PET AND SPECT IN PSYCHIATRY

Foreword
References
Preface
Contents
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 in Relation to Pharmacodynamics
			1.2.3	 Pathophysiology Biomarkers for Diagnosis or Efficacy Studies
		1.3	 Radioligand Development: Targeting Neurology and Psychiatry
		References
	2: Brain PET Quantification in Neuropsychiatric Research
		2.1	 Introduction
			2.1.1	 Types of Tracers Used in Psychiatry
		2.2	 Quantitative PET Imaging
			2.2.1	 Dynamic PET Quantification
			2.2.2	 Input Functions
			2.2.3	 Compartmental Analysis and Model Selections
				2.2.3.1	 One-Tissue Compartmental Model (1TCM)
				2.2.3.2	 Two- and Three-Tissue Compartment Model (2TCM and 3TCM)
				2.2.3.3	 Reference Regions
				2.2.3.4	 Model Selections
			2.2.4	 Graphical Analysis Methods
			2.2.5	 Semiquantitative Methods
			2.2.6	 Neurotransmission Quantification
		2.3	 News in Neuropsychiatric Research Using Hybrid PET/MRI
		References
	3: The Role of P-Glycoprotein at the Blood–Brain Barrier in Neurological and Psychiatric Disease
		3.1	 Introduction
		3.2	 Architecture of the BBB
			3.2.1	 Endothelial Cells
			3.2.2	 Tight Junctions
			3.2.3	 Pericytes
			3.2.4	 Astrocytes
			3.2.5	 Microglia
			3.2.6	 Neurons
			3.2.7	 Neurovascular Unit
		3.3	 Transport across the BBB
			3.3.1	 Carrier-Mediated Transport
			3.3.2	 Receptor-Mediated Transport
			3.3.3	 Active Efflux Transporters
			3.3.4	 Cerebrovascular Enzymatic Characteristics of the BBB
		3.4	 P-Glycoprotein
			3.4.1	 Localization and Function of P-gp
			3.4.2	 Avid and Weak Substrates of P-gp
			3.4.3	 Inhibitors of P-gp
			3.4.4	 Inducers, Activators and Regulation of P-gp
			3.4.5	 Non-P-gp-Mediated Efflux Transport at the BBB
			3.4.6	 BCRP
			3.4.7	 MRP Family and MRP-1
		3.5	 In Vivo Imaging of the P-gp Function
			3.5.1	 [94mTC]Sestamibi
			3.5.2	 [11C]Verapamil and (R)-[11C]Verapamil
			3.5.3	 [18F]MC225
			3.5.4	 [11C]Loperamide and [11C]N-Desmethyl-Loperamide
			3.5.5	 [18F]Paclitaxel and [18F]Fluoro-Paclitaxel
			3.5.6	 [11C]Laniquidar
			3.5.7	 [11C]Tariquidar
			3.5.8	 [11C]Phenytoin
			3.5.9	 [11C]Metoclopramide
		3.6	 Pharmacokinetic Modelling of P-gp PET Tracers
		3.7	 Drug Resistance and Drug–Drug Interactions
			3.7.1	 Polymorphisms and Genotyping
			3.7.2	 Intestinal P-gp Expression
		3.8	 P-gp in Psychiatric Diseases
			3.8.1	 Depressive Disorder and Antidepressants
			3.8.2	 Schizophrenia and Antipsychotics
			3.8.3	 The Hypothalamic–Pituitary–Adrenocortical (HPA) Axis and P-gp
		3.9	 The Role of Ageing and Neurodegeneration in P-gp Functionality
			3.9.1	 Alzheimer’s Disease and the Function of P-gp
			3.9.2	 Gut–Brain Axis and P-gp
		3.10	 Concluding Remarks and Future Directions
		References
Part II: Depression and Related Disorders
	4: Molecular Imaging of Depressive Disorders
		4.1	 Introduction
		4.2	 Metabolism and Cerebral Blood Flow
		4.3	 Imaging of Monoamine Systems
			4.3.1	 Serotonin
				4.3.1.1	 Serotonin Synthesis
				4.3.1.2	 Serotonin Transporter (SERT) Imaging
					Unipolar Depression
					Bipolar Depression
					SERT Availability in Unipolar and Bipolar Depression
					SERT Occupancy During Antidepressant Treatment
