The Biological Basis of Mental Health - 4th Edition
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The Biological Basis of
Mental Health
Fourth edition
William T. Blows
Cover image credit: © Getty Images
Fourth edition published 2022
by Routledge
2 Park Square, Milton Park, Abingdon, Oxon, OX14 4RN
and by Routledge
52 Vanderbilt Avenue, New York, NY 10017
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
utilised in any form or by any electronic, mechanical, or other means, now
known or hereafter invented, including photocopying and recording, or in any
information storage or retrieval system, without permission in writing from the
publishers.
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
