Autism and Environmental Factors

Omar Bagasra, Claflin University, Orangeburg, South Carolina, USA. Cherilyn Heggen, Immunologist, Florida, USA. Illustrations by Muhammad I. Hossain, Orangeburg, South Carolina, USA.

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


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


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


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


?]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 and Maternal Antibodies: A Double Jeopardy 235


Are there Examples of Such an Immune Mechanism? 236


Rh Incompatibility 236


ABO Incompatibility 237


Why are Fetal Neuroantigens Immunogenic to the Maternal Immune System? 238


Is There Any Evidence of a Link Between Synthetic Chemicals Exposure, Neurotoxicity, and Autoimmunity? 241


The Relationship between Autoimmunity and ASD 241


The Detection of Fetal Brain Neuroantigens in the Maternal Blood 241


What are the Functions of the Neuroantigens that are Being Destroyed by the Maternal Antibodies? 243


Animal Models and Neuroantibodies to Autism 245


Rhesus Macaques Model 245


Studies Using Rodent Models 246


Why Do Some Autistic Children Have Bigger Brains? 246


Is There a Link between Autoimmunity and Other Forms of Neurodevelopmental or Neurodegenerative Disorders? 248


A Chicken and Egg Conundrum 250


Tourette Syndrome and Obsessive Compulsive Disorder 250


Other Contributing Factors in Neuropsychiatric Disorders 250


Infectious Flu Virus 250


Influenza Vaccine and Narcolepsy 250


Other Viral and Nonviral Infections 252


Blood Brain Barrier 254


What is the BBB? 254


Summary and Conclusions 256


References 257


9 Vaccines and Autism 261


Childhood Vaccines and Regressive Autism 261


Politics Versus Science in the Vaccination Era 262


A Short Glimpse of the History of Vaccines: Justification for Using Vaccines 264


What is in the Vaccines? 265


Thimerosal 270


What is the Evidence That Organomercurial Vaccines Pose a Higher Risk of Regressive Autism? 272


Why Thimerosal?]Containing Vaccines are Harmful: A Scientific Narrative 273


How Much Mercury is Given to Children Before the Age of 3 years? 274


Why Do Only Small Numbers of Children Develop Regressive Autism After Vaccination? 274


Can Measurements of Abnormal Cytokines Identify Children Who Are at Increased Risk for Regressive ASD? 278


Summary of Contributing Immunological Factors to ASD 278


References 279


Epilogue 287


Index 291