Biological Psychiatry [2 Vols]

Cover......Page 1
Biological Psychiatry......Page 2
Contents......Page 7
Contributors......Page 11
Preface......Page 18
Part A BASIC PRINCIPLES......Page 19
Foundational Claim 1: Mental Disorders as Brain Disorders......Page 21
Foundational Claim 2: Causes and Reasons......Page 22
General Conceptual Issues in Biological Psychiatry: First Pass......Page 23
THE HISTORY OF BIOLOGICAL PSYCHIATRY......Page 24
The Nineteenth Century and After......Page 25
Neglected Models of Biological Psychiatry......Page 26
Data Capture in Biological Psychiatry......Page 27
Data Processing in Biological Psychiatry......Page 34
Data Interpreting and Reporting in Biological Psychiatry......Page 38
CONCLUSIONS......Page 40
REFERENCES......Page 41
THE PSYCHOMETRIC TRIANGLE......Page 43
Internal Validity......Page 44
External Validity......Page 46
PROCEDURAL ALGORITHMS VERSUS RATING SCALES......Page 47
THE MEASUREMENT OF CHRONIC STRESS......Page 49
THE SUBJECTIVE QUALITY OF LIFE DIMENSIONS......Page 50
CONCLUSION......Page 51
REFERENCES......Page 52
ANIMAL MODELS CONSTITUTE THEORIES ABOUT DISORDERS......Page 55
Construct Validity is Necessary......Page 56
The Role of Stress......Page 57
Impairments in Information Processing......Page 58
REFERENCES......Page 59
NA Nuclei, Pathways and Receptors......Page 63
Introduction......Page 65
DA Nuclei, Pathways and Receptors......Page 66
Physiology of DA Neurons and Transmitter Release......Page 67
Postsynaptic Effects of DA......Page 69
Behavioural and Clinical Significance of DA Neurons......Page 70
Biochemistry......Page 71
Transmitter Release and Activity of 5-HT Neurons......Page 72
5-HT Reuptake......Page 73
Behavioural and Clinical Significance......Page 74
REFERENCES......Page 75
NMDA Receptors......Page 85
Kainate Receptors......Page 88
Location of Metabotropic Glutamate Receptors......Page 89
Signal Transduction and Second-Messenger Systems......Page 90
Physiology of Metabotropic Glutamate Receptors......Page 92
Functions of Metabotropic Glutamate Receptors......Page 93
Vesicular Glutamate Transporter......Page 94
Cellular Excitatory Amino Acid Transporters......Page 95
REFERENCES......Page 98
Hypothalamic Neuropeptides......Page 103
Brain-Born Opioid Peptides......Page 106
Brain-Born Gastrointestinal or Brain–Gut Neuropeptides......Page 107
Other Neuropeptides......Page 108
Hypothalamus......Page 110
PEPTIDERGIC TRANSMISSION......Page 111
REFERENCES......Page 112
OVERVIEW OF COMPONENTS AND CONTROL MECHANISMS......Page 115
Limitations of Stimulation Tests......Page 116
THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS......Page 117
Hypothalamic-Pituitary-Adrenal Axis Abnormalities in Depression......Page 118
OVERVIEW OF HYPOTHALAMIC-PITUITARY-THYROID AXIS COMPONENTS AND FUNCTION......Page 120
Hypothalamic-Pituitary-Thyroid Axis Dysfunction in Patients with Primary Psychiatric Disorders......Page 121
THE HYPOTHALAMIC-PITUITARY-GONAD AXIS......Page 122
OXYTOCIN AND VASOPRESSIN......Page 123
SUMMARY AND CONCLUSION......Page 124
REFERENCES......Page 125
The Innate Immune Response......Page 129
Methods Commonly Used in the Laboratory to Measure Immune Functions......Page 131
NEURAL-IMMUNE INTERACTIONS Neural Effects on Immune Regulation......Page 132
Immunological Influences on Central Nervous System Activities......Page 133
Neurotransmitters and Neurohormones......Page 134
Medical Illness......Page 135
REFERENCES......Page 137
From Peripheral to Central Psychophysiology......Page 141
From Lower to Higher Levels, and from Simple to Complex Neural Regulation......Page 143
From Efferent Processes to Reciprocal Interactions......Page 147
From Global to Specific Influences on Mind and Body......Page 148
Anxiety......Page 149
Schizophrenia Spectrum Disorders......Page 150
Psychophysiological Relations......Page 151
Psychophysiological Inference......Page 152
REFERENCES......Page 153
Examining Patients with Delineated Brain Damage: The Lesion Method......Page 157
Techniques for Determining Physiological Activity......Page 158
Assessment of Behaviour......Page 160
PRINCIPLES OF HUMAN BRAIN ORGANIZATION FOR MENTAL FUNCTION......Page 162
Lateralization of Function......Page 163
Association Areas......Page 164
REFERENCES......Page 168
INTRODUCTION......Page 173
History......Page 174
History......Page 175
History......Page 176
Basic Principles......Page 177
Basic Principles......Page 178
History......Page 179
History......Page 180
Basic Approaches......Page 181
Basic Approaches......Page 182
ACKNOWLEDGEMENTS......Page 183
REFERENCES......Page 184
Patterns of Inheritance......Page 185
Human Variation and its Components......Page 187
Chromosomes......Page 188
Storage of Information in DNA......Page 189
Codons, Amino Acids and Polypeptides......Page 190
The Mitochondrial Genome......Page 191
Family, Twin and Adoption Studies......Page 192
Methods of Statistical Analysis used in Family, Twin and Adoption Studies......Page 194
Association Studies......Page 195
Emerging Methods for Genotyping......Page 196
Gene Expression......Page 197
REFERENCES......Page 198
INTRODUCTION......Page 199
ENVIRONMENT INTERACTION......Page 200
EMPIRICAL EXAMPLES......Page 201
POWER......Page 202
DISCUSSION......Page 203
REFERENCES......Page 204
