PET and SPECT in Psychiatry

Description

PET and SPECT in Psychiatry showcases the combined expertise of renowned authors whose dedication to the investigation of psychiatric disease through nuclear medicine technology has achieved international recognition. The classical psychiatric disorders as well as other subjects – such as suicide, sleep, eating disorders, and autism – are discussed and the latest results in functional neuroimaging are detailed. Most chapters are written jointly by a clinical psychiatrist and a nuclear medicine expert to ensure a multidisciplinary approach. This state of the art compendium will be valuable to all who have an interest in the field of neuroscience, from the psychiatrist and the radiologist/nuclear medicine specialist to the interested general practitioner and cognitive psychologist. It is the first volume of a trilogy on PET and SPECT imaging in the neurosciences; other volumes will focus on PET and SPECT in neurology and PET and SPECT of neurobiological systems. Foreword Preface Contents Contributors Part I: Basics 1: Neuroimaging in Psychiatric Drug Development and Radioligand Development for New Targets 1.1 Introduction 1.2 PET Application for Drug Development 1.2.1 PET Microdosing for Pharmacokinetic Evaluation 1.2.2 PET Receptor Occupancy to Demonstrate Target Engagement and in Relation to Pharmacodynamics 1.2.3 Pathophysiology Biomarkers for Diagnosis or Efficacy Studies 1.3 Radioligand Development: Targeting Neurology and Psychiatry References 2: PET Quantification in Neuropsychiatry 2.1 Introduction 2.2 Dynamic PET Quantification 2.3 Compartmental Modeling of Brain Perfusion 2.4 One-Tissue Compartmental Model 2.5 Two- and Three-Tissue Compartment Model 2.6 Model Selection 2.7 Graphical Analysis Methods 2.8 Input Functions 2.9 Steady-State PET Measurements Using a Bolus/Constant Infusion References 3: Pharmacological Interventions That Have the Potential to Alter Neurotransmitter Levels in the Human Brain 3.1 Introduction 3.2 History of Microdialysis 3.3 Methodology of Microdialysis 3.4 Pharmacological Interventions for Serotonin 3.4.1 Manipulation of Extracellular Serotonin Levels Through Synthesis and Reuptake Inhibition 3.4.2 Manipulation of Extracellular Serotonin Levels Through Synthesis, Reuptake Inhibition, and Receptors Involved in the Regulation of Release and/or Synthesis 3.4.3 Manipulation of Extracellular Serotonin Levels with Releasing Agents 3.4.4 Manipulation of Extracellular Serotonin Levels Through Interaction with the Noradrenergic System 3.4.5 Manipulation of Extracellular Serotonin Levels Through Interaction with the GABA-A System 3.5 Discussion 3.5.1 General Translational Aspects 3.5.2 Specific Translational Aspects Related to Microdialysis Conclusion References 4: The Role of P-Glycoprotein in Psychiatric Disorders and in Psychiatric Treatment 4.1 Introduction 4.2 Components of the BBB 4.2.1 Endothelial Cells 4.2.2 Tight Junctions 4.2.3 Astrocytes, Microglia and Pericytes 4.2.4 Neurons 4.3 Transport Across the BBB 4.3.1 Carrier-Mediated Transport 4.3.2 Receptor-Mediated Transport 4.3.3 Efflux Transport 4.4 Localisation and Function of P-gp 4.5 In Vivo Imaging of P-gp at the BBB 4.6 Relevance of P-gp in Relation to Antidepressants, Mood Stabilisers and Antipsychotics 4.7 Modulation of P-gp at the BBB by Stress (In Vitro Studies) 4.8 Depressive Disorder, Stress-Related Disorders and P-gp 4.9 The Role of Ageing and Neurodegeneration in P-gp Functionality 4.10 Polymorphisms of P-gp and Their Effect on Function 4.11 Non-P-gp-Mediated Efflux