				4.3.1.3	 Serotonin Receptor Imaging
					5-HT1A
					5-HT1B
					5-HT2A
			4.3.2	 Dopamine
				4.3.2.1	 Dopamine Synthesis
				4.3.2.2	 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
				4.3.2.3	 Postsynaptic 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
			4.3.3	 Monoamine Oxidase Imaging
			4.3.4	 Monoamine Depletion Imaging
				4.3.4.1	 Acute Tryptophan Depletion (ATD)
				4.3.4.2	 AMPT
				4.3.4.3	 Depletion and Depressive Episodes
		4.4	 New Perspectives
			4.4.1	 Ongoing Radioligand Development for Imaging Serotonergic Neurotransmission
			4.4.2	 Imaging of the Norepinephrine System
			4.4.3	 Radioligands for Glutamate Targets
			4.4.4	 Imaging of the Central Opioid System
			4.4.5	 Imaging Inflammation and Depression
			4.4.6	 Imaging of Other Neurotransmitter Systems and Neuropeptides
			4.4.7	 Imaging the Blood–Brain Barrier
			4.4.8	 Imaging Synaptic Density
			4.4.9	 Multimodal (Molecular) Imaging
		4.5	 Discussion and Conclusions
		References
	5: SPECT and PET in Late-Life Depression
		5.1	 The Concept of Late-Life Depression
			5.1.1	 Prevalence and Burden of LLD
			5.1.2	 Late-Onset Depressive Disorder
		5.2	 Neuroimaging Findings
			5.2.1	 Imaging of Cerebral Blood Flow
			5.2.2	 Imaging of Cerebral Glucose Metabolism
			5.2.3	 Imaging of Cerebral Neurotransmitter Systems and of Cerebral Protein Deposition
			5.2.4	 Imaging of Metabotropic Glutamate Receptors and of Neuroinflammation
		5.3	 Conclusion
		References
	6: Neuroimaging in Seasons and Winter Depression
		6.1	 Introduction
		6.2	 Structural and Functional Magnetic Resonance Imaging
			6.2.1	 Structural MRI Studies
			6.2.2	 Functional MRI (fMRI) Studies
		6.3	 Single-Photon Emission Computed Tomography (SPECT) Studies
		6.4	 Positron Emission Tomography (PET) Studies
		6.5	 Summary
		References
	7: Bipolar Disorders
		7.1	 Introduction
		7.2	 PET/SPECT
			7.2.1	 General Information
			7.2.2	 Cerebral Blood Flow and Cerebral Metabolism
				7.2.2.1	 Prefrontal Cortex
				7.2.2.2	 Limbic System and Subcortical Structures
				7.2.2.3	 Other Cortical Regions
				7.2.2.4	 Corticolimbic Theory of Mood Disorders
			7.2.3	 Neurotransmitter Studies
				7.2.3.1	 Serotonin
				7.2.3.2	 Dopamine
				7.2.3.3	 Norepinephrine
				7.2.3.4	 Choline
		7.3	 Other Pathophysiological Models
			7.3.1	 Neuroinflammation
			7.3.2	 White Matter Tract Integrity Disruption
			7.3.3	 Mitochondrial Dysfunction
		7.4	 Conclusion
		References
	8: PET and SPECT in Psychiatric Complications of Parkinson’s Disease
		8.1	 Introduction
		8.2	 Depression in Parkinson’s Disease
			8.2.1	 Dopamine and Depression in Parkinson’s Disease
			8.2.2	 Serotonin and Depression in Parkinson’s Disease
			8.2.3	 Glucose Metabolism and Cerebral Blood Flow in Parkinson’s Disease Depression
		8.3	 Psychosis in Parkinson’s Disease
		8.4	 Impulse Control Disorders in Parkinson’s Disease
			8.4.1	 Dopaminergic Tracers
			8.4.2	 Other Tracers
		8.5	 Personality Changes in Parkinson’s Disease
		8.6	 Conclusions
		References
	9: Psychiatric Disorders in Dementia
		9.1	 Dementia: Definition and Epidemiology
			9.1.1	 Definition
