The Biological Basis of Mental Health

This book explores the underlying biology and neuroscience associated with mental health
and wellbeing.
This fully revised fourth edition includes new chapters on behavioural science and brain–
gut and brain–gender connections, as well as expanded content on memory and genetics.
Integrating up-to-date pharmacological and genetic research with an understanding of envi-
ronmental factors that impact on human biology, The Biological Basis of Mental Health
covers topics including brain development, neural communication, neurotransmitters and
receptors, hormones and behaviour, genetic disorders, pharmacology, substance misuse,
anxiety, schizophrenia, depression, epilepsy, subcortical degenerative diseases of the brain,
dementia, developmental disorders and sleep.
This unique textbook is an essential read for all healthcare students, practitioners and
educators with an interest in mental health and neuroscience.

William T. Blows was formerly a lecturer at City University of London, UK, where he
taught biology to nurses.
The Biological Basis of
Mental Health
Fourth edition

William T. Blows
Cover image credit: © Getty Images

Fourth edition published 2022

by Routledge
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and by Routledge
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Routledge is an imprint of the Taylor & Francis Group, an informa business
© 2022 William T. Blows
The right of William T. Blows to be identified as author of this work has been
asserted by him in accordance with sections 77 and 78 of the Copyright, Designs
and Patents Act 1988.
All rights reserved. No part of this book may be reprinted or reproduced or
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Trademark notice: Product or corporate names may be trademarks or registered
trademarks, and are used only for identification and explanation without intent to
infringe.
First edition published by Routledge 2003
Fourth edition published by Routledge 2022
British Library Cataloguing-in-Publication Data
A catalogue record for this book is available from the British Library
Library of Congress Cataloging-in-Publication Data
A catalog record has been requested for this book
ISBN: 978-0-367-56319-6 (hbk)
ISBN: 978-0-367-56318-9 (pbk)
ISBN: 978-1-003-09727-3 (ebk)
DOI: 10.4324/9781003097273
Typeset in Times New Roman
by Deanta Global Publishing Services, Chennai, India
Contents

List of figures xii

List of tables xvii
Preface xx

1 Introduction to the brain 1

Introduction: The overall structure of the brain 1
The cerebrum 4
The limbic system 9
The thalamus, hypothalamus and pituitary gland 9
The basal ganglia, cerebellum and claustrum 12
The brain stem 16
The main connectivity pathways involved in mental health 18
The meninges and cerebrospinal fluid 19
The blood–brain barrier (BBB) 21
The central, peripheral and autonomic nervous systems 21
The basic principles of brain pathologies affecting mental health 23
Mental health problems related to the COVID-19 pandemic (2019–2022) 24
Brain biomarkers 25
Key points 25
Notes 27
References 27

2 Brain development 28
Introduction 28
The nervous system up to birth 28
The debate: When does consciousness start? 31
The brain at birth 32
Infant and child brain development 34
The teenage brain 36
Hormone influences on brain development 38
Nutritional influences on brain development 39
Key points 42
Note 43
References 43

vi­ Contents
3 Neural communication 44
The neuron 44
Neurotransmission 47
Synapses 50
Neuroglia 54
Key points 58
References 59

4 Neurotransmitters and receptors 60

Introduction to neurotransmitters 60
Receptors 61
The amine neurotransmitters 63
The amino acid neurotransmitters 69
The peptide neurotransmitters 75
Endogenous opioids 77
Other neurotransmitters 80
Key points 83
Notes 84
References 85

5 The brain–body connections: Gut microbiota, immunity and brain gender 86

The gut microbiota and immunity 86
Brain gender 92
Key points 94
Notes 95
References 95

6 Hormones 97
Introduction: Hormones, form and function 97
The pituitary gland and hormones 99
The thyroid hormones 100
Hormones from the adrenal cortex 101
Hormones from the adrenal medulla 104
Sex hormones 105
Key points 105
Notes 107
References 107

7 Behaviour 108
Introduction 108
Aggression 109
Antisocial, criminal and psychopathic behaviour 112
Introverts and extroverts 115
Creativity 116
Exercise and the brain 116
 Contents  vii
Behavioural disorders 118
Eating disorders 120
Key points 126
Notes 127
References 127

8 Genetics I: Introduction and autosomes 129

Introduction 129
Chromosomes and genes 129
Disorders of inheritance 135
Autosomal genetic disorders 136
Chromosomes 137
Key points 152
Note 153
References 153

9 Genetics II: Sex chromosomes and gene disorders 155

The sex chromosomes: X and Y 155
Immediate early genes (IEGs) and late response genes 161
Epigenome and genomic imprinting disorders 161
Key points 165
Note 166
References 166

10 Pharmacology 167
Introduction 167
Pharmacokinetics 168
Pharmacodynamics 173
Pharmacotherapeutics 175
Pharmacogenetics and pharmacomicrobiomics 187
Key points 187
Note 188
References 188

11 Illicit substance use disorders 189

Introduction and the brain reward pathway 189
The opiate drugs 192
Cocaine 197
Amphetamines and other dopamine-enhancing drugs 198
Cannabis 202
The hallucinogenic drugs 207
Drugs of addiction used in medicine 210
Key points 211
Notes 212
References 212
viii­ Contents
12 Common substance misuse 214
Alcohol 214
Nicotine 217
Caffeine 219
Key points 220
Notes 221
References 221

13 Emotions 222
Introduction 222
The limbic system 222
The amygdala 224
Happiness 227
Religious experiences 228
Love 228
Music 229
The paranormal 233
Emotional intelligence 234
Key points 235
References 236

14 Stress, anxiety and fear 237

The biology of stress 237
Physical effects of stress and General Adaptation Syndrome 242
Stress and child abuse 243
The biology of fear 246
Anxiety disorders 248
Anxiety-related personality disorders 257
Genetics of anxiety disorders 258
The anxiolytic drugs 258
Key points 260
Notes 260
References 260

15 Schizophrenia 262
Introduction 262
The genetic influence in schizophrenia 264
Brain pathology 267
Neurodevelopment and the “big brain” theory 275
The biochemical changes in schizophrenia 276
The possible role of environmental factors 278
Schizoaffective disorder and schizoid-related personality disorders 279
Key points 281
Notes 282
References 282
 Contents  ix
16 The antipsychotic drugs 284
Introduction 284
The first-generation antipsychotics 284
The second-generation antipsychotics (atypical antipsychotics) 288
Issues related to antipsychotic drugs 291
Pharmacokinetics of the antipsychotics 292
Key points 293
References 293

17 Affective disorders 294

Introduction 294
Mood disorders 296
Suicide 303
Brain pathology 305
Biochemistry 307
Immunity 312
Electroconvulsive therapy (ECT) 315
Depression in young people 315
Key points 316
Notes 317
References 317

18 Antidepressant drugs 318

Introduction: The antidepressant drugs 318
Tricyclic and related antidepressants 319
Selective serotonin re-uptake inhibitors (SSRI) 320
Other antidepressants 322
Monoamine oxidase inhibitors (MAOI) 322
Pharmacokinetics of the antidepressants 324
Antidepressant issues 324
Mood-stabilising drugs 327
Key points 329
References 329

19 Epilepsy 331
Introduction 331
Types of seizures 331
The electroencephalogram (EEG) 333
Factors involved in the cause of epilepsy 334
The pathophysiology of epilepsy 336
Tonic–clonic (grand mal) seizures 339
Temporal lobe (psychomotor) epilepsy and hippocampal sclerosis 341
Jacksonian seizures 342
Infantile spasms and febrile convulsions 343
Childhood epilepsies 343
x­ Contents
The anticonvulsant drugs 344
The pharmacokinetics of the antiepileptic drugs 348
The side-effects of the anticonvulsant drugs 348
Anticonvulsant drug interactions and withdrawal 348
Key points 349
Notes 350
References 350

20 Subcortical degenerative disorders of the brain 351

Introduction: The basal ganglia 351
Parkinson disease (PD) 353
The anti-Parkinson drugs 357
Other drugs 360
Other treatments 360
Huntington disease (HD) 361
Genetics 362
Treatment of Huntington disease 364
Wilson disease and Harvey disease 364
History: The strange case of Harvey disease 366
Key points 366
Notes 368
References 368

21 Memory and learning 369

The hippocampus 369
Memory I: Introduction 370
Memory II: The biology 372
Memory III: Memory loss 375
Mild cognitive impairment (MCI) 375
Functional cognitive disorder (FCD) 376
Future drug treatment for memory loss 376
Learning 377
Learning disorders 377
Key points 380
Notes 381
References 381

22 The ageing brain and dementia 382

The natural ageing brain 382
The dementias 388
Alzheimer disease (AD) 389
The neuropathology of Alzheimer disease 390
Dementia with cortical Lewy bodies (DCLB) 402
Vascular dementia 402
 Contents  xi
Frontotemporal dementia (FTD) (Pick disease) 403
Limbic-predominant age-related TDP-43 encephalopathy (LATE) 404
Drugs used in dementia 404
Key points 407
Notes 407
References 408

23 Communication and developmental disorders 410

Introduction 410
Communication disorders 410
Developmental disorders 412
Intellectual disability 422
Key points 427
Notes 428
References 428

24 Sleep 429
Introduction 429
Why we sleep 429
The physiology of the waking state 432
Physiology of sleep 436
Dreams 443
Effects of sleep loss on health 446
Sleep disorders 448
Sleep medication 452
Key points 454
Notes 455
References 455

Genetics index: Genes, chromosomes, genetic terms and syndromes 457

Index 461
Figures

1.1 Structural classification of the central nervous system 2

1.2 Exploded view of the brain seen from the left side, showing the main
components 3
1.3 A functional map of the left cerebral cortex showing important
Brodmann numbers 4
1.4 Left view of the brain to show the insular 7
1.5 Coronal section through the brain 9
1.6 Close up of the basal ganglia 11
1.7 The basal ganglia motor loop 12
1.8 Stylistic sketch of the main connections from the claustrum 14
1.9 Sagittal section through the brain stem and cerebellum 15
1.10 Coronal section through the brain stem 16
1.11 Sagittal section through the brain stem 17
1.12 Stylistic plan of connectivity 20
1.13 The meninges between the brain and the skull 20
1.14 Simplified scheme of the autonomic nervous system (ANS) 22
2.1 Neurulation 29
2.2 The neuropores 29
2.3 Cerebral cortical cell development 30
2.4 Lateral views of the folding brain during development 32
2.5 Reflexes at birth 33
2.6 (A) Omega-3 and (B) omega-6 fatty acids 41
3.1 The neuron 45
3.2 Axonal transportation 46
3.3 Resting potential in the neuronal membrane 47
3.4 The action potential as seen on an oscilloscope screen 48
3.5 Sodium–potassium pumps 49
3.6 An unmyelinated axon 50
3.7 A section of myelinated axon 51
3.8 A synapse 51
3.9 Events at a synapse during an action potential 52
3.10 Two types of postsynaptic receptor 53
3.11 Astrocytes 55


