The Inflamed Mind
Page 22
profiling the peripheral immune system 201
scientific explosion of 59
in the twenty-first-century century 20–1, 24
understanding human behaviour and depression 114
indigestion 130–1
infant mortality rate 167, 168
infection 5, 6, 7, 12–13
and the gut 28–9
high infant mortality rate 167, 168
inflammation and 21–7
macrophages and 40
prediction by genes 170–1
survival of early humans 167
winter births and 218
inflamed depression 177
inflamed mind 11–15
inflammation
adversity and/or conflict 176
ageing and 148–9
in the arterial wall 60
biomarkers of 113–14
blood tests 186
of the blood vessels 59
as a cause of depression 5, 6, 7, 8, 11–12, 114–15
experiments 12–13
indisputable link 16
microglial activation 143
natural selection 14–15
studies 12, 13–14
collateral damage 140
early understandings of 22–4
immunity and 24–6
infection and 21–7
of the joints 58
nervous reflex control of 129
obesity and 148
response from immune system 5–6
of the salivary glands 59
seasonal variations 149
in the skin 59
of the spine 59
of the thyroid gland 59
see also acute inflammation; causality
inflammatory biomarkers 152, 204
measurement of 115–16
inflammatory cytokines 31, 129, 136, 148, 210
inflammatory disease 146
inflammatory genes 168, 170
inflammatory hormones 23
inflammatory microglial cells 124
inflammatory proteins 10, 58, 127, 144
inflammatory reflex 128, 130, 204
injury 22, 24
insanity 160–1, 161–2
Institute for Brain and Mental Health 207
Institute of Psychiatry 76, 79
insulin 22, 41, 107
interferon 120–1
intermittent colitis 188
iproniazid 91–2, 93
clinical trials 91–2, 93, 94
development path for depression 104
effectiveness of 104
marketing of 94
prolonging and intensifying effect of adrenaline 99–100
as a psychic energiser 94, 95
selection from candidates drugs 104
treatment for depression 94
irritable bowel syndrome (IBS) 188
Jesus of Nazareth 74–5
joints 56, 57, 58
Kline, Nathan 92–5
Kraepelin, Emil 162, 165, 208, 214–15
auto-intoxication theory 216–17
cause of psychosis 215–16
proposal for eugenics programme 216
kynurenine 143
Le malade imaginaire (Molière) 86
Lamarck, Jean-Baptiste 164–5
Lasker Prize 65, 94
leaky gut syndrome 188
leper colonies 170
libido 80–2
life expectancy 2, 151, 162, 165, 184, 211
Life (magazine) 93
lipopolysaccharide (LPS) 37–8, 39–40, 139, 140
liver disease 70, 120
local blood vessels 24
lockjaw 26–7
long-term medical conditions 61
LPS (lipopolysaccharide) 37–8, 39–40, 139, 140
lumbar punctures 109
LY110140 (later Prozac) 105
lymph nodes 9, 31, 32, 33, 34, 128
location of 34–5
lymphatic vessels 32, 127–8
lymphocytes 21, 23, 33, 34, 38, 39, 40–1, 57, 176
macrophages 21, 23, 24, 57, 130, 148, 188
bereavement and 152
communication
cell-to-cell 30, 31–5
secretion of cytokines 30–1
coordination of 29–30
defence of self against attack 28, 29, 33, 39–40
collateral damage 40
defence of the gut 29
foam cells 60
genes and 170–1
identification of LPS (lipopolysaccha ride) 37–8, 39–40
innate wisdom 36, 38, 39
life of 30
location of 28, 29
pre-programmed by natural selection 37
rapid response 35–6, 37–8
magnetic resonance imaging (MRI) see fMRI scans
Maini, Ravinder 65
major depressive disorder (MDD) see MDD (major depressive disorder)
major life events 150, 151
mania 161
manic-depressive insanity 215
manic euphoria 213
mathematics 47–8
Maudsley, Henry 160–1, 162, 165
mental disorders 164
Maudsley Hospital 1, 106
MDD (major depressive disorder) 71–2, 134, 140, 144, 184
bodily disease and 147
inflammation and 144
sufferers worldwide 198
medical apartheid 183–5
medicinal herbs 84–5
medicine
acute inflammation 22
of the body machine 71
change and 176
eugenics 165
European 70
Hippocratic 70, 87
influence of Descartes 45
and the Remicade high 67–8
see also Cartesian dualism; Descartes, René; inflammation
meditation 206–7
melancholia 69, 70, 161
ancient treatments for 71
cognitive (cogitatione defixus) 69
emotional (angor animi) 69
root causes of 70
see also depression
menopausal transition 176
mental disorders
Charles Darwin’s views 162–4
Henry Maudsley’s views 162, 164
mental health
anti-inflammatory drugs 203
link to physical health 113
measurement by clinical trials 201–2