Transport at the BBB 4.12 Concluding Remarks and Future Directions References Part II: Depression and Related Disorders 5: Molecular Imaging of Depressive Disorders 5.1 Introduction 5.2 Metabolism and Cerebral Blood Flow 5.3 Imaging of Monoamine Systems 5.3.1 Serotonin 5.3.1.1 Serotonin Synthesis 5.3.1.2 Serotonin Transporter (SERT) Imaging Unipolar Depression Bipolar Depression SERT Availability in Unipolar and Bipolar Depression SERT Occupancy During Antidepressant Treatment 5.3.1.3 Serotonin Receptor Imaging 5-HT 1A 5-HT 1B 5-HT 2A 5.3.2 Dopamine 5.3.2.1 Dopamine Synthesis 5.3.2.2 Dopamine Transporter Imaging MDD Patients Versus Controls BD Patients Versus Controls DAT Imaging in Healthy Controls and Its Association with Mood DAT Imaging in Other Neuropsychiatric Disorders and Its Association with Depression Presynaptic Markers and Treatment 5.3.2.3 Postsynaptic Imaging Dopamine Receptor Imaging MDD Patients Versus Controls BD Patients Versus Controls Dopamine Receptor Imaging in Other Neuropsychiatric Disorders and Its Association with Depression Dopamine Receptor Markers and Treatment General Remarks Related to Dopaminergic Receptor Imaging in Unipolar and Bipolar Depression 5.3.3 Monoamine Oxidase Imaging 5.3.4 Monoamine Depletion Imaging 5.3.4.1 ATD 5.3.4.2 AMPT 5.3.4.3 Depletion and Depressive Episodes 5.4 New Perspectives 5.4.1 Radioligand Development for Imaging Serotonergic Neurotransmission 5.4.2 Imaging of Other Neurotransmitter Systems 5.4.3 Imaging Inflammation and Depression 5.4.4 Imaging the Blood–Brain Barrier 5.4.5 Multimodal (Molecular) Imaging 5.5 Discussion and Conclusions References 6: Functional Brain Imaging of Suicidal Behavior 6.1 Introduction 6.2 Methods 6.3 Results/Review of the Literature 6.3.1 PET Studies 6.3.2 SPECT Studies 6.4 Discussion Conclusion References 7: SPECT and PET in Late-Life Depression 7.1 The Concept of Late-Life Depression 7.1.1 Prevalence and Burden of Late-Life Depression 7.1.2 Late-Onset Depressive Disorder 7.2 Neuroimaging Findings 7.2.1 Imaging of Cerebral Blood Flow 7.2.2 Imaging of Cerebral Glucose Metabolism 7.2.3 Imaging of Cerebral Neurotransmitter Systems and of Cerebral Protein Deposition Conclusion References 8: Neuroimaging in Seasons and Winter Depression 8.1 Introduction 8.2 Structural and Functional Magnetic Resonance Imaging 8.2.1 Structural MRI Studies 8.2.2 Functional MRI (fMRI) Studies 8.3 Single Photon Emission Computed Tomography (SPECT) 8.4 Positron Emission Tomography (PET) 8.5 Summary References 9: Bipolar Disorders 9.1 Introduction 9.2 PET/SPECT 9.2.1 General Information 9.2.2 Cerebral Blood Flow and Cerebral Metabolism 9.2.2.1 Prefrontal Cortex 9.2.2.2 Limbic System and Subcortical Structures 9.2.2.3 Other Cortical Regions 9.2.2.4 Corticolimbic Theory of Mood Disorders 9.2.3 Neurotransmitter Studies 9.2.3.1 Serotonin 9.2.3.2 Dopamine 9.2.3.3 Choline 9.3 Other Pathophysiological Models 9.3.1 Neuroinflammation 9.3.2 White Matter Tract Integrity Disruption 9.3.3 Mitochondrial Dysfunction Conclusion References 10: PET and SPECT in Psychiatric Complications of Parkinson’s Disease 10.1 Introduction 10.2 Depression in Parkinson’s Disease 10.2.1 Dopamine and Depression in Parkinson’s Disease 10.2.2 Serotonin and Depression in Parkinson’s Disease 10.2.3 Glucose Metabolism and Cerebral Blood Flow in Parkinson’s Disease Depression 10.3 Psychosis in Parkinson’s Disease 10.4 Impulse Control Disorders in Parkinson’s Disease 10.4.1 Dopaminergic Tracers 10.4.2 Other Tracers 10.5 Personality Changes in Parkinson’s Disease Conclusions References 11: Psychiatric Disorders in Dementia 11.1 Dementia: Definition and Epidemiology 11.1.1 Definition 11.1.2 Prevalence and Incidence 11.1.3 Alzheimer’s Disease (AD) and Specific Dementia Syndromes 11.1.3.1 Alzheimer’s Disease (AD) Diagnosis Pathophysiological Mechanisms 11.1.3.2 Other Dementia Subtypes Dementia with Lewy Bodies (DLB) Frontotemporal Dementia (FTD) 11.2 Behavioral and Psychological Signs and Symptoms of Dementia (BPSD) 11.2.1 Delusional Ideation and Hallucinations: The Psychotic Syndrome 11.2.2 Agitation and Aggression 11.2.3 Diurnal Rhythm Disturbances 11.2.4 Depression 11.2.5 Activity Disturbances 11.2.6 Anxieties and Phobias 11.2.7 Apathy 11.3 Behavioral Assessment Scales 11.3.1 Middelheim Frontality Score (MFS) 11.3.2 Behavioral Pathology in Alzheimer’s Disease Rating Scale (Behave-AD) 11.3.3 Cohen-Mansfield Agitation Inventory (CMAI) 11.3.4 Geriatric Depression Scale (GDS) 11.3.5 Cornell Scale for Depression in Dementia (CSDD) 11.3.6 Neuropsychiatric Inventory (NPI) 11.4 PET in the Differential Diagnosis of Dementia 11.4.1 Radioligands and Compounds 11.5 PET Imaging in Neuropsychiatric Disturbances of Dementia 11.5.1 Alzheimer’s Disease 11.5.1.1 Depression and Apathy 11.5.1.2 Psychosis 11.5.1.3 Other Behavioral Syndromes 11.5.2 Other Dementia Subtypes 11.6 SPECT in the Differential Diagnosis of Dementia 11.6.1 99m Tc-HMPAO-SPECT 11.6.2 [ 123 I]-IMP-SPECT 11.6.3 SPECT Imaging with Cholinergic and Monoaminergic Radioligands 11.6.4 SPECT Imaging of Neuroinflammation 11.6.5 SPECT-Tracers Imaging Aβ-Plaques 11.7 SPECT Imaging in Neuropsychiatric Disturbances of Dementia 11.7.1 Alzheimer’s Disease 11.7.1.1 Depression 11.7.1.2 Apathy 11.7.1.3 Psychosis 11.7.1.4 Activity Disturbances 11.7.1.5 Aggression 11.7.1.6 Sleep Disorders 11.7.2 Other Dementia Subtypes 11.8 Concluding Remarks References 12: Imaging of the Antidepressant Drug Response Using SPECT and PET 12.1 Introduction 12.2 SPECT and PET Imaging in Psychiatric Disorders 12.3 SPECT and PET Imaging in Depression 12.3.1 SPECT and PET Imaging of Dopamine Receptors 12.3.2 SPECT and PET Imaging of Dopamine Transporters 12.3.3 SPECT and PET Imaging of Serotonin Receptors 12.3.4 SPECT and PET Imaging of Serotonin Transporters 12.4 SPECT and PET Imaging of the Antidepressant Drug Response 12.4.1 Levodopa and Selegiline 12.4.2 Moclobemide and St. John’s Wort 12.4.3 The SSRIs 12.4.3.1 Citalopram 12.4.3.2 Escitalopram 12.4.3.3 Fluoxetine 12.4.3.4 Paroxetine 12.4.3.5 Fluvoxamine 12.4.4 The NDRIs and SNRIs 12.4.4.1 Bupropion 12.4.4.2 Venlafaxine 12.4.5 The TCAs 12.4.5.1 Nortriptyline and Sertraline 12.4.5.2 Amitriptyline 12.4.5.3 Desipramine 12.5 SPECT and PET Imaging of the Blood–brain Barrier in Depression and the Antidepressant Response 12.6 SPECT and PET Imaging of Monoamine Precursors, LAT Transport and the Antidepressant Response 12.7 Discussion Conclusion References Part III: Anxiety Disorders 13: Neurotransmission: A Review of PET and SPECT Studies in Anxiety Disorders 13.1 Anxiety, Genes and Environment 13.1.1 Anxiety Aetiology 13.2 Anxiety and Brain Imaging 13.2.1 Meta-analysis and Anxiety Neuroimaging 13.2.2 Anxiety, Symptom Provocation and the Fear Network 13.2.3 Anxiety and Neurotransmission 13.2.4 Anxiety Treatment and Brain Function 13.3 Multiple Mechanisms Mediating Anxiety References 14: Neurobiology of Posttraumatic Stress Disorder: The Role of Nuclear Neuroimaging 14.1 Introduction 14.2 A Neurobiological Model of PTSD 14.3 Neurochemistry of PTSD 14.3.1 Serotonergic System 14.3.2 Noradrenergic System 14.3.3 Gamma-Aminobutyric Acid (GABA) System 