 Figures  xiii
3.12 Astrocytes near a GABA synapse 56
4.1 The structure of three compounds 61
4.2 An excitatory metabotropic receptor 62
4.3 An inhibitory metabotropic receptor 63
4.4 The formation of dopamine, noradrenaline and adrenaline 64
4.5 The main dopamine pathways 65
4.6 The main noradrenaline pathways 66
4.7 The main serotonin pathways 67
4.8 The formation of serotonin from the amino acid tryptophan 68
4.9 The synthesis of glutamate and gamma-aminobutyric acid (GABA) 70
4.10 The main glutamate pathways 71
4.11 The main gamma-aminobutyric acid (GABA) pathways 72
4.12 The NMDA glutamate receptor 73
4.13 The gamma-aminobutyric acid (GABA) inhibitory receptor (GABAA) 74
4.14 The main aspartate pathways 75
4.15 The main somatostatin pathways 78
4.16 The main enkephalin pathways 79
4.17 The synthesis of acetylcholine 80
4.18 The main acetylcholine pathways 82
4.19 The main histamine pathways 83
5.1 The human digestive system showing areas of low and high microbiota 88
5.2 Mechanisms for communications between the gut microbiota and the brain 90
5.3 The brain and immune systems working together 91
6.1 Hormones and receptors 98
6.2 The complex of hormone and receptor 98
6.3 The pituitary gland, the hypothalamus and the pituitary hormones 99
6.4 The hypothalamo–pituitary–adrenal (HPA) axis 100
6.5 Flow diagram of the production of various steroidal (lipid-based) hormones 102
6.6 Adrenogenital syndrome 103
6.7 Adrenogenitalism 104
6.8 The sympathetic nervous system 104
7.1 Aggression 111
7.2 Exercise increases the brain’s production of BDNF (brain-derived
neurotrophic factor) 117
7.3 The conversion from proBDNF to mature BDNF (mBDNF) 118
7.4 Adipose feedback to the brain 121
7.5 The liver control of hunger 122
8.1 The normal human karyotype 130
8.2 Dominant gene inheritance 131
8.3 Recessive gene inheritance 131
8.4 The genetic code for alanine 132
8.5 The gene locus 133
8.6 Genetic mutations 134
8.7 The human karyotype showing monosomy 136
xiv­ Figures
8.8 Down syndrome karyotype, showing trisomy at chromosome 21 150
9.1 Inheritance patterns of normal sex determination 156
9.2 Sperm meets ovum 156
9.3 Abnormal clustering together of the XY chromosomes 157
9.4 An abnormal sperm carries both XY and meets a normal ovum 157
9.5 Fragile X syndrome 159
9.6 Normal imprinting and imprinting errors in Angelman and Prader-Willi
syndromes 163
10.1 Drug absorption 170
10.2 Illustration of a drug half-life 172
10.3 The enterohepatic cycle 174
10.4 Agonist and antagonist drugs 175
10.5 Simplified illustration of drug action on movement of substances in or out
of the cell 176
10.6 Therapeutic window 178
10.7 Pharmacokinetic interaction 184
10.8 Drug interaction in the liver 185
10.9 Pharmacodynamic interactions 186
11.1 Lateral view of a mid-section through the brain 190
11.2 The same view as in Figure 11.1a showing the main pathways from the
substantia nigra (SN) to the nucleus accumbens (NA) 191
11.3 Effects on the reward pathway when opiate binds to the VTA mu receptor 193
11.4 Pathways of the extended amygdala 194
11.5 Opiate binding to the mu receptor 195
11.6 The action of amphetamines and cocaine at the dopaminergic synapse 197
11.7 Ecstasy intake and the events that follow 200
11.8 Methamphetamine (METH) affects dopamine (DA) release from
dopaminergic neurons 201
11.9 The very similar structure of tetrahydrocannabinol (THC) and cannabidiol
(CBD) 203
11.10 Tetrahydrocannabinol (THC) binds to cannabinoid receptors 203
11.11 Cannabis causes dopamine release in the nucleus accumbens 204
11.12 POMC neurons and appetite 206
11.13 Molecular structure of serotonin, LSD and psilocin 208
12.1 The alcohol metabolic pathway 217
12.2 Long-term caffeine consumption 220
13.1 The main components of the limbic system 223
13.2 Inputs and outputs of the amygdala 224
13.3 The brain stem nuclei are influenced by the amygdala 227
13.4 The brain areas involved in love 229
13.5 The brain areas involved in music 230
13.6 The planum temporale 233
14.1 Pathway from the thalamus to the hypothalamus during stress 238
14.2 The neuroendocrine response to stress 239
 Figures  xv
14.3 Effects of acute stress and raised cortisol on the cell 240
14.4 Effects of chronic stress and persistently raised hormones on the neuron 240
14.5 Some effects of chronic stress on body systems 241
14.6 The General Adaptation Syndrome (GAS) 243
14.7 Stressful events on a young child 244
14.8 Brain areas involved in fear 247
14.9 The brain areas involved in GAD 250
14.10 Fear within the amygdala 251
14.11 The loop extending from the orbitofrontal cortex to the cingulate gyrus (CG) 255
14.12 The mechanism of GLO1 and MG in anxiety-related behaviour 259
15.1 The “Wnt pathway” 266
15.2 Cell losses in schizophrenia 269
15.3 Schematic view of the hippocampal complex 271
15.4 The hippocampal complex shown within the brain 272
15.5 The trisynaptic pathway in the hippocampus 272
15.6 The four main types of dopaminergic pathway 276
15.7 The factors affecting the cause of schizophrenia 280
16.1 The chemical structures of some important antipsychotic drugs 285
16.2 The atypical antipsychotic effects on the mesocortical and mesolimbic systems 289
16.3 The “hit and run” theory of atypical antipsychotic activity 290
17.1 Factors affecting the PKC enzyme system 298
17.2 Location of the pineal gland 302
17.3 The areas of the world with a high suicide rate 304
17.4 Some areas of the brain involved in depression 306
17.5 The diffuse modulatory systems 308
17.6 The HPA (hypothalamo–pituitary–adrenal axis) and HPT (hypothalamo-
pituitary-thyroid) axis 310
17.7 The effect of blood cortisol concentration on adrenocortical hormone (ACTH) 311
17.8 The relationship between cortisol concentrations and cytokine production 314
18.1 Structure of some important antidepressants 319
18.2 The short-term and long-term effects of SSRI drugs on the serotonin neurones 321
18.3 The mTOR cell signalling pathway and synaptogenesis in the postsynaptic
neuron 326
18.4 The intracellular actions of lithium 328
19.1 The normal electroencephalogram (EEG) tracing 334
19.2 The EEG seen in absences (or petit mal seizures) 335
19.3 The EEG seen in simple partial seizures 336
19.4 The EEG seen in complex partial seizures 337
19.5 The EEG seen in general tonic–clonic (or grand mal) seizures 337
19.6 The action of anticonvulsant drugs 346
20.1 Pathways changes involved in Parkinson Disease 352
20.2 The pathway in which MPTP causes neuronal damage and losses 357
20.3 Action of drugs on levodopa levels reaching the brain 359
20.4 Section through the brain to show changes as a result of Huntington disease 361
xvi­ Figures
20.5 The functions of the huntingtin (Htt) protein 364
20.6 Wilson disease 365
21.1 Hippocampus internal pathways important for memory 370
21.2 Connections of the hippocampus important in memory 372
21.3 Overview of LTP formation in the Schaffer pathway of the hippocampus 373
21.4 The magnocellular layer (layers 1 and 2) of the lateral geniculate nucleus of
the thalamus, which are disrupted in dyslexia 379
22.1 The brain gets old 383
22.2 Brain sections: normal and Alzheimer disorder 390
22.3 Amyloid protein in the brain 391
22.4 The formation of neurofibrillary tangles 393
22.5 The effects of APOE4 in the development of Alzheimer disease 396
22.6 The APOEε-4 and cyclophilin A pathways in Alzheimer disease 397
22.7 The inflammatory response in Alzheimer disease 400
22.8 Ampakine drug action 406
23.1 Simplified diagram of the MAPK and MTOR pathways in ASD 416
23.2 The cerebellum, dorsal view showing the vermis 417
23.3 The normal cerebellum and as seen in Joubert syndrome 418
23.4 Phenylalanine hydroxylase action 423
23.5 Fetal alcohol syndrome (FAS) 424
23.6 Effects of smoking during pregnancy on the fetal brain 425
24.1 Schematic view of the CSF day and night cleansing cycle 431
24.2 Somatic homeostasis hypothesis (SHY) 433
24.3 Brain waves at different sleep periods 434
24.4 Section through the front part of the brain to show the neurological and
orexin pathways involved in establishing and maintaining the wakeful state 435
24.5 The 8-hour sleep cycle 436
24.6 Schematic plan of the neurology of sleep atonia 437
24.7 Simplified REM pathways 438
24.8 Simplified NREM pathways 440
24.9 NREM sleep promoting areas of the anterior hypothalamus 441
24.10 The SCN and light impulses from the retina in light and dark 442
24.11 Dreams 444
24.12 Nightmares 446
Tables

