Handbook of Anxiety and Fear
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Table of contents
- Cover
- List of Contributorsv
- Prefaceix
- Acknowledgmentsxi
- Contentsxiii
- Section 1: Introduction1
- Chapter 1.1. Introduction to the handbook on fear and anxiety3
- References6
- Section 2: Animal Models of Anxiety, Fear and Defense9
- Chapter 2.1. Theoretical approaches to the modeling of anxiety in animals11
- I. Introduction11
- II. The nature of anxiety11
- III. The nature of an animal model15
- IV. The nature of a specific test: the elevated plus-maze18
- V. Other animal models of anxiety21
- VI. Models of anxiety and their control by the brain23
- VII. Conclusions23
- References25
- Chapter 2.2. The use of conditioning tasks to model fear and anxiety29
- I. A deceptively simple experiment30
- II. A brief history of Pavlovian fear conditioning32
- III. Behavioral measures of conditional fear33
- IV. Other unconditional stimuli35
- V. Key developments in the neuroanatomy of fear conditioning36
- VI. Pavlovian extinction38
- VII. Individual differences in anxiety disorders40
- VIII. Post-traumatic stress disorder41
- IX. Conclusion43
- Acknowledgment43
- References43
- Chapter 2.3. Extinction of fear: from animal studies to clinical interventions49
- I. Introduction49
- II. Behavioral features of extinction50
- III. Theoretical accounts of extinction52
- IV. Facilitation of extinction by d-cycloserine52
- V. Emerging evidence for multiple mechanisms of extinction56
- VI. Conclusion59
- Acknowledgments59
- References60
- Chapter 2.4. Defensive behaviors, fear, and anxiety63
- I. Fear and anxiety63
- II. Defensive behaviors: what, when, where, and why?64
- III. Relationships to learning69
- IV. Danger learning: conditioning to painful unconditioned stimuli (US)70
- V. Unconditioned and conditioned responses to non-painful stimuli (predators or predator odors)71
- VI. Learning of defense to partial predator stimuli71
- VII. Effects of stress and stress ameliorating conditions on defense71
- VIII. Defense and learning: relationship to anxiety72
- IX. Responses to anxiolytic and panicolytic drugs72
- X. Human defensive behaviors73
- XI. Defensive behavior, fear, and anxiety76
- References77
- Chapter 2.5. Unconditioned models of fear and anxiety81
- I. Introduction81
- II. Models82
- III. Ethological approaches: predator confrontation86
- IV. Conclusions90
- References93
- Section 3: Neural Systems for Anxiety, Fear, and Defense101
- Chapter 3.1. Brain mechanisms of Pavlovian and instrumental aversive conditioning103
- I. Introduction103
- II. Pavlovian fear conditioning104
- III. Aversive instrumental conditioning109
- IV. Using EFF to investigate an aversive ‘‘motive circuit’’114
- V. Summary/conclusions116
- Abbreviations117
- References117
- Chapter 3.2. Neural systems activated in response to predators and partial predator stimuli125
- I. Introduction125
- II. The hypothalamus and its central role in the organization of anti-predator defensive responses126
- III. The medial hypothalamic defensive system127
- IV. Neural inputs to the medial hypothalamic defensive system128
- V. Neural outputs from the medial hypothalamic defensive system133
- VI. Overview of the circuits involved in processing anti-predator defensive responses135
- VII. Neural systems involved in anti-predator contextual conditioning responses136
- References137
- Chapter 3.3. A behavioral and neural systems comparison of unconditioned and conditioned defensive b141
- I. Neural system analysis: comparison among models using Pavlovian fear conditioning or predator-rel141
- II. Comparisons of use of conditioned and unconditioned animal models of anxiety over time145
- III. Validity of animal models of fear and anxiety148
- Appendix: accessing articles using conditioned and unconditioned models of anxiety151
- References152
- Section 4: The Pharmacology of Anxiety, Fear, and Defense155
- Chapter 4.1. Peptide receptor ligands to treat anxiety disorders157
- I. Introduction157
- II. Neuropeptide systems in anxiety patients160
- III. Anxiety-related behavior and neuropeptides: preclinical evidence166
- IV. Neurochemical evidence linking neuropeptides and the mechanism of action of clinically used anxi179
- V. Many peptide candidates: convergence onto common pathways?185
- VI. Development of small molecule, non-peptide compounds for peptidergic targets187
- VII. Conclusion195
- References195
- Chapter 4.2. Subtype-selective GABAA/benzodiazepine receptor ligands for the treatment of anxiety di223
- I. Introduction223
- II. A brief history of anxiolytic development and use224
