9780849327322

Understanding Autism: From Basic Neuroscience to Treatment

by ;
  • ISBN13:

    9780849327322

  • ISBN10:

    0849327326

  • Edition: 1st
  • Format: Hardcover
  • Copyright: 2006-04-25
  • Publisher: CRC Press

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Summary

Taking an all-inclusive look at the subject, Understanding Autism: From Basic Neuroscience to Treatment reviews state-of-the-art research on the diagnosis, treatment, and prevention of autism. The book addresses potential mechanisms that may underlie the development of autism and the neural systems that are likely to be affected by these molecular, genetic, and infectious etiologies. It reviews key findings that inform diagnosis, epidemiology, clinical neuroscience, and treatment.The book concludes with a discussion of the economic cost of autism and provides a biomedical and public health perspective of the impact of this devastating disease. With chapters authored by clinical and basic researchers at the forefront of molecular and systems neuroscience, clinical neuroscience, and health economics, the book presents a powerful and comprehensive synthesis of current research on autism and its underlying neural substrates. The book's two editors are considered elite pioneers in this area of research. Dr. Rubenstein was recently elected to the highly prestigious Institute of the Medicine, an honor reserved for those most committed to professional achievement and public service.

Table of Contents

Chapter 1 Autism Spectrum Disorders: Phenotype and Diagnosis 1(24)
Catherine Lord and Sarah J. Spence
The Spectrum of Autistic Disorders
1(2)
The Phenotype
3(8)
Core Features
3(2)
Social and Communication Deficits in ASD
3(1)
Repetitive and Restricted Behaviors and Interests
4(1)
Sex Differences
5(1)
Other Associated Features
5(4)
ASD and Cognitive Impairments
5(1)
Relationship to Sensory and Motor Impairments
6(1)
Relationship to Epilepsy
7(1)
Macrocephaly in ASD
7(1)
Comorbid Psychiatric Diagnoses
8(1)
Developmental Trajectories
9(1)
Prognoses for ASD
10(1)
Relationship to Disorders with Known Etiology
11(1)
Neurogenetic Syndromes
11(1)
Diagnosis and Assessment
12(2)
Standardized Diagnoses
13(1)
Summary and Conclusions
14(1)
Acknowledgments
15(1)
References
15(10)
Chapter 2 Past and Future Perspectives on Autism Epidemiology 25(24)
Eric Fombonne
Introduction
26(1)
Selection of Studies
26(1)
Survey Descriptions
26(5)
Study Designs
31(1)
Characteristics of Autistic Samples
31(1)
Prevalence Estimations
32(4)
Autistic Disorder
32(1)
Unspecified PDDs — PDDNOS (Pervasive Development Disorder Not Otherwise Specified)
32(1)
Asperger Syndrome (AS) and Childhood Disintegrative Disorder (CDD)
33(3)
Prevalence for Combined PDDs
36(1)
Time Trends
36(6)
Referral Statistics
38(1)
Comparison of Cross-Sectional Epidemiological Surveys
39(1)
Repeat Surveys in Defined Geographical Areas
40(1)
Successive Birth Cohorts
41(1)
Incidence Studies
42(1)
Conclusion on Time Trends
42(1)
Correlates of Autism
42(1)
Associated Medical Conditions
42(1)
Autism, Race, and Immigrant Status
42(1)
Autism and Social Class
43(1)
Cluster Reports
43(1)
Conclusion
44(1)
References
45(4)
Chapter 3 Genetic Basis of Autism 49(26)
Elena Bonora, Janine A. Lamb, Gabrielle Barnby, Anthony J. Bailey, and Anthony P. Monaco
Autism: General Characteristics
49(1)
Evidence for Autism as a Genetic Disorder
50(1)
Genetic Models for Autism Susceptibility
51(1)
Chromosomal Abnormalities in Autism
52(1)
Identification of Autism Susceptibility Genes
53(1)
Linkage Analysis in Autism
54(3)
Candidate Gene Studies for Autism
57(4)
Candidate Genes on Chromosome 7
58(2)
Candidate Genes on Chromosome 15
60(1)
