Understanding Autism: From Basic Neuroscience to Treatment

by Moldin; Steven O.

• ISBN13: 9780849327322
• ISBN10: 0849327326
• Edition: 1st
• Format: Hardcover
• Copyright: 2006-04-25
• Publisher: CRC Press

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