- III. Benzodiazepines and GABAA receptor heterogeneity225
- IV. Subtype-dependent effects of benzodiazepines: evidence from transgenic mice227
- V. Subtype-dependent effects of benzodiazepines: recent findings with subtype-selective ligands227
- VI. Reducing anxiety selectively: how might this work?231
- VII. Controversies and comments: points of contention between (and within) the ‘‘old’’ and t236
- VIII. Where do we go from here?237
- Acknowledgments238
- References238
- Chapter 4.3. Modulation of anxiety behaviors by 5-HT-interacting drugs241
- I. Introduction241
- II. The serotonin system in the central nervous system242
- III. Human findings: serotonin and pathological anxiety243
- IV.Human findings: experimental studies with patients244
- V. Neuroendocrine studies245
- VI. Human findings: experimental studies with healthy volunteers246
- VII. Human studies: neuroimaging247
- VIII. Summary of clinical studies248
- IX. Serotonin and defensive behavior in animal models248
- X. Dual role of serotonin251
- XI. Serotonin and the hippocampus254
- XII. Genetic manipulations of the 5-HT system254
- XIII.Plasticity of the 5-HT systems and anxiety257
- XIV. Mechanisms of the anxiolytic effects of SSRIs and buspirone257
- XV. Conclusions259
- References259
- Chapter 4.4. The glutamatergic system as a potential therapeutic target for the treatment of anxiety269
- I. Introduction269
- II. Glutamate receptor diversity270
- III. Glutamate receptor structure271
- IV. Advancing glutamate receptor research in anxiety: selective molecules and mutant animals272
- V. Animal models of anxiety276
- VI. Modelling cognitive dysfunction in anxiety278
- VII. Pharmacology of glutamate in animal models of anxiety278
- VIII. NMDA receptors283
- IX. AMPA receptors285
- X. mGluRs285
- XI. Conclusions and future directions287
- References288
- Chapter 4.5. The endocannabinoid system and anxiety responses303
- I. Introduction303
- II. The endocannabinoid system304
- III. Effects of cannabinoids on anxiety308
- IV. Role of the endocannabinoid system in anxiety310
- V. Methodological issues in the study of endocannabinoids in anxiety312
- VI. Mechanisms for the endocannabinoid role in anxiety313
- VII. Endocannabinoids as a pharmacological target for anxiety treatment315
- VIII. Conclusions316
- Acknowledgments316
- References316
- Chapter 4.6. Genetic factors underlying anxiety-behavior: a meta-analysis of rodent studies involvin325
- I. Introduction325
- II. Are some particular behavioral tests used in these studies?326
- III. Which genetic method has been used?343
- IV. Was there any particular choice of construction (knock-in, knock-out, and over-expressed models)343
- V. Which phenotypes are observed?344
- VI. Can these results be explained by the species or the strain used?344
- VII. Did this strategy enable to precise the brain area involved in these processes?345
- VIII. Is the contribution of the genetic factor limited to the developmental period?345
- IX. Do the effects of the mutation correlate with the results of pharmacological challenge?345
- X. Does the mutation modify the response to anxiolytic or anxiogenic agents?346
- XI. What do these findings tell us about the link between neurotransmitter systems and anxiety? Do t346
- XII. Conclusion and perspectives347
- References348
- Chapter 4.7. The pharmacology of anxiolysis355
- I. Introduction355
- II. Recent developments and emerging targets355
- III. Concluding remarks and future directions359
- References359
- Section 5: Handbook of Fear and Anxiety: Clinical and Experimental Considerations363
- Chapter 5.1. Phenomenology of anxiety disorders365
- I. Anxiety disorders: clinical features365
- II. Social anxiety disorder (SAnD)366
- III. Obsessive-compulsive disorder371
- IV. Panic disorder376
- V. Generalized anxiety disorder381
- VI. Post-traumatic stress disorder385
- VII. Conclusions388
- Abbreviations388
- References388
- Chapter 5.2. How effective are current drug treatments for anxiety disorders, and how could they be395
- I. Which pharmacological treatments are efficacious in anxiety disorders?395
- II. What is the mechanism of action in anxiety disorders?396
- III. Do randomised controlled trials reveal consistent differences in efficacy?398
- IV. Why don’t randomised controlled trials reveal more differences between treatments?398
- V. Could clinical outcomes be improved with better use of current treatments?399
- VI. Can psychological therapies enhance the efficacy of pharmacological treatments?400
- VII. Could clinical outcomes be improved, with new targets for anxiolytic drugs?401
