Table Of ContentRETHINKING AUTISM
Variation and Complexity
LYNN WATERHOUSE
Professor, Graduate Global Studies,
Center for Global Engagement,
Director Emeritus, Child Behavior Study,
The College of New Jersey,
Ewing, NJ
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FOREWORD
Autism is a clinical reality. Autism has been around, if not from the begin-
ning of time, at least for thousands of years. It has been on the minds of
people not affected by autism for a minimum of two centuries, albeit under
different labels. It has been in the medical textbooks for nigh on seventy
years (or more than a hundred if you just think of the word that Bleuler
once coined for autism as a core symptom of schizophrenia). As a word, it
has come from relative obscurity to the forefront of everyone’s mind in little
more than a decade. It is now the best-funded neurodevelopmental disorder,
in terms of research, in many parts of the world. It is said to be at once one
of the most common neuropsychiatric disorders and the most devastating.
Its prevalence has purportedly increased, although the evidence supporting
this claim is equivocal to say the least. Yet it remains an illusive butterfly,
escaping clear-cut definition. Operationalized criteria have tried to capture
it for years, and such criteria have changed, usually without a strong scien-
tific evidence base to support any shift from one algorithm to another.
Having said this, I realize it may sound as though I do not “believe” in
autism. To the contrary, I am acutely aware of the reality of autism; my
endless flow of patients is convincing in itself. However, the fact is that we
do not know what autism “is.” I have been in the field for forty years, and I
can honestly say that I do not believe we are any closer now than twenty
years ago to a real understanding of what it is about autism that makes
experienced clinicians “certain” that it is autism regardless of whether
operationalized criteria for the disorder are met or not. The gestalt of
autism has yet to be semantically conceptualized.
For more than twenty years we have had sufficient knowledge about
“autism” to know that the unitary concept of it (and even that of an (= one)
autism “spectrum” disorder) will not take us further in research or clinical
practice. Unfortunately, this insight has been overshadowed by populist cries
for cures (or even of one cure) and uncovering the cause of autism. We have
been hitting a wall for a long time, and there has been little in terms of well-
funded research and service development that would indicate that a scien-
tifically sound change of track might be in the offing.
Lynn Waterhouse, with her long clinical and research experience of
autism and other “early symptomatic syndromes eliciting neurodevelop-
mental clinical examinations” (ESSENCE), has written the definitive text
that, if read and pondered, will guide us onto new tracks in the field. She
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x Foreword
takes apart the whole argument that autism is “one,” and a concept that can
be studied without attention to subgrouping. She does it in the most didac-
tic and systematic way, arguing her point, step by step, bit by bit. And the
best thing about it is, she does it with such humor, verve and intelligence
that, far from simply sweeping you away, she leaves you feeling convinced
and scientifically supported at a much higher level than before — on safe
ground.
This book is a must for researchers and specialist clinicians in neurode-
velopment. Not least, it needs to be read by all those influential people at
top levels who, through lobbying, scientific advisory boards and committees
of funding bodies, now funnel huge amounts of money to the study of —
and intervention for — “one autism.” Lynn Waterhouse’s book will guide
the quest for supporting clinical and research work focusing on the autisms
(with all their complex connections with all the other ESSENCE) rather
than on “pure” autism per se.
Christopher Gillberg, MD, PhD
Professor of Child and Adolescent Psychiatry
Gillberg Neuropsychiatry Centre (gnc.gu.se)
Gothenburg University, Sweden
Institute of Child Health, London, UK
Glasgow University, Glasgow, UK
PREFACE
The public, the National Institutes of Health, and the American Psychiatric
Association have supported a vision of autism as a single disorder or spec-
trum of closely related disorders. However, the research evidence does not
support this vision. In fact, all the research to date on autism suggests the
opposite: that “Autism” is not one disorder or many “Autisms” but is a set
of symptoms. The heterogeneity and associated disorders suggest that autism
symptoms, like fever, are not themselves a disorder or multiple disorders.
Instead, autism symptoms signal a wide range of underlying disorders. This
book lays out all the research evidence for readers to draw their own con-
clusions. If, after reading through this, you come to believe as I do that
autism symptoms are exactly that—symptoms, our next step is to shift
research to the many underlying brain dysfunctions and their causes in
order to more effectively find the neurobiological targets for potential treat-
ments for those who suffer from autism symptoms.