The Hypothalamus as our Sexiest Part......Page 207
The Sexually Dimorphic Nucleus of the Preoptic Area......Page 208
The Suprachiasmatic Nucleus in Relation to Sex and Sexual Orientation......Page 213
Other Sexually Dimorphic Hypothalamic Structures......Page 214
The Bed Nucleus of the Stria Terminalis......Page 215
Sex Differences in the Supraoptic and Paraventricular Nuclei......Page 216
Mechanism of Sexual Differentiation of the Brain......Page 217
Sexual Differentiation, the Hypothalamus and the Amygdala......Page 218
Transsexuality and Other Gender Identity Problems......Page 219
Homosexuality......Page 220
CONCLUSIONS......Page 221
REFERENCES......Page 222
Part B CLINICAL SYNDROMES......Page 229
XV Cognitive Disorders......Page 231
INTRODUCTION......Page 233
Epigenetic Models of Dementia with Naturally Occurring Features......Page 235
Experimentally Induced Epigenetic Models of Dementia......Page 236
Experimentally Induced Genetic Models of Dementia......Page 238
Models of Psychosis and Depression Associated with Cognitive Dysfunction......Page 239
Models of Attention Deficit Hyperactivity Disorder......Page 240
Animal Cognition is not a Unitary Process......Page 241
Measurement of Disease-Relevant Types of Behaviour......Page 242
Testing Cognitive Function......Page 243
REFERENCES......Page 244
DEMENTIAS......Page 253
Dementia of the Alzheimer’s Type......Page 254
MEMORY DISORDERS......Page 256
Korsakoff’s Syndrome......Page 257
MDMA-Induced Memory Deficits......Page 258
DELIRIUM......Page 259
REFERENCES......Page 260
GABA and Cognition......Page 265
Glutamate and Cognition......Page 267
Alzheimer’s Dementia......Page 268
Alcohol-Induced Dementia......Page 271
Vascular Dementia......Page 272
REFERENCES......Page 273
NEUROPEPTIDE NEUROBIOLOGY......Page 279
VASOPRESSIN......Page 280
SUBSTANCE P......Page 281
ENDOGENOUS OPIOIDS......Page 282
CHOLECYSTOKININ......Page 283
Somatostatin in Alzheimer’s Disease......Page 284
Corticotropin-Releasing Factor in Alzheimer’s Disease......Page 285
REFERENCES......Page 286
THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS......Page 291
Effects on Memory Sustained by the Hippocampus......Page 292
Effects on Memory Sustained by the Frontal Lobes......Page 293
Unhealthy Ageing......Page 294
MODULATORY INFLUENCES OF CORTICOSTEROIDS ON MEMORY......Page 295
Chronic Modulatory Effects of Corticosteroids......Page 296
REFERENCES......Page 297
IS ALZHEIMER’S DISEASE AN IMMUNOLOGICAL DISORDER?......Page 301
GLIAL CELLS......Page 302
Glial Activation in the Alzheimer’s Diseased Brain......Page 303
INTERLEUKIN 1 AND 6 AND BRAIN ACUTE-PHASE RESPONSE......Page 304
COMPLEMENT ATTACK IN THE ALZHEIMER’S DISEASED BRAIN......Page 305
TRANSGENIC ALZHEIMER’S DISEASE MOUSE MODELS AND NEUROINFLAMMATION......Page 306
REFERENCES......Page 307
Auditory P300 in Alzheimer’s Disease......Page 313
Olfaction in Alzheimer’s Disease......Page 315
Apolipoprotein E......Page 316
DOWN’S SYNDROME......Page 318
HUNTINGTON’S CHOREA......Page 319
AGEING......Page 320
REFERENCES......Page 322
Neuropsychological Assessment and Cognitive Disorders......Page 327
Mental Retardation......Page 329
Pervasive Developmental Disorders......Page 330
Attention Deficit Hyperactivity Disorder......Page 331
Learning Disorders......Page 332
Defining Cognitive Dysfunction......Page 333
Differentiating Cognitive Dysfunction from Other Mental Disorders......Page 334
Primary Cognitive Disorders......Page 337
Secondary Cognitive Disorders......Page 344
Structural Neuroimaging......Page 349
REFERENCES......Page 350
Anatomical Substrate of Memory......Page 353
The Ageing Process and Mild Cognitive Impairment......Page 355
Alzheimer’s Disease......Page 356
Diffuse Lewy Body Disease......Page 359
Pick’s Disease......Page 360
Corticobasal Ganglionic Degeneration......Page 362
Frontotemporal Dementia......Page 363
Progressive Supranuclear Palsy......Page 364
Transmissible Spongiform Encephalopathies......Page 365
REFERENCES......Page 367
Functional Imaging......Page 371
VASCULAR DEMENTIA......Page 373
Steele–Richardson Disease......Page 374
REFERENCES......Page 375
ALZHEIMER’S DISEASE......Page 379
Molecular Genetics......Page 380
Genotype–Phenotype Correlations in Familial Early-Onset Alzheimer’s Disease......Page 382
Molecular Genetics......Page 383
Population Attribution......Page 384
Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy......Page 385
Autosomal Dominant Dementia......Page 386
REFERENCES......Page 387
REVIEW OF ALZHEIMER’S DISEASE MOLECULAR BIOLOGY AND GENETICS......Page 395
Medications or Supplements......Page 396
Atherosclerotic Risk Factors......Page 397
Lifestyle Factors......Page 398
ALLELE STATUS......Page 399
REFERENCES......Page 400
Effects of Oestrogen Replacement Therapy......Page 405
Biological Basis for Gender Differences in Alzheimer’s Disease......Page 406
Possible Mechanisms for Gender Differences in Vascular Dementia......Page 407
REFERENCES......Page 408
Treatment Strategies Based on Knowledge of Aetiology and Pathogenic Mechanisms of Dementia of the Alzheimer Type......Page 411
Symptomatic Treatment of Core Symptomatology......Page 412
REFERENCES......Page 416
XVI Substance-Related Disorders......Page 420
