SUSTAINABLE DEVELOPMENT
Innovate. Sustain. Transform.
Save up to 30% on top Physical Sciences & Engineering titles!
The Neuroscience of Autism Spectrum Disorders
- 1st Edition - October 25, 2012
- Editors: Joseph D. Buxbaum, Patrick R. Hof
- Language: English
- Hardback ISBN:9 7 8 - 0 - 1 2 - 3 9 1 9 2 4 - 3
- eBook ISBN:9 7 8 - 0 - 1 2 - 3 9 1 9 3 0 - 4
Autism is no longer considered a rare disease, and the Center for Disease Control now estimates that upwards of 730,000 children in the US struggle with this isolating brain di… Read more
Purchase options
Institutional subscription on ScienceDirect
Request a sales quoteAutism is no longer considered a rare disease, and the Center for Disease Control now estimates that upwards of 730,000 children in the US struggle with this isolating brain disorder. New research is leading to greater understanding of and ability to treat the disorder at an earlier age. It is hoped that further genetic and imaging studies will lead to biologically based diagnostic techniques that could help speed detection and allow early, more effective intervention.
Edited by two leaders in the field, this volume offers a current survey and synthesis of the most important findings of the neuroscience behind autism of the past 20 years. With chapters authored by experts in each topic, the volume explores etiology, neuropathology, imaging, and pathways/models. Offering a broad background of ASDs with a unique focus on neurobiology, the volume offers more than the others on the market with a strictly clinical focus or a single authored perspective that fails to offer expert, comprehensive coverage. Researchers and graduate students alike with an interest in developmental disorders and autism will benefit, as will autism specialists across psychology and medicine looking to expand their expertise.
- Uniquely explores ASDs from a neurobiological angle, looking to uncover the molecular/cellular basis rather than to merely catalog the commonly used behavioral interventions
- Comprehensive coverage synthesizes widely dispersed research, serving as one-stop shopping for neurodevelopmental disorder researchers and autism specialists
- Edited work with chapters authored by leaders in the field around the globe – the broadest, most expert coverage available
Neuroscientists at all levels interested in neurodevelopmental disorders and autism, autism specialists looking to expand their expertise
Contributors
Introduction
Section I: Autism Spectrum Disorders
Chapter 1.1. Epidemiology of Autism Spectrum Disorders
Introduction
Selection of Studies
Study Designs
Prevalence Estimations
Time Trends in Prevalence and Their Interpretation
Other Correlates: Race, Immigrant, and Socioeconomic Status
Conclusion
Challenges and Future Directions
Suggested Reading
References
Chapter 1.2. The Behavioral Manifestations of Autism Spectrum Disorders
Historical Perspectives on ASD Behavioral Manifestations
Core Features of ASD
Heterogeneity in Behavioral Manifestations of ASD
Diagnosis and Classification of ASD
Summary and Conclusions
References
Chapter 1.3. Early Manifestations of Autism Spectrum Disorders
Early Biological Markers
Behavioral Manifestations in Retrospective Reports
Prospective Studies
Theoretical Considerations
Clinical Implications
References
Chapter 1.4. Asperger Syndrome and its Relationships to Autism
Diagnostic Concept
Epidemiology and Comorbidity
Etiology and Pathophysiology
Assessment
Treatment, Interventions, and Outcome
Developmental Course and Outcome
Future Directions
References
Chapter 1.5. Behavioral and Psychosocial Interventions for Individuals with ASD
Early Intensive Behavioral Intervention
School-Based Treatment Approaches
Interventions Addressing Socialization Impairments
Communication Interventions
Treatments for Behavioral and Psychiatric Problems
Anxiety-Management Interventions
Auxiliary and Complementary/Alternative Treatment Approaches
Future Directions for Behavioral and Psychosocial Interventions in ASD
References