			9.1.2	 Prevalence and Incidence
			9.1.3	 Alzheimer’s Disease (AD) and Specific Dementia Syndromes
				9.1.3.1	 Alzheimer’s Disease (AD)
					Diagnosis
					Pathophysiological Mechanisms
				9.1.3.2	 Other Dementia Subtypes
					Dementia with Lewy Bodies (DLB)
					Frontotemporal Dementia (FTD)
		9.2	 Behavioral and Psychological Signs and Symptoms of Dementia (BPSD)
			9.2.1	 Delusional Ideation and Hallucinations: The Psychotic Syndrome
			9.2.2	 Agitation and Aggression
			9.2.3	 Diurnal Rhythm Disturbances
			9.2.4	 Depression
			9.2.5	 Activity Disturbances
			9.2.6	 Anxieties and Phobias
			9.2.7	 Apathy
		9.3	 Behavioral Assessment Scales
			9.3.1	 Middelheim Frontality Score (MFS)
			9.3.2	 Behavioral Pathology in Alzheimer’s Disease Rating Scale (Behave-AD)
			9.3.3	 Cohen-Mansfield Agitation Inventory (CMAI)
			9.3.4	 Geriatric Depression Scale (GDS)
			9.3.5	 Cornell Scale for Depression in Dementia (CSDD)
			9.3.6	 Neuropsychiatric Inventory (NPI)
			9.3.7	 Other Behavioral Assessment Scales
		9.4	 PET in the Differential Diagnosis of Dementia
			9.4.1	 Radioligands and Compounds
		9.5	 PET Imaging in Neuropsychiatric Disturbances of Dementia
			9.5.1	 Alzheimer’s Disease and Mild Cognitive Impairment
				9.5.1.1	 Depression
				9.5.1.2	 Apathy
				9.5.1.3	 Psychosis
				9.5.1.4	 Agitation
				9.5.1.5	 Other Behavioral Disturbances
			9.5.2	 Other Dementia Subtypes
		9.6	 SPECT in the Differential Diagnosis of Dementia
			9.6.1	 99mTc-HMPAO-SPECT
			9.6.2	 123I-IMP-SPECT
			9.6.3	 SPECT Imaging with Cholinergic and Monoaminergic Radioligands
			9.6.4	 SPECT Imaging of Neuroinflammation
			9.6.5	 SPECT Tracers Imaging Aβ Plaques
		9.7	 SPECT Imaging in Neuropsychiatric Disturbances of Dementia
			9.7.1	 Alzheimer’s Disease
				9.7.1.1	 Depression
				9.7.1.2	 Apathy
				9.7.1.3	 Psychosis
				9.7.1.4	 Activity Disturbances
				9.7.1.5	 Agitation and Aggression
				9.7.1.6	 Sleep Disorders
				9.7.1.7	 Other Behavioral Disturbances
			9.7.2	 Other Dementia Subtypes
		9.8	 Concluding Remarks
		References
Part III: Anxiety Disorders
	10: PET and SPECT Studies in Anxiety Disorders
		10.1	 Anxiety, Genes, and Environment
			10.1.1	 Anxiety Etiology
		10.2	 Anxiety and Brain Imaging
			10.2.1	 Anxiety, Symptom Provocation, and the Fear Network
			10.2.2	 Anxiety and Neurotransmission
			10.2.3	 Anxiety Treatment and Brain Function
		10.3	 Multiple Mechanisms Mediating Anxiety
		References
	11: Neurobiology of Posttraumatic Stress Disorder
		11.1	 PTSD
		11.2	 PTSD and Neuroimaging Studies
		11.3	 Regions Implicated in PTSD
			11.3.1	 Hippocampus
			11.3.2	 Amygdala
			11.3.3	 Prefrontal Cortex
			11.3.4	 Amygdala and Prefrontal Cortex
			11.3.5	 Insula
			11.3.6	 Broca’s Area
			11.3.7	 Retrosplenial Cortex
			11.3.8	 Thalamus
			11.3.9	 Caudate Nucleus
			11.3.10	 Cerebellum
		11.4	 Connectivity Studies
		11.5	 PTSD and Dissociative Symptoms
		11.6	 Conclusions
		References
	12: Neuroimaging in PTSD-Related Psychotherapies
		12.1	 Introduction
		12.2	 Neuroimaging in PTSD Psychotherapies
			12.2.1	 First Studies (1999–2012)
			12.2.2	 Recent Studies
			12.2.3	 Outcome Studies