Functional Candidate Genes: A Role for Other Neurotransmitters in Autism
60(1)
Studies of Other Candidate Genes
61(1)
Large-Scale Association Studies in Autism
61(1)
The Use of DNA Array Technology in Autism
62(1)
Considerations for Complex Disease Gene Mapping
62(3)
Conclusions and Future Perspectives
65(1)
Acknowledgments
66(1)
Electronic Resources
66(1)
References
67(8)
Chapter 4 Finding Genes in Spite of Heterogeneity: Endophenotypes, QTL Mapping, and Expression Profiling in Autism 75(20)
Daniel H. Geschwind and Maricela Alarcón
Introduction
76(1)
Making Sense of Complexity: The Need to Link Brain, Genes, and Behavior
76(1)
Autism: A Complex and Genetically Heterogeneous Trait
77(1)
Current Status of Autism Linkage
77(1)
Approach #1 Endophenotypes in Mental Disorders
78(2)
Endophenotypes also Inform the Use of Animal Models
78(1)
Linkage in Large Families
79(1)
Extending Endophenotype Analysis to Autism: Preliminary Success or Signs of Trouble?
80(3)
Language
81(1)
Social Behavior and Cognition
81(2)
RRB s
83(1)
Modeling Other Endophenotypes and the Autism Continuum: Structural Equation Modeling
83(4)
The Next Step — Structural Equation Modeling (SEM)
84(1)
Phenotypic Models
85(1)
Genetic Models
86(1)
Approach #2 Microarray and Bioinformatic Analysis of Gene Expression: Untested but not Unworthy
87(2)
References
89(6)
Chapter 5 A Mixed Epigenetic and Genetic and Mixed De Novo and Inherited Model for Autism 95(18)
Arthur L. Beaudet and Huda Y. Zoghbi
Possibility of Epigenetic and de novo Factors in Autism
95(1)
Epigenetics and Disease
96(1)
Genomic Imprinting and Disease
97(1)
Genetics vs. Epigenetics in Autism
98(2)
Relevance of Fragile X Syndrome, Rett Syndrome, and Chromosome 15q11-q13
100(7)
Rett Syndrome and Autism
101(1)
Chromosome 15q11-q13 and Autism
102(3)
Possible Role of Genes on the X or Y Chromosomes in Autism
105(2)
References
107(6)
Chapter 6 Neurobiology of Related Disorders: Fragile X Syndrome 113(20)
Usha Narayanan and Stephen T. Warren
Introduction
113(1)
The Gene Causing Fragile X: FMR1
114(1)
Triplet Repeat Expansion in Fragile X
115(1)
FMRP: The Protein Product of the Disease Gene in Fragile X Syndrome
116(1)
FMRP and the Neuronal Phenotype in Fragile X Syndrome
117(3)
Fragile X Therapeutics
120(1)
Fragile X and Autism
121(1)
Etiology of Autism
121(1)
Finding the Disease-Causing Gene: Insight from Fragile X
122(1)
References
123(10)
Chapter 7 Fear and Anxiety Pathways 133(22)
Kevin S. LaBar and Joseph E. LeDoux
Introduction
133(1)
The Functions of Fear and Anxiety
134(1)
Fear Conditioning as a Model System for Studying Emotional Learning and Memory
134(2)
The Neural Circuitry for Fear Learning
136(7)
Acquiring Fears to Danger Signals: Role of the Amygdala
136(3)
Prefrontal–Amygdala Interactions during Fear Extinction
139(2)
The Hippocampus and Fear of Environmental Contexts
141(2)
Fear Conditioning in Humans
143(4)
Psychophysiological Studies
143(1)
Neuropsychological Investigations in Brain-Lesioned Patients
143(1)
Functional Neuroimaging of Conditioned Fear Pathways
144(1)
Fear Conditioning in Anxiety Disorders
145(2)
Fear and Anxiety Pathways: Implications for Autism Research
147(1)
Conclusions
147(1)
References
148(7)
Chapter 8 Cerebellar Networks and Autism: An Anatomical Hypothesis 155(20)
Richard P. Dum and Peter L. Strick
Introduction
155(1)
Cerebellar Structural Alterations in Autism
156(2)
Circuit Dysfunction Hypotheses
158(5)
Cerebello-Limbic Circuit
158(1)
Cerebello-Thalamo-Cortical Circuit
159(4)
Macroarchitecture of Cerebro-Cerebellar Loops
163(3)
What Is the Full Extent of the Cerebellar Influence over the Cerebral Cortex?
166(1)
Summary and Conclusions
167(1)
References
168(7)
Chapter 9 Language in Autism 175(30)
Matthew Walenski, Helen Tager-Flusberg, and Michael T. Ullman