1.1 Brain pathways involved in mental health 19

1.2 Functions of the autonomic nervous system 23
2.1 Comparison of prefrontal cortex development between children of different
IQ test scores 36
2.2 The vitamins involved in brain development and function 39
2.3 Some of the important minerals involved in brain development and function 40
4.1 The main functions of the dopamine receptors 66
4.2 Classes of serotonin receptors and their intracellular actions 69
4.3 The affinity of endogenous opiates for opiate receptors 80
5.1 List of the common organisms and their locations within the human microbiota 87
5.2 The components of the immune system 90
5.3 Sex differences in terms of task performance that were previously assigned
to the brain 94
7.1 The top five genes linked to aggression 110
7.2 Some genes linked to psychopathy 114
7.3 Some genes linked to obesity 124
8.1 Proportions of genes in common between relatives of different degrees 136
8.2 Chromosome 1. Some genes causing mental health–associated disorders 138
8.3 Chromosome 2. Some genes causing mental health–associated disorders 139
8.4 Chromosome 3. Some genes causing mental health–associated disorders 139
8.5 Chromosome 4. Some genes causing mental health–associated disorders 140
8.6 Chromosome 5. Some genes causing mental health–associated disorders 140
8.7 Chromosome 6. Some genes causing mental health–associated disorders 141
8.8 Chromosome 7. Some genes causing mental health–associated disorders 142
8.9 Chromosome 8. Some genes causing mental health–associated disorders 143
8.10 Chromosome 9. Some genes causing mental health–associated disorders 143
8.11 Chromosome 10. Some genes causing mental health–associated disorders 144
8.12 Chromosome 11. Some genes causing mental health–associated disorders 144
8.13 Chromosome 12. Some genes causing mental health–associated disorders 145
8.14 Chromosome 13. Some genes causing mental health–associated disorders 145
8.15 Chromosome 14. Some genes causing mental health–associated disorders 146
8.16 Chromosome 15. Some genes causing mental health–associated disorders 146


xviii­ Tables
8.17 Chromosome 16. Some genes causing mental health–associated disorders 147
8.18 Chromosome 17. Some genes causing mental health–associated disorders 148
8.19 Chromosome 18. Some genes causing mental health–associated disorders 148
8.20 Chromosome 19. Some genes causing mental health–associated disorders 149
8.21 Chromosome 20. Some gene mutations causing mental–health associated
disorders 149
8.22 Chromosome 21. Some gene mutations causing mental–health associated
disorders 149
8.23 Changes in the incidence of Down syndrome with maternal age 150
8.24 Chromosome 22. Some gene mutations causing mental–health associated
disorders 152
9.1 The X chromosome showing the major genes linked to mental
health disorders 158
9.2 The male Y chromosome showing the sex determination gene SRY
at locus Yp11.2 160
9.3 Some immediate early genes (IEGs) 161
10.1 Routes of drug administration 169
10.2 Different types of dry oral medication 176
10.3 Different types of liquid medication 177
11.1 Some drug interactions with opiates 196
11.2 Some drug interactions with methadone 196
11.3 Some genes affected and activated in cocaine misuse 199
11.4 Some drug interactions with cocaine 199
11.5 Drug interactions with amphetamines 202
11.6 Drug interactions with cannabinoids 207
12.1 Some drug interactions with alcohol 217
12.2 The effects of inhaling nicotine on non-smokers and smokers 218
12.3 Some drug interactions with nicotine 219
12.4 Comparison of caffeine content in different consumables 219
13.1 Musical genes 232
14.1 Some genes proposed for anxiety-related disorders 256
15.1 The symptoms of schizophrenia 263
15.2 Genetic risk of developing schizophrenia 264
15.3 The major genes linked to schizophrenia 265
15.4 Some possible biomarkers for schizophrenia 270
16.1 The effects and side-effects of the phenothiazine antipsychotic drugs 285
16.2 Receptor affinity for the major antipsychotic drugs 288
17.1 Previous and current classifications of depression 295
17.2 The symptoms of depression 295
17.3 Some genes linked to MDD 296
17.4 Some important genes linked to postpartum depression (PPD) 300
17.5 The psychoimmunological changes reported in depression 312
18.1 Some other antidepressants 322
 Tables  xix
19.1 The known causes of seizures 338
19.2 Some genes involved in epilepsy 338
19.3 Stages of a tonic–clonic fit 340
19.4 Immediate first aid required at each stage of the fit 340
19.5 Genes linked to ADNFLE syndrome 344
19.6 The classification of the antiepileptic drugs 345
19.7 Drugs used in specific epileptic categories 347
20.1 The genetic involvement in Parkinson disease 355
20.2 The Polyglutamine (PolyQ) diseases 363
21.1 Types of memory 371
21.2 Types of amnesia 376
22.1 The spectrum of Batten disease 385
22.2 Some important genes linked to Alzheimer and Pick diseases 395
22.3 The distinction between Alzheimer disease (AD) and dementia with cortical
Lewy bodies (DCLB) 402
23.1 Genes linked to stuttering 411
23.2 Major genes linked to ASD 414
23.3 Genes involved in Joubert syndrome 419
23.4 Eleven genes involved in childhood disintegrative disorder, which are
co-expressed and interact 420
23.5 The MECP2 spectrum of disorders 422
24.1 Sleep and the risk of catching the common cold 447
24.2 Teenage sleep loss in America, UK, Korea and Japan 447
24.3 Some common causes of insomnia 448
24.4 Genes linked to the sleep–wake cycle and sleep disorders 449
Preface

This book explores the underlying biology associated with the pathology of mental health
disorders and the related nervous system. Fully revised for this fourth edition, each chapter
has been updated to include the latest research, ideas and concepts in each field. There are
new chapters and new illustrations.
This fourth edition has expanded to accommodate much of the new genetics and epigenet-
ics of mental health research, with the basic genetics section now covered over two chap-
ters, with every chromosome shown as a map of mental health–related genes. Also, genetic
chapters are linked to specific disorders. This is to reflect the huge amount of research that is
taking place in mental health genetics, which will pave the way towards a better understand
of causation of disease and provide a basis for more individualised therapies.
In addition, there are new sections on the mental health links with exercise, gut microbiol-
ogy, immunity, brain gender, behaviour, memory and learning, “COVID-19” infection; and
new chapters on specific drug therapies for the major disorders.
Accessible and engaging, this is an essential text for students of mental health studies as
well as practitioners and educators in this field.


1 Introduction to the brain

•• Introduction: The overall structure of the brain

•• The cerebrum
•• The limbic system
•• The thalamus, hypothalamus and pituitary gland
•• The basal ganglia, cerebellum and claustrum
•• The brain stem
•• The main connectivity pathways involved in mental health
•• The meninges and cerebrospinal fluid
•• The central nervous system and autonomic nervous system
•• The principal brain pathologies affecting mental health
•• Brain biomarkers
•• Key points

Introduction: The overall structure of the brain

The human brain is one of Nature’s greatest achievements. It is the development of the brain
which has allowed humans to progress from their humble origins to putting a man on the
moon. This chapter consists of an overview of the brain and contains many references to
other pages where the area of the brain in question is explored further in more detail, usu-
ally in relation to a particular mental health pathology. At the simplest level, the brain works
something like a computer, but this is a computer like no other. It has been said that to build
a computer to do everything the human brain does, the computer would have to be the size of
Europe. Similar to a computer, the brain has an input (called a sensory nervous system) and
an output (called a motor nervous system). Between these two systems, the brain carries out
cognitive functions, i.e. mental processing such as thought, language, intellect, memory and
interpretation of the world about us.
As with a computer, things can go wrong with the brain, and when they do, symptoms
occur, just as with any other organ. The pathological conditions associated with the brain
may be either neurological or psychological (or psychiatric), depending on the degree of
physical disturbance (neurological) or mental health disturbance (psychological or psychiat-
ric) identified. These two types of brain dysfunction are becoming increasingly overlapped,
with the distinction between them becoming blurred. This is because we are learning that
neurological conditions often involve disturbance of the mind, and that mental health distur-
bance has some degree of physical (or biological) basis.

DOI: 10.4324/9781003097273-1
2­ Introduction to the brain

Forebrain (Prosencephalon)

Telencephalon

Cerebrum
Amygdala
Hippocampus
Basal ganglia

Diencephalon
Brain

Thalamus
Hypothalamus
Epithalamus
Subthalamus

Midbrain (Mesencephalon)
CNS

Midbrain

Hindbrain (Rhombencephalon)

Cerebellum
Pons
Spinal
Medulla
cord

Figure 1.1 Structural classification of the central nervous system.

The brain can be divided into several anatomical, developmental and functional areas as
we move downwards from the top towards the base. Generally, the three major divisions are
(Figures 1.1 and 1.2):

1. Forebrain (prosencephalon);
2. Midbrain (mesencephalon);
3. Hindbrain (rhombencephalon).

The forebrain is divided into two regions:

1. The telencephalon, consisting of the cerebrum and some underlying structures, notably
the basal ganglia, the hippocampus and the amygdala;
2. The diencephalon, notably the thalamus and hypothalamus.

The cerebrum (or cerebral cortex, i.e. cortex means surface layer), at the top, is the larg-
est and most advanced region of the brain, carrying out all our cognitive and conscious
 Introduction to the brain 3

Central Parietal
sulcus lobe
Frontal
lobe
Occipital
lobe

Cerebrum

Temporal lobe

Sylvian
fissure
(Lateral sulcus) Caudate
nucleus
Thalamus
Globus pallidus Basal Ganglia

Putamen

Posterior
Anterior

Amygdala
Hippocampus

Hypothalamus
Optic chiasma
Pituitary
gland
Midbrain
Brain
Pons
stem
Medulla
Spinal
Cerebellum
cord

Figure 1.2 Exploded view of the brain seen from the left side, showing the main components.

processes. Beneath this is the limbic system (mainly the hippocampus and the amygdala),
the areas concerned with preservation of both the individual and the species. This is the
area involved in emotions such as fear, and behavioural patterns such as eating, which are
designed to keep us alive. Beneath this are the basal ganglia areas, involved in control of
movement at a subconscious (automatic) level.
The midbrain is part of the brain stem between the forebrain above and the hindbrain
below.
The hindbrain consists of the medulla and the pons (parts of the brain stem) and the
cerebellum. The brain stem (pons and medulla) are involved in keeping the individual
alive at the physiological level, such as controlling the heart rate, the blood pressure and the
4­ Introduction to the brain
lungs, amongst other functions. The cerebellum is a key structure controlling balance and
movement.
At tissue level, the areas of the brain are formed from either grey matter, made from the
cell bodies of neurons (brain cells); or white matter, made from the axons of neurons col-
lected together (Chapter 3). Grey matter dominates the outer surfaces (or cortex) of the brain,
with white matter inside. The cerebral cortex is folded into gyri (singular gyrus, i.e. the top
of a fold), and sulci (singular sulcus, i.e. the channel between the gyri) in order to increase
the surface area for the purpose of packing in more neurons. Cell bodies which are separate
from the main outer surface, i.e. patches of grey matter deeper down inside the white matter,
are called ganglia (e.g. the basal ganglia). Nuclei are clusters of grey matter which have a
specific controlling function (e.g. the cranial nerve nuclei of the brain stem). Several areas of
the brain, such as the thalamus and hypothalamus, are actually collections of several dis-
tinct nuclei which are linked together by one name because they are anatomically positioned
together, and they have similar, related functions.

The cerebrum
The largest and uppermost area of the brain, the cerebrum (Figures 1.2 and 1.3), is divided
into two hemispheres, the left and right cerebral hemispheres, which are linked by the cor-
pus callosum, a connection which allows the two halves to communicate with each other.
The surface of each hemisphere is divided into four lobes: the frontal, parietal, temporal and
occipital lobes. Brodmann numbers (Figure 1.3) form an internationally agreed numbering

Figure 1.3 A functional map of the left cerebral cortex showing important Brodmann numbers (see
text for functions).
 Introduction to the brain 5
system to identify and map the major areas of the cerebral cortex (outer surface) according
to their functions.