		12.3	 General Discussion
		12.4	 Conclusions
		References
	13: Neuroimaging of Obsessive-Compulsive Disorder: Insights into Serotonergic Mechanisms
		13.1	 Overview
			13.1.1	 Hypothesized Braking System Model of OCD
		13.2	 Neurobiology
			13.2.1	 Brain Circuits
			13.2.2	 Neurochemistry
				13.2.2.1	 Serotonin
				13.2.2.2	 Dopamine
		13.3	 Dimensions Vs. Diagnosis
		13.4	 α-[11C]MTrp
			13.4.1	 Baseline Measurements of Serotonin Synthesis in OCD
			13.4.2	 The Effects of Treatment on Serotonin Synthesis in OCD
			13.4.3	 Comparisons of α-[11C]MTrp Findings Across Psychiatric Populations
		13.5	 Concluding Remarks
		References
Part IV: Psychosis and Cognitive Disorders
	14: Dopamine and Response to Antipsychotic Medication
		14.1	 Introduction
		14.2	 The Role of Dopamine in the Pathogenesis of Schizophrenia
			14.2.1	 Evidence from Early in Vitro Research
			14.2.2	 The Investigations of Dopamine Receptors in Schizophrenia
			14.2.3	 Presynaptic Dopamine Regulation and Positive Symptoms
			14.2.4	 Presynaptic Dopamine Regulation and Cognitive Impairment/Negative Symptoms
		14.3	 Challenges to the Dopamine Hypothesis of Schizophrenia
		14.4	 Dopamine and Treatment Response
			14.4.1	 PET and SPECT Findings in Treatment-Responsive Schizophrenia
			14.4.2	 Blockade of Dopamine D2 Receptors and Clinical Response
			14.4.3	 Presynaptic Regulation of Dopamine
			14.4.4	 Implications for Novel Dopaminergic Agents
		14.5	 PET and SPECT Findings in Treatment-Resistant Schizophrenia
			14.5.1	 Definition of Treatment-Resistant Schizophrenia
			14.5.2	 Dopamine and Treatment-Resistant Schizophrenia
			14.5.3	 Glutamate and Treatment-Resistant Schizophrenia
			14.5.4	 Clozapine and Treatment-Resistant Schizophrenia
			14.5.5	 Therapeutic Targets for Treatment-Resistant Schizophrenia
		14.6	 Conclusion
		References
	15: Acetylcholine Imaging in Psychosis
		15.1	 Introduction
		15.2	 Cholinergic Neurotransmission
			15.2.1	 Nicotinic Receptors
			15.2.2	 Muscarinic Receptors
		15.3	 Cholinergic System in Psychosis
			15.3.1	 Nicotinic PET/SPECT Imaging in Psychosis
				15.3.1.1	 Post-Mortem Studies
				15.3.1.2	 In Vivo Studies
			15.3.2	 Muscarinic PET/SPECT Imaging in Psychosis
				15.3.2.1	 Post-Mortem Studies
				15.3.2.2	 In Vivo Studies
		15.4	 Conclusion and Future Directions
			15.4.1	 Cholinergic Transporter Imaging
		15.5	 Concluding Remarks
		References
	16: Molecular Imaging in Schizophrenia Spectrum Disorders
		16.1	 The Disease
		16.2	 The Hypotheses
		16.3	 Human Imaging Studies
		16.4	 Small-Animal Studies
		References
	17: Neuroimaging Findings in Patients with Hallucinations: Evidence from Neurodegenerative and Psychiatric Conditions
		17.1	 Introduction
		17.2	 PET and SPECT Imaging of Hallucinations in Neurodegeneration
			17.2.1	 PET and SPECT Findings on Hallucinations in Parkinson’s Disease
			17.2.2	 PET and SPECT Findings on Hallucinations in Dementia with Lewy Bodies
			17.2.3	 PET and SPECT Findings on Hallucinations in Alzheimer’s Disease
		17.3	 PET and SPECT Imaging of Hallucinations in Psychiatric Conditions
		17.4	 Neurotransmitter Imaging of Hallucinations
		17.5	 Discussion