Chapter 1.6. Current Trends in the Pharmacological Treatment of Autism Spectrum Disorders
Introduction
Aggression
Attention Deficit and Hyperactivity
Anxiety and Repetitive Behaviors
Conclusions
Acknowledgment
References
Chapter 1.7. Novel Therapeutics in Autism Spectrum Disorders
Introduction
Challenges for Novel Therapeutics in ASD
Translating Genomic Advances into Novel Therapeutics
Other Potential Novel Pharmacological Targets
Conclusions
References
Section II: Etiology of Autism Spectrum Disorders
Chapter 2.1. Etiological Heterogeneity in Autism Spectrum Disorders: Role of Rare Variants
Introduction
Genetic Disorders Strongly Associated with ASD
Genetic Overlap between ASD and Intellectual Disability
Genetic Overlap between ASD and Epilepsy
Metabolic Disorders Associated with ASD
Other Examples of Etiological Subgroups Associated with ASD
Myriad Biological Pathways
Conclusion
References
Chapter 2.2. Copy Number Variation in Autism Spectrum Disorders
Introduction and Background
Genetics of ASD
ASD-Related Syndromes and Chromosomal Abnormalities
Copy Number Variation: Technological Methods and Interpretation
Copy Number Variation in ASD
Conclusions and Future Studies
Acknowledgments
References
Chapter 2.3. Common Genetic Variants in Autism Spectrum Disorders
Introduction
Linkage Studies in Autism
Association Studies in Autism
Conclusions
References
Chapter 2.4. Next-Generation Sequencing For Gene and Pathway Discovery and Analysis in Autism Spectrum Disorders
Introduction
Next-Generation Sequencing Technologies
Pyrosequencing
Application of Next-Generation Sequencing Technologies in Human Disease
Next-Generation Sequencing In Autism Spectrum Disorders
Conclusion
References
Chapter 2.5. Mitochondria and Autism Spectrum Disorders
The Birth of Mitochondrial Medicine
What is Definite Mitochondrial Disease?
Epidemiology of Mitochondrial Disease
Definite Mitochondrial Disease is a Rare Cause of Autism Spectrum Disorders
Mitochondrial Disease and Autism Respond Differently to the Same Treatments
Nuclear Mitochondrial Genocartography and CNVs
Mitochondria and the Control of CNVs, DNA Instability, and Repair
Mitocellular Hormesis
Mitochondrial Functions in Metabolism
Mitochondrial Functions in Innate Immunity
Regression
Storm, Flare, and Fade Responses
The Possible Role of Purinergic Signaling in Autism Spectrum Disorders
Summary
Acknowledgments
References
Chapter 2.6. Parental and Perinatal Risk Factors for Autism: Epidemiological Findings and Potential Mechanisms
Introduction
Advancing Parental Age and Risk of ASD
Growth Restriction and Preterm Birth
Integration of Study Results: A Meta-Analysis of Epidemiological Studies of Parental Age, Preterm Birth and Growth Restriction, and Risk of ASD
Advancing Maternal Age
Advancing Paternal Age
Growth Restriction and Preterm Birth
Summary of Meta-Analysis
Potential Etiological Mechanisms
Conclusions and Future Directions
Acknowledgments
References
Chapter 2.7. The Environment in Autism Spectrum Disorders
Background
Exogenous Medically Related Factors
Maternal Lifestyle Factors
Environmental Chemicals
Summary and Future Directions
References
Chapter 2.8. Hormonal Influences in Typical Development: Implications for Autism
Sex Biases in Clinical Conditions
Typical Sex Differences and ASC
Human Behavioral Sex Differences and Exposure to Hormones
The Role of Fetal Testosterone in Cognitive Sex Differences and Autistic Traits
Summary of the Cambridge Child Development Project
Additional Considerations
Limitations of Measuring Prenatal Exposure to Hormones in Amniotic Fluid
Further Evidence Implicating Testosterone in Autism
Future Directions
Conclusions
References
Chapter 2.9. Immune Abnormalities and Autism Spectrum Disorders
Historical Relationship of Immune Abnormalities with ASD
Introduction to the Immune System
Abnormalities in Innate Immunity in ASD
Abnormalities in the Adaptive Immune Response in ASD
Autoimmunity
Conclusions
References
Section III: Brain Imaging and Neuropathology of Autism Spectrum Disorders