The frontal lobes

The frontal lobes are at the front of both cerebral hemispheres (Figures 1.2 and 1.3). They
contain the main motor cortex (motor = movement) (Brodmann 4), each side controlling
muscles on the opposite side of the body, i.e. the left motor cortex controls most of the mus-
cles on the right side and vice versa. This is because the long motor axons (called pyramidal
tracts) cross further down in the brain and cord. In addition, the premotor cortex and the
supplementary motor area (SMA) together make up Brodmann 6 area, just anterior to the
main motor cortex. They are both involved in motor planning, a process that is vital for the
swift and accurate execution of complex motor tasks. Speech motor areas (Brodmann 44 and
45), also known as Broca’s area, control the muscles of speech.
The frontal lobes also have areas concerned with the following range of important higher
intellectual activities:

1 Achieving and sustaining awareness, attention and concentration;

2 Carrying out language activities, both spoken and in thought;
3 Maintaining memory;
4 Forming part of the pathways involved in emotions, i.e. emotional control;
5 Carrying out complex skills involving visual space (i.e. visuospatial tasks) which
require, for example, sequence planning or detailed copying of figures;
6 Performing executive functions such as monitoring one’s own performance and mak-
ing corrections as required, formulating and achieving goals, planning, judgement and
reasoning.

The frontal lobes are the last part of the brain to mature, i.e. during the twenties, so teenag-
ers function with reduced levels of emotional control and reasoning. The frontal lobes are
the main centres of consciousness, particularly of self (i.e. self-awareness). The prefrontal
cortex (PFC) is that part of the frontal lobes at the very front of the brain behind the fore-
head. The orbitofrontal cortex (OFC) is that part of the PFC immediately above the eye
sockets (called orbits). It is one of the most complex parts of the brain. The OFC has strong
connections with the amygdala and it is sometimes considered to be part of the limbic associ-
ated cortex. As such it has a critical role in evaluating and moderation limbic functions. In
addition, all sensory stimuli (vision, hearing etc.), are first processed by the relevant sensory
areas, then pass onto the posterior orbitofrontal cortex, which uses this sensory input to guide
behaviour, learning, memory and pleasure-seeking activity. In this way it has a vital role to
play in higher executive functions, such as decision making and adaptive learning.
The medial prefrontal cortex (mPFC) is active when thinking about oneself. Much of
our thought processes, particularly planning (which requires forward thinking towards
the future), reasoning and deduction, are carried out by the frontal lobes, and the PFC in
particular. It has the most neural connections, it makes the most complex integrations with
other systems and it requires more than twice the energy needed by other brain areas such
as the limbic system. Thought processing, unlike other brain functions, does not rely on
sensory input directly; it is an “internal” mental function. Thought does require, however,
processed information on the environment supplied via the sensory areas of the brain and
influenced by the hippocampus (Figure 1.2), combined with previous stored information
6­ Introduction to the brain
and knowledge, in particular knowledge of language. Because thought content and pro-
cessing is strongly influenced by the hippocampus, any disruption of the hippocampus, as
in schizophrenia, causes symptoms such as thought disorder (Chapter 15). Many compo-
nents of what we regard as our personality are due to the activities of the frontal lobes.
It should therefore not be surprising to learn that many psychiatric disorders, and some
specific mental health symptoms, either manifest within or involve the frontal lobes of the
brain, such as schizophrenia (Chapter 15), obsessive-compulsive disorder (Chapter 14)
and behavioural disorders (Chapter 7). No wonder that one of the very few psychosurgical
operations carried out in the past for mental health reasons was a prefrontal leucotomy,
which involved severing pathways leading away from the frontal lobes to the other parts
of the brain.

The parietal lobes

The parietal lobes involve the main somatic (i.e. soma = body, thus somatic = from the
body) sensory cortex (Brodmann 1, 2 and 3), and the somatic sensory association area
(Brodmann 5 and 7) (Figures 1.2 and 1.3). Association areas are essential for the interpreta-
tion and memory of senses, and therefore the understanding of sensory stimuli. This is impor-
tant because the brain is itself shut away from the world inside the skull. The only way the
brain is going to know what is happening outside the skull, i.e. in the external environment,
is via the sensory nervous system, and by its ability to interpret those signals brought in by
the sensory system. Association areas are therefore crucial in the brain’s understanding of
the world around us. A language area, also known as Wernicke’s area, occurs partly within
the parietal (Brodmann 39) and the temporal lobes (Brodmann 22), and is the main site for
understanding and formulation of spoken sentences.

The temporal lobes

The temporal lobes house the auditory area for the conscious sensation of hearing (Brodmann
41 and 42) and the auditory association area (Brodmann 22, part of Wernicke’s area). What
we actually hear is generated in the temporal lobe auditory area and not in the ears. Ears are
organs necessary to convert sound waves into nerve impulses. The temporal lobes make
sense of these impulses as conscious sound. Temporal lobes are also involved in the creation
of personality and is involved in emotional responses to sensory stimuli.

The insular cortex

This is the part of the cortex that lies deep within the lateral sulcus (also known as the
Sylvian fissure) and separates the temporal, frontal and parietal lobes on both sides. The
insular cortex cannot be seen from the outside without opening the lateral sulcus (Figure 1.4).
The functions of the insular are not well understood, but are related to

1 Sensorimotor processing of visceral interoceptive information (i.e. monitoring sensory

information from internal organs, especially from the gut, e.g. pain);
2 Olfactogustatory processing of sensory information of taste and smell;
3 Socio-emotional processing linking an emotional concept to sensory information, e.g.
disgust, fear, empathy and risk-taking;
4 Cognitive processing in relation to new ideas and experiences (e.g. learning).
 Introduction to the brain 7

Lateral sulcus
closed in
natural
(a) position

Lateral sulcus opened

to show insular
cortex below

(b)

Figure 1.4 Left view of the brain to show the insular: (a) The lateral sulcus is normally closed and the
insular cannot be seen; (b) The lateral sulcus is opened to view the insular.

The human insular cortex has generated a great deal of interest in neuroscience, not least
because it is involved in a number of psychiatric conditions (Uddin et al. 2017).

The occipital lobes

The occipital lobes have the main visual cortex (Brodmann 17) and the visual association
areas (Brodmann 18 and 19) (Figures 1.2 and 1.3) (Blows 2000a). This is therefore the con-
scious area for vision; that is, as with the temporal lobes and hearing, we actually “see” the
world with the back of the brain. The eyes only convert light energy into nerve impulses; it is
the occipital lobes that make sense of these impulses as a conscious visual picture.

Functions of the cerebrum

One of the most important functions of the cerebrum is the government of three impor-
tant aspects of consciousness: awareness (sensory); cognition (e.g. thought); and response
(motor). The entire cortex plays a role in consciousness, although for the most part, the
parietal, temporal and occipital lobes are involved with conscious interpretation of sensory
stimuli from the body, ears and eyes respectively. The frontal lobes are concerned with cog-
nition and consciousness of the “self”. A brief discussion of consciousness can be found in
Chapter 2 (see also Blows 2018, Chapter 10, and Blows 2000b).
The left hemisphere of the cerebrum is dominant for several functions, notably fine motor
control, logic, analytical work, language and verbal tasks. Fine motor control means digital
8­ Introduction to the brain
and hand movements, an essential part of many activities. Since most of the motor (i.e.
pyramidal) fibres cross in the medulla, the dominance of motor control in the left hemi-
sphere makes most people right handed. However, we know that it is entirely normal for
left-handed people to be an exception to this, although left-handed dominance has not always
been accepted by society. The right hemisphere is dominant for non-language skills, spatial
perception and artistic and musical endeavours. People who have a general dominance of
left hemisphere function are sometimes called thinkers, whilst those with right hemisphere
function dominance are sometimes referred to as creators. This is an oversimplification,
and gives an image of the two hemispheres working in isolation. This is not true; they work
together, communicating with each other through the corpus callosum that joins the left
hemisphere with the right hemisphere (Marieb and Hoehn 2019).
Sleep is a vital function for the brain and is discussed in detail in Chapter 24.
During waking hours, the brain is able to concentrate on the specific task at hand, but there
are times when the brain is allowed to wander, and not concentrate on anything. During this
time, it would be easy to suspect that the brain is inactive, but this is far from the truth. The
brain appears to be active on “internal matters” rather than “external matters”, but these inter-
nal matters remain unknown to us, and have therefore been called dark energy.1 The default
mode network (DMN) is the system in the brain responsible for this period of dark energy;
it is a system which keeps active even when the brain is not apparently doing anything. This
is rather similar to a car engine “ticking over” or “running idle” when not involved in moving
the car. The DMN is probably involved in establishing and maintaining consciousness, and
it keeps the brain in a state of instant readiness for when the moment comes that focus on a
specific activity becomes necessary. Prior to the discovery of the DMN, neurologists thought
that the brain was cycling between moments of no activity and moderate activity, but now
the new concept is that the brain is cycling between moderate activity and high activity. This,
plus the notion that the brain is active during sleep, suggests that, from birth to death, the
brain never rests. The main areas of the brain that make up the DMN are the ventral and dor-
somedial prefrontal cortex, the inferior and medial parietal cortex, the lateral temporal
cortex, the hippocampus and the posterior cingulate cortex (some of these areas are dis-
cussed in chapters related to specific mental health disorders). Other areas are also involved,
but these regions appear to control the activity levels of the brain’s idle state. This discovery
may be important for mental health because there is growing evidence that altered connec-
tions in the DMN are possibly linked to disorders such as autism, depression, Alzheimer
disease (AD) and even schizophrenia. In fact, some researchers are suggesting that one day,
AD may be classified as a disorder of the DMN (Raichle 2010).
The salience network (The main connectivity pathways involved in mental health, this
chapter) is another set of brain connections linking two main areas, the anterior insula
and the dorsal anterior cingulate cortex. As with the DMN, the salience network also
involves other brain areas including the amygdala, the ventral tegmental area (VTA) and
the ventral striatum, i.e. the ventral corpus striatum (The basal ganglia, this chapter).
The salience network monitors and filters the constant stream of incoming sensory stimuli
to select which is the most salient (or relevant) to pass on to the rest of the brain. Only the
most important sensory stimuli become salient, e.g. aspects currently under our attention,
surprise stimuli and potential threats to our wellbeing. Without this process, the brain would
be constantly overwhelmed and swamped with irrelevant sensory data. A third network, the
executive network, is active during focused thinking and helps us to attain goals. It uses
working memory (Chapter 21), and is normally active when the DMN is switched off (see
Creativity, Chapter 7) (Beaty and Kenett 2020).
 Introduction to the brain 9
Learning and memory are also two vital functions for the cerebrum. Learning is the pro-
cess by which long-term memory is formed. These subjects are covered in more detail in
Chapter 21.