			17.5.1	 Visual Hallucinations in Lewy Body Disease
			17.5.2	 Auditory Hallucinations in Schizophrenia
			17.5.3	 Common and Distinct Mechanisms of Hallucinations across Diagnoses and Sensory Modalities
			17.5.4	 Conclusions
		References
	18: TSPO Imaging in Psychiatric Disorders
		18.1	 Introduction
		18.2	 Psychotic Disorders
		18.3	 Depression
		18.4	 Substance Use Disorders
		18.5	 Other Disorders
		18.6	 Methodological Considerations
		18.7	 Conclusions
		References
	19: Neuroimaging in Delirium
		19.1	 Introduction
		19.2	 Neuroimaging in Clinical Practice
		19.3	 Neuroimaging and the Pathophysiology of Delirium
			19.3.1	 CT/MRI: Structural Neuroimaging
			19.3.2	 Functional MRI
			19.3.3	 SPECT
			19.3.4	 PET
		19.4	 Methodological Considerations and Recommendations for Future Investigations
		19.5	 Conclusion
		References
Part V: Impulse Control and Related Disorders
	20: PET and SPECT in Personality Disorders
		20.1	 Introduction
		20.2	 Borderline Personality Disorder (BPD)
		20.3	 Schizotypal Personality Disorder (SPD)
		20.4	 Antisocial Personality Disorder (ASPD)
		References
	21: Abnormalities of Neurotransmission in Drug Addiction
		21.1	 Introduction
		21.2	 Alcohol
			21.2.1	 Dopaminergic System
				21.2.1.1	 Dopamine Synthesis and Presynaptic Function
				21.2.1.2	 Dopamine Transporter
				21.2.1.3	 Dopamine D2/D3 Receptors
				21.2.1.4	 Dopamine Release
				21.2.1.5	 Monoamine Oxidase
			21.2.2	 Serotonergic System
				21.2.2.1	 Serotonin Transporter
				21.2.2.2	 5-HT1A and 5-HT1B Receptors
				21.2.2.3	 Serotonin Synthesis
				21.2.2.4	 Serotonergic Challenge
			21.2.3	 GABAergic System
				21.2.3.1	 GABA Receptors
				21.2.3.2	 GABAergic Challenge
			21.2.4	 Opioidergic System
			21.2.5	 Glutamatergic System
			21.2.6	 Endocannabinoid System
			21.2.7	 Cholinergic System
			21.2.8	 Conclusion
		21.3	 Tobacco
			21.3.1	 Cholinergic System
			21.3.2	 Dopaminergic System
				21.3.2.1	 Dopamine Release
				21.3.2.2	 Dopamine Receptors
				21.3.2.3	 Dopamine Transporter
				21.3.2.4	 Dopamine Synthesis
				21.3.2.5	 Monoamine Oxidase
			21.3.3	 GABAergic System
			21.3.4	 Serotonergic System
			21.3.5	 Opioidergic System
			21.3.6	 Conclusion
		21.4	 Cannabis
			21.4.1	 Dopaminergic System
				21.4.1.1	 Dopamine D2/D3 Receptors
				21.4.1.2	 Dopamine Transporter
				21.4.1.3	 Dopamine Synthesis
				21.4.1.4	 Dopamine Release
			21.4.2	 Endocannabinoid System
				21.4.2.1	 CB1 Receptors
				21.4.2.2	 Fatty Acid Amide Hydrolase
			21.4.3	 Cholinergic System
			21.4.4	 Conclusion
		21.5	 Opioids
			21.5.1	 Dopaminergic System
				21.5.1.1	 Dopamine D2/D3 Receptors
				21.5.1.2	 Dopamine Transporter
			21.5.2	 Opioidergic System
			21.5.3	 Serotonergic System
			21.5.4	 GABAergic System
			21.5.5	 Conclusion
		21.6	 Stimulants
			21.6.1	 Dopaminergic System
				21.6.1.1	 Dopamine D2/D3 Receptors
				21.6.1.2	 Dopamine Transporter
				21.6.1.3	 Dopamine Synthesis
				21.6.1.4	 Sensitization
			21.6.2	 Other Neurotransmitter Systems
			21.6.3	 Conclusion
		21.7	 Chapter Summary
		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: SPECT and PET in Eating Disorders