Introduction
175(1)
Language and Communication in ASD: The Evidence
176(7)
Pragmatic Deficits
176(2)
Nonverbal Communicative Gesture
177(1)
Speech Acts
177(1)
Conversational Discourse
177(1)
Pragmatic Functions of Prosody
178(1)
Interpreting Nonliteral Language
178(1)
Grammar and Lexicon
178(5)
Grammatical Abilities
179(2)
Lexical Abilities
181(1)
Neuroimaging Studies
181(2)
Formulaic Speech
183(1)
Integrative Theories of Language in ASD
183(10)
Pragmatics and Theory of Mind
183(2)
Grammar, Lexicon, and the PDH
185(21)
ASD Profile of Procedural System Functions
188(3)
ASD Profile of the Declarative Memory System
191(2)
The Neurobiology of Procedural and Declarative Memory Brain Structures in ASD
193(1)
Summary and Conclusion
193(1)
Acknowledgments
194(1)
References
194(11)
Chapter 10 Prefrontal Cortex 205(22)
Joseph L. Price
Introduction
205(1)
Structure
206(4)
Dorsolateral Prefrontal Cortex: Caudal, Dorsal, and Ventral
207(2)
Ventromedial Prefrontal Cortex: Orbital and Medial
209(1)
Connections
210(5)
Intrinsic Connections
211(2)
Sensory Inputs to Ventrolateral Prefrontal Region
213(1)
Parietal Connections of Caudolateral Prefrontal Region
213(1)
Nonsensory Associations of Dorsomedial and Medial Prefrontal Regions
214(1)
Motor and Visceromotor Outputs
215(1)
Functions
215(6)
Orbital Cortex: Food and Reward?
215(1)
Ventrolateral Convexity: Object-Related Selection and Judgment, Working Memory and Language?
216(2)
Caudolateral Prefrontal Cortex: Visuo-Spatial and Auditory-Spatial Coordination?
218(1)
Dorsomedial Prefrontal Cortex: Monitoring of Self-Referential Information?
218(1)
Medial Prefrontal Network: Visceral Modulation, Emotion, and Monitoring of Internal State?
219(2)
References
221(6)
Chapter 11 The Social Brain, Amygdala, and Autism 227(28)
Cynthia M. Schumann, Melissa D. Bauman, Christopher J. Machado, and David G. Amaral
Introduction
228(1)
Social Behavior: What and Where
228(17)
Role of the Amygdala in Social Behavior
229(2)
Electrophysiological Recording and Functional Neuroimaging Studies
229(2)
Lesion Studies with Nonhuman Primates
231(1)
Current Theories regarding the Amygdala and Social Behavior
231(6)
The Amygdala Assigns an Emotional Significance to Social Stimuli
231(1)
The Amygdala Detects Threat or Danger in the Environment
232(1)
Behavioral Changes Resulting from Damage to the Amygdala in Adult Macaque Monkeys
232(1)
Behavioral Changes Resulting from Damage to the Amygdala in Neonatal Macaque Monkeys
233(3)
Human Patients with Amygdala Lesions
236(1)
Summary of Amygdala and Social Behavior
237(1)
The Amygdala and Autism
237(19)
Functional MRI Studies of the Amygdala in Autism
237(1)
Structural MRI Studies of the Amygdala in Autism
238(2)
Postmortem Studies of the Amygdala in Autism
240(3)
Amygdala Dysfunction May Contribute to Symptoms of Autism
243(1)
Abnormal Amygdala Function May Impact Social Processing
244(1)
Conclusions
245(1)
References
246(9)
Chapter 12 The Thalamus and Neuromodulatory Systems 255(22)
Mircea Steriade
Autism and the Thalamus
255(1)
Intrathalamic and Corticothalamic Neuronal Circuitry
256(7)
Thalamic Projections of Brain Stem and Forebrain Neuromodulatory Systems
259(1)
Thalamic Projections of Glutamatergic and Cholinergic Brain Stem Reticular Neurons
259(3)
Thalamic Projections of Brain Stem and Hypothalamic Monoaminergic Systems
262(1)
Basal Forebrain Projections to the Thalamus
262(1)
Brain Stem—Thalamic Neurons during Tonic and Phasic Activation Processes
263(6)
Modulatory Actions on Thalamocortical and Thalamic Inhibitory Neurons
269(3)
References
272(5)
Chapter 13 Modeling Features of Autism in Animals 277(26)
Paul H. Patterson
Introduction
277(2)
Genetic Manipulation
279(7)
X Chromosome Loci
