Stress, the brain and depression

Can traumatic life events cause depression? Studies generally point to a connection between adverse life events and depression. However, establishing a causal rather than associative connection, the key concern of this book, is more problematic. What neurobiological changes may be induced by stress and depression, and to what extent do these changes correspond? The authors structure their examination around three major themes: the pathophysiological role of stress in depression; whether or not a subtype of depression exists that is particularly stress-inducible; and, finally, how best to diagnose and treat depression in relation to its biological underpinnings.

Author Notes

Herman M. van Praag was Head and Professor of Psychiatry at the University of Groningen, Utrecht, the Albert Einstein College of Medicine, New York, USA, and the University of Maastricht.

Preface	p. xi
1 Diagnosing depression	p. 1
1.1 Diagnosing and classifying	p. 1
1.2 Diagnosing depression	p. 1
1.2.1 The nosological approach	p. 1
1.2.2 Problems inherent to nosological systems	p. 2
1.2.3 The syndromal approach	p. 5
1.2.4 Problems inherent to the syndromal approach	p. 6
1.2.5 The dimensional/functional approach	p. 6
1.3 Multi-tier diagnosing	p. 7
1.4 Conclusions	p. 8
2 Traumatic life events: general issues	p. 12
2.1 History	p. 12
2.2 Definitions	p. 13
2.2.1 The stress syndrome	p. 13
2.2.2 Coping with the stress syndrome	p. 14
2.3 Life events and psychiatric classification	p. 15
2.4 Life events and abnormal mental states	p. 16
2.5 Life events and personality structure	p. 18
2.6 Genetic and environmental variables influencing exposure to life events	p. 19
2.6.1 Life events do not occur capriciously	p. 19
2.6.2 Genes and environment	p. 19
2.7 Conclusions	p. 21
3 Life events and depression: preliminary issues	p. 24
3.1 The agenda	p. 24
3.2 Border issues	p. 24
3.2.1 Distress versus depression	p. 24
3.2.2 Chronic depression versus personality-related depressive traits	p. 26
3.3 Meaning of the term life event	p. 27
3.3.1 Definition	p. 27
3.3.2 Heterogeneity	p. 27
External events	p. 27
Internal events	p. 28
Dependent and independent life events	p. 28
Controllability	p. 29
Type of event	p. 29
Conclusion	p. 30
3.4 How to assess life events?	p. 30
3.4.1 Checklists	p. 30
3.4.2 Structured interviews	p. 31
3.4.3 De-subjectivation	p. 32
3.4.4 Conclusion	p. 33
3.5 What is meant with the term causation?	p. 33
3.6 Conclusions	p. 34
4 Life events and depression: is there a causal connection?	p. 38
4.1 What kind of evidence is needed?	p. 38
4.2 Life events preceding depression	p. 38
4.2.1 Acute events	p. 38
4.2.2 Chronic difficulties	p. 40
4.3 Vulnerability	p. 41
4.4 Life events, personality and depression	p. 43
4.4.1 A triad?	p. 43
4.4.2 Depression and personality	p. 43
4.4.3 Life events and personality	p. 45
4.4.4 Congruence	p. 46
4.4.5 Conclusions	p. 47
4.5 Early adversity, life events, personality and depression	p. 47
4.6 Genes, life events, personality and depression	p. 48
4.7 Life events and recovery from depression	p. 50
4.8 Conclusions	p. 51
5 Genetics of depression	p. 59
5.1 Introduction	p. 59
5.2 Genetics of depression	p. 59
5.2.1 Genetic epidemiology of depression	p. 59
5.2.2 Molecular genetics of depression	p. 60
5.3 Genes and environment	p. 63
5.4 The depression exophenotype	p. 64
5.4.1 Depression as a discrete and a continuous trait	p. 65
5.4.2 Genetics of the qualitative phenotype	p. 65
Family studies	p. 65
Twin studies	p. 66
5.4.3 Genetics of the quantitative phenotype	p. 67
5.4.4 Genetics of the comorbid phenotype	p. 69
5.5 The depression endophenotype	p. 69
5.6 The genetics of personality and depression	p. 70
5.7 Development and genes	p. 70
5.8 Molecular genetic findings	p. 71
5.9 Do environmental factors create enduring liabilities to depression?	p. 71
5.10 Conclusion	p. 72
6 Gene-environment correlation and interaction in depression	p. 78
6.1 Gene-environment relationships	p. 78
6.1.1 Correlation: genes influence environmental exposure	p. 78
6.1.2 Synergism: genes and environment co-participate in the same cause	p. 79
Models describing gene-environment synergism	p. 80
6.1.3 Genes and environment add to each other's effect	p. 82
6.1.4 Genes and environment multiply each other's effects	p. 82
6.2 Research findings on gene-environment interaction and correlation	p. 83
6.2.1 Gene-environment correlation	p. 83
6.2.2 Gene-environment interaction	p. 84
6.3 Conclusion	p. 87
7 Monoamines and depression	p. 91
7.1 The beginnings	p. 91
7.2 Serotonin and depression	p. 92
7.2.1 Localization of serotonergic circuits	p. 92
7.2.2 Serotonin metabolism	p. 92
7.2.3 In vivo receptor studies	p. 96
5-HT receptors and depression	p. 96
5-HT[subscript 1A] receptors	p. 99
5-HT[subscript 1B(D)] receptors	p. 102