		23.1	 Introduction
		23.2	 Anorexia and Brain Perfusion
		23.3	 Bulimia and Brain Perfusion
		23.4	 Anorexia and Cerebral Metabolism of Glucose
		23.5	 Anorexia and Brown Fat Activity
		23.6	 Bulimia and Cerebral Metabolism of Glucose
		23.7	 Alterations of the Serotonergic System in Eating Disorders
		23.8	 Alterations of Other Neurotransmitter Systems in Eating Disorders
		23.9	 Conclusion
		References
	24: Impulsivity Imaging
		24.1	 Overview
			24.1.1	 Introduction/Definition
			24.1.2	 Why Is the Study of Impulsivity Important?
			24.1.3	 How Is Impulsivity Currently Diagnosed or Measured?
			24.1.4	 What Is the Pathophysiology of Impulsivity?
			24.1.5	 The Role of Functional Imaging
			24.1.6	 How Can We Image Impulsivity?
				24.1.6.1	 Dopaminergic Neurotransmission
				24.1.6.2	 Serotonergic Neurotransmission
				24.1.6.3	 Noradrenergic Neurotransmission
				24.1.6.4	 The Potential Role of PET and SPECT in Evaluating Response to Treatment, Prognosis and Drug Development
		24.2	 Clinical Applications
			24.2.1	 Neurology
				24.2.1.1	 Attention Deficit Hyperactivity Disorder (ADHD)
				24.2.1.2	 Pathophysiological Changes
				24.2.1.3	 Additional Studies Involving SPECT and PET Imaging
				24.2.1.4	 Promising Future Roles of SPECT and PET
					Treatment and Response Evaluation in ADHD
					Genetic Imaging
				24.2.1.5	 Parkinson’s Disease (PD)
					Functional Imaging with SPECT and PET
					Treatment of Impulsive Disorders in Parkinson’s Disease
			24.2.2	 Psychiatry
				24.2.2.1	 Cluster B Personality Disorders and Bipolar Disorder
					Diagnosis
					Pathophysiology
					Neuroimaging
					Anatomical Imaging
					Functional Imaging
					Studies Involving Imaging with SPECT
					Studies Involving Imaging with PET
				24.2.2.2	 Substance Abuse
		24.3	 Conclusion
		References
	25: Brain SPECT in the Behaviourally Disordered Dog
		25.1	 History of Behavioural Brain Research in Animal Models
		25.2	 Studies on Canine Brain Pathophysiology
			25.2.1	 SPECT of the Impulsive-Aggressive Dog
			25.2.2	 5-HT2A-Receptor Imaging as a Biomarker in Canine Behavioural Research
		25.3	 Treatment Modalities in Behavioural Disordered Dogs
			25.3.1	 Selective Serotonin Reuptake Inhibitors in the Treatment of Impulsive-Aggressive Behaviour in Dogs
			25.3.2	 PET and SPECT Imaging in Canine Transcranial Magnetic Stimulation (TMS)
		25.4	 Confounding Factors in Canine Functional Brain Imaging Studies
			25.4.1	 Anaesthesia
			25.4.2	 Resolution Limits
		25.5	 Conclusion
		References
	26: Obesity: An Addiction? Imaging of Neurotransmitter Systems in Obesity
		26.1	 Introduction
		26.2	 Imaging Findings on Neurotransmitter Systems in Obesity
			26.2.1	 The Dopaminergic System
			26.2.2	 The Serotonergic System
			26.2.3	 The Noradrenergic System
			26.2.4	 The Opioid System
			26.2.5	 The Cannabinoid System
		26.3	 Discussion
			26.3.1	 Discussion of Findings on the Dopaminergic System
			26.3.2	 Discussion of Findings on the Serotonergic System
			26.3.3	 Conclusion
		References
	27: Neuroimaging Studies of Psychopathy
		27.1	 Neuroimaging Data on Psychopathy: Summary of Results
		27.2	 Methodological Issues
			27.2.1	 Two Different Uses of the Term “Psychopathy”
