetal Development 123 Association between 2D:4D Ratio and Brain Connection Development 129 Male and Female Estrogen and Testosterone Hormone Regulations 130 Are there Synthetic Chemicals that Humans Are Not Evolutionarily Exposed To? 130 Why Male Gender Bias? 131 Male and Female Brains in a Test Tube 132 Effects of Three Different Levels of Testosterone on Neuronal Morphology 133 Molecular Basis of Gender Bias in ASD 134 References 136 6 Maternal Twins and Male Gender Bias in Autism Spectrum Disorders 143 The Conundrum of ASD Discordance in Maternal Twins 146 Role of Environment in Maternal Twins revealed by Numerous Methods under Many Conditions 149 What Types of Discordance are Observed in Maternal Twins? 149 Differences in Frontal and Limbic Brain Activation in Monozygotic Twin Pairs Discordant for Severe Stressful Life Events 150 Structural Connectivity of the Brain of a Child with ASD and That of the Unaffected Identical Twin 150 Differences in Genomic and Epigenomic Expression in Monozygotic Twins Discordant for Rett Syndrome 150 Differences in CNV between Discordant Monozygotic Twins with Congenital Heart Defects 151 History of Autism Becoming a Genetic Disease 151 Many Diseases That Were Considered Genetic are Being Reassessed 152 De Novo Mutations 156 To find a Scientific Analysis of ASD Genesis 158 What are Neuroblastomas? 159 What Method Did We Use? 160 Possible Etiologies of Autism 160 Epigenetic Explained 160 Epigenetic Changes and the Environment: How Lifestyle Can Influence Epigenetic Change from One Generation to the Next 161 Factors Other Than Environment That May Be Contributing to ASD 161 Older Age of Mother and Increased Risk 161 Conclusion and Summary 163 References 163 viii Contents 7 Autism and Exposure to Environmental Chemicals 169 Contribution of Fragrances to ASD 178 Effects of Fragrances on Male Oxytocin‐Receptor Positive Neurons 184 Effects of Fragrances on Female Oxytocin‐Receptor Positive Neurons 186 How Synthetic Chemicals in Fragrances Affect Fetal Brain Development 186 Synthetic Musks 186 How Do Synthetic Musks Get Into the Food Chain? 189 How Are People Exposed to Synthetic Musks? 189 Musks in Food 191 Diethyl Phthalate 191 Octinoxate 193 Benzyl Benzoate and Benzyl Salicylate 194 d‐Limonene 194 α‐Pinene 195 Synthetic EDCs 195 Why Is It Important To Look at EDCs and Their Potential Effects on Our Next Generations? 196 Where in Fetal Life Are Androgen Receptors Expressed? 199 Why Testosterone is Essential for Engineering a Male Brain 200 Spatial Memory 207 Anxiety‐Related Behavior 207 Play Fighting and Aggression 208 Adverse Effects of EDCs and Their Mechanisms of Action 208 Effects of Testosterone or AR Mimicking EDCs 211 Early Puberty in Males 214 Change in Sex Ratio 215 Effects of EDCs on Neurodevelopmental and Neuroendocrine Systems 215 EDC Effects on Steroid Hormone Receptors in the Brain 217 Are the EDCs and other Synthetic Chemicals Depopulating the Human Race? 219 Summary 223 References 224 8 Maternal Antibodies to Fetal Brain Neurons and Autism 235 Link between Damage to the Fetal Brain

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