medical apartheid 183–5
and physical health in the NHS 177
research using animals 137–8
undiagnosed/untreated physical disorders of patients 179–82
see also depression
mental illness 75, 184–5
mental information 11
Merck 90
mercury 88
mice 64, 91, 139–40, 192–3, 218
microglial cells 21, 23, 127, 140, 209, 210–11
activation 142, 142–3
net effect of 143
collateral damage 140, 141
response to inflammatory signals 140
microscopic anatomy 77
microscopic staining techniques 96
mind and body 51, 52, 54–5
connection between 112, 113
medical apartheid 183–5
split in specialist medical services 179
see also Cartesian dualism
mindfulness training 206
minocycline 187
MOI (medically orthodox ideology) position 83
Molière 86–7, 106–7, 147
mood states 112, 113, 174
mortality 5, 6
Mrs P. (patient) 3–4, 11, 43–4, 55–6, 57, 58, 61, 62, 171, 183
multiple sclerosis 6, 61
Mycobacterium tuberculosis 91, 104
naso-genital theory 79
natural selection 14–15, 36, 37, 158–9
depression and 162
emotional facial expression 163
genes controlling the immune sys
tem 167
genetic inheritance 164–5
heritability of mental disorders 162–4
modern evolutionary synthesis 165
see also genes
nerve cells 21, 136–7
analysis through staining techniques 96, 97
in animals 13
chemical signalling 99
collateral damage from microglial cells 141
communications across 98–9
electrical signals 99
in Freud’s theory 80, 81
poisoned 26–7
proteins 21–2
serotonin producing 105–6, 108
serotonin receptors 105
synaptic connections between 95–6, 106, 141
synaptic gaps 96, 97, 98, 99, 129
syncytium of nervous tissue 98
toxic 143
nerve-stimulating devices 178
nervous reflex 51
nervous system 9, 27, 95, 96, 106
neuro-immunology 8–11, 114, 177–8
alternative treatments 178
definition 9
schizophrenia and 218–19
neuroscience 9
neurotransmitters 95, 97, 99, 129
see also adrenaline; noradrenaline
New York 91
NHS (National Health Service) 17, 18, 55, 82
physical and mental health 177
nihilistic delusions 73
NMDA 219
Nobel Prize 98
non-self 22, 24, 27, 28
noradrenaline 99, 100, 101, 105, 153
obesity 148, 181, 189
olfactomedin 4 174
omega sign 163
organisms 22
organotherapy 217
panaceas 196–7
for Alzheimer’s disease 212
pancreas 41
panic attacks 179, 182
Paracelsus 62–3, 87–90, 170
parity of esteem 177
penicillin 90
periodontitis 188, 210
peripheral inflammation 176
pharmaceutical industry 90, 178
drugs for depression
broken business model 191, 192, 194, 195–6, 200
commercial blockbusters 194
failure rate in trials 194
high market demand 191
investment 190, 193–4
lack of biological data 194–5
low returns on investment 190, 191
“one size fits all” approach to trials 194
reduced spending on R&D 190, 191
wonder drugs 90
see also drugs
pharynx 31
phlegm 70
physical disease 146–7, 147–8
physical disorders 113, 182
physical health
link to mental health 113
in the NHS 177
physical inflammation 11
physicians
17th and 18th-century
scepticism about 85 -6
diagnosing patients 185–7
blood tests 186–7
identifying low-grade inflammation 189
prescribing drugs 187–8
English, pre-1850s 70
notoriety of 86
specialists in physical domain 179
working across the Cartesian divide 220
physics 48
physiology 48
pineal gland 49, 50, 51
role in human body machine 52
pituitary gland 50
placebo effect 67–8, 92, 193
anti-TNF antibodies 203–4
clinical trials of anti-inflammatory drugs 203–4
negative results 204
positive results 204
Remicade high 67–8
plaques 208, 209, 211, 216
Pott, Percival 122
poverty 152
precocious dementia 215
progressive dementia 212
Project for a Scientific Psychology (Freud) 79–80
proteins 10, 17, 21–2, 41, 209
interaction of 24
see also antibodies; C-reactive protein (CRP); inflammatory proteins
Prozac 3, 16, 90, 102, 103, 105, 190, 192, 197
development path 104
launch of 112
obscurely published papers 112
Prozac Nation 102
psoriasis 59
psychiatric disorders 162
psychiatric patients
life expectancy 184
medical apartheid 184
psychiatrists 95, 177
immuno-psychiatrists 115, 116
specialists in mental domain 179
psychiatry
alcoholism and 164
eugenics 165
standard textbooks on 102–3
psychic energy 79–80, 81
psycho-pharmacological revolution 101
psychoactive drugs 84
