Psychiatric and Behavioral Aspects of Epilepsy: Current Perspectives and Mechanisms (Current Topics in Behavioral Neurosciences, 55)

Preface
	Reference
Contents
Part I: Discovery Science
Cognition, Behavior, and Psychosocial Effects of Seizures in the Developing Brain
	1 Introduction
	2 Laboratory Assessment of Seizure-Induced Cognitive and Behavioral Changes
	3 Changes in Cognitive and Behavioral Development
		3.1 Cognition, Learning, and Memory
		3.2 Psychiatric Outcomes
	4 Supporting Neuropsychiatric Development
	5 Conclusions
	References
In Up to My Ears and Temporal Lobes: Effects of Early Life Stress on Epilepsy Development
	1 Introduction
	2 Convulsive Seizures, Early Life Stress, and the Effects of Age
		2.1 Prenatal Stress and Early Life Seizure Susceptibility
		2.2 Postnatal Stress and Early Life Seizure Susceptibility
		2.3 Prenatal Stress and Seizure Susceptibility in Adulthood
		2.4 Postnatal Stress and Seizure Susceptibility in Adulthood
	3 Non-convulsive Seizures
		3.1 Poor Maternal Care and Non-convulsive Seizures
		3.2 Early Life Environment or Handling and Non-convulsive Seizures
	4 Sex Effects Mediating Early Life Stress in Epilepsy
	5 Possible Mechanisms for the Effects of Early Life Stress on Epilepsy
		5.1 Glucocorticoids and the Hypothalamic-Pituitary-Adrenal Axis
		5.2 Neuroinflammation
		5.3 Inhibitory and Excitatory Mechanisms
		5.4 Temporal Lobe Structures
	6 Discussion
	References
Does Stress Trigger Seizures? Evidence from Experimental Models
	1 Introduction
	2 Stress Physiology
	3 Stress and Neurosteroids
	4 Relationship Between Stress and Epilepsy
	5 Stress Management and Epilepsy
	6 Conclusions and Future Perspectives
	References
Alterations of Neuronal Dynamics as a Mechanism for Cognitive Impairment in Epilepsy
	1 Introduction
	2 Epileptiform Activity and Cognitive Impairment
	3 Physiological Causes of Epilepsy
		3.1 Epileptogenesis
			3.1.1 Reorganization of the ``Dentate Gate´´ (Fig. 1)
			3.1.2 Cell Death in CA1 and CA3
			3.1.3 Anatomical Reorganization in Connected Structures
		3.2 Genetic Epilepsies
	4 Functional Consequences at the Circuit Level
		4.1 GABA Activity and Development
		4.2 The Dentate Gate, Sparsification, and Pattern Separation (Fig. 4a)
		4.3 Attractor Dynamics, Pattern Completion, and Cell Assemblies in CA1-3
	5 Impact on Neural Coding
	6 Impact on Oscillations and Cognitive Functions
		6.1 Major Brain Rhythms and Their Function
			6.1.1 Θ (5-12 Hz) Oscillation in Epilepsy
			6.1.2 γ Oscillations (30-60 Hz; 60-90 Hz) and Epilepsy
			6.1.3 Normal (90-300 Hz) and Pathological (300-600 Hz) HFOs
	7 Interneuronopathies, Neuronal Dynamics, and Cognition
		7.1 Interneuronopathies in Epilepsy
	8 Conclusion
	References
Mechanisms of Psychiatric Comorbidities in Epilepsy
	1 Shared Neurobiology of Psychiatric Illnesses and Epilepsy
		1.1 Bidirectional Relationship Between Psychiatric Illnesses and Epilepsy
		1.2 Shared Risk Factors for Psychiatric Illnesses and Epilepsy
		1.3 Anticonvulsant Actions of Antidepressant Treatments/Impact of AEDs on Psychiatric Illnesses
	2 Mechanisms Mediating the Comorbidity of Psychiatric Illnesses and Epilepsy
		2.1 Altered Neurotransmitters
			2.1.1 Monoamines
			2.1.2 Glutamate
			2.1.3 GABA
		2.2 Hypothalamic-Pituitary-Adrenal (HPA) Axis Dysfunction
		2.3 Network/Structural Abnormalities
		2.4 Other Proposed Mechanisms
			2.4.1 Neurogenesis
			2.4.2 BDNF
			2.4.3 Inflammation
	3 Women with Epilepsy
	4 Concluding Remarks
	References
Disease Modification in Epilepsy: Behavioural Accompaniments
	1 Introduction
	2 Mechanisms and Potential Targets
	3 Animal Models and Data Interpretation: Kindling Example
	4 Genetic Epilepsies Lesson
	5 Conclusive Remarks
	References
Part II: Clinical Science
Peri-Ictal and Para-Ictal Psychiatric Phenomena: A Relatively Common Yet Unrecognized Disorder
	1 Introduction
	2 Peri-Ictal Behavioral Manifestations
		2.1 Pre-Ictal Symptoms
		2.2 Ictal Symptoms
		2.3 Post-Ictal Symptoms
	3 Para-Ictal (``Alternative´´) Behavioral Manifestations
	4 Association Between Peri-Ictal and Interictal Behavioral Manifestations
	5 Conclusion
	References
Psychotic Disorders in Epilepsy: Do They Differ from Primary Psychosis?