279(1)
15q11-q13 Locus
280(1)
Oxytocin and Vasopressin
280(1)
Serotonin
281(2)
DLX
283(1)
Engrailed
284(1)
Acetylcholine Receptor
284(1)
Dishevelled
285(1)
μ–Opioid Receptor
285(1)
Deer Mouse
285(1)
Reelin
286(1)
Environmental Manipulation
286(5)
Thalidomide and Valproic Acid
286(2)
Maternal Infection
288(2)
Postnatal Viral Infection
290(1)
Postnatal Vaccination
290(1)
Lesion
291(2)
Amygdala
291(1)
Cerebellum
292(1)
Perspectives
293(1)
Acknowledgments
293(1)
References
293(10)
Chapter 14 Neuroanatomical and Neurochemical Studies of the Autistic Brain: Current Thought and Future Directions 303(20)
Margaret L. Bauman, George Anderson, Elaine Perry, and Melissa Ray
Introduction
303(1)
Neuroanatomical Observations
304(1)
The Limbic System
305(1)
The Cerebellum and Brain Stem
306(2)
Neurotransmitter Systems
308(7)
Norepinephrine
308(1)
Dopamine
309(1)
Serotonin
309(2)
Acetylcholine
311(4)
Summary and Future Directions
315(1)
Acknowledgments
316(1)
References
317(6)
Chapter 15 The Social Brain in Autism: Perspectives from Neuropsychology and Neuroimaging 323(26)
Robert T. Schultz, Katarzyna Chawarska, and Fred R. Volkmar
Introduction
323(1)
Social Deficits as the Hallmark of Autism
324(4)
Theoretical Understanding of Social Dysfunction in Autism
325(1)
Developmental Aspects of Social Deficits in Autism
326(2)
Joint Attention and Gaze Monitoring in Autism
327(1)
Brain Mechanisms in Autism
328(9)
Studies of Social Perception
329(5)
Face Identity Perception
330(1)
Neural Bases of Face Recognition
331(1)
Facial Expression Perception
332(1)
The Neural Basis of Facial Expression Perception
333(1)
Studies of Social Cognition
334(1)
Functional Neuroimaging Studies of Social Cognition
334(1)
Social Motivation
335(2)
Summary and Conclusions
337(1)
Acknowledgments
337(1)
References
338(11)
Chapter 16 Structural Neuroimaging 349(30)
Ruth A. Carper, Graham M. Wideman, and Eric Courchesne
Introduction
349(1)
Review of Recent Structural Imaging Literature
350(11)
Brain Size and Head Size in Autism
350(2)
Cerebral Findings
352(7)
Early Childhood
352(2)
Late Childhood through Adulthood
354(4)
Specific White Matter Findings
358(1)
Neuropathological Findings
358(1)
Cerebellum
359(1)
Limbic System
360(1)
Basal Ganglia
361(1)
Mechanisms
361(4)
Possible Abnormalities of Neuroproliferation
362(2)
Possible Inflammatory Processes
364(1)
Future Directions in Neuroimaging
365(7)
Advances in MRI Scanner Hardware and Software
366(1)
The Challenge of Automated Morphological Processing
367(4)
VBM — A Controversial Quantitation Technique
367(3)
Surface Reconstruction and Morphology
370(1)
Diffusion-Weighted Imaging, Diffusion Tensor Imaging, White Matter Orientation, and Tractography
371(1)
Conclusion
372(1)
References
373(6)
Chapter 17 Neuropsychology and Neurophysiology of Autism Spectrum Disorders 379(38)
Nancy J. Minshew, Sara J. Webb, Diane L. Williams, and Geraldine Dawson
Introduction
380(1)
The Complex Information Processing Model
381(8)
Further Articulation of What "Complex Information Processing" Means
385(2)
Neuroimaging Validation of the Cognitive Profile
387(1)
Confirmation of Reduced Information Processing Capacity
387(1)
Underconnectivity and Overconnectivity of Neocortical Systems
388(1)
Another Aspect of the Information Processing Impairment: Local-Global Processing
389(3)
Interrelationships between Local-Global Processing, Object Processing, and Face Processing
391(1)
Extending the Local-Global Processing Account to High-Level Tasks
391(1)
Executive Function and Abstraction: The Nonsocial Impairments in Autism
392(3)
Abstract Reasoning
393(1)
Deficits in Part-Whole Processing and in Abstraction: A Basis for Restricted and Repetitive Behavior
394(1)