5-HT[subscript 2] receptors	p. 102
5-HT receptors and therapeutic activity of present-day antidepressants	p. 103
5-HT transporter	p. 104
7.2.4 Postmortem receptor studies	p. 104
7.2.5 Genetic studies	p. 105
7.2.6 Conclusions	p. 107
7.3 Noradrenaline and depression	p. 107
7.3.1 Localization	p. 107
7.3.2 Noradrenaline metabolism	p. 108
7.3.3 Noradrenaline receptor studies	p. 110
7.3.4 Conclusions	p. 113
7.4 Dopamine and depression	p. 114
7.4.1 Localization	p. 114
7.4.2 Dopamine metabolism	p. 114
7.4.3 DA receptor studies	p. 116
7.4.4 DA and antidepressant action	p. 117
7.4.5 Conclusions	p. 117
7.5 Behavioural correlates of the monoaminergic disturbances in depression	p. 118
7.6 Some animal data on 5-HT ergic regulation anxiety and aggression	p. 123
7.7 Conclusions	p. 127
8 Stress hormones and depression	p. 144
8.1 Stress and stress response	p. 144
8.2 Stress and the HPA system	p. 145
8.2.1 The stress response	p. 145
8.2.2 The hypothalamic-pituitary-adrenal response	p. 146
8.2.3 Cortisol: permissive, feedback and preparatory actions	p. 148
8.2.4 Brain corticosteroid receptors	p. 150
8.2.5 Heterogeneity of the stress response	p. 154
8.2.6 The pacemaker	p. 155
8.3 Depression and the HPA system	p. 155
8.4 CRH and HPA axis abnormalities: stress-related or depression-related?	p. 161
8.4.1 How should the question be phrased?	p. 161
8.4.2 Antidepressants and the HPA axis	p. 162
8.4.3 CRH, a depressogenic substance?	p. 163
CRH localization and CRH receptors	p. 163
Effects of CRH in animals	p. 164
CRH and depression	p. 166
CRH, corticosteroids, depression and brain morphology	p. 167
8.4.4 CRH, corticosteroids and early life stress in animals	p. 171
Early life stress and stressor responsivity	p. 171
Mechanisms underlying immediate and long-term effects of maternal separation	p. 173
Persistent effects of mother-pup interaction	p. 176
8.4.5 The behavioural effects of early life stress in humans	p. 179
Behavioural effects of childhood adversity	p. 180
Childhood adversity and dysfunction of the HPA axis	p. 183
Posttraumatic stress disorder	p. 185
Childhood adversity and structural changes in the brain	p. 187
8.4.6 Cortisol and the functioning of monoaminergic systems	p. 189
HPA axis and serotonin	p. 189
HPA axis and noradrenalin	p. 193
HPA axis and dopamine	p. 195
Conclusions	p. 196
8.4.7 Glucocorticoids and antidepressant action	p. 197
8.5 Conclusions	p. 200
9 Stress, the brain and depression	p. 225
9.1 The stress syndrome and depression: psychopathological and biological overlap	p. 225
9.2 Depression, anxiety and aggression: the concept of comorbidity	p. 227
9.3 Comorbidity of depression, anxiety and aggression: some numbers	p. 229
9.3.1 Intercorrelation of the symptoms of mood lowering, anxiety and aggressivity	p. 229
9.3.2 Comorbidity of mood disorders and anxiety disorders	p. 229
9.3.3 Comorbidity of depression and personality disorder	p. 230
9.4 Comorbidity of anxiety and depression: ways the problem has been approached	p. 231
9.4.1 Hierarchical exclusion rules	p. 231
9.4.2 Combination diagnoses	p. 232
Atypical depression	p. 232
Mixed anxiety-depression disorder	p. 234
9.5 Relationship between anxiety and mood disorders	p. 236
9.6 Anxiety and aggression as pacemakers of depression	p. 236
9.6.1 Anxiety, aggression and mood	p. 236
9.6.2 Anxiety/aggression and depression: psychopathological aspects	p. 236
9.6.3 Anxiety/aggression and depression: biological aspects	p. 238
Serotonin	p. 238
Stress (CRH/cortisol)--serotonin interactions	p. 238
Psychopharmacological observations	p. 239
9.6.4 Anxiety/aggression-driven depression: aspects of personality structure	p. 239
9.6.5 Anxiety/aggression-driven depression: a psycho-bio-psychopathological bridge hypothesis	p. 243
9.6.6 Anxiety/aggression-driven depression: therapeutic expectations	p. 245
9.7 Anxiety/aggression-driven depression: diagnostic implications	p. 246
9.7.1 Diagnostic acuity: a condition sine qua non for biological stress research	p. 246
9.7.2 Functionalization of psychiatric diagnosing	p. 247
9.7.3 Importance of functionalization for the diagnostic process in psychiatry	p. 248
9.7.4 Functionalization of diagnosis and the construct of anxiety/aggression-driven depression	p. 249
9.7.5 Verticalization of psychiatric diagnosing	p. 249
9.7.6 Approaches towards verticalization of psychiatric diagnoses	p. 249
9.7.7 Importance of verticalization for the diagnostic process in psychiatry	p. 250
9.8 Consequences of diagnostic renewal for biological psychiatric and psychopharmacological research	p. 251
9.9 Conclusions	p. 252
Epilogue	p. 260
Stress-induced depression	p. 260
Vulnerabilities	p. 261
Recognizability	p. 262
Diagnostic strategies	p. 263
Name index	p. 265
Subject index	p. 274

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