CRITERIA FOR EVALUATING ANIMAL MODELS OF SUBSTANCE DEPENDENCE......Page 421
Operant Intravenous Drug Self-Administration......Page 422
Evaluation of Self-Administration Techniques......Page 423
Evaluation of ICSS......Page 424
Conditioned Reinforcement Paradigm......Page 425
Evaluation Of Drug Discrimination Procedures......Page 426
Second-Order Schedules......Page 427
SUMMARY AND CONCLUSIONS......Page 428
REFERENCES......Page 429
Taurine......Page 433
Conclusion 1......Page 434
Effect of Ethanol on GABA......Page 435
PSYCHOSTIMULANT DEPENDENCE AND AMINO ACID TRANSMITTERS......Page 436
ACKNOWLEDGEMENTS......Page 437
REFERENCES......Page 438
Glucocorticoid Negative Feedback......Page 443
Opiate Abuse and Glucocorticoid Negative Feedback......Page 444
Cocaine Abuse and Sensitivity to Stress......Page 445
HPA Axis Activity in Subjects with High and Low Risk of Alcoholism......Page 446
SUMMARY OF CHANGES IN ACTIVITY OF THE HPA AXIS OBSERVED DURING DIFFERENT PHASES OF DRUG ABUSE Exposure to Drugs......Page 447
Changes in Glucocorticoid Secretion During Abstinence......Page 448
REFERENCES......Page 449
Immune Modulation......Page 453
Prenatal Ethanol Exposure......Page 455
Alcohol and Liver Disease......Page 456
Clinical Relevance......Page 457
HPA Axis and ANS......Page 459
Immune Modulation......Page 460
Clinical Relevance......Page 462
Immune Modulation......Page 463
Neuroendocrine and Autonomic Involvement......Page 465
Summary (See Tables XVI-4.7–XVI-4.10)......Page 466
Clinical Relevance......Page 467
Immune Modulation......Page 468
SYNTHETIC DRUGS LSD......Page 469
3,4-Methylenedioxymethamphetamine......Page 470
Amphetamines......Page 472
REFERENCES......Page 474
Sensory Evoked Potentials......Page 485
The P300 Component of the Event-Related Potential......Page 486
Other Components of the ERP......Page 491
EEG......Page 492
COCAINE ERP/EP......Page 494
EEG......Page 496
EEG......Page 498
EEG......Page 499
EEG......Page 500
MDMA (‘ECSTASY’)......Page 501
EEG......Page 502
CUE REACTIVITY......Page 503
Findings and Interpretations......Page 504
A Model for Substance Abuse......Page 506
REFERENCES......Page 507
Neurocognitive Effects of Wernicke–Korsakoff Syndrome......Page 513
Neuropsychological Profile Associated with Alcohol-Induced Dementia......Page 514
Neuropsychological Functioning in Alcohol Abuse and Dependence......Page 515
CANNABIS......Page 516
COCAINE......Page 517
‘ECSTASY’......Page 519
OPIATES......Page 521
REFERENCES......Page 522
‘Somatic’ Dependence Signs......Page 527
NEUROANATOMY OF DRUG REWARD......Page 529
Nucleus Accumbens......Page 530
Ventral Tegmental Area......Page 532
Medial Prefrontal Cortex......Page 533
REFERENCES......Page 534
ALCOHOL......Page 541
Chronic Alcoholism: Cerebral Metabolism and Cerebral Blood Flow......Page 542
Alcohol and Benzodiazepine Challenge Studies......Page 543
Pharmacokinetics......Page 544
Chronic Cocaine Abuse, D2 Dopamine Receptors, Dopamine Transporters and Dopamine Release......Page 545
Cocaine, Cerebral Metabolism and Cerebral Blood Flow......Page 546
CENTRAL STIMULANTS: METHAMPHETAMINE Dopamine Transporter and D2 Dopamine Receptor......Page 547
OPIOIDS......Page 548
NICOTINE......Page 549
REFERENCES......Page 550
CHALLENGES TO IDENTIFICATION OF GENES FOR COMPLEX DISORDERS......Page 555
Twin Studies......Page 556
What is the Phenotype?......Page 557
Age......Page 558
Polysubstance Use......Page 559
SUMMARY......Page 560
REFERENCES......Page 561
Psychiatric Comorbidity......Page 565
Alcohol......Page 566
Medical......Page 567
REFERENCES......Page 568
NICOTINE......Page 571
Maintaining Abstinence......Page 572
Methadone......Page 575
Buprenorphine......Page 576
Opiate Detoxification......Page 577
Mood Stabilizers......Page 578
REFERENCES......Page 579
XVII Schizophrenia and Other Psychotic Disorders......Page 584
SCREENING TESTS FOR SCHIZOPHRENIA......Page 585
SIMULATION MODELS: A GENERAL INTRODUCTION......Page 588
SIMULATION MODELS FOR SCHIZOPHRENIA: PHARMACOLOGICAL APPROACHES......Page 591
SIMULATION MODELS FOR SCHIZOPHRENIA: AETIOLOGICAL APPROACHES......Page 592
REFERENCES......Page 594
Evidence for Dopamine Dysfunction......Page 599
SEROTONIN......Page 601
BEYOND DOPAMINE AND SEROTONIN......Page 602
REFERENCES......Page 603
Anatomical and Physiological Considerations......Page 605
EAA Receptor Regulation by Antipsychotics......Page 606
NMDA RECEPTOR-BASED TREATMENT APPROACHES......Page 607
ADDITIONAL GLUTAMATERGIC DYSFUNCTION MECHANISMS AND TREATMENT APPROACHES......Page 611
GABA/Dopamine Interactions......Page 612
TREATMENT APPROACHES......Page 613
REFERENCES......Page 614
NEURONAL DEVELOPMENT AND NEUROPEPTIDES......Page 619
Brain–Gut Peptides......Page 620
Hormones Released from the Hypothalamus......Page 623
Others (Orexin, Nociceptin)......Page 624
THE FUTURE OF NEUROPEPTIDES IN PSYCHIATRY......Page 625
REFERENCES......Page 626
INTRODUCTION......Page 631
THE CONCEPT OF INNATE AND ADAPTIVE IMMUNITY IN HUMANS......Page 632
GENETICS AND SCHIZOPHRENIA......Page 633
NEURODEVELOPMENTAL HYPOTHESIS......Page 634
IL-6 IN THE CNS......Page 635
T-HELPER-2 CELL ACTIVATION IN SCHIZOPHRENIA......Page 636
TH-1 SYSTEM AND ANTIPSYCHOTIC THERAPY......Page 637
REFERENCES......Page 638
Quantitative Eye Movements......Page 643
EEG......Page 644