Chapter 3.1. Structural and Functional MRI Studies of Autism Spectrum Disorders
Introduction
Structural Magnetic Resonance Imaging
Functional Magnetic Resonance Imaging
Conclusions
Acknowledgments
References
Chapter 3.2. DTI and Tractography in the Autistic Brain
Introduction
Diffusion as a Random Process
Diffusion in the Brain
How MR can Measure Diffusion
The Diffusion Tensor Model of Microstructure
Diffusion and Scalar Measures in ASD
Population Statistics and Pattern Classifiers Based on DTI
DTI Tractography
Advanced Tract Metrics and Full Brain Networks
High-Angular-Resolution Diffusion Imaging (HARDI)
Glossary
References
Chapter 3.3. Attentional Network Deficits in Autism Spectrum Disorders
Introduction
Attention as an Organ System
Impairments of Attentional Functions and their Neural Substrates in Autism
The Attention Model of Autism
Conclusion
Acknowledgments
References
Chapter 3.4. The Cerebellum in Autism Spectrum Disorders
Introduction
Gross Anatomic Structure
Microscopic Observations in the Cerebellum and Related Olive
The Role of the Cerebellum in ASD – Clinical Implications
Future Directions
Conclusion
Acknowledgments
References
Chapter 3.5. The Amygdala in Autism Spectrum Disorders
Introduction
The Typically Developing Amygdala
Typical Function of the Amygdala
Amygdala Functional Abnormalities in Autism Spectrum Disorders
Structural Abnormalities in the Amygdala in Autism Spectrum Disorders
Cellular Abnormalities in the Amygdala in Autism Spectrum Disorders
Summary
References
Chapter 3.6. Discrete Cortical Neuropathology in Autism Spectrum Disorders
Whole-Brain Changes
Prefrontal Cortex
Inferior Frontal Cortex
Fusiform Gyrus
Frontoinsular Cortex
Anterior Cingulate Cortex
Posterior Cingulate Cortex
Hippocampus
Conclusion
Acknowledgments
References
Chapter 3.7. The Minicolumnopathy of Autism Spectrum Disorders
Introduction
Corticogenesis
Cortical Modularity
The Minicolumnopathy of Autism Spectrum Disorder
References
Chapter 3.8. Inhibitory and Excitatory Systems in Autism Spectrum Disorders
The Excitation: Inhibition Hypothesis of Autism
Experimental Evidence of Changes in the GABAergic System in Autism
Experimental Evidence of Changes in the Glutamatergic System in ASD
Neuroimaging Studies of the GABAergic and Glutamatergic Systems in ASD
Experimental Evidence of Changes in the Serotonergic System in Autism and its Importance for Pharmacotherapeutic Treatment
Neuroimaging Studies of the Serotonergic System in ASD
Additional Comments and Conclusions
References
Chapter 3.9. Clinicopathological Stratification of Idiopathic Autism and Autism with 15q11.2–q13 Duplications
Genetic Factors in Autism
Duplications of Chromosome 15q11q13
Gene Expression in dup(15)
Clinical Characteristics
Neuropathology of Autism with dup(15) and of Idiopathic Autism
Increased Prevalence of Brain Transient Overgrowth and Macrocephaly in Idiopathic Autism and Microcephaly in dup(15) Autism
Neuropathological Stratification of Developmental Abnormalities in Dup(15) and Idiopathic Autism Cohorts
Heterotopias
Dysplasia
Causative Link between Developmental Neuropathological Changes, Epilepsy, and Sudden Death in Childhood
The Link between Dysplastic Changes in the Cerebellar Flocculus and Atypical Gaze
Increased Levels of Secreted Amyloid Precursor Protein-α (sAPP-α) and Reduced Levels of Aβ40 and Aβ42 in the Blood Plasma
Enhanced Accumulation of N-Terminal Truncated Aβ in Neuronal Cytoplasm
Stratification of Aβ Accumulation in Neurons in the dup(15) Autism and Idiopathic Autism
Aβ1-40 and Aβ1-42 in Diffuse Plaques in Autism
Closing Remarks
Acknowledgements
References
Section IV: Brain Imaging and Neuropathology of Autism Spectrum Disorders
Chapter 4.1. Mouse Behavioral Models for Autism Spectrum Disorders
Behavioral Characteristics of Autism Spectrum Disorders in Humans
Genetics and Pathophysiology of Autism Spectrum Disorders
Models of Autism Spectrum Disorders Using Inbred Strains of Mice
Models of Autism Spectrum Disorders Using Shank3 Mice
Future Directions with Animal Models
References