14.3.4 Opioid System 14.3.5 Dopaminergic System 14.3.6 Nicotinic System 14.3.7 Hypothalamic-Pituitary-Adrenal (HPA) Axis Conclusion References 15: Neuroimaging in PTSD-Related Psychotherapies 15.1 Introduction 15.2 Neuroimaging in PTSD Psychotherapies 15.3 General Discussion Conclusions References 16: Dissociative Identity Disorder and Fantasy Proneness: A Positron Emission Tomography Study of Authentic and Enacted Dissociative Identity States 16.1 Introduction 16.1.1 Brain Imaging Studies in DID 16.1.2 DID and Fantasy Proneness 16.2 Methods 16.2.1 Participants 16.2.2 Image Acquisition and Data Processing Intermezzo: The Study’s General Linear Model 16.2.3 Statistical Inference and Reporting 16.3 Results 16.3.1 Comparing Simulated and Pathological Identity States 16.3.1.1 Within-Identity State Trauma-Related Memory Script Effects 16.3.1.2 Between-Identity State Trauma-Related Memory Script Effects 16.4 Discussion References 17: OCD: Serotonergic Mechanisms 17.1 Overview 17.1.1 Hypothesized Braking System Model of OCD 17.2 Neurobiology 17.2.1 Brain Circuits 17.2.2 Neurochemistry 17.2.2.1 Serotonin 17.2.2.2 Dopamine 17.3 Dimensions vs Category 17.3.1 α-[ 11 C]MTrp 17.3.2 Baseline Measurements of Serotonin Synthesis in OCD 17.3.3 The Effects of Treatment on Serotonin Synthesis in OCD 17.4 Concluding Remarks References Part IV: Psychosis and Cognitive Disorders 18: Molecular Imaging in Schizophrenia Spectrum Disorders 18.1 The Disease 18.2 The Hypotheses 18.3 Human Imaging Studies 18.4 Small-Animal Studies References 19: Neuroimaging of Delirium 19.1 Introduction 19.2 Neuroimaging 19.2.1 Feasibility 19.2.2 CT 19.2.3 MRI: Structural Imaging 19.2.4 MRI: Functional Imaging 19.2.5 SPECT 19.3 Methodological Issues and Recommendations for Future Investigations Conclusion References 20: PET and SPECT Findings in Patients with Hallucinations 20.1 Introduction 20.2 Brain Activity in Patients Prone to Hallucinations 20.3 Brain Activity During Hallucinations 20.4 Case Reports 20.5 Brain Activity During Performance of Cognitive Tasks 20.6 Neurochemistry Underlying Hallucinations 20.7 Discussion References Part V: Impulse Control and Related Disorders 21: PET and SPECT in Personality Disorders 21.1 Introduction 21.2 Borderline Personality Disorder (BPD) 21.3 Schizotypal Personality Disorder (SPD) 21.4 Antisocial Personality Disorder (ASPD) References 22: Molecular Imaging Studies in Stimulant Addiction: A Cross-Species Perspective 22.1 Introduction 22.2 SPECT/PET Studies in Addiction 22.2.1 Studies in Animals 22.2.2 Studies in Humans 22.3 PET/SPECT Studies in ADHD 22.3.1 Studies in Animals 22.3.2 Studies in Humans 22.4 Conclusions and Future Perspectives References 23: Abnormalities in Reward Processing in Drug Addiction: Lessons from Neuropsychology and Neuroimaging Studies 23.1 Short Account of the Phenomenology and Neurobiology of Drug Addiction 23.2 Behavioral Evidence Suggesting Enhanced Processing of Drug as Compared to Nondrug Cues 23.2.1 Subjective Self-Reports 23.2.2 Objective Choice Behavior 23.2.3 Cognitive Processes 23.3 Use of Money in Neuroimaging Studies in Drug- 23.4 Other Nonmonetary Reward 23.5 The Underlying Mechanism for a Possible Reward Value Shift in Drug Addiction 23.6 Conflicting Results 23.7 Summary and Conclusions 23.8 Future Directions References 24: SPECT and PET in Eating Disorders 24.1 Introduction 24.2 Anorexia and Brain Perfusion 24.3 Bulimia and Brain Perfusion 24.4 Anorexia and Cerebral Metabolism of Glucose 24.5 Bulimia and Cerebral Metabolism of Glucose 24.6 Alterations of the Serotonergic System in Eating Disorders 24.7 Alterations of Other Neurotransmitter Systems in Eating Disorders Conclusion References 25: Impulsivity Imaging 25.1 Overview 25.1.1 Introduction/Definition 25.1.2 Why Is the Study of Impulsivity Important? 