The book begins with a description of what is required for a group of
symptoms to be considered a single disorder and then presents the evidence
that demonstrates that autism cannot be a single disorder. There is no repli-
cated evidence of a shared pathophysiology that accounts for a majority of
cases of autism. There is no drug treatment that directly addresses the symp-
toms of autism. All autism diagnostic symptoms—social interaction impair-
ment, repetitive and restricted behaviors, and sensory abnormalities—vary
in form and severity. Equally important, the expression of autism nearly
always occurs with one or more additional non-diagnostic symptoms
including but not limited to intellectual disability, attention deficit/hyper-
activity disorder symptoms, perceptual problems, motor disorders, epilepsy,
and language development problems. In addition, research findings do not
support the vision of multiple autisms. No meaningful subgroups of autism
have been discovered, and genetic and environmental risk factors tie autism
symptoms to many other disorders and outcomes.
The eight chapters of this book offer evidence for extensiveness of
heterogeneity in autism. Chapter 1 summarizes variation in autism, and
Chapter 2 outlines symptom variation in siblings with autism, siblings at
risk for autism, and other family members of individuals with autism.
Chapter 3 reports evidence for varied social brain circuit deficits in autism,
Chapter 4 reviews the many gene and chromosomal risk factors that
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xii Preface
link autism symptoms to other disorders, and Chapter 5 catalogs environ-
mental risk factors that link autism symptoms to other symptoms and dis-
orders. Chapter 6 matches savant and superior mental skills in autism with
the same skills in typical individuals. Chapter 7 considers the variation in
autism prevalence rates and reviews claims that DSM-5 diagnostic criteria
for autism spectrum disorder may limit both heterogeneity and prevalence.
Chapter 8 proposes that researchers and theorists have been unable to con-
struct validated diagnostic criteria or valid unifying theories of autism
because the causes, brain deficits, and behaviors found for autism are so
varied.
Given the accumulated evidence, the book concludes that autism is not,
in fact, a single disorder or a spectrum of related disorders. Why does this
matter? It matters because if you are searching for the cure for fever, you are
trying to cure a symptom, and are not focusing on the real disorder, which
is the pathogen whose effects on the body triggered the immune system to
generate a fever. Researchers should stop the continually failing quest to
find a brain dysfunction that unifies autism. Evidence has demonstrated that
a unifying brain dysfunction does not exist. Ending this quest will free
researchers to concentrate on causes, plural, for the brain dysfunctions,
plural, that generate the full range of symptoms expressed by individuals.
The complex relationship between causes and brain dysfunctions alone is a
difficult problem, but the diagnosis of autism has complicated the task by
errantly defining a set of symptoms as evidence for a single disorder or
spectrum of closely related disorders.
Research should instead focus on the developmental brain disruptions
that cause autism symptoms along with other symptoms, and focus on etio-
logical agents that cause developmental brain disruptions. All individuals
expressing autism symptoms and who have a known genetic or chromosomal
disorder such as fragile X syndrome or Down syndrome should be identified
as having fragile X syndrome with autism symptoms or Down syndrome
with autism symptoms. All individuals expressing autism symptoms who have
suffered known environmental insults such as fetal alcohol syndrome or
extreme prematurity should be identified as having fetal alcohol syndrome
with autism symptoms or extreme prematurity with autism symptoms. As
research isolates more causes for autism symptoms co-occurring with other
symptoms, an expanding set of neurobiological targets would accrue.
The rejection of the vision of autism as a set of subgroups will also yield
benefits in research. If researchers stop searching for autism symptom sub-
groups—the “Autisms”—and accept that a range of more varied symptoms
Preface xiii
results from global brain development disruptions caused by risk factors,
they will be freed to focus on the mechanisms of disruption. Understanding
the mechanisms of brain disruption is the basis for translational research.
Advances in the understanding of causes for autism symptoms that occur
with associated non-autism symptoms will depend on increased knowledge
of the genetics, epigenetics, and gene–environment interactions involved in
brain development, as well as increased knowledge of environmental risk
factors for brain development. Advances will also depend on increased
knowledge of individual brain circuits, the whole brain connectome, and
the mechanisms of the dynamic processes involved in brain development.
The disorders discovered as causes for autism symptoms will not be autism.
However, future discoveries should be able to better isolate specific brain cir-
cuits that when disrupted result in neurodevelopmental social impairment.
ACKNOWLEDGEMENTS
My deepest debt is to the 340 children and adolescents with autism and
their parents who participated in my studies over many years. Thank you all.
Because our research was longitudinal, I visited each child and adolescent
many times. The individual variation among you was and is remarkable.
Although I told every parent our studies would not yield any treatment
for autism, nonetheless, many parents did hope that something would come
of our findings. Their belief in the potential of autism research shamed me.
As our research and the research of others uncovered more and more varia-
tion in behavior, brain deficits, and risk factors for autism, I felt the intense
frustration that most autism researchers and most parents have felt. Shame
and frustration are powerful motivators. They propelled me to read every
piece of research I could, and pressed me to repeatedly question why no
shared brain deficit for autism could be found.