PSYCHOPHYSIOLOGICAL STUDIES AND AETIOLOGICAL FACTORS......Page 645
CONCLUSIONS......Page 646
REFERENCES......Page 647
Attentional Functions......Page 649
Memory......Page 650
Executive Functions......Page 651
Integrative Approaches......Page 652
Course of the Deficits......Page 653
Theory of Mind......Page 654
Source Monitoring......Page 655
Cognitive Deficits in Non-Psychotic Relatives......Page 656
Impact of Cognitive Deficits on Daily Functioning......Page 657
Cognitive Remediation......Page 658
CONCLUDING REMARKS......Page 659
REFERENCES......Page 660
Magnetic Resonance Imaging (MRI) Studies......Page 667
Positron-Emission Tomography (PET) Resting Studies......Page 668
Cognitive Activation Studies......Page 669
Imaging Symptoms......Page 673
OVERALL CONCLUSION......Page 676
REFERENCES......Page 677
GENETIC RISK......Page 681
Linkage Studies......Page 682
Association Studies......Page 683
Refining the Phenotype......Page 685
Molecular Epidemiology......Page 686
REFERENCES......Page 687
INFLUENCE OF ENVIRONMENTAL FACTORS......Page 691
IMPACT OF GENE AND ENVIRONMENTAL INTERACTION: SCHIZOTAXIA......Page 692
Schizotaxia and Alternative Phenotypes for Schizophrenia......Page 693
REFERENCES......Page 694
THE AGEING BRAIN......Page 697
CLINICAL DIFFERENCES BETWEEN MALES AND FEMALES WITH SCHIZOPHRENIA......Page 698
NEUROCOGNITION AND NEUROIMAGING......Page 699
BRAIN DIFFERENCES AS AN EXPLANATION FOR GENDER DIFFERENCES IN SCHIZOPHRENIA......Page 700
REFERENCES......Page 701
CLASSIFICATION OF ANTIPSYCHOTICS......Page 703
Dopamine......Page 704
Other Neurotransmitters that may be Involved in Antipsychotic Mechanisms of Action......Page 705
Cardiac Side Effects......Page 706
Intermittent or Targeted Medication......Page 707
Olanzapine......Page 708
Adverse Events with Atypical Antipsychotics......Page 709
TREATMENT RESISTANCE IN SCHIZOPHRENIA......Page 710
Patients Who do not Respond Adequately to Clozapine......Page 711
Treatment-Resistant Patients Unwilling or Unable to Take Clozapine......Page 712
REFERENCES......Page 714
XVIII Mood Disorders......Page 720
Predictive Validity......Page 721
Construct Validity......Page 722
Heterogeneity of Depression......Page 723
THE DIATHESIS/STRESS CONCEPT......Page 724
Acute Stress Models......Page 725
Chronic Stress Models......Page 727
Social Dominance Models......Page 729
Social Separation......Page 730
Genetic Models......Page 731
Developmental Models......Page 732
Lesion Model......Page 733
EVALUATION......Page 734
REFERENCES......Page 736
Seasonality of Serotonergic Function......Page 745
Tryptophan-Depletion Studies......Page 746
5-HT1A Receptor Imaging in Depression......Page 749
Catecholamine Depletion Studies......Page 750
SUMMARY......Page 751
REFERENCES......Page 752
GABA and Animal Models of Stress and Depression......Page 757
Evidence of GABAergic Abnormalities in Mood Disorder Patients......Page 758
GABA’s Role in the Treatment of Mood Disorders......Page 760
Evidence of Glutamatergic Abnormalities in Mood Disorder Patients......Page 761
NMDA Antagonist as Antidepressant Agents......Page 762
REFERENCES......Page 763
CHOLECYSTOKININ (CCK)......Page 769
VASOPRESSIN AND OXYTOCIN......Page 770
CONCLUSIONS......Page 771
REFERENCES......Page 772
HPA Axis Function......Page 775
Measures of HPA Axis Function......Page 777
CRH......Page 778
DEHYDROEPIANDROSTERONE AND DHEA(S)......Page 780
Prolactin......Page 781
HYPOTHALAMIC–PITUITARY–THYROID AXIS AND MOOD DISORDERS......Page 782
Mood Disorders and Thyroid Function......Page 783
Thyroid Treatment Modalities for Psychiatric Conditions......Page 784
GONADAL HORMONES AND MOOD DISORDERS......Page 785
REFERENCES......Page 786
Electrodermal Activity......Page 795
Cardiovascular Measures......Page 796
Eye Movements......Page 797
Quantitative Electroencephalogram (QEEG)......Page 798
Event-Related Potentials (ERPs)......Page 800
Sleep Studies......Page 801
CONCLUSIONS......Page 802
REFERENCES......Page 803
Cognition and Psychosis......Page 809
Cognition and Anxiety......Page 810
Neural Correlates of Executive Function......Page 811
Memory......Page 812
Neural Correlates of Memory......Page 813
Neural Correlates of Attention......Page 814
CONCLUSION......Page 815
REFERENCES......Page 816
Difficulties for an Experimental Psychopathology of Mood Disorders......Page 821
The Monoaminergic Hypothesis......Page 822
The Hypothalamic-pituitary-adrenal Axis, Stress, and the Neurotrophic Hypothesis......Page 824
Functional Imaging......Page 826
Integration of Different Approaches......Page 827
HYPOTHESIS AND CONCLUSION......Page 828
REFERENCES......Page 829
Dopamine and Motor Function......Page 833
Serotonin......Page 834
Sleep Deprivation......Page 835
Pharmacotherapy......Page 836
EFFECTS OF AGE, CHRONICITY AND TREATMENT RESISTANCE: IRREVERSIBLE AND REVERSIBLE CHANGES......Page 837
Treatment Resistance......Page 838
EXPERIMENTAL APPROACHES TO DEPRESSION: COMPLEX MODELS......Page 839
Mood Induction and Neuropsychological Paradigms......Page 840
REFERENCES......Page 842
Chromosome X......Page 847
Chromosome 11......Page 848
ANTICIPATION AND EXPANDED TRINUCLEOTIDE REPEAT SEQUENCES......Page 849
REFERENCES......Page 850
Episode Sensitization......Page 853
EARLY MATERNAL SEPARATION......Page 855