Other Models for Autism: Social Cognition, a Core Diagnostic Phenotype
395(7)
Early Social Impairments
395(1)
Face Processing: Early Emerging Impairments
396(2)
Evidence for Early Impairment in Facial Emotion Processing and Memory
398(1)
Explanations for Face Processing Impairments
398(2)
Theory of Mind (ToM)
400(2)
Oculomotor and Postural Physiology: Beyond Neuropsychological Tests
402(3)
Oculomotor Physiology
402(2)
Postural Physiology
404(1)
Conclusion
405(2)
Concluding Remarks Regarding Social Deficits
406(1)
Closing Comments
406(1)
Perspectives for Future Research
407(1)
Acknowledgments
407(1)
References
408(9)
Chapter 18 Pharmacological Treatments 417(26)
Christopher J. McDougle, David J. Posey, and Kimberly A. Stigler
Introduction
417(1)
Motor Hyperactivity and Inattention
418(4)
Psychostimulants
418(3)
Alpha, Adrenergic Agonists
421(1)
Interfering Stereotypical and Repetitive Behavior
422(4)
Clomipramine
423(1)
Fluvoxamine
424(1)
Fluoxetine
425(1)
Other SSRIs
425(1)
Aggression and Self-Injurious Behavior
426(6)
Haloperidol
426(2)
Clozapine
428(1)
Risperidone
428(1)
Olanzapine
429(1)
Quetiapine
430(1)
Ziprasidone
431(1)
Aripiprazole
431(1)
Core Social Impairment
432(2)
Drugs Affecting Glutamate Function
432(1)
D-Cycloserine
433(1)
Summary and Future Directions
434(2)
Coactive Pharmacological Treatment Strategies
435(1)
Acknowledgments
436(1)
References
436(7)
Chapter 19 Behavioral, Educational, and Developmental Treatments for Autism 443(32)
Sally J. Rogers and Sally Ozonoff
Introduction
444(1)
Language Interventions
444(6)
Studies Using a Didactic Behavioral Approach
444(2)
The Naturalistic Behavioral Language Interventions
446(2)
Developmental Language Approaches
448(2)
Social Interventions
450(3)
Interventions with Younger or Less Verbal Children
450(3)
Adult Use of Dyadic Engagement
450(1)
Self-Management Techniques
451(1)
Games with Objects
451(1)
Pivotal Response Training
451(1)
Peer-Mediated Interactions
451(1)
Role-Playing Games
452(1)
Peers as Tutors
452(1)
Peers Using PRT
453(1)
Integrated Playgroup
453(1)
Interventions for Older and More Verbal Children
453(2)
Social Skills Training
453(2)
Special Interest Games
455(1)
Repetitive and Restrictive Behavioral Repertoire
455(3)
Comprehensive Intervention Approaches for Preschoolers
458(4)
The Work of Ivar Lovaas and Colleagues
458(2)
Developmentally Oriented Treatments
460(2)
New Approaches
462(1)
Conclusions
463(1)
Acknowledgments
464(1)
References
464(11)
Chapter 20 The Costs of Autism 475(28)
Michael L. Ganz
Introduction
476(1)
Overview of Costs
477(3)
Components of Cost
477(1)
Direct Medical Costs
478(1)
Direct Nonmedical Costs
478(1)
Indirect Costs
478(1)
Sources of Costs and Methods for Constructing Cost Estimates
478(2)
Perspective
480(1)
Methods
480(2)
Review of the Literature and Calculation of Costs
482(9)
Direct Medical Costs
482(4)
Physician, Outpatient, and Clinic Services
482(1)
Dental
483(1)
Prescription Medications
483(1)
Complementary and Alternative Therapies
483(1)
Behavioral Therapies
484(1)
Hospital and Emergency Department Services
485(1)
Allied Health, Equipment, Supplies, and Home Health
485(1)
Medically Related Travel
486(1)
Summary
486(1)
Direct Nonmedical Costs
486(4)
Child Care
486(1)
Adult Care
487(1)
Respite Care and Family Care
487(1)
Home and Car Modifications
487(1)
Special Education
487(1)
Supported Employment
488(1)
Other
489(1)
Summary
490(1)
Indirect Costs
490(3)
Productivity Losses of People with Autism
490(1)
Productivity Losses of Parents of People with Autism
490(1)
Summary
491(1)
Results and Sensitivity Analyses
491(2)
Discussion
493(4)
Directions for Future Research
497(1)
Acknowledgments
497(1)
References
498(5)
Index 503

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