The limbic system

The limbic system is the brain’s emotional centre, and it is also important for learning and
for maintaining the brain’s role in relation to a sense of human needs and safety. The sys-
tem consists of a ring of structures, notably the amygdala, the hippocampus, the cingulate
gyrus, the mammillary bodies of the hypothalamus and the orbitofrontal cortex. These
are described in other chapters related to specific mental health functions, e.g. the amygdala
and cingulate cortex (Chapter 13) and the hippocampus (Chapter 21).

The thalamus, hypothalamus and pituitary gland

The thalamus
The thalamus is a collection of more than 30 nuclei situated underneath the cerebrum, close
to the midline of the brain on each side (Figure 1.5) (Blows 2000c). The nuclei are set in four
main groups: anterior, medial, midline and lateral. The thalamus is the sensory relay station,
i.e. sensory impulses originating in the body (somatic) or the special senses (e.g. vision and
hearing) pass into the thalamus, from where they are relayed to the appropriate part of the cere-
brum. Visual nerve impulses from the retina must be relayed by the thalamus to the visual cor-
tex of the occipital lobes (Brodmann 17, Figure 1.3), and nerve impulses generated from sound
by the ear are relayed by the thalamus to the auditory cortex in the temporal lobes (Brodmann
41 and 42, Figure 1.3). Even somatic sensations from the body, e.g. touch or pain, are relayed

Cerebral cortex
Corpus callosum

Caudate nucleus
Lateral ventricle
Thalamus

Right Left
side P side
P
G G

MB
Hippocampus

Claustrum Claustrum

Figure 1.5 Coronal section through the brain showing the location of the cerebral cortex, corpus
callosum, thalamus, hippocampus, mammillary bodies (MB) of the hypothalamus and parts
of the basal ganglia. P = putamen, G = globus pallidus.
10­ Introduction to the brain
by the thalamus to the appropriate part of the sensory cortex in the parietal lobes (Brodmann 1,
2 and 3, Figure 1.3). The sensory cortex has a cellular layout rather like a body plan, with cells
in specific sites on the cortex accepting sensations from particular parts of the body. Impulses
arising from the toes, for example, would be directed by the thalamus to the cortex occurring
down the midline division where cells linked to toes are found, whilst impulses destined for the
cells that accept sensations from the face would be directed to the lateral aspect of the cortex
(Blows 2000b). Pain is the only sensation that is “conscious” at both thalamic and cerebral lev-
els, whilst all other sensations must arrive at the cerebrum before we become aware of them.
The thalamus also focuses attention to specific sensations by making certain sensory areas
of the cerebrum more receptive to sensory stimuli and other areas less receptive. Integration
of some different sensory stimuli takes place inside the thalamus, a process essential for full
appreciation of the information received by the sense organs.
The thalamus has a motor function as well. One particular thalamic nucleus links with the
premotor cortex (Brodmann 6) of the frontal lobes, influencing motor function by increasing
the focus of attention on the motor activity in progress. This influence is normally deacti-
vated by the basal ganglia motor loop when no movement is happening, or is activated
when movement begins (Figures 1.6, 1.7).

The hypothalamus
The hypothalamus occurs as a collection of nuclei at the base of the brain (Figure 1.4) (Blows
2000c). These nuclei are arranged in anterior, posterior, ventromedial, dorsomedial and lat-
eral groups. The mammillary body, a bulbous part of the hypothalamus, is a member of
the posterior group of nuclei and a useful landmark on the under-surface of the brain. The
hypothalamus is connected to the pituitary gland by a narrow stalk, the pituitary stalk (or
infundibulum) (Marieb and Hoehn 2019).
The hypothalamus has a wide range of functions and controlling centres:

1 It is part of the reticular formation (The brain stem, this chapter) that controls the
sleep–wake cycle (Chapter 24); the role of the hypothalamus is that of the alerting
centre. It wakes the brain from sleep by sending impulses out to the cerebrum.
2 It controls the body’s temperature via the temperature regulation centre, keeping the
body at 37°C. By monitoring blood temperature and acting as a thermostat, it corrects
the temperature if it goes too high or too low. The anterior part of the hypothalamus
controls heat loss if the body gets too hot (e.g. by promoting sweating) and the posterior
part controls heat conservation if the body gets too cold (thermoregulation is discussed
in detail in Blows 2018).
3 It regulates eating by giving a feeling of fullness (satiation), which prevents further
food intake. This is the function of the satiety centre within the ventromedial part of the
hypothalamus. Hunger and the seeking of both food and drink, however, are controlled
by the lateral part of the hypothalamus (Chapters 7 and 13).
4 It controls the functions of both the sympathetic and parasympathetic components of
the autonomic nervous system (ANS).
5 It influences sexual activity in combination with other regions of the brain.
6 It plays a role in emotions.
7 It controls the hormonal output of the pituitary gland, both anterior and posterior lobes,
by the following mechanisms:
Anterior pituitary lobe. Releasing hormones (RH) or inhibiting hormones (IH)
(sometimes called releasing or inhibiting factors) pass down from the hypothalamus into
 Introduction to the brain 11

Cerebral cortex

Right Left

Corpus callosum

Caudate Lateral Lateral Caudate

nucleus ventricle ventricle nucleus

Thalamus Thalamus

Putamen Putamen
3
ST ST

Globus pallidus Globus pallidus

Substantia nigra
(a) Ventral pallidum Ventral pallidum

Cerebrum

Caudate nucleus
Globus pallidus
Putamen
Thalamus

Nucleus
accumbens
Cerebellum
Ventral
pallidum
Amygdala
Substantia nigra
Brain
Stem
(b)

Figure 1.6 Close up of the basal ganglia, (a) coronal section; (b) lateral view. ST = subthalamus, 3 =
third ventricle.

the anterior lobe and either release or inhibit the release of the anterior lobe hormones.
Anterior pituitary lobe hormones are:
•• Growth hormone – as the name suggests, it is important for growth;
•• Adrenocorticotropic hormone (ACTH), which acts on the adrenal cortex to stim-
ulate the production of cortisol (Chapter 6);
•• Thyroid-stimulating hormone (TSH), which acts on the thyroid gland and causes
release of the thyroid hormones T3 and T4 (Chapter 6);
•• Prolactin, which promotes breast milk production during breastfeeding;
12­ Introduction to the brain

Cerebral cortex
+

+
Putamen
Thalamus
+
– –
+

GPe – –
GPi + STN +
–
SNc –
SNr
+
SN

Figure 1.7 The basal ganglia motor loop. Input to the putamen comes from the cortex. This activates
(+) neurons running from the putamen to the globus pallidus (GP) which, in turn, then
deactivates (-) neurons linking the globus pallidus with the thalamus. Note: These globus
pallidus neurons were preventing (i.e. inhibiting, shown as -) any feedback from the
thalamus to the cerebral cortex. However, deactivation from the putamen has removed this
inhibition, and the thalamus then is free to feed back to the cortex (+), more precisely, the
supplementary motor area (SMA) of area 6 of the motor cortex. Additional pathways to and
from the substantia nigra (SN) and the subthalamic nucleus (STN) have various controls
over the loop.

•• Follicle-stimulating hormone (FSH), which stimulates the ovarian follicles to

mature the ova (egg cells) in females and stimulates cells in the male testes to pro-
duce sperm;
•• Luteinising hormone (LH), which promotes ovulation in females and stimulates
the production of testosterone from the male testes.
Posterior pituitary lobe. The hormones that are released from the posterior lobe are
produced in the hypothalamus. They pass down into the pituitary gland, where they are
stored and released by hypothalamic control. These hypothalamic hormones are:
•• Antidiuretic hormone (ADH), from the supraoptic nucleus of the hypothalamus,
a hormone which is released into the blood and acts on the renal nephron to con-
serve water;
•• Oxytocin, from the paraventricular nucleus of the hypothalamus, a hormone
which is released into the blood and causes smooth-muscle contraction (for exam-
ple, it contracts the uterus during labour), and also contraction of special breast cells
which push milk towards the nipple during breastfeeding. It also appears to drive
maternal behaviour and social attachment – a so-called “bonding molecule”. This
hormone may have benefits for autistic children, in combination with other thera-
pies (autism spectrum disorder, Chapter 23).

The basal ganglia, cerebellum and claustrum

The basal ganglia and the cerebellum are part of what is called the extrapyramidal
tract system, that is, they control the finer details of skeletal muscle movement at a
 Introduction to the brain 13
subconscious level (Blows 2000c, 2018). The extrapyramidal tract side-effects of drugs
such as antipsychotics are caused by disturbance to this system, particularly the basal
ganglia (Chapter 16).

The basal ganglia

The word ganglia means a set of neuronal cell bodies set apart from the main cell bodies of
the cerebrum, and basal means they are low down within the white matter. The basal gan-
glia are made up of five main nuclei: the putamen, the caudate nucleus, the pallidum, the
substantia nigra and the subthalamus (it is important not to muddle the thalamus with the
hypothalamus and the subthalamus) (Figure 1.6). Several terms are used to describe the dif-
ferent ways in which some of these nuclei are grouped.

•• The corpus (or dorsal) striatum is the area involving the putamen and the caudate
nucleus combined, with the main pyramidal motor pathways, called the internal cap-
sule, passing between them.
•• The putamen is also part of the lentiform nucleus, which also includes the globus pal-
lidus (Figure 1.6).
•• The word striatum (meaning striped) includes the dorsal striatum plus the ventral stria-
tum (which includes the nucleus accumbens).
•• The pallidum consists of a large component, the globus pallidus above, plus the much
smaller extension below, the ventral pallidum.