REPEATED MATERNAL DEPRIVATION: BRIEF SEPARATIONS VERSUS LONGER SEPARATIONS......Page 857
Pathological versus Adaptive Changes in Gene Expression......Page 858
BRAIN MICROSTRUCTURE CHANGES: ENVIRONMENTAL AND PHARMACOLOGICAL INFLUENCES......Page 861
POTENTIAL NEUROTROPHIC AND NEUROPROTECTIVE EFFECTS OF LITHIUM CARBONATE......Page 863
REFERENCES......Page 864
XVIII-12 Female-Specific Mood Disorders......Page 867
MENARCHE AND MOOD DISORDERS IN ADOLESCENCE......Page 868
PREMENSTRUAL DYSPHORIA......Page 869
POST-PARTUM DEPRESSION......Page 870
PERIMENOPAUSE, MENOPAUSE AND BEYOND......Page 872
REFERENCES......Page 873
Antidepressant Drugs......Page 879
Antidepressant Psychotherapies......Page 881
Novel Drug Therapies for Depression......Page 882
Other Somatic Therapies for Depression......Page 883
Non-Somatic Therapies for Depression......Page 884
Antimanic Drugs......Page 885
Other Somatic Therapies for Bipolar Disorder......Page 887
REFERENCES......Page 888
XIX Anxiety Disorders......Page 895
INTRODUCTION......Page 897
MODELS OF GENERALIZED ANXIETY DISORDER......Page 899
Fear-Potentiated Startle......Page 900
MODELS OF PANIC DISORDER......Page 901
Chemical Stimulation of the Dorsal Periaqueductal Grey......Page 902
The Elevated T-maze......Page 903
Acral Lick Dermatitis......Page 905
CONCLUDING REMARKS......Page 906
REFERENCES......Page 907
THE NEUROPSYCHOLOGY OF ANXIETY......Page 913
THE NEUROPSYCHOLOGY OF THE AMINERGIC SYSTEMS1......Page 914
Cholinergic Systems......Page 915
Dopaminergic Systems......Page 916
Noradrenergic Systems......Page 917
Serotonergic Systems......Page 918
AMINERGIC INVOLVEMENT IN CLINICAL ANXIETY......Page 921
Specific Dopaminergic Involvement......Page 922
Specific Noradrenergic Involvement......Page 923
Specific Serotonergic Involvement......Page 924
Involvement of Monoaminoxidase and COMT......Page 925
AMINERGIC INVOLVEMENT IN PERSONALITY......Page 926
REFERENCES......Page 927
Early Anxiolytics Acting via a GABAergic Mechanism......Page 933
The Discovery of Benzodiazepines......Page 934
Mechanisms of Action......Page 935
Drugs of the Future Acting at the GABAA Receptor Subtypes......Page 941
Generalized Anxiety Disorder (GAD)......Page 942
Obsessive Compulsive Disorder (OCD)......Page 943
REFERENCES......Page 944
Human Studies......Page 947
CORTICOTROPHIN-RELEASING FACTOR AND ANXIETY......Page 948
Human Studies......Page 949
Animals Models......Page 950
Animals Studies......Page 951
Human Studies......Page 952
REFERENCES......Page 953
History of Neuroendocrinology......Page 957
Syndromal Versus Matrix Diagnosis......Page 958
Neuroendocrinology, Psychophysiology and Post-Traumatic Symptoms......Page 959
The HPA Axis......Page 960
CRH, the ‘Stress Superhormone’......Page 961
The Hypothalamo-Pituitary-Thyroid Axis......Page 963
REFERENCES......Page 964
STRESS AND IMMUNE FUNCTION......Page 969
PANIC DISORDER......Page 970
POST-TRAUMATIC STRESS DISORDER......Page 971
Drug Treatments......Page 972
CONCLUSIONS......Page 973
REFERENCES......Page 974
Specific Phobia......Page 977
Social Phobia......Page 979
Agoraphobia......Page 980
Theoretical Models for the Development of Panic Disorder and Psychophysiological Response Patterns......Page 981
Hemisphere Asymmetry and General Negative Emotional Dispositions......Page 982
GENERALIZED ANXIETY DISORDER......Page 983
Psychophysiological Responses to Mental Imagery......Page 984
Psychophysiological Responses to Intense but Neutral Stimulation (Auditory Startle)......Page 985
ANS Activity......Page 986
REFERENCES......Page 987
INTRODUCTION......Page 993
Neuroimaging Studies......Page 994
Cognitive Studies......Page 995
PANIC DISORDER......Page 996
Neuroimaging Studies......Page 997
Cognitive Studies......Page 998
Cognitive Studies......Page 999
DISCUSSION......Page 1000
REFERENCES......Page 1001
Fear Conditioning: Animal Research......Page 1007
Studies of Humans with Brain Lesions......Page 1008
POST-TRAUMATIC STRESS DISORDER (PTSD)......Page 1009
Fear Conditioning, PTSD Symptoms and Functional Neuroimaging Studies in PTSD......Page 1010
PANIC DISORDER (PD)......Page 1011
SOCIAL PHOBIA (SoP) AND SPECIFIC PHOBIAS (SpP)......Page 1013
GENERALIZED ANXIETY DISORDER (GAD)......Page 1015
REFERENCES......Page 1016
Changes in Brain Metabolism or Activation......Page 1021
IN MAN......Page 1022
Panic Disorder......Page 1024
SEROTONIN (5HT)......Page 1025
Social Phobia......Page 1026
REFERENCES......Page 1027
Segregation Studies......Page 1029
Molecular Genetics......Page 1030
Twin Studies......Page 1032
Family Studies......Page 1033
Molecular Genetics......Page 1034
Twin Studies......Page 1037
REFERENCES......Page 1038
ANXIETY DISORDERS: INTRODUCTION......Page 1043
Gender Differences in GAD......Page 1044
Gender Differences in Panic Disorder......Page 1045
Panic Disorder and Female Reproductive Cycles......Page 1046
SOCIAL ANXIETY DISORDER......Page 1047
OCD......Page 1048
Gender Differences in OCD......Page 1049
OCD and Female Reproductive Cycle Events......Page 1050
Gender Differences in PTSD......Page 1051
REFERENCES......Page 1052
Benzodiazepines in Panic Disorder......Page 1057
Resolution of Panic Attacks......Page 1058
Overall Impairment......Page 1059
5-HT RECEPTOR ANTAGONISTS......Page 1060