Chapter 4.2. Nonhuman Primate Models for Autism Spectrum Disorders
Validity Measures
Advantages and Limitations of Nonhuman Primate Models
Modeling Features of Autism in Nonhuman Primates
Maternal Auto-Antibody Model
Conclusions
Acknowledgments
References
Chapter 4.3. Inducible Pluripotent Stem Cells In Autism Spectrum Disorders
A Novel and Complementary Model for Studying Autism Spectrum Disorders
Limitations of iPSCs for Disease Modeling
Modeling Monogenetic and Single Locus ASD using iPSCs
Modeling Idiopathic ASD using iPSCS
Using Human Neurons as a Drug-Screening Platform for New Treatments for ASD
Conclusion and Perspectives
Acknowledgments
References
Chapter 4.4. A 15q11–q13 Duplication Mouse Model of Autism Spectrum Disorders
Autism
Human Chromosome 15q11–q13
Mouse Chromosome Engineering
A Mouse Model for 15q Duplication
ASD-Like Behavior of 15q Duplication Mice
Abnormal Serotonin in 15q Duplication Mice
A Mouse Model of Autism
Epigenetics of 15q Duplication
Acknowledgment
References
Chapter 4.5. Fragile X Syndrome and Autism Spectrum Disorders
Background on Fragile X Syndrome
Clinical Association with Autism/ASD
Differences between FXS Autism and Non-FXS Autism
Potential Gene Modifiers of the FXS Behavioral Phenotype
Female and Carrier Phenotypes
The Molecular Nature of the Fragile X Mutation
FMRP
Animal Models
The mGluR Theory of Fragile X
New Drug Trials in FXS
References
Chapter 4.6. MeCP2 and Autism Spectrum Disorders
Introduction
Structure and Function of MeCP2
Developmental MeCP2 Expression in the Brain
MeCP2 and ASD Mouse Models
RTT Rescue in Mouse Models
Future Directions
Conclusions
Acknowledgments
References
Chapter 4.7. SHANK2 and SHANK3 Mutations Implicate Glutamate Signaling Abnormalities in Autism Spectrum Disorders
The Shank Family
Shank Domain Interactions in the Postsynaptic Density
Physiological Function of Shank Proteins
Clinical Relevance
Animal Models Derived from Shank Mutations
Shank and Other Monogenic forms of ASD and Glutamate Signaling
Conclusions
References
Chapter 4.8. PI3K Signaling and miRNA Regulation in Autism Spectrum Disorders
Introduction
Genetic Influences
Monogenic Disorders in ASD
Common Molecular Pathway: PI3K/Akt/mTOR Pathway
Synaptic Dysfunction in ASD – Effects of PI3K/Akt/mTOR Signaling
Biogenesis and Function of Brain-Expressed microRNAs
Activity-Dependent microRNAs Regulate Brain Plasticity
Potential Regulation of the PI3K/Akt/mTOR Pathway by ASD-Altered microRNAs
Enrichment of Autism-Related Genes as Targets of ASD Dysregulated microRNAs
microRNAs Controlling the PI3K/Akt/mTOR Pathway are Altered in Rett Syndrome
Conclusion
References
Chapter 4.9. Getting from 1,000 Genes to a Triad of Symptoms: The Emerging Role of Systems Biology in Autism Spectrum Disorders
Introduction
Systems-Level Analysis of High-Risk ASD Genes
Systems-Level Analysis of Copy Number Variants in ASD
Systems-Level Analysis of ASD-Associated Single Nucleotide Polymorphisms
Systems-Level Analysis of Gene Expression Changes in ASD Brain Samples
Systems-Level Analysis of Genes Impacted by De Novo Single Nucleotide Variation in ASD
Conclusions
References
Index
- No. of pages: 496
- Language: English
- Edition: 1
- Published: October 25, 2012
- Imprint: Academic Press
- Hardback ISBN: 9780123919243
- eBook ISBN: 9780123919304
JB
Joseph D. Buxbaum
Dr. Joseph Buxbaum is a world-renowned molecular geneticist who has been intimately affiliated with the Seaver Autism Center since joining the faculty at Mount Sinai in 1997. Dr. Buxbaum was recruited in part to establish a molecular genetics program in autism spectrum conditions within Mount Sinai. As such, he was the Director of Molecular Genetics in the Seaver Autism Center for seven years and took over Directorship of the Seaver Autism Center itself in 2008. Dr. Buxbaum has focused on understanding the molecular and genetic basis of autism spectrum conditions, which will allow for a better understanding of what causes them, leading to the development of novel therapeutics for the negative aspects of these disorders.