Collectively, the function of the basal ganglia is the fine control of muscle contraction
(Marieb and Hoehn 2019). The corpus striatum receives input from the main motor and sen-
sory areas of the cerebrum, as well as inputs from the thalamus, subthalamus and brain stem
(particularly the substantia nigra). Degeneration of the caudate nucleus is seen in Huntington
disease, where excessive uncontrollable movement is a major symptom (Chapter 20). Output
from the corpus striatum passes via the globus pallidus to the motor areas of the frontal lobes.
The globus pallidus has several vital functions, notably the control of trunk and limb move-
ments, including the positioning of limbs just prior to the movements of the digits, a function
of the main motor cortex.
The globus pallidus and the putamen are also involved in the basal ganglia motor loop
(Figure 1.6, Blows 2018). When the body is not moving, the globus pallidus inhibits a par-
ticular thalamic nucleus which, when active, influences movement. As movement starts,
stimulation of the putamen causes a blocking of the globus pallidus, removing the inhibition
on the thalamus. The thalamus then becomes free to influence the main motor areas of the
frontal lobes.
The substantia nigra is particularly important as the area decreasing muscle tone, the
state of tension within a muscle, which is essential for the muscle to achieve full contrac-
tion. The axonal tracts coming from the substantia nigra to go to the corpus striatum are the
nigrostriatal pathway, and these neurons use the neurotransmitter dopamine (Chapter 4).
Degeneration of the substantia nigra causes Parkinson disease, and Parkinsonian-like symp-
toms are a feature of some drug side-effects (Chapter 16).
The subthalamus has the role of inhibiting excessive motor activity from the cerebral
motor cortex (i.e. acting as a breaking system for the pyramidal tracts). Disturbance
of this function can result in excessive pyramidal activity affecting skeletal muscle
contraction.
14­ Introduction to the brain
Apart from Huntington disease and Parkinson disease, disturbance of basal ganglia func-
tion includes several other different movement disorders, which are described in relation to
psychotropic drug side-effects (Chapter 16).

The claustrum
The claustrum is a bilateral thin strip of grey matter that is positioned between the insular
cortex and the putamen (Figure 1.5). It has extensive and complex connections to both the
cerebral cortex and to a number of subcortical areas (Figure 1.8). The functions of the claus-
trum remain unclear, although theories suggest it may have a role in consciousness, spatial
navigation and rapid-eye movement (REM) sleep (Chapter 24), and it may act as a mediator
for brain activity between the cortex and subcortical areas. The importance of the claustrum
in relation to mental health is:

•• Lesions of the claustrum have been linked to delusions and hallucinations (Chapter 15).
•• It is possibly involved in the spread of abnormal impulses during an epileptic fit (Chapter
19).

The cerebellum
The cerebellum (Figure 1.9) is another part of the extrapyramidal tract system, controlling
muscle function at a subconscious level (Blows 2000d). There are two hemispheres, as in
the cerebrum, but unlike the cerebrum it is much smaller and tucked beneath the occipital
lobes, occupying the region posterior to the brain stem. There are just three main lobes: the
anterior, posterior and flocculonodular lobes. Each lobe is further subdivided into smaller

ANTERIOR TRACT to prefrontal cortex Brodmann 11, 12, 10

POSTERIOR TRACT to visual cortex Brodmann 17, 18, 19

SUPERIOR TRACT to sensory-motor areas Brodmann 1, 2, 3, 4, 6, 7, 8

CLAUSTRUM

LATERAL TRACT to auditory cortex Brodmann 41, 42, 39

to basal ganglia (caudate nucleus, putamen,

MEDIAL TRACT
globus pallidus)

BILATERAL CONNECTION to contralateral Brodmann 6, 8, 9

INTER CLAUSTRAL to opposite claustrum

SUBCORTICAL to thalamus, hypothalamus amygdala

Figure 1.8 Stylistic sketch of the main connections from the claustrum.

 Introduction to the brain 15

Cerebral cortex

us callosum
Corp

Hypothalamus
Pituitary gland
Midbrain
Cerebellum Pons
Medulla tem
in s
Bra

Figure 1.9 Sagittal section through the brain stem and cerebellum.

regions of surface area. This surface is made of grey matter, which is folded to increase the
area to about 75% of the surface area of the cerebrum. There is white matter below the sur-
face, and at the core of this white matter are further patches of grey matter, the cerebellar
nuclei. The routes for impulses to pass into and out of the cerebellum are through the brain
stem via the cerebellar peduncles, i.e. foot-like connections between the cerebellum and the
brain stem (Marieb and Hoehn 2019).
The functions of the cerebellum are as follows:

1 To maintain the balance of the body. The cerebellum makes fine adjustments to mus-
cle tensions to stabilise body position, especially when upright, to prevent falling over.
Sensory feedback on balance to the cerebellum comes from somatic proprioception
(sensory information on body position from muscles, tendons and joints), and vestibular
information from the semicircular canals of the inner ear. The proprioception impulses
enter the anterior lobe of the cerebellum, whilst vestibular impulses pass into the floc-
culonodular lobe;
2 To smooth out muscle movement, preventing erratic movements and facilitating fine,
well-controlled movements
3 To increase muscle tone in opposition to the substantia nigra (The basal ganglia, this
chapter);
4 To effect synergy, i.e. a collection of different muscle movements made simultaneously
to achieve a particular objective. The cerebellum creates a motor plan, whereby multiple
16­ Introduction to the brain
muscles function together in one activity. A good example is the coordination required
to catch a ball which is moving towards you. Visual information on the nature of the
object, its speed and direction, is flashed to the cerebellum. The entire muscle sequence
needed to catch the ball is planned, slightly ahead of time (to allow for movement of
the ball whilst planning and muscle movement takes place), and the activity is then
executed.

These skills are not present in the newborn infant. The cerebellum has to learn, by trial and
error, to balance the body, to smooth and coordinate muscle activity and to interact with
moving objects (Chapter 2). Parents can often identify the moments in the development of
a child when the cerebellum achieves a new skill, such as the first moment the infant stands
unsupported, balancing on both legs. Repeated attempts at a skill, along with sensory feed-
back, improve the cerebellum’s ability to learn and perfect that skill. Practice makes perfect
could be rewritten to read practice makes better cerebellar function.

The brain stem

This part of the brain is the most primitive in that it carries out the basic functions of living
(Blows 2000d). It is the lowest area of the brain (Figures 1.10 and 1.11) and is continuous
with the spinal cord. The distinction between brain stem above and cord below is approxi-
mately at the level of the foramen magnum, the “large window” at the base of the skull
through which the spinal cord emerges.

Figure 1.10 Coronal section through the brain stem showing area of the reticular formation (cross-
hatched) and the main centres of the sleep–wake cycle, the sleep and alerting centres in
the hypothalamus (Chapter 24). Impulses from these centres are distributed either to the
cortex via the thalamus or to the body via the spinal cord, as shown by the arrows.
 Introduction to the brain 17

Corpus callosum

ex
ort
ral c
um
Cereb Sept
NA

Cerebellum
Mesocortical

VTA
Hypothalamus
Medial
forebrain Pons
Pituitary
gland bundle Medulla
(Mesolimbic)

Figure 1.11 Sagittal section through the brain stem showing the ventral tegmental area (VTA) and the
main pathways: the mesolimbic pathways (through the medial forebrain bundle) and the
mesocortical pathways.

The brain stem is divided into three parts, the uppermost part being the midbrain. Below
this and bulging anteriorly is the pons, and the lowest part is the medulla (Figure 1.9). The
pons is often referred to as bulbar, meaning it is swollen like a bulb. The brain stem houses
many nuclei, a number of which are those that control the functions of most of the 12 pairs of
cranial nerves (numbers III to XII arise from the brain stem). Cranial nerves are the nerves
that come directly from the brain. Cranial nerves I (olfactory) and II (optic) come from the
brain at a higher level than the brain stem.
The midbrain is the smallest part of the brain stem, just above the pons. Here, cranial
nerve nuclei numbers III (oculomotor) and IV (trochlear) are found. These nerves and their
nuclei are concerned with eye movements.
The pons has cranial nerve nuclei numbers V (trigeminal), VI (abducent), VII (facial) and
VIII (vestibulocochlear). Two other nuclei are part of the respiratory control centres shared
with the medulla.
The medulla is the lowest part of the brain stem. The remaining cranial nerve nuclei are
found here with their associated nerves: IX (glossopharyngeal), X (Vagus), XI (accessory)
and XII (hypoglossal). The medulla also contains the vital centres which keep the body
alive: the cardiac centre, essential for heart function; the respiratory centres (shared
with the pons), which together keep the individual breathing; and the vasomotor centre
(VMC), a diffuse set of nuclei which collectively influence peripheral vascular resistance,
part of the mechanism for maintaining blood pressure. The medulla is also the location for
a number of reflexes which, again, are primitive responses to stimuli designed to protect
the body against harm or even death. Such reflexes include the gag reflex (which prevents
unwanted substances from entering the throat), the corneal reflex (which prevents injury
to the front of the eye by shutting the lids if something touches the eye), and the pupil-
lary reflex (which shuts down the pupil in bright light, preventing light-induced retinal
injury). Some of these reflexes are used in neurological investigations to assess brain stem
function.
18­ Introduction to the brain
Parts of the medulla, the pons, the midbrain and the upper cord contain discrete patches of
small nuclei, referred to as the reticular formation (RF) (Figure 1.9) (Blows 2000d). These
nuclei have connections with many parts of the brain. The reticular formation has the role of
inhibiting those sensory stimuli entering the brain that can be considered as repetitive, weak
or unnecessary, allowing only strong, significant or unusual impulses to pass. Other mecha-
nisms such as vomiting, swallowing, coughing and sneezing are brain stem RF-mediated
functions, and are all linked to the function of respiration in some way. Part of the RF is the
reticular activating system (RAS) (Figure 1.9), i.e. those RF components that are responsi-
ble for the sleep–wake cycle (Chapter 24). One other important nucleus in the brain stem is
the ventral tegmental area (VTA) with a pathway leading to the nucleus accumbens (Figure
1.10). The VTA is important as the start of the reward pathway of the brain linked to sub-
stance misuse (Chapter 11).

The main connectivity pathways involved in mental health

In order for the brain to work properly, there has to be coordinated activity within the cir-
cuitry that forms the pathways (or networks) inside the brain. Networks are formed from
collections of neuronal axons linking different brain areas with each other, and with other
parts of the nervous system. This connectivity between diverse areas of the brain ensures that
no brain area acts in isolation, and that probably all brain functions involve processing by
several, if not multiple, parts of the brain. This becomes important in mental health because
normal brain activity is dependent on the different areas contributing their function through
these network pathways. Failure of specific network activity, or connectivity, is now being
linked to various mental health disorders and is seen as a factor in producing symptoms. The
major pathways of the brain that are chiefly involved in mental health disorders, psycho-
tropic (affecting the mind) drug activity and drug side-effects are shown in Table 1.1.
Connectivity refers to various components of the brain being linked by two aspects:

•• White matter (axonal pathways or tracts), physically joining two or more parts of the
brain, and known as structural connectivity;
•• Two or more parts working together to achieve a common goal, known as functional
connectivity. This moves beyond the concept of distinct functional brain areas, and
introduces the idea of multiple areas connected together, each single area contributing
towards a specific function.