psychoanalysis 94
development under Freud 82
diversification of theory 82
origins of 79–80, 82
see also Freud, Sigmund
psychopathy 162
psychosis 177, 213–14
causes of 213–14, 215, 215–16
diagnosis 214
see also schizophrenia
psychotherapy 16, 82, 83, 103
talking with patients 83
public speaking 153, 154–5
schoolteachers study 154–5
Ramón y Cajal, Santiago 96, 97
random genetic mutations 159
rats 12–13, 139, 140, 218
Reagan, Ronald 208
receptors 22
cytokine 30, 127, 128
serotonin 105
reflexes 128–9
Cartesian 184
Hering-Breuer reflex 78, 128
inflammatory reflex 128, 130, 204
Remicade 65
Remicade high 67–8, 203
placebo effect 67–8
repurposing 200
respiratory system 27
rheumatoid arthritis 3–4, 6, 43, 44, 55–7, 62
anti-TNF drugs 64–6, 201
global market 65–6
success of 65
diagnosis by blood tests 58
disorder of the immune system 63
fatigue and 66
medical explanation of 56–7
stimulation of the vagus nerve 132
rheumatoid/rheumatic disease 56, 58, 64, 66, 70
rheumatologists
attention to physical disease 44
inattention to psychological or behavioural symptoms 44–5
indifference of 44
Roche 90, 90–1
clinical trials of iproniazid 91–2, 93
placebo effect 92
marketing of iproniazid 94
root canal surgery 4–5, 6, 14
sadness 163
salt 88
Schildkraut, Joseph 100–1, 105
schizophrenia 94, 162, 173, 178, 184, 185, 216
causes of 216
dread of diagnosis 214
genetic heritability 216, 217
neuro-immunology and 218–19
psychiatric meaning of 214
risk genes 217
complement component 4 (C4) 217
whole-body disease 216
winter births 218
science
God and 53–4
scientific breakthroughs 113
scientific theory 113
scrotal cancer 122
Sea View Hospital 91–2, 94
seasonal affective disorder 149
selective serotonin reuptake inhibitors (SSRIs) see SSRIs (selective serotonin reuptake inhibitors)
self-help 189
self proteins 41
self, the
antibodies mistakenly directed against 41
defence from non-self 22, 24, 27, 28
senile dementia 208
sensory information 46
serotonin 13, 97, 99, 101, 104, 143, 205
basic functions of the nervous system 106
biologically ancient 105
biomarkers 108–10
deficiency in brain 1–2, 105–6, 109–10, 124
depression and 106
measurement in nerve cells 108
brain scanning or neuroimaging 108
cost of technology 108
measurements in the blood 108–9
in worm brains 105
see also SSRIs (selective serotonin reuptake inhibitors)
sex glands 216–17
sexual abuse 157–8
sickness behaviour 12–13, 120, 139, 168, 169
natural selection 170
social withdrawal 169, 170
Sjogren’s syndrome 59
SLE (systemic lupus erythematosus) 58–9, 59
sleep disturbance 66
Sloane, Sir Hans 85, 87
business model 85
social cleansing 165
social isolation 152
social rejection 150
social selection 165
social stress 18, 150, 151, 153, 156, 175, 180–1
Trier social stress test 154–5
social withdrawal 169, 170
societies of apothecaries 84–5
soul, the 47, 49
location of 49–50, 51
spatial resolution 136–7
spinal taps 109
spleen 9, 32, 33, 35, 129, 130, 204, 205
SSRIs (selective serotonin reuptake inhibitors) 1–2, 103, 106, 107, 108, 109, 111, 143, 189
clinical trials 101–2
St Bartholomew’s Hospital 122–3
teaching method 123–4
staining techniques 96
stigma 74–5, 83, 110, 156, 172, 183
stress 150–5
adrenaline rush 155
child abuse 153
debt 152
in early years 156
epidemiological study 152–3
impact on the immune system 152
interference with hormonal system 155
loss of important relationship 150
major life events 150, 151
bereavement 151, 152
divorce 151
poverty 152
public questioning 153–4
public speaking 153, 154–5, 206
schoolteachers study 154–5
social isolation 152
social rejection 150
social stress 18, 150, 151, 153, 156, 175, 180–1
stress management 206–7
strokes 151, 152
suicide 61, 73, 184
sulphur 88
swelling 24
synapses 13, 99, 124, 142, 143
synaptic plasticity 142
syphilis 88, 90
tail suspension test 192–3, 195
tangles 208, 209, 216
tau proteins 209
TB (tuberculosis) 86, 90
anti-TB drugs 90–1
iproniazid see iproniazid
of the spine 122
test faces 163
tetanus 26–7, 28, 38
therapeutic relationships 83
thymus gland 35
thyroid cells 59
TNF (tumour necrosis factor) 64–6
tonsils 35
transference 80
transmitters 142–3
transplant surgery 6
TREM2 212
tribes 166–74, 175