Introduction......Page 1061
SSRIs vs Clomipramine......Page 1062
Conclusion......Page 1063
Selective Serotonin Reuptake Inhibitors......Page 1064
5-HT Agonists......Page 1065
Pharmacological Approaches......Page 1067
Non-Pharmacologic Approaches......Page 1070
SSRIs in the Treatment of PTSD......Page 1071
Future Directions in the Treatment of PTSD......Page 1072
REFERENCES......Page 1073
SYNDROMES OF SOMATIZATION AND THEIR CLASSIFICATION......Page 1081
SOMATIZATION-ASSOCIATED DISORDERS: OVERLAPPING OR DISTINCT FEATURES?......Page 1082
COMORBIDITY PATTERNS......Page 1083
GENDER EFFECTS......Page 1084
NEUROPSYCHOLOGICAL ASPECTS......Page 1085
GENE–ENVIRONMENT INTERACTIONS......Page 1086
ENDOCRINOLOGICAL ASPECTS......Page 1087
IMMUNOLOGICAL ASPECTS......Page 1088
Autonomic and Peripheral Physiological Activity......Page 1089
Management of Somatoform Disorders......Page 1090
Pharmacological Treatment......Page 1091
REFERENCES......Page 1092
THE CONCEPT OF DISSOCIATION......Page 1097
PTSD, DISSOCIATION, AND STRESS RESPONSES......Page 1098
Substance-Induced Dissociative-Like Symptoms in Healthy Individuals......Page 1099
HPA-Axis......Page 1100
KEY BRAIN STRUCTURES IN INTEGRATIVE FUNCTIONS......Page 1101
Thalamus......Page 1102
NEUROBIOLOGICAL MODELS OF DISSOCIATIVE DISORDERS DID and Epilepsy......Page 1103
THE THEORY OF STRUCTURAL DISSOCIATION......Page 1104
Emotional Operating Systems......Page 1105
The ANP Involves Systems that Manage Daily Life and Promote Survival of the Species......Page 1106
Post-traumatic Integrative Failure......Page 1107
Differences Between ANP and EP on Subliminal Threat Exposure......Page 1108
EP-Dependent Responsivity to Threat......Page 1109
CONCLUSION......Page 1110
REFERENCES......Page 1111
Hypoactive Sexual Desire Disorder......Page 1117
SEXUAL AROUSAL DISORDERS......Page 1118
Female Sexual Arousal Disorder......Page 1119
Male Erectile Disorder......Page 1120
Physiological Factors......Page 1121
Premature Ejaculation......Page 1122
Dyspareunia......Page 1123
PARAPHILIAS......Page 1124
GENDER IDENTITY DISORDER......Page 1128
REFERENCES......Page 1129
XXIII Eating Disorders......Page 1133
INTRODUCTION......Page 1135
Genetic Models of Anorexia......Page 1136
Physiological Models of Anorexia......Page 1137
The Leptin System......Page 1138
The Tubby Mouse......Page 1139
Quantitative Trait Loci for Obesity......Page 1140
REFERENCES......Page 1141
MONOAMINES......Page 1145
DOPAMINE......Page 1146
SEROTONIN......Page 1147
REFERENCES......Page 1149
Other Peripheral Signals of Energy Homeostasis......Page 1153
Hypothalamic Regulation of Appetite......Page 1154
Anorexia Nervosa......Page 1156
Binge-Eating Disorder......Page 1158
REFERENCES......Page 1159
Leptin Constitutes an Adiposity Signal Inhibiting Long-Term Meal Size......Page 1167
Rewarding and Motivational Aspects of Feeding......Page 1168
Interleukin-1β Acts on the Vagus Nerve to Induce Anorexia......Page 1170
ANOREXIA NERVOSA......Page 1171
CONCLUSION......Page 1172
REFERENCES......Page 1173
LIMITATIONS OF PSYCHOPHYSIOLOGICAL ASSESSMENT IN EATING DISORDERS......Page 1177
REACTIVITY TO FOOD CUES IN STATES OF NORMAL AND ABNORMAL PHYSIOLOGY OR PSYCHOPATHOLOGY......Page 1179
Conclusion......Page 1180
STRESS AND BULIMIA NERVOSA......Page 1181
REFERENCES......Page 1182
NEUROPSYCHOLOGICAL FINDINGS IN FORMER PRISONERS OF WAR AND IN NON-EATING DISORDERED, NORMAL WEIGHT DIETERS......Page 1185
NEUROPSYCHOLOGICAL FINDINGS IN THE ACUTE STATE OF THE EATING DISORDER......Page 1186
Percentage of Patients with Neuropsychological Deficits......Page 1187
Neurochemical Changes......Page 1188
REFERENCES......Page 1189
Eating, Hunger and Satiety......Page 1191
Body Image and Anosognosia......Page 1192
Cognitive Deficit......Page 1193
Disorders of Eating Associated with Brain Lesions......Page 1194
CONCLUSION......Page 1195
REFERENCES......Page 1196
Computed Tomography......Page 1198
Magnetic Resonance Imaging......Page 1199
Single Photon Emission Computed Tomography......Page 1200
Magnetic Resonance Spectroscopy......Page 1201
CONCLUSION......Page 1202
REFERENCES......Page 1203
Twin Studies......Page 1206
Personality and Physical Characteristics......Page 1207
Linkage Studies......Page 1208
REFERENCES......Page 1209
Pharmacotherapy of Bulimia Nervosa......Page 1212
Psychotherapy of Bulimia Nervosa......Page 1213
Pharmacotherapy of Binge-Eating Disorder......Page 1214
Pharmacotherapy of Anorexia Nervosa......Page 1215
Psychotherapy of Anorexia Nervosa......Page 1216
REFERENCES......Page 1217
XXIV Sleep Disorders......Page 1221
Narcoleptic Dogs and Mice......Page 1223
Maternal Food and Alcohol Intake......Page 1224
The Clock Mutation......Page 1225
Light Effects......Page 1226
Acute Stress......Page 1227
REFERENCES......Page 1228
XXIV-2 Neurotransmitter Systems Regulating Sleep-Wake States......Page 1233
Glutamate......Page 1234
Noradrenaline......Page 1235
Dopamine......Page 1236
Serotonin......Page 1237
Corticotrophin-releasing hormone In summary......Page 1238
Growth hormone-releasing hormone (GHRH)......Page 1239
Noradrenaline, serotonin and histamine......Page 1240
In conclusion,......Page 1241
REFERENCES......Page 1242
SLEEP EEG AND SLEEP-ASSOCIATED HORMONE SECRETION IN YOUNG NORMAL HUMAN ADULTS......Page 1247