These two aspects of connectivity, when considered together, indicate that there are at least
four major networks:

1. The default mode network (DMN), described under Functions of the cerebrum (this
chapter);
2. The salience network (SN) described under Functions of the cerebrum (this chapter);
3. The affective network (AF), which connects the amygdala, orbitofrontal cortex, the
temporal cortex, the pallidum (globus pallidus and ventral pallidum) and insular cortex.
This network is involved in emotions (Chapter 13) and mood (Chapter 17);
4. The cognitive control network (also known as the central executive network, or fron-
toparietal network), which consists mostly of the dorsolateral prefrontal cortex and
posterior parietal cortex, and is a major network for cognitive processing such as creativ-
ity (Chapter 7) and working memory (Chapter 21).
 Introduction to the brain 19
Table 1.1 Brain pathways involved in mental health.

Pathway Pathway Importance to mental health

From To

Mesolimbic Brain stem Limbic system Probably involved in

pathway positive symptoms in
schizophrenia
Mesocortical Brain stem Cerebral cortex Probably involved in
pathway negative symptoms in
schizophrenia
Nigrostriatal Substantia nigra Corpus striatum Site of extrapyramidal side-
pathway effects of drugs and of
Parkinson disease
Diffuse modulatory Brain stem Many parts of Appears to be involved in
systems limbic area and depression and possibly
cerebral cortex eating disorders
Median forebrain Brain stem Frontal lobe of Involved in the brain
bundle cerebrum reward pathways which
are implicated in drug
addiction
Dorsolateral Frontal lobe Head of caudate Involved in deficits of frontal
prefrontal circuit (Brodmann 9 and nucleus (basal lobe executive functions
10) ganglia)
Lateral orbitofrontal Prefrontal cortex Caudate nucleus Involved in mood and
circuit (Brodmann 10) personality changes
Anterior cingulate Anterior cingulate Several areas of Involved in speech and
circuit gyrus (Brodmann brain stem and emotional loss, and apathy
24) of the frontal basal ganglia
lobe

The collective term for all the specific connections within the brain that function together is
the connectome (Figure 1.12).
In addition to the four networks identified above, a cognitive fatigue network is postu-
lated to include the striatum of the basal ganglia, the dorsolateral prefrontal cortex, the
dorsal anterior cingulate cortex and the anterior insula. This observation is mostly based
on functional connectivity rather than structural connectivity. It would appear that as other
areas of the brain get tired of cognitive processes and reduce their activity, these brain areas
increase their activity. It is not fully understood why this is the case.

The meninges and cerebrospinal fluid

The brain and the cord are covered by membranes called the meninges, which form three lay-
ers (Figure 1.13). The innermost layer is the pia mater (“gentle mother”), the middle layer is
the arachnoid mater (“spider mother”) and the outermost layer is the dura mater (“tough
mother”). Between the arachnoid mater and pia mater is the subarachnoid space containing
a watery fluid called cerebrospinal fluid (CSF). This is formed from blood plasma inside the
ventricles of the brain, i.e. the cavities within the brain substance (Marieb and Hoehn 2019).
CSF fills the two lateral ventricles, the third ventricle and the fourth ventricle before it
flows out into the subarachnoid space. From here it circulates over the brain and cord surface
before being absorbed back into blood via small projections of the arachnoid mater called
20­ Introduction to the brain

Pallidum
Orbito-
frontal

Temporal HC

Prefrontal
Insular
AFF Amygdala DMN

VTA

ve
it i
Cingulate Parietal gn
Co
SAL

Corpus
Striatum

Figure 1.12 Stylistic plan of connectivity. The default mode network (DMN), the affective network
(AFF), the salient network (SAL) and the cognitive network (CN) are shown here through
major connections. Other more minor connections are not shown. HC = hippocampus;
VTA = ventral tegmental area.

Figure 1.13 The meninges between the brain and the skull.

 Introduction to the brain 21
villi. CSF also flows from the fourth ventricle through the central canal of the cord. CSF has
several important functions:

1 It protects the central nervous system by acting as a water jacket, giving a cushioning
effect to the central nervous system. This is a very important function, helping to reduce
brain injury in accidents involving the head.
2 It provides support and flotation for the brain, which would otherwise weigh 30 times
heavier without it!
3 It delivers nutrition to some parts of the nervous system, since the CSF contains not just
water but also some minerals and glucose.
4 It acts as part of an excretory pathway for the end products of neurotransmitter metabo-
lism (known as metabolites) and some psychoactive drugs. These wastes pass from the
brain into the CSF, then into the blood, which then goes on to the kidneys for filtering
and the excretion of the wastes in urine.

CSF is often very important in mental health because of this role as an excretory pathway.
One investigation, called lumbar puncture, is a method of collecting a sample of CSF in
which the excretory waste products from brain chemicals or drugs can be measured (Blows
2002a). A needle is put into the spinal subarachnoid space below the level of lumbar vertebra
2 (L2) so as not to hit the solid spinal cord. The quantity of metabolite found in the CSF sam-
ple gives an indication of the amount of neurotransmitter that is active in the brain.

The blood–brain barrier (BBB)

As a way of protecting the brain against toxic damage, a series of barriers exist which allow
only beneficial substances to pass into the brain from the blood under normal circumstances.
The main barrier is the blood–brain barrier (BBB), a layer of cells lining the microscopic
blood capillaries that pass through the brain. The cells of the BBB are capillary endothelial
cells, mural cells (e.g. pericytes) (Chapter 24) and astrocytes. Pericytes are embedded in
the basement membrane of the smallest capillary vessels. The cells of the BBB selectively
allow substances to gain entry to the brain either by direct passage or by transportation using
a transporter protein. Other substances, considered potentially harmful to the brain, will
remain in the blood. There is a similar barrier between the CSF and the brain. The BBB is
important when considering drugs, because some drugs pass the BBB directly but others do
not. Some must be converted into a different form before passage is possible. A good exam-
ple is the drug levodopa, which will pass the BBB, but if converted to dopamine it will not
pass the BBB (Chapter 20).

The central, peripheral and autonomic nervous systems

The central nervous system (CNS) consists of the brain and spinal cord. Outside of this,
i.e. the nerves, make up the peripheral nervous system (PNS). Nerves can be motor (taking
impulses to muscles for movement), sensory (conveying sensations back to the brain) or a
mix of motor and sensory. Often mixed nerves also contain neurons of the autonomic nerv-
ous system. Nerves are also classified into cranial nerves (those that come directly off the
brain and do not involve the spinal cord) and spinal nerves (those that come off the spinal
cord) (Figure 1.14).
22­ Introduction to the brain
The autonomic nervous system (ANS) is that part of the peripheral nervous system that
functions automatically, i.e. without conscious control. The two parts of the ANS are the
sympathetic and parasympathetic systems (Figure 1.14). Sympathetic neurons come exclu-
sively from the thoracic cord (T1–T12, Figure 1.13), and parasympathetic neurons come
from the brain stem (via cranial nerves) (The brain stem, this chapter) and the sacral segment
of the cord. The two systems act between them to stabilise many physiological parameters
(e.g. heart rate is stabilised at an average of 72 beats per minute at rest), but the two parts

Figure 1.14 Simplified scheme of the autonomic nervous system (ANS). Cranial nerves (III, VII, IX
and X) are shown in roman numerals. T = thoracic, S = sacral.
 Introduction to the brain 23
Table 1.2 Functions of the autonomic nervous system.

Target organ (or Sympathetic function Parasympathetic function

system)

Mental alertness Increases No effect

Eye (pupil) Dilates Constricts
Heart muscle Increased heart rate and force of Decreased heart rate
contraction
Coronary arteries Dilated Constricted
Blood pressure Raised Lowered
Bronchi Dilated Constricted
Digestive tract Reduced peristalsis and increased Increased peristalsis and decreased
sphincter tone sphincter tone
Stomach Reduces digestion Increases hydrochloric acid
Liver/blood glucose Glucose released from glycogen No effect
into blood
Kidney Decreased urine produced No effect
Bladder Allowed to fill, internal sphincter Emptied, sphincter opened
closed
Adrenal medulla Releases adrenaline No effect
Metabolism Increased No effect
Skin Increased sweating No effect

allow the parameters to change when it becomes appropriate (e.g. the heart rate can increase
or decrease depending on the circumstances). The sympathetic component serves to increase
those parameters, and this is useful for reactions to adverse stimuli, such as fear. Sympathetic
responses to stimuli such as fear result in, amongst other things, fast pulse rates, sweating and
increased respiration, and these are important in speeding up oxygen delivery to the tissues
for a physical response to the cause of the fear. The parasympathetic component often causes
an opposite effect by reducing the physical parameters, e.g. slower heart and breathing rates,
at times of rest. The range of functions for each system can be seen in Table 1.2.
Excessive sympathetic activity is seen in anxiety and phobic states when patients come into
contact with their fears. Some parameters do not have an opposing parasympathetic activity.

The basic principles of brain pathologies affecting mental health

Pathology is the study of the nature and causation of disease. Disease is either congenital
(“born with”, i.e. the condition is present from birth, and therefore occurred before birth), or
acquired (occurs at a later date after birth). Of the congenital causes, some may be heredi-
tary (i.e. passed to the infant from the parent through gene errors, called mutations), or
teratogenic (i.e. caused by a harmful chemical or viral agent passing through the placenta
from mother to fetus, either a microorganism, a drug or a toxin, causing harm or malforma-
tion of the fetus) (Chapter 23).
Of the acquired causes, there are a number of different categories which can involve the
brain and therefore cause symptoms of mental health disorder, as follows:

