The Molecular Basis of Autism

437 Pages·2015·8.586 MB·English

by  S. Hossein Fatemi (eds.)

Contemporary Clinical Neuroscience
For further volumes:
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S. Hossein Fatemi
Editor
The Molecular Basis of Autism
1 3
Editor
S. Hossein Fatemi M.D., Ph.D., FACPsych
Professor, Departments of Psychiatry and
Neuroscience
MMC 392
University of Minnesota Medical School
Minneapolis
Minnesota
USA
Contemporary Clinical Neuroscience
ISBN 978-1-4939-2189-8 ISBN 978-1-4939-2190-4 (eBook)
DOI 10.1007/978-1-4939-2190-4
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To my father, S. Mehdi Fatemi, and to my
family, S. Ali Fatemi, M.D., Naheed Fatemi,
Parvin Fatemi, S. Mohammad Fatemi,
Neelufaar Fatemi, Maryam Jalali-Mousavi,
and my mother, Fatemeh Fatemi
Foreword
The book entitled “The Molecular Basis of Autism” has brought together over 40
autism experts to combine their expertise in defining the biological basis of this se-
vere neurodevelopmental disorder. The book comprehensively describes the latest
research on the roles of potential biomarkers (i.e., oxytocin, neurexins, and neuro-
ligins) and classical neurotransmitter systems (i.e., γ-aminobutyric acid (GABA),
glutamate, dopamine, acetylcholine, and serotonin) as well as the epidemiology,
genetics and epigenetics of autism. Its overall importance may lie in the descrip-
tion of emerging findings related to potential novel treatments and biologically
based diagnostic methods. For example, deficits in GABAergic and glutamatergic
signaling have been replicated in human and animal experiments. Aberrations in
glutamatergic transmission are also described, for instance the increased levels of
metabotropic glutamate receptor 5 (mGluR5) that have been observed in subjects
with idiopathic autism as well as fragile X syndrome (FXS), and also in a mouse
model of FXS. These findings might open new avenues for therapeutic intervention
such as the use of modulators for mGluR5. In conclusion, I believe that this collec-
tion of chapters will be important to the field of psychiatry as well as neurology,
neuroscience, and pharmacology.
Arvid Carlsson, MD, PhD
Göteborg, Sweden
vii
Preface
Autism is a major, debilitating neurodevelopmental disorder with shared genetic
and environmental etiologies and a rising prevalence. Since the initial discovery
of this disorder by Leo Kanner, there has been an explosion of new knowledge
about its etiopathogenesis. The Molecular Basis of Autism provides the current state
of knowledge about the etiology and treatment of this disorder. In the following
twenty chapters, various contributors present up-to-date discussions of the state of
knowledge on important aspects of autism. In part one of the book, chapters cover
clinical topics of interest such as history of discovery of autism, diagnostic features,
epidemiology, genetics, epigenetics, immunology, neuroimaging, neuropathology,
pharmacology and behavioral treatment modalities. In part two, chapters deal with
involvement of a number of neurotransmitters, proteins, and brain markers that may
influence etiopathogenesis of autism such as dopamine, glutamate, serotonin, oxy-
tocin, vasopressin, acetylcholine, Reelin, gamma-aminobutyric acid (GABA), frag-
ile X mental retardation protein (FMRP), neurexins and neuroligins, neurotrophins,
as well as novel mechanisms of disease production such as cognition and motor
control and oxidative stress and mitochondrial dysfunction in causation of autism. It
is hoped that this timely collection of chapters will provide a comprehensive guide
for scientists and clinicians regarding the biology of this disorder.
S. Hossein Fatemi, MD, PhD, FACPsych
Minneapolis, Minnesota
ix
Acknowledgments
I am most grateful to Professor Mario Manto for the original proposal to edit this book.
I am especially indebted to Mr. Timothy D. Folsom and Ms. Jennifer M. Bredemeier
for help with various aspects of editing this book. I am also grateful to the authors who
have generously given their valuable time to write the various chapters in this book.
Finally, I am thankful to Ms. Simina Calin, Mr. Kevin Wright, Mr. Jacob Rosati, and
Ms. Nikita Dhiwar of Springer for the excellent job in publishing this book.
S. Hossein Fatemi, MD, PhD, FACPsych
Minneapolis, Minnesota
xi
Contents
Part I Clinical Aspects of Autism
1 A Brief History of Autism .......................................................................... 3
Fred R. Volkmar
2 Autism Spectrum Disorder: Diagnostic Considerations ........................ 15
Goerge M. Realmuto
3 Epidemiologic Features of Autism Spectrum Disorders ........................ 23
R. S. Kirby
4 G enetics of Autism Spectrum Disorders: The Opportunity
and Challenge in the Genetics Clinic ....................................................... 33
Yi Wang, Ping Wang, Xiu Xu, Jennifer Goldstein, Allyn McConkie,
Sau W. Cheung and Yong-hui Jiang
5 Epigenetic Regulation in Autism .............................................................. 67
Cyril J. Peter, Abraham Reichenberg and Schahram Akbarian
6 Immunology of Autism .............................................................................. 93
Destanie R. Rose and Paul Ashwood
7 Neuroimaging in Autism Spectrum Disorders ........................................ 117
Danielle Baribeau and Evdokia Anagnostou
8 The Neuropathology of Autism ................................................................. 153
Manuel F. Casanova
9 Pharmacology of Autism Spectrum Disorder .......................................... 173
Donald E. Greydanus, Gabriel Kaplan and Dilip R. Patel
10 Behavioral Therapies ................................................................................. 195
V. Mark Durand
xiii
xiv Contents
Part II Basic Science Aspects of Autism
11 Autism and Dopamine................................................................................ 213
Guy Mittleman and Charles D. Blaha
12 Autism and Glutamate ............................................................................... 243
Maria L. Carlsson
13 Serotonin in Autism Spectrum Disorder: Insights from
Human Studies and Animal Models ......................................................... 257
Natalia Benza and Diane C. Chugani
14 Oxytocin and Vasopressin in Autism and Genetic Syndromes .............. 275
Tal Levin-Decanini, Sunday M. Francis, Angela Sagar,
Wensheng Liu, C. Sue Carter and Suma Jacob
15 Molecular Basis of Cholinergic Changes in Autism
Spectrum Disorders and Relevance for Treatment Interventions ......... 307
Elizabeta B. Mukaetova-Ladinska and Elaine K. Perry
16 Reelin, GABA, FMRP, and Autism .......................................................... 337
Timothy D. Folsom and S. Hossein Fatemi
17 The Role of Neurexins and Neuroligins in Autism .................................. 361
Amy C. Reichelt and James Dachtler
18 Neurotrophins, Their Receptors and Autism:
Ligand vs. Receptor Abnormalities .......................................................... 383
Elizabeth M. Sajdel-Sulkowska
19 Cognition, Motor Control and Other Aspects of Autism:
A Pragmatic Review ................................................................................... 393
James W. Howell and Detlef H. Heck
20 Increased Vulnerability to Oxidative Stress
and Mitochondrial Dysfunction in Autism .............................................. 407
Abha Chauhan and Ved Chauhan
Index .................................................................................................................. 427