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The Neuroscience of Autism Spectrum Disorders
 
 

The Neuroscience of Autism Spectrum Disorders, 1st Edition

 
The Neuroscience of Autism Spectrum Disorders, 1st Edition,Joseph Buxbaum,Patrick Hof,ISBN9780123919243
 
 
 

Buxbaum   &   Hof   

Academic Press

9780123919243

9780123919304

496

276 X 216

The must-have review of neurobiological research that increases understanding of and ability to treat ASDs

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Key Features

  • 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

Description

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 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.

Readership

Neuroscientists at all levels interested in neurodevelopmental disorders and autism, autism specialists looking to expand their expertise

Joseph 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, USA

Patrick 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, USA

View additional works by Patrick R. Hof

The Neuroscience of Autism Spectrum Disorders, 1st Edition

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

 
 
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