•• Traumatic. Physical injury, for example, damage to the brain from a blow to the head
(Blows 2018). Long-term complications of brain injury include epilepsy and depression
(Traumatic brain injury, Chapter 22).
24­ Introduction to the brain
•• Neoplastic. New growths of the brain, either benign or malignant, such as meningioma,
a new growth of the meninges. Many malignant new growths in the brain are known
as secondaries because they are formed from metastases, i.e. cells broken free from a
primary growth elsewhere (Blows 2005). New growths of the brain can cause confusion,
personality changes and fits.
•• Nutritional. Deficiency or excess of a dietary nutrient, e.g. a vitamin or mineral, can
cause a brain malformation or reduced level of neurotransmitter. An absence of adequate
protein in the diet would reduce the amount of neurotransmitters in the brain that relied
on a supply of amines, since amines are derived from protein.
•• Allergic. The adverse reaction of the immune system to a foreign substance (called an
antigen) (Blows 2005). An antigen is any foreign substance, often a protein that enters
the body and provokes an immune reaction. Such reactions can affect the brain to cause
fits, confusion or loss of consciousness.
•• Metabolic. Abnormal changes in cellular metabolism that often produce toxic wastes,
which can cause confusion, fits or reduced levels of consciousness. An example of this
is an excess production of urea which then enters the blood causing uraemia.
•• Degenerative. Deterioration and the ultimate death of cells due to age-related and other
pathological changes (notably loss of blood supply). Degeneration of brain cells causes
disorders such as dementia and Parkinson disease. Age-related degeneration of the arterial
walls supplying blood to the brain can cause strokes (also known as cerebrovascular acci-
dents, or CVA), which can cause confusion, fits and loss of consciousness (Blows 2018).
•• Psychological. Disorders caused by environmental stress and mental trauma, often over
a long period, e.g. anxiety states and depression.
•• Iatrogenic. Health-related “injuries” caused by the medical and nursing profession.
Examples are drug side-effects, caused when a drug is prescribed by the doctor; a punc-
ture wound caused by the nurse during the administration of an injection; or a pressure
sore caused by a patient being immobilised in one position for too long. Some are inevi-
table (e.g. wounds and other trauma caused during surgery), but others are preventable,
and medical and nursing staff should be working to minimise the harmful effects of their
actions as much as possible.
•• Idiopathic. This means “of unknown cause”. Research has done much to reduce the num-
ber of disorders that fall into this category, and much progress has been achieved in find-
ing the cause of many psychiatric disorders. However, there is still much more research
to be done in order to remove some very important brain disorders from this category.
•• Inflammatory. Inflammation produces redness (rubor), swelling (tumor), pain (dolor)
and heat (calor), with a corresponding loss of function. It may be due to an immune reac-
tion to microorganisms (infection) or other antigens, such as cancer cells (sterile reaction)
(Blows 2005). Inflammation involving the brain could be meningitis (inflammation of
the meninges covering the brain) or encephalitis (inflammation of the brain itself).

Mental health problems related to the COVID-19 pandemic (2019–2022)

The viral pandemic of 2019–2022 (Coronavirus; SARS2-CoV-2), which causes the disease
COVID-19, has killed thousands of people worldwide through the severe effects it has on
the respiratory system. But emerging from this is a growing understanding of the devastating
effects of this viral infection on the mental health of survivors. This is due, in part, to the viral
invasion of the nervous system and the immune response, but also due to the population lock-
down measures that were put in place for many weeks in an attempt to control the viral spread.
 Introduction to the brain 25
Coronavirus enters the brain first by invading the olfactory bulb, the area responsible for
the sense of smell, and this is why a loss of smell (anosmia) is a primary early symptom. From
there it invades the hippocampus, the area for short-term memory conversion to long-term
memory (Chapter 21). Once in the brain, one of the most important and early effects of this
COVID-19 infection is delirium. This is a state of rapid and acute confusion, with disorien-
tation, drowsiness, restlessness, hallucinations and incoherent speech. It has been variously
reported in around 55%–65% of severely ill patients, mostly in the elderly. Hospitalisation
(i.e. coming into a strange environment with people one does not know) makes delirium
worse if it is not recognised and managed carefully. Its presence marks a poorer outcome to
the disease. The link between delirium and dementia is now well established, although the
mechanism involved is not well understood. Delirium (from any cause) increases the risk of
dementia later in life, and people with dementia can deteriorate quickly into delirium if they
catch the virus (Factors affecting brain ageing and dementia, Chapter 22).
A closely related condition is encephalopathy,3 causing brain fog or COVID brain,
where the individual is confused and suffers with headaches and short-term memory loss,
which usually starts some weeks after the coronavirus infection began. This is caused not by
the virus but by immune chemicals called cytokines, which are released from immune cells
into the blood to fight the infection.
Mood disorders (Chapter 17) and anxiety (Chapter 14) occur in about 15% of COVID-19
patients, sometimes at the same time. Post-traumatic stress disorder (PTSD, Chapter 14) was
particularly prevalent in about 30% of those surviving the SARS 2002 and 2004 outbreaks
and in those surviving the MERS4 2012 outbreak, and is expected to be a similar figure
for COVID-19. PTSD, anxiety and depression are also disorders triggered by the extended
periods of lockdown and social distancing put in place during the pandemic. Memory and
attention impairment are other cognitive problems reported by survivors.
Obsessive-compulsive disorder (OCD, Chapter 14), linked to a phobia (Chapter 14), is
also exacerbated by the COVID-19 pandemic, and in some cases the disorders may be caused
by it. Mysophobia (or germophobia) is the fear of bacterial or viral contamination, and it
can be linked to an obsession about the state of sanitation of the environment, with the com-
pulsion to maintain a repetitive cleaning routine to keep the environment clean.

Brain biomarkers
Brain biomarkers are biological agents which can be measured and monitored over time, and
therefore act as indicators of the presence of a particular disease (i.e. diagnostic biomarkers)
or can be used to assess the progress of treatment. They may also indicate the prognosis (i.e.
prognostic biomarkers) of a particular disorder. Such biomarkers for the brain are often chem-
ical or biological agents collected from blood or cerebrospinal fluid (The meninges and cer-
ebrospinal fluid, this chapter). Various brain biomarkers are referred to in the related chapters.

Key points
The cerebrum
•• The cerebrum is the largest part of the brain, carrying out our cognitive and conscious
processes.
•• The frontal lobes are a major part of the brain involved in many mental health functions;
in particular, they are the site of consciousness of the “self” and thinking.
26­ Introduction to the brain
The limbic system
•• The limbic system below the cerebrum is involved in preservation of the individual and
the species, and involves emotions and controlling behavioural patterns.
•• The amygdala is the emotional centre of the brain.
•• The functions of the hippocampus are short-term memory, learning and emotional
behaviour and influencing thought.

The thalamus and hypothalamus

•• The thalamus is the sensory relay station, passing sensations to the cerebrum.
•• The hypothalamus has a wide range of functions, notably temperature control, regula-
tion of eating, alerting the brain after sleep and controlling both the pituitary gland’s
hormones and the autonomic nervous system.

The basal ganglia and the cerebellum

•• Below the limbic area are the basal ganglia and the cerebellum, areas involved in control
of movement at a subconscious level (i.e. part of the extrapyramidal tract system).
•• The function of the substantia nigra is the reduction of muscle tone.
•• The functions of the cerebellum are fine control of balance, smoothing out muscle move-
ment and synergy.

The brain stem

•• The brain stem has the nuclei that control the cranial nerve functions and the vital cen-
tres, such as respiration, cardiac function and blood pressure.
•• The brain stem houses the reticular formation and the reticular activating system that is
involved in the sleep–wake cycle.

The meninges and cerebrospinal fluid

•• The brain and the cord are covered by the meninges in three layers: the pia mater, the
arachnoid mater and the dura mater.
•• Between the arachnoid mater and pia mater is the subarachnoid space containing cer-
ebrospinal fluid (CSF).
•• Two lateral ventricles, the third ventricle and the fourth ventricle inside the brain, are
filled with CSF.
•• Lumbar puncture is a method of collecting a sample of CSF from the subarachnoid space
below the lumbar vertebra 2 (L2) level.

The autonomic and peripheral nervous systems

•• The peripheral nervous system consists of the nerves extending outside the central nerv-
ous system (brain and spinal cord).
•• Those from the brain are cranial nerves; those from the spinal cord are spinal nerves.
•• The autonomic nervous system consists of sympathetic neurons (from the thoracic spi-
nal cord) and parasympathetic neurons (from the brain stem and sacral spinal cord).
 Introduction to the brain 27
•• The sympathetic and parasympathetic systems mostly have opposite functions: the sym-
pathetic is for getting the body ready for a response to adverse stimuli, such as fear, and
the parasympathetic is active during rest and relaxation.

Notes
1 Not to be confused with the term dark energy used in space and astronomical research, although the
term dark in both cases refers to something that is unknown and cannot be measured directly, only
through its effects.
2 SARS is Severe Acute Respiratory Syndrome, a type of coronavirus (SARS-CoV).
3 Encephalopathy is disease or damage to the brain causing malfunction of the brain.
4 MERS is Middle East Respiratory Syndrome, a rare type of coronavirus (MERS-CoV).

References
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Blows, W. T. (2000a) The nervous system, part 1. Nursing Times, 96(35): 41–44.
Blows, W. T. (2000b) The nervous system, part 2. Nursing Times, 96(40): 45–48.
Blows, W. T. (2000c) The nervous system, part 3. Nursing Times, 96(44): 45–48.
Blows, W. T. (2000d) The nervous system, part 4. Nursing Times, 96(48): 47–50.
Blows, W. T. (2002) Diagnostic investigations. Part 1. Lumbar puncture. Nursing Times, 98(36):
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Blows, W. T. (2005) The Biological Basis of Nursing: Cancer. Routledge, London.
Blows, W. T. (2018) The Biological Basis of Clinical Observations (3rd edition). Routledge, Abingdon,
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Education Limited, Harlow, UK.
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2 Brain development

•• Introduction
•• The nervous system up to birth
•• The debate: When does consciousness start?
•• The brain at birth
•• Infant and child brain development
•• The teenage brain
•• Hormone influences on brain development
•• Nutritional influences on brain development
•• Key points

Introduction
Although the human brain is fully in place at birth, with many of its functions working, it still
has a lot more development to do. That means it will not be completely mature until at least
the person’s mid-20s, and some say it will be 30 years before it is fully mature. Being locked
up inside a bony box (the skull), the brain relies entirely for much of that development on
the sensory nervous system. It is through the senses that the brain keeps in contact with the
outside world, and it is the outside world that has the biggest influence on the brain (Blows
2003), in terms of both learning and functional development. Therefore the brain can only
make progress in development if the sensory systems are fully functioning. Fortunately, the
sensory systems are always the most advanced at all ages and stages of development.

The nervous system up to birth

The human nervous system starts as a groove forming along what will become the back of the
early embryo. This groove deepens and closes over to form a tube, the neural tube. Forming
this groove and the neural tube is a process called neurulation (Figure 2.1). The enclosed
lumen within the tube is destined to become the ventricular system of the brain and the
canal down the centre of the cord, and will eventually contain a watery fluid called cerebro-
spinal fluid (CSF) (Chapter 1). The head (rostral) end of the tube and the tail (caudal) end
initially remain open to the amniotic fluid that bathes the entire embryo. These tubal open-
ings (called neuropores) will close between 26 and 28 days, the days counted from the start
of pregnancy, i.e. conception (Figure 2.2). While the tube itself becomes the central nervous
system (CNS, i.e. the brain and spinal cord), cells that originate from the tube form a crest
(the neural crest) (Figure 2.1) between the tube and the embryonic surface, and this crest
will develop into the peripheral nervous system (PNS, i.e. the peripheral nerves).

DOI: 10.4324/9781003097273-2