25.1.3 How Is Impulsivity Currently Diagnosed or Measured? 25.1.4 What Is the Pathophysiology of Impulsivity? 25.1.5 The Role of Functional Imaging 25.1.6 How Can We Image Impulsivity? 25.1.6.1 Dopaminergic Neurotransmission 25.1.6.2 Serotonergic Neurotransmission 25.1.6.3 Noradrenergic Neurotransmission 25.1.6.4 The Potential Role of PET and SPECT in Evaluating Response to Treatment, Prognosis and Drug Development 25.2 Clinical Applications 25.2.1 Neurology 25.2.1.1 Attention Deficit Hyperactivity Disorder (ADHD) 25.2.1.2 Pathophysiological Changes 25.2.1.3 Additional Studies Involving SPECT and PET Imaging 25.2.1.4 Promising Future Roles of SPECT and PET Treatment and Response Evaluation in ADHD Genetics Imaging 25.2.1.5 Parkinson’s Disease (PD) Functional Imaging with SPECT and PET Treatment of Impulsive Disorders in Parkinson’s Disease 25.2.2 Psychiatry 25.2.2.1 Cluster B Personality Disorders and Bipolar Disorder Diagnosis Pathophysiology Neuroimaging Anatomical Imaging Functional Imaging Studies Involving Imaging with SPECT Studies Involving Imaging with PET 25.2.2.2 Substance Abuse Conclusion References 26: Brain SPECT in the Impulsive-Aggressive Dog 26.1 History of Behavioural Brain Research in Animal Models 26.2 Studies on Canine Brain Pathophysiology 26.2.1 SPECT of the Impulsive-Aggressive Dog 26.2.2 5-HT 2A -Receptor Imaging as a Biomarker in Canine Behavioural Research 26.3 Selective Serotonin Reuptake Inhibitors in the Treatment of Impulsive-Aggressive Behaviour in Dogs 26.4 Confounding Factors in Canine Functional Brain Imaging Studies 26.4.1 Anaesthesia 26.4.2 Resolution Limits Conclusion References 27: Obesity an Addiction? Imaging of Neurotransmitter Systems in Obesity 27.1 Introduction 27.2 Imaging Findings on Neurotransmitter Systems in Obesity 27.2.1 The Dopaminergic System 27.2.2 The Serotonergic System 27.3 Discussion 27.3.1 Discussion of Findings on the Dopaminergic System 27.3.2 Discussion of Findings on the Serotonergic System 27.3.3 Conclusion References 28: Neuroimaging Studies of Psychopathy 28.1 Neuroimaging Data on Psychopathy: Summary of Results 28.2 Methodological Issues 28.2.1 Two Different Uses of the Term “Psychopathy” 28.2.2 Inconsistent Criteria for Identifying Psychopaths 28.2.3 Consideration of Psychopathic Subtypes Conclusion References 29: Neurobiology of Aggression: Neuroimaging Findings 29.1 Introduction 29.2 Neurobiology of Aggression 29.2.1 Genetics of Aggression 29.2.2 Brain Function 29.2.3 Structural Imaging 29.2.4 PET/SPECT Findings 29.2.5 Serotonin and Dopamine in Aggression 29.3 Aggression in Schizophrenia 29.3.1 Neuroimaging Studies 29.3.1.1 MRI Studies 29.3.1.2 SPECT and PET Studies Conclusion Literature Part VI: Miscellaneous Subjects 30: Application of PET and SPECT to the Study of Autism Spectrum Disorders 30.1 Focal and Global Brain Alterations in Glucose Metabolism 30.1.1 Increased Global Brain Glucose Metabolism in Autism 30.1.2 Regional Brain Glucose Metabolism Alterations in Autism and Related Disorders 30.1.2.1 Brain Glucose Metabolism in Autism 30.1.2.2 Glucose Metabolism in Autism and Infantile Spasms 30.1.2.3 Glucose Metabolism and Tryptophan Metabolism in Children with Autism and Tuberous Sclerosis 30.2 Focal and Global Brain alterations Cerebral Blood Flow 30.2.1 Resting Cerebral Blood Flow 30.2.2 Blood