Additionally, Dr. Buxbaum heads the Laboratory of Molecular Neuropsychiatry, which has taken the findings of the causes of autism and translated them into animal models where therapeutic approaches can be evaluated. In this context, Dr. Buxbaum has established the Autism Model Systems Initiative, which makes use of multiple experimental systems to develop and evaluate novel therapeutics in autism spectrum conditions.
Dr. Buxbaum has taken the lead in collaborations with multiple independent sites to ensure that the best science in the service of the families is carried out. Dr. Buxbaum is a lead investigator in the Autism Genetics Consortium, the Autism Genome Project, and the Autism Case Control Cohort, and is a part of the Psychiatric Genetics Consortium. These large Consortia have the benefit of advancing the best science at the fastest pace.
As the founder and co-leader of the Autism Sequencing Consortium, Dr. Buxbaum is part of an international group of scientists who share autism samples, data, and ideas in order to accelerate our understanding of the causes and treatments of autism.
Dr. Buxbaum, the G. Harold and Leila Y. Mathers Professor, has received numerous awards for his research. He has received recognition from the American College of Neuropsychopharmacology (ACNP) in the form of the Daniel H. Efron award for "excellence in research in neuropsychophamacology" (2005), as well as from the Eden Institute Foundation for his "commitment and dedication to improving the quality of life in individuals with autism" (2008). In 2010, Dr. Buxbaum received the Richard D. Todd Memorial Award from the International Society of Psychiatric Genetics, the Joel Elkes Research Award from ACNP, and the Evans Research Award from the Marine Biological Laboratory. He also received the 2011 Dean’s Award for Excellence in Translational Science. Dr. Buxbaum has published over 150 publications in esteemed journals and his work on autism and related conditions has been published in major journals including Nature, Nature Genetics, Proceedings of the National Academy of Sciences, Molecular Psychiatry, and Biological Psychiatry. He is the co-Editor-in-chief of Molecular Autism, a journal that publishes cutting-edge research in autism genetics.
To read Dr. Buxbaum's blog, visit http://scitechconnect.elsevier.com/category/neuroscience/
Affiliations and expertise
Department of Psychiatry, Mount Sinai School of Medicine, New York, New York, USAPH
Patrick R. Hof
Dr. Hof is the Irving and Dorothy Regenstreif Research Professor of Neuroscience and the Vice-Chair of the Department of Neuroscience at the Icahn School of Medicine at Mount Sinai in New York. He also leads the Center of Excellence on Brain Aging of the Friedman Brain Institute. His laboratory has extensive expertise in the pathology of neuropsychiatric disorders and has established an international reputation in quantitative approaches to neuroanatomy and studies of brain evolution.
Dr. Hof earned his MD from the University of Geneva, School of Medicine in Switzerland. He came to the USA as a postgraduate fellow at the Research Institute of Scripps Clinic, La Jolla, CA. In 1989 he came to Mount Sinai School of Medicine as a Senior Research Associate and joined the Faculty there in 1990. He is also a Professor of Geriatrics and Ophthalmology at Mount Sinai.
Dr. Hof's research is directed towards the study of selective neuronal vulnerability in dementing illnesses and aging using classical neuropathologic as well as modern quantitative morphologic methods to determine the cellular features that render the human brain uniquely vulnerable to degenerative disorders. Dr. Hof also conducts analyses of the distribution and connectivity patterns of pyramidal neuron subpopulations in the macaque monkey cerebral cortex in young and very old animals to study possible age-related changes in the neurochemical characteristics of the neurons of origin of corticocortical projections. He develops stereologic, high-resolution morphometric, and imaging tools for the quantitative study of neuroanatomical specimens and brain atlas development. Among his major contributions, Dr. Hof demonstrated that specific neurons are selectively vulnerable in dementing disorders such as Alzheimer’s disease. He has made contributions to quantifying the differences between normal aging brains and Alzheimer’s disease, as well as other mental illnesses such as schizophrenia and autism. Dr. Hof is also the curator of a mammalian brain collection that includes a large series of great ape specimens, as well as an extensive sample of marine mammals. He has contributed considerably to our understanding of the structure of the cetacean brain and has identified, in select mammalian brains, specific neuronal types in parts of the cerebral cortex known to be involved in social awareness, judgment, and attention, that can be considered as markers of adaptive mechanisms and functions in response to particular ecological pressures.
Affiliations and expertise
Fishberg Department of Neuroscience, Mount Sinai School of Medicine, New York, New York, USARead The Neuroscience of Autism Spectrum Disorders on ScienceDirect