CHANGES OF SLEEP DURING AGEING......Page 1248
Psychiatric Disorders......Page 1249
Dyssomnias......Page 1253
Sleep-Wake Rhythm Disorders......Page 1254
Disturbed Rhythms due to Environmental Influences......Page 1255
HPA Hormones......Page 1256
HPS System......Page 1258
Oestrogen Replacement Therapy......Page 1259
REFERENCES......Page 1260
INDIGENOUS MICROBIAL FLORA AND CYTOKINE STIMULATION IN THE HEALTHY INDIVIDUAL......Page 1265
CHANGES IN SLEEP DURING ACUTE INFECTIONS OR CHALLENGE WITH MICROBIAL COMPONENTS......Page 1266
SLEEP ALTERATIONS IN CHRONIC INFECTIONS AND CHRONIC INFLAMMATORY STATES......Page 1267
IL1β and TNFα......Page 1268
Prolactin......Page 1270
SLEEP DEPRIVATION AND IMMUNE CONSEQUENCES......Page 1271
REFERENCES......Page 1272
INTRODUCTION......Page 1277
SLEEP PHYSIOLOGY: DESCRIPTIVE ASPECTS......Page 1278
SLEEP COGNITION: DESCRIPTIVE ASPECTS......Page 1281
Dyssomnias......Page 1282
Parasomnias......Page 1283
MENTAL DISORDERS......Page 1284
Mood Disorders......Page 1285
ACKNOWLEDGEMENTS......Page 1286
REFERENCES......Page 1287
PRIMARY INSOMNIA......Page 1293
Cognition......Page 1294
SLEEP APNOEA......Page 1295
Cognition......Page 1296
NARCOLEPSY......Page 1298
REFERENCES......Page 1299
REGULATION OF CIRCADIAN RHYTHMS......Page 1303
HOW IS WAKEFULNESS MAINTAINED?......Page 1304
REM SLEEP: BRAINSTEM MECHANISMS AND LIMBIC/PARALIMBIC ACTIVATION......Page 1305
REFERENCES......Page 1306
Sleep as a Period Favourable to Brain Plasticity......Page 1309
Periodic Leg Movements......Page 1310
REFERENCES......Page 1311
GENETICS OF SLEEP IN NORMAL MAN: TWIN STUDIES......Page 1313
NIGHTMARES, SLEEPWALKING AND SLEEPTALKING......Page 1314
REFERENCES......Page 1315
SLEEP CHANGES ACROSS AGE AND SEX......Page 1317
HORMONAL INFLUENCES: MENSTRUATION, PREGNANCY, LACTATION, AND MENOPAUSE......Page 1319
Pregnancy......Page 1320
Fibromyalgia......Page 1321
Sleep Apnoea......Page 1322
REFERENCES......Page 1323
RELAXATION AND NON-PHARMACOLOGICAL TECHNIQUES......Page 1325
LONG-ACTING COMPOUNDS......Page 1326
BENZODIAZEPINE-LIKE HYPNOTICS......Page 1327
Zolpidem......Page 1328
IMPLICATIONS OF SUBTYPE-SELECTIVE BENZODIAZEPINE RECEPTOR LIGAND HYPNOTICS......Page 1329
CONCLUSIONS......Page 1330
REFERENCES......Page 1331
XXV Psychobiology of Impulse-Control Disorders Not Otherwise Specified (NOS)......Page 1333
Hypothalamus......Page 1334
Amygdala......Page 1335
Prefrontal Cortex......Page 1336
Serotonin Function......Page 1337
Other Neurotransmitter Systems......Page 1338
Endocrine Studies......Page 1339
Pharmacological Challenge Studies......Page 1340
NEUROGENETICS......Page 1341
THERAPEUTIC INTERVENTIONS......Page 1342
REFERENCES......Page 1343
XXVI Personality Disorders......Page 1349
BASIC DIMENSIONS OF PERSONALITY......Page 1351
Gene-Oriented Approach......Page 1352
Behaviour-Oriented Approach......Page 1353
Harm Avoidance......Page 1354
Selection Procedure......Page 1355
PERSONALITY DIMENSION: GLOBAL SURVEY......Page 1356
PERSONALITY DIMENSION: BRAIN, BODY, AND BEHAVIOUR......Page 1357
EPILOGUE......Page 1358
REFERENCES......Page 1359
DIMENSIONAL APPROACHES TO PERSONALITY......Page 1363
Serotonin......Page 1364
Dopamine......Page 1365
GABA (Gamma-Aminobutyric Acid)......Page 1366
REFERENCES......Page 1367
Personality Dimensions......Page 1371
NEUROENDOCRINE MEASUREMENT......Page 1372
ASOCIAL FACTOR......Page 1373
DISCUSSION......Page 1374
REFERENCES......Page 1375
The Skin Conductance Orienting Response (SCOR) and Schizotypal PD......Page 1379
Smooth Pursuit Eye Movement (SPEM) and Schizotypal PD......Page 1380
HR Studies and Antisocial Behaviour......Page 1381
SC Studies and Antisocial Behaviour......Page 1382
Psychophysiological Study of Borderline PD......Page 1383
Psychophysiological Studies of Avoidant PD......Page 1384
Psychophysiological Studies of Type A Personality......Page 1385
REFERENCES......Page 1386
General Findings......Page 1389
General Findings......Page 1392
REFERENCES......Page 1393
XXVI-6 Functional Neuroanatomy and Brain Imaging of Personality and its Disorders......Page 1395
TEMPERAMENT AND SUBDIVISIONS OF THE LIMBIC SYSTEM......Page 1396
THE SEPTAL SUBDIVISION AND HARM AVOIDANCE......Page 1397
THE THALAMO-CINGULATE SUBDIVISION AND REWARD DEPENDENCE......Page 1398
THE STRIATO-THALAMIC SUBDIVISION AND PERSISTENCE......Page 1399
HIGHER COGNITIVE FUNCTIONS OF FRONTAL CORTEX......Page 1400
CONCLUSIONS......Page 1401
REFERENCES......Page 1402
PERSONALITY DISORDERS— A DIAGNOSTIC DILEMMA......Page 1405
TOWARDS GENETIC DISSECTION OF PDs......Page 1406
Serotonergic Gene Pathway......Page 1407
Dopaminergic Gene Pathway......Page 1412
Monoamine Metabolic Gene Pathway......Page 1417
Miscellaneous Genes......Page 1418
GENE–ENVIRONMENT INTERACTION......Page 1419
CONCLUSIONS......Page 1421
REFERENCES......Page 1422
CATEGORICAL AND DIMENSIONAL MODELS OF PERSONALITY DISORDERS......Page 1431
ENVIRONMENTAL FACTORS IN PERSONALITY......Page 1432
INTERACTIONS BETWEEN RISK FACTORS FOR PERSONALITY DISORDERS......Page 1433
REFERENCES......Page 1434