Flow Changes During the Performance of Tasks 30.3 Protein Synthesis in Pervasive Developmental Disorder 30.4 Studies of Neurotransmitter Function with PET and SPECT in Autism 30.4.1 Dopamine Precursor and Transporter Studies 30.4.2 Serotonin Precursor, Transporter, and Receptor Studies 30.4.3 GABA A Receptor Binding Studies 30.4.4 Acetylcholine 30.5 Conclusions and Future Directions References 31: PET and SPECT Imaging in ADHD 31.1 Introduction 31.2 Aetiology 31.3 Neuroanatomy 31.4 Structural Imaging 31.5 Functional Imaging: Cerebral Blood Flow and Glucose Metabolism 31.6 Task-Related Functional Imaging 31.7 Response to Pharmacological Treatment 31.8 Neurotransmitter Systems 31.9 Dopaminergic System 31.10 Noradrenergic System 31.11 Serotonergic System 31.12 Linkage Between Neurotransmitter Systems and Genotypes 31.12.1 Correlation with Clinical Symptoms 31.13 Conclusions 31.14 Limitations References 32: SPECT and PET Imaging of Apathy 32.1 What Is Apathy? 32.2 What Is Known About Its Anatomical Bases? 32.3 How Does Apathy Reflect on Molecular Imaging? 32.3.1 SPECT Studies 32.3.2 PET Studies Conclusion References 33: PET and SPECT Studies in the Chronic Fatigue Syndrome/Myalgic Encephalomyelitis 33.1 Introduction 33.1.1 What Is Chronic Fatigue Syndrome? 33.1.2 Classification of Chronic Fatigue Syndrome/ Myalgic Encephalomyelitis 33.1.3 Nuclear Medicine Studies in CFS/ME 33.2 SPECT Studies in Patients with CFS/ME 33.2.1 99m Tc-HMPAO 33.2.2 123 I-IMP 33.2.3 201 Thallium 33.3 PET Studies in Patients with CFS/ME 33.3.1 18 F-FDG 33.3.2 Serotonin Tracers 33.4 Discussion and Conclusions 33.5 Future Perspectives References 34: PET and SPECT in Sleep Disorders 34.1 Introduction 34.2 Narcolepsy 34.2.1 Acetylcholine, Serotonin, and Dopamine Functions in Narcolepsy 34.2.2 Brain Glucose Metabolism and Perfusion in Narcoleptic Individuals 34.2.3 Neural Correlates of Cataplexy 34.2.4 Pharmacological Treatment of Narcolepsy 34.2.4.1 Methylphenidate 34.2.4.2 Modafinil 34.2.5 Summary 34.3 Restless Legs Syndrome and Periodic Limb Movements 34.3.1 Restless Legs Syndrome 34.3.2 Periodic Limb Movements 34.3.3 Summary 34.4 Parasomnias 34.4.1 Sleepwalking 34.4.2 REM Sleep Behavior Disorder 34.4.3 Summary 34.5 Insomnia 34.5.1 Idiopathic Insomnia 34.5.2 Fatal Familial Insomnia 34.5.3 Neuroimaging of Sleep in Depression 34.5.4 Summary 34.6 General Conclusions References 35: PET and SPECT Imaging of Non-pharmacological Interventions for Psychiatric Disorders 35.1 Introduction 35.2 Neuroimaging Findings in Depression and Obsessive–Compulsive Disorder 35.3 PET and SPECT in Electrical Neurostimulation 35.3.1 Deep Brain Stimulation 35.3.2 Vagus Nerve Stimulation 35.3.3 Transcranial Magnetic Stimulation 35.3.3.1 Dorsolateral Prefrontal Cortex as a Target of rTMS Stimulation in Depression 35.3.3.2 Neuronavigated rTMS 35.3.3.3 Pretreatment rCBF as an rTMS Response Predictor 35.3.3.4 TMS and Imaging of Dopamine Activity 35.3.3.5 TMS in Schizophrenia 35.3.4 Electroconvulsive Therapy 35.3.4.1 Glucose Metabolism Changes in ECT 35.3.4.2 Long-Term Effect of ECT 35.3.4.3 Serotonin and Dopamine Changes in ECT 35.4 Cognitive Behavior Therapy 35.4.1 Imaging of Cognitive Behavior Therapy in Obsessive–Compulsive Disorder 35.4.2 Imaging of Cognitive Behavior Therapy in Depression 35.4.3 Dopamine and Serotonin Changes After Cognitive Behavior Therapy 35.5 Lesioning Procedures 35.5.1 Anterior Cingulotomy 35.5.2 Subcaudate Tractotomy 35.5.3 Limbic Leucotomy 35.5.4 Anterior Capsulotomy Conclusions References The Editors Reviewers Anthology of Apologies Index