			27.2.2	 Inconsistent Criteria for Identifying Psychopaths
			27.2.3	 Consideration of Psychopathic Subtypes
		27.3	 Conclusion
		References
	28: Mapping and Imaging the Aggressive Brain in Animals and Humans
		28.1	 General Introduction Aggressive and Violent Behavior
			28.1.1	 Different forms of agression in animals and humans
			28.1.2	 Violence Is the Pathology of Functional Aggressive Behavior
		28.2	 Brain Regions and Neural Circuit Mechanisms Underlying the Regulation of Aggressive Behavior
		28.3	 The Main Nodes/Network Components of the Aggressive Brain
			28.3.1	 Hypothalamus
			28.3.2	 Amygdala/BNST
			28.3.3	 Septum/Hippocampus
			28.3.4	 Prefrontal Cortex (PFC), Orbitofrontal Cortex (OFC), and Anterior Cingulate Cortex (ACC)
			28.3.5	 Periaqueductal Gray (PAG)
			28.3.6	 Lateral Habenula (LHb)
		28.4	 Neurochemical and Hormonal Modulation of the Aggressive Neural Network
		28.5	 Serotonin
		28.6	 Dopamine
		28.7	 Glutamate/GABA
		28.8	 Hormones of the HPA (Cortisol/Corticosterone) and HPG Axis (Testosterone)
		28.9	 Vasopressin and Oxytocin
		28.10	 Concluding Remarks and Future Directions
		References
Part VI: Miscellaneous Subjects
	29: Application of PET and SPECT to the Study of Autism Spectrum Disorders
		29.1	 Introduction
		29.2	 Focal and Global Brain Alterations in Glucose Metabolism
			29.2.1 Increased Global Brain Glucose Metabolism in Autism
			29.2.2 Regional Brain Glucose Metabolism Alterations in Autism and Related Disorders
				29.2.2.1	 Brain Glucose Metabolism in Autism
				29.2.2.2	 Glucose Metabolism in Autism and Infantile Spasms
				29.2.2.3	 Glucose Metabolism and Tryptophan Metabolism in Children with Autism and Tuberous Sclerosis
		29.3	 Focal and Global Brain Alterations Cerebral Blood Flow
			29.3.1 Resting Cerebral Blood Flow
			29.3.2 Blood Flow Changes During the Performance of Tasks
		29.4	 Protein Synthesis in Pervasive Developmental Disorder
		29.5	 Neuroinflammation in ASD
		29.6	 Studies of Neurotransmitter Function with PET and SPECT in Autism
			29.6.1 Dopamine Precursor and Transporter Studies
			29.6.2 Serotonin Precursor, Transporter, and Receptor Studies
			29.6.3 GABAA Receptor Binding Studies
			29.6.4 Acetylcholine
		29.7	 Glutamate
		29.8	 Conclusions and Future Directions
		References
	30: PET and SPECT Imaging in ADHD
		30.1	 Introduction
		30.2	 Aetiology
		30.3	 Neuroanatomy
		30.4	 Structural Imaging
		30.5	 Functional Imaging: Cerebral Blood Flow and Glucose Metabolism
		30.6	 Task-Related Functional Imaging
		30.7	 Response to Pharmacological Treatment
		30.8	 Neurotransmitter Systems
		30.9	 Dopaminergic System
		30.10	 Noradrenergic System
		30.11	 Serotonergic System
		30.12	 Linkage Between Neurotransmitter Systems and Genotypes
			30.12.1	 Correlation with Clinical Symptoms
		30.13	 Conclusions
		30.14	 Limitations
		References
	31: SPECT and PET Imaging of Apathy
		31.1	 Introduction
		31.2	 What Is Apathy?
		31.3	 Apathy Theoretical Framework: What Is Known About Its Anatomical Bases?
		31.4	 How Is Apathy Reflected in Molecular Imaging?
			31.4.1	 SPECT Perfusion Studies
			31.4.2	 [18F]FDG-PET Studies
			31.4.3	 PET Imaging in Parkinson’s Disease (Baseline and Stimulation)