XXVI-9 The Psychopharmacological Treatment of Personality Disorders Royce Lee and Emil Coccaro INTRODUCTION This chapter will present available evidence on the psychopharma-cological treatment of personality disorders. Clinical and theoretical implications of axis I/II and Axis II/II comorbidity in the treatment of patients with personality disorders will be discussed. Biological correlates of some of the major symptoms of personality disorders will provide the rationale for a review of the evidence for psy-chopharmacological treatment of personality disorders. These will be presented by medication class to facilitate an understanding of the evidence for the efficacy of these treatments. PERSONALITY DISORDERS IN THE CLINICAL SETTING The estimated prevalence of personality disorders in the commu-nity is approximately 6–11% (Samuels et al., 1994; Reich et al., 1989), with Cluster B personality disorders being the most com-mon (4–5.4%), followed by cluster C (1.7–3.4%) and Cluster A (<0.1%). Evidence suggests that many personality-disordered peo-ple in the community who could benefit from treatment do not receive it. This holds true in clinical settings, where personality disorders, in general, are underdiagnosed (Zimmerman and Mattia, 1999). Paradoxically, personality disorders may be disproportionately represented in outpatient and inpatient treatment settings (Zimmer-man and Coryell, 1989). This may be due to the significant mor-bidity associated with them. Personality-disordered patients tend to function at lower levels than those without such disorders (Mehlum et al., 1991), report more frequent adverse events in their lives (Maier et al., 1992), and have elevated rates of divorce, substance abuse, and suicide (Zimmerman and Coryell, 1989). This is the case despite relatively heavy use of clinical services by some, but not all, persons with Axis II diagnoses. A recent study of treatment uti-lization by patients with personality disorder found that those with borderline personality disorder, compared to depressives, were more likely to have received every class of psychopharmacological med-ication, from twice as many trials of antidepressants to 10 times as many trials of antipsychotic medications. They had also received more psychosocial treatments than the depressive comparison group with the exception of family/couples therapy and self-help groups (Bender et al., 2001). These results were consistent with earlier reports in persons diagnosed with borderline personality disorder (BPD) of more frequent hospitalization, a 20% lifetime incidence of suicide attempt (McGlashan et al., 1986), and extensive use of outpatient mental health services (Perry and Cooper, 1985; Skodol et al., 1983). Patients with personality disorders may also be more difficult to treat than most patients, with less treatment compliance (Bender et al., 2001), less favourable Axis I treatment outcomes (Reich et al., 1991), and more frequently aborted treatments. In research settings, it is not uncommon for up to two-thirds or more of personality-disordered subjects to drop out of treatment stud-ies (Skodol et al., 1983), a finding which mirrors clinical reports of their intensive but intermittent contact with outpatient services (McGlashan et al., 1986). COMORBIDITY IN PERSONALITY DISORDERS Comorbidity in personality disorders may represent the random co-occurrence of independent disorders, co-occurrence of different disorders sharing a common aetiology or pathophysiology, or differ-ent disorders that have a causal relation between them (McGlashan et al., 2000). The frequency of Axis II/Axis II comorbidity may be in part due to the fact that psychiatric nosology since DSM-III has favoured a trend towards more frequent comorbidity through the use of operationalized criteria, structured diagnostic interviews, and less stringent exclusionary rules. In some cases as well, Axis I/II and Axis II/II comorbidity could reflect the limitations of categorical diagnoses in characterizing the behavioural dimensions, that may underlie them. Clinically, the possibility of the existence of comorbid conditions in the personality-disordered patient must be carefully evaluated for the following reasons: 1. to identify other conditions with relatively well-defined treat-ments— for example, the presence of a medical disorder, mood disorder, or anxiety disorder 2. to identify other conditions whose symptoms may be aggravated by proposed treatments— for example, the presence of bipolar I disorder in a patient considering the trial of an antidepressant 3. to identify disorders whose symptoms may account for the set of behaviours in questions, including such disorders as post-traumatic stress disorder (PTSD) or social anxiety disorder 4. to identify conditions whose course may be complicated by the presence of a personality disorder, such as refractory depression 5. because comorbidity may be markedly more frequent in clinical settings than community settings, as shown by comparisons between the two (Samuels et al., 1994), possibly due to the selection for treatment of patients with more than one disorder and more functional impairment. CLUSTER A Schizotypal personality disorder is the most commonly encountered Cluster A personality disorder in clinical settings. It frequently Biological Psychiatry: Edited by H. D’haenen, J.A. den Boer and P. Willner. ISBN 0-471-49198-5  2002 John Wiley & Sons, Ltd.......Page 1437
INDEX......Page 1448