- VIII. Could clinical outcomes be improved through using genetic approaches?402
- IX. The insights offered by studies of pharmacological modulation of emotion processing403
- X. Do neuroimaging studies explain the neuroanatomy of the treatment response?404
- References405
- Chapter 5.3. Experimental models: panic and fear413
- I. Introduction413
- II. Sodium lactate and other hyperosmotic infusion techniques415
- III. Carbon dioxide418
- IV. Cholecystokinin420
- V. Voluntary hyperventilation423
- VI. Doxapram425
- VII. Other experimental models of panic425
- VIII. General conclusions427
- Abbreviations427
- References427
- Chapter 5.4. Principles and findings from human imaging of anxiety disorders437
- I. Introduction437
- II. Choice of imaging modality438
- III. Molecular imaging440
- IV. Molecular imaging in anxiety disorders443
- References450
- Chapter 5.5. Stress hormones and anxiety disorders455
- I. Introduction: stress, fear and anxiety455
- II. Anxiety disorders and stressful events: is there a connection? – The role of life events456
- III. Stress response systems: stress and neuroendocrine regulation457
- IV. Links between HPA and noradrenergic function in animal studies457
- V. The SNS in anxiety disorders465
- VI. Summary and conclusions467
- References468
- Chapter 5.6. The genetics of human anxiety disorders475
- I. Introduction475
- II. Genetic epidemiology475
- III. Molecular genetics484
- IV. Functional genetics495
- V. Summary and further directions496
- Abbreviations497
- References498
- Subject Index511
This Handbook brings together and integrates comprehensively the core approaches to fear and anxiety. Its four sections: Animal models; neural systems; pharmacology; and clinical approaches, provide a range of perspectives that interact to produce new light on these important and sometimes dysfunctional emotions. Fear and anxiety are analyzed as patterns that have evolved on the basis of their adaptive functioning in response to threat. These patterns are stringently selected, providing a close fit with environmental situations and events; they are highly conservative across mammalian species, producing important similarities, along with some systematic differences, in their human expression in comparison to that of nonhuman mammals. These patterns are described, with attention to both adaptive and maladaptive components, and related to new understanding of neuroanatomic, neurotransmitter, and genetic mechanisms. Although chapters in the volume acknowledge important differences in views of fear and anxiety stemming from animal vs. human research, the emphasis of the volume is on a search for an integrated view that will facilitate the use of animal models of anxiety to predict drug response in people; on new technologies that will enable direct evaluation of biological mechanisms in anxiety disorders; and on strengthening the analysis of anxiety disorders as biological phenomena.
• Integrates animal and human research on fear and anxiety
• Presents emerging and developing fields of human anxiety research including imaging of anxiety disorders, the genetics of anxiety, the pharmacology of anxiolysis, recent developments in classification of anxiety disorders, linking these to animal work
• Covers basic research on innate and conditioned responses to threat
• Presents work from the major laboratories, on fear learning and extinction
• Reviews research on an array of neurotransmitter and neuromodulator systems related to fear and anxiety
• Compares models, and neural systems for learned versus unlearned responses to threat
• Relates the findings to the study, diagnostics, and treatment of anxiety disorders, the major source of mental illness in modern society (26 % of Americans are affected by anxiety disorders!)
• Integrates animal and human research on fear and anxiety
• Presents emerging and developing fields of human anxiety research including imaging of anxiety disorders, the genetics of anxiety, the pharmacology of anxiolysis, recent developments in classification of anxiety disorders, linking these to animal work
• Covers basic research on innate and conditioned responses to threat
• Presents work from the major laboratories, on fear learning and extinction
• Reviews research on an array of neurotransmitter and neuromodulator systems related to fear and anxiety
• Compares models, and neural systems for learned versus unlearned responses to threat
• Relates the findings to the study, diagnostics, and treatment of anxiety disorders, the major source of mental illness in modern society (26 % of Americans are affected by anxiety disorders!)