			31.4.4	 Amyloid and Tau PET Imaging
		31.5	 Conclusion
		References
	32: PET/SPECT/MRI/fMRI Studies in the Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
		32.1	 Introduction
			32.1.1	 Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
			32.1.2	 Classification of ME/CFS
		32.2	 MRI Morphometry Studies in Patients with ME/CFS
		32.3	 fMRI Study in Patients with ME/CFS
		32.4	 Hypoperfusion in Patients with ME/CFS Demonstrated by SPECT and PET
		32.5	 18F-FDG-PET Study
		32.6	 Deterioration of the Serotonergic System
		32.7	 Neuroinflammation Demonstrated by PET
		32.8	 Integrated PET Studies with a Variety of Blood Biomarkers
		32.9	 Discussion and Conclusions
		References
	33: Sleep Disorders
		33.1	 Introduction
		33.2	 Central Hypersomnolence Disorders
			33.2.1	 Narcolepsy
				33.2.1.1	 Acetylcholine, Serotonin, and Dopamine Functions in Narcolepsy
				33.2.1.2	 Brain Glucose Metabolism and Perfusion in Narcoleptic Individuals
				33.2.1.3	 Neural Correlates of Cataplexy
				33.2.1.4	 Pharmacological Treatment of Narcolepsy
					Methylphenidate
					Modafinil
				33.2.1.5	 Narcolepsy Type 2
				33.2.1.6	 Summary
			33.2.2	 Idiopathic Hypersomnia
		33.3	 Restless Legs Syndrome and Periodic Limb Movements
			33.3.1	 Restless Legs Syndrome
			33.3.2	 Periodic Limb Movements
			33.3.3	 Summary
		33.4	 Parasomnias
			33.4.1	 Sleepwalking
			33.4.2	 REM Sleep Behavior Disorder
				33.4.2.1	 Hypo- and Hyperperfusions in RBD
				33.4.2.2	 Dopaminergic Imaging
				33.4.2.3	 Metabolic Brain Networks
			33.4.3	 Summary
		33.5	 Insomnia
			33.5.1	 Primary Insomnia
			33.5.2	 Fatal Familial Insomnia
			33.5.3	 Neuroimaging of Sleep in Depression
			33.5.4	 Summary
		33.6	 General Conclusions
		References
	34: PET and SPECT Imaging of Non-pharmacological Interventions for Psychiatric Disorders
		34.1	 Introduction
		34.2	 Neuroimaging Findings in Depression and Obsessive–Compulsive Disorder
		34.3	 PET and SPECT in Electrical Neurostimulation
			34.3.1	 Deep Brain Stimulation
				34.3.1.1	 DBS in OCD
				34.3.1.2	 DBS in Depression
				34.3.1.3	 DBS in Anorexia Nervosa
			34.3.2	 Vagus Nerve Stimulation
			34.3.3	 Transcranial Magnetic Stimulation
				34.3.3.1	 Dorsolateral Prefrontal Cortex as a Target of rTMS Stimulation in Depression
				34.3.3.2	 Neuronavigated rTMS
				34.3.3.3	 Pretreatment rCBF as an rTMS Response Predictor
					Baseline Hypometabolism
					Baseline Connectivity
				34.3.3.4	 TMS and Imaging of Dopamine Activity
				34.3.3.5	 TMS in Schizophrenia
			34.3.4	 Electroconvulsive Therapy
				34.3.4.1	 Glucose Metabolism Changes in ECT
				34.3.4.2	 Long-Term Effect of ECT
				34.3.4.3	 Serotonin and Dopamine Changes in ECT
		34.4	 Psychotherapy
			34.4.1	 Imaging of Psychotherapy in Obsessive–Compulsive Disorder
			34.4.2	 Imaging of Psychotherapy in Depression
				34.4.2.1	 Neuroinflammation Biomarker Changes in Depression After CBT
				34.4.2.2	 Dopamine and Serotonin Changes in Depression After Cognitive Behavioral Therapy
		34.5	 Lesioning Procedures
			34.5.1	 Anterior Cingulotomy
			34.5.2	 Subcaudate Tractotomy
			34.5.3	 Limbic Leucotomy
			34.5.4	 Anterior Capsulotomy
		34.6	 Conclusions
		References