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Misbuilding Brains: Biological Causes of Neurodevelopmental Divergence and Disorder [Pehme köide]

(University of Edinburgh)
  • Formaat: Paperback / softback, 336 pages
  • Ilmumisaeg: 02-Jul-2026
  • Kirjastus: John Wiley & Sons Inc
  • ISBN-10: 1394164734
  • ISBN-13: 9781394164738
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  • Formaat: Paperback / softback, 336 pages
  • Ilmumisaeg: 02-Jul-2026
  • Kirjastus: John Wiley & Sons Inc
  • ISBN-10: 1394164734
  • ISBN-13: 9781394164738
Teised raamatud teemal:
Exploring the origins of brain development, diversity, and disorders

Misbuilding Brains: Biological Causes of Neurodevelopmental Divergence and Disorder offers detailed insights into human brain development from embryo to maturity, and how genetics and environment combine to produce diversity, common mental health conditions, and major neurodevelopmental disorders. Beginning with an explanation of brain development and function, the book explores how variability in our genomes and environment impact iterative growth processes before discussing where, when, and how specific neurodevelopmental disorders and neurodivergent conditions arise across the life course. It includes clinical conditions at all stages of life, from those appearing prenatally, in childhood, and in adolescence to diseases of the elderly that likely start early in life. A final outlook discusses the potential to prevent or treat these conditions.

Combining the latest findings from developmental neurobiology, human genetics, pathology, pharmacology, toxicology, physiology, psychiatry, and psychology, this book includes:





Easily accessible content, using explanatory illustrations to help describe biological mechanisms and state-of-the art technologies to investigate neurodevelopmental diversity Normal brain development from conception to maturity with diagrams that clarify anatomy and define anatomical terms The nature of the genome, including its composition, replication, and function, and environmental factors from physical to socioeconomic that impact brain development In-depth coverage across the full range of neurodevelopmental conditions, from neurodivergence to overt anatomical neurodevelopmental disorders at all stages of life

This book is an essential resource for students and researchers in biological and biomedical sciences, including neurology, psychiatry, and clinical psychology, seeking to understand the biological causes of neurodivergence and neurodevelopmental disorders.
Preface xi