The call made in 2010 by Dr. Thomas Insel, Director of the National
Institutes of Mental Health, and his colleague Dr. Philip Wang for research-
ers to rethink mental illness was the match that lit the kindling for this book.
This book and its title are a direct response to their call. They doubted the
validity of psychiatric diagnostic categories, and their doubt affirmed my
own. I would also like to thank Dr. Sanislow and his colleagues, as well as an
anonymous reviewer for providing the analogy to fever as a symptom.
Elsevier editors made this book possible. I am most grateful to Nikki
Levy for her belief in the book’s thesis, for her patience and continued
support throughout the writing of the book, and for her key contributions
to this Preface. I would like to thank Caroline Johnson for her care and
kindness. Last but nonetheless, first, Colin Macnee was the most erudite,
funny, polite, and thoughtful of copy editors.
Most importantly, I owe this book to the three loving, supportive, and
brilliant critics in my life, each of whom proposed challenges to the thesis
of this book. Do you have enough evidence? My husband, Michael, is an
archaeologist who believes the best ratio of data to theory is the ratio of
stars in the Milky Way to the sun. What are the core mechanisms? My son,
Bennett, is an engineer who has imagined and built many things that have
never before existed. Happily, unlike the Russian engineers of the past, who
were forced to stand with their families under the bridges they had designed
while multitudes of soldiers on horses pounded over them, the tests of my
son’s inventions do not endanger my grandsons: calculations and model
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xvi Acknowledgements
simulations have replaced horses and riders. What are the specific differences
between brain disruptions? My daughter, Emily, is a molecular neurobiolo-
gist and physician. Her work on BDNF in neurogenesis sharpened my
attention to the complexity in the brain that neuroscience has yet to delin-
eate. Moreover, seeing her dedication to the treatment and well-being of
her patients increased my feelings of obligation to all the children and ado-
lescents with autism I have studied.
1
CHAPTER
Autism Heterogeneity
Contents
Autism Heterogeneity is Extensive and Unexplained 3
Autism Heterogeneity has Blocked Medical Treatment Discovery 4
Diagnostic Criteria have not Constrained Autism Heterogeneity 4
Variation in Autism Diagnostic Features 6
Variation in Autism Brain Deficits, Medical Conditions, and Non-Diagnostic
Symptoms 8
Variation in Genetic Risk Factors for Autism 9
Variation in Environmental Risk Factors for Autism 10
Summary: Variation Exists in all Autism Domains 11
Autism Subgroups and Unifying Theories for Autism have Addressed Heterogeneity 12
Competing Proposals for Autism Subgroups 13
Competing Brain Deficit Theories of Autism 14
Autism is Unified by a Shared Brain Disruption in Social Information Processing 15
Autism is Unified by a Failure to Sparsify Information to Prototypes 15
Autism is Unified by the Failure to Have a Theory Of Mind 16
Autism is Unified by Brain Underconnectivity 16
Autism is Unified by Impaired Attention to Biological Motion 17
Competing Genetic Risk Factor Theories of Autism 18
Competing Speculative Environmental Cause Theories of Autism 20
The Wakefield Vaccine Theory Fraud 20
Two Harmful Theories of Environmental Causes for Autism 21
Four Foolishly Speculative Theories of Environmental Causes for Autism 21
Competing Gene–Environment Interaction Theories of Autism 22
Subgroups and Unifying Theories have not Explained the Variation in Autism 23
Has Autism been Reified? 24
Saving the Phenomena of Autism Variation 27
How Should We View the Variation in Autism? 27
Serious Concerns for Maintaining the Autism Diagnosis 30
Eight Claims Concerning Autism Variation and the Autism Diagnosis 31
Chapter 1 Claim 1: Autism Heterogeneity is Meaningful 31
Chapter 2 Claim 2: Autism Symptom Heterogeneity Exists in Family Members 32
Chapter 3 Claim 3: The Social Brain is a Complex Super-Network 33
Chapter 4 Claim 4: Genetic Risk Factors Link Autism to Many Other Disorders 33
Chapter 5 Claim 5: Environmental Risk Factors Link Autism to Many Other Outcomes 35
Chapter 6 Claim 6: Savant Skills, Special Skills, and Intelligence Vary Widely in Autism 36
Chapter 7 Claim 7: Increasing Prevalence and the Problem Of Diagnosis 37
Chapter 8 Claim 8: Autism Symptoms Exist but the Disorder Remains Elusive 37
Summary of the Eight Claims Regarding Autism Variation 40
Rethinking Autism © 2013 Elsevier Inc.
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