	1 Comparisons Between Definitions of Primary Psychoses and Psychoses in PWE
		1.1 Definitions of Primary Psychoses in the DSM-5
		1.2 Postictal Psychosis
		1.3 Interictal Psychoses
			1.3.1 Co-morbid Schizophrenia
			1.3.2 Iatrogenic Psychotic Disorder
			1.3.3 Forced Normalization
			1.3.4 AED-induced Psychotic Disorder (AIPD)
			1.3.5 Interictal Psychosis
		1.4 Summary
	2 Question A: Is Postictal Psychosis Different from a Brief Psychotic Disorder?
	3 Question B: Does Epilepsy Facilitate or Prevent the Development of Psychotic Disorders?
	4 Is Epileptic Interictal Psychosis Different from Schizophrenia (Question C)?
		4.1 Are Negative Symptoms Less Remarkable in Interictal Psychosis Compared to Process Schizophrenia?
		4.2 Is Dysphoric or Viscous Personality Trait Identified in Patients with Interictal Psychosis?
		4.3 Are ``bizarre´´ Complaints More Common in Patients with Process Schizophrenia than in Patients with Interictal Psychosis?
		4.4 Representative Cases
	5 Conclusion
	References
Suicidality in Epilepsy: Does It Share Common Pathogenic Mechanisms with Epilepsy?
	1 Introduction
	2 Suicide in Epilepsy
		2.1 Epidemiology of Suicidality
		2.2 Understanding Suicidal Behavior
		2.3 Risk Factors for Suicidal Behavior
		2.4 Suicidal Behavior in Persons with Epilepsy
		2.5 Risk Factors for Suicide in Epilepsy
	3 Neurobiology of Depression
		3.1 Monoamine Hypothesis
		3.2 Hypothalamic-Pituitary-Adrenal Axis and Hippocampal Dysfunction
		3.3 Neurotrophic Factors Hypothesis
		3.4 Neural Networks of Depression
	4 Pathogenic Neurobiological Mechanisms in Suicidality and Epilepsy
		4.1 Neurotransmitters in Neurobiology of Suicidality and Epilepsy
			4.1.1 Serotonergic System Dysfunction
				Serotonin Transporter
					Serotonin Transporter Genes and Suicidal Behavior
				Serotonergic Receptors
					Serotonergic Receptors Genes and Suicidal Behavior
				Tryptophan Hydroxylase
					Tryptophan Hydroxylase Genes and Suicidal Behavior
				Monoamine Oxidase
					Monoamine Oxidase Genes and Suicidal Behavior
				Heritability and Serotonin System Candidate Genes in Suicidal Behavior
			4.1.2 Noradrenergic System Dysfunction
			4.1.3 Glutamatergic and γ-Aminobutyric Acid System Dysfunction
			4.1.4 Dopaminergic System Dysfunction
		4.2 Hypothalamic-Pituitary-Adrenal Axis in Neurobiology of Suicidality and Epilepsy
			4.2.1 Hypothalamic-Pituitary-Adrenal Axis Genes and Suicidal Behavior
		4.3 Neurotrophins in Neurobiology of Suicidality and Epilepsy
		4.4 Neuroimmune Dysfunction in Neurobiology of Suicidality and Epilepsy
			4.4.1 Cytokines in Suicidal Behavior
			4.4.2 Immune Deficiency and Suicidal Behavior
			4.4.3 Inflammation and Suicidal Behavior
				Mechanisms of Inflammation in Suicidal Behavior
			4.4.4 Traumatic Brain Injury and Suicidal Behavior
			4.4.5 Vitamin D Deficiency and Suicidal Behavior
			4.4.6 Cytokines as Therapeutic Modulators in Epilepsy, Depression, and Suicidal Behavior
	5