Glossary xiii

Introduction xix

Part I Our Growing Brains 1

1 The Development of Brain Structure 3

A Framework for Understanding Prenatal Brain Development 3

Ways of Discovering How Brain Cells Are Created 3

An Overview of the Development and Diversification of Brain Cells 4

Ways of Describing Structures Anatomically 6

The Early Stages of Brain Growth 8

Gastrulation and the First Signs of Brain Tissue 8

From Neural Plate to Neural Tube 9

Patterning: Specifying the Subdivisions of the Early Brain 11

Subsequent Growth of the Neural Tube 12

The Development of Brain Cell Numbers, Locations and Types 15

Brain Cell Proliferation 15

Migration: Getting the Right Types of Cells to the Right Places 18

The Structural Maturation of Brain Cells of Various Types 21

The Development of Neural Circuits 24

Axon Development 24

Circuit Formation 25

A Role for Cell Death Throughout Brain Development 26

Summary 26

2 Brain Function and Its Development 29

The Functions of the Brains Major Regions 30

The Brains Major Anatomical Features 30

The Functions of Human Neocortex 32

The Functions of the Hippocampus, Cerebellum and Basal Ganglia 34

The Organization of Function Within Brain Regions 35

Neuronal Function and Its Development 36

How Neurons Send Electrical Impulses 36

How Neurons Communicate with Each Other 37

How the Brains Neurons Work Together to Make Decisions 40

How the Brains Activity Affects the Function of Its Synapses 41

How Glial Cells Directly Assist the Functions of Neurons 45

Holistic Understanding of Brain Function and Its Development 46

Ways to Study Holistically What Our Brain Does at Different Ages 46

A Holistic View of Our Developing Brains 51

A Holistic View of Mature Brain Function 53

The Effect of the Brains Experiences on Its Developing Functions 55

Language Development 56

The Development of High-Level

Executive Function 57

Emotional and Social Development 57

Summary 58

3 Disordered and Neurodivergent Phenotypes 61

Anatomical Abnormalities 62

Functional Disorders 68

Abnormalities of Posture and Movement 69

Neurodevelopmental Delay: An Overview 70

Types of Neurodevelopmental Delay: Three Case Studies 73

Intellectual Disability 74

Disorders of Communication 75

Disorders of Perception: An Overview 77

Disorders of Perception: Case Histories 78

Disorders of Mood or Emotion 80

Neurodivergence 81

Summary 82

Part II Ultimate Causes of Neurodiversity and Neurodevelopmental Disorder
85

4 Genetic Variation 87

The Nature of DNA 87

How Variation in DNA Comes About 90

DNA Molecules Are Prone to Develop Errors 90

Some Errors in DNA Remain Uncorrected, Creating Mutations 93

Mutations Can Pass to the Next Generation 94

Mutations Can Persist with Different Frequencies in the Population 94

Categorizing Types of Genetic Variation 95

Nuclear DNA Variants Can Be of Many Different Sizes 95

Nuclear DNA Variants Can Arise in Many Different Ways and Be of Many
Different Types 95

Mitochondrial DNA Is Particularly Prone to Variation 97

Why Only Some Genetic Variants Affect People 100

A Variants Location in the Genome Matters 100

When Variants Arise and How They Affect Cells Matter 103

How Genetic Variants Can Affect People 103

Variants in Protein-coding Regions Can Affect the Proteins Produced in Many
Different Ways 103

Variants in Regions That Do Not Code for Protein Can Affect the Individual
for Many Reasons 108

Large Variants Involving Protein-coding or Non-coding Regions Are Likely to
Affect the Individual 109

How Changes in Proteins Might Affect People 109

The Effects of Changes in Proteins Depend on Many Things 109

Changes in Some Proteins Affect DNA Replication, Repair or 3-dimensional
State 110

Changes in Some Proteins Affect the Control of Gene Expression 112

Changes in Some Proteins Affect the Structure of Cells and Tissues 113

Changes in Some Proteins Affect Other Cellular Activities 113

The Inheritance of DNA Variations 114

The Human Population Contains Many Alleles of Our Genes 114

Harmful Alleles Can Persist in the Human Gene Pool 115

Genetic Factors Determine the Impact of Inheriting a Harmful Allele in
Nuclear DNA 116

Epigenetic Factors Determine the Impact of Inheriting a Harmful Allele in
Nuclear DNA 118

Factors Determining the Impact of Inheriting a Harmful Allele in
Mitochondrial DNA 120

Causes of Diversity and Disorder Involving Multiple Variants 121

Many Causes of Diversity and Disorder Involve Numerous Alleles Rather Than
Just One 121

How We Investigate the Ultimate Causes of Diversity and Disorder Involving
Multiple Variants 122

Summary 126

5 Environmental Variation Affecting the Developing Brain 127

Ways of Identifying the Effects of Environmental Variation 129

The Growth of Epidemiology as a Science 129

Longitudinal Epidemiological Studies 130

Recent Advances in Epidemiological Research 130

Specific Environmental Factors 132

Exposure to Harmful Chemicals 132

Infections 133

Effects from Metabolic Disorders Occurring Outside the Brain 134

Autoimmunity 135

Malnutrition 135

Physical Trauma 135

Preterm Birth 135

Complex Environmental Factors 136

Socio-economic Disparities and Environmental Stressors 137

Interpersonal Relationships and Lifestyle 138

The Microbiome 138

The Climate 139

Summary 139

6 Ultimate Causes of Specific Neurodevelopmental Conditions 141

Disorders Caused Mainly by Genetic Variation 142

Early Discoveries of Chromosomal Abnormalities 142

More Recent Advances in Understanding Chromosomal Abnormalities 143

Approaches to Understanding Monogenic Disorders 145

Identified Monogenic Disorders 149

Even Monogenic Disorders Might Be Polygenic 149

Multifactorial Causes of Disorder and Divergence 159

The Origins of Most Disorder and Divergence Are Multifactorial 159

Prenatal Multifactorial Disorders 162

Multifactorial Conditions Emerging at Birth or in Early Childhood 164

Multifactorial Conditions Emerging Later in Childhood 164

Multifactorial Conditions Emerging in Adolescence and Early Adulthood 167

Summary 172

Part III Proximate Causes of Neurodevelopmental Disorder and Neurodiversity
Linking Ultimate Causes to Phenotypes 175

7 Proximate Causes of Prenatal Disorders 177

The Microenvironment of Developing Brain Cells 180

Some Extracellular Components Are Relatively Static 181

Cell Signalling Molecules and Second Messenger Pathways Are More Dynamic
181

Primary Cilia Mediate Much Intercellular Signalling 185

How the Earliest Steps in Brain Development Can Be Derailed 185

Derailment of Neural Induction 185

Derailment of Neurulation 188

How Cell Proliferation Can Be Disrupted 192

How Genetic Variants Might Affect Cell Proliferation 192

Genetic Variants Can Directly Affect the Machinery of Dividing Cells 193

Transcription Factor Variants Can Have Indirect Effects on the Machinery of
Dividing Cells 195

Signalling Molecule Variants Can Have Indirect Effects on the Machinery of
Dividing Cells 196

Variants Affecting Primary Cilia Can Interfere with Signalling and Affect
Proliferation 198

How Environmental Variation Can Affect Cell Proliferation 198

How Cell Migration Can Be Disrupted 199

Mechanisms of Cell Migration in the Developing Brain 202

Genetic Variants Directly Affecting the Mechanics of Migrating Cells 202

Some Genetic Variants Affect Migrating Cells Less Directly 205

How Environmental Variation Can Affect Cell Migration 206

How the Specification of Cell Types Can Be Disrupted 206

How Transcription Factor Disruption Can Derail Cell Specification 207

How Signalling Molecule Disruption Can Derail Cell Specification 211

How the Development of Neuronal Connections Can Be Disrupted 212

Disruption of Axon Growth and Guidance 212

Disruption of Dendrite and Synapse Formation 213

Genetic Variants Can Affect Brain Development by Altering General Support
Mechanisms 214

Effects on DNA Integrity 214

Effects on RNA Synthesis or Processing 215

Effects on Proteostasis 215

Effects on Structural Proteins 217

Effects on the Metabolic Processing of Molecules Other Than Proteins 218

Summary 218

8 Proximate Causes of Childhood Conditions 221

An Overview of This
Chapters Content and Layout 221

How Genetic Variants Can Directly Affect the Brains Electrical Components
222

Effects on Electrical Transmission Along Nerves 222

Effects on Myelination 225

Effects on Synaptic Transmission 225

Effects on Synaptic Plasticity 227

Indirect Ways in Which Genetic Variants Can Affect the Brains Electrical
Components 229

Variants Affecting Gene Expression 230

Variants Affecting Proteostasis 234

Variants Affecting Structural Proteins 236

Variants Affecting General Metabolic Processes 236

The Proximate Causes of Polygenic and Multifactorial Conditions in Childhood
241

Epilepsy 243

Autism 243

ADHD 245

Tourette Syndrome 246

OCD 246

Summary 246

9 Proximate Causes of Conditions Emerging in Adolescence or Adulthood 249

How Defined Genetic Variants Can Cause Disorders After Childhood 250

Huntington Disease 250

Amyotrophic Lateral Sclerosis and Frontotemporal Dementia 253

Spinocerebellar Ataxia 253

Leukodystrophies 254

Inherited Cerebral Vasculopathies 254

How Specific Environmental Factors Can Affect the Maturing Brain 255

How Multifactorial Conditions of Adolescence and Adulthood Might Be Caused
256

Schizophrenia and Bipolar Disorder 256

Major Depression 258

How Disrupted Development Might Contribute to Degeneration at Older Ages
260

Alzheimer Disease 260

Parkinson Disease 262

Summary 264

Afterword 265

References 273

Index 000
David J. Price is Professor of Developmental Neurobiology at the University of Edinburgh. He qualified in Medicine in Edinburgh in 1981 and trained as a junior doctor in medicine, surgery, and psychiatry before obtaining a DPhil at the University of Oxford in 1985. He has written two books and over 200 original research papers on brain development. He was elected a Fellow of the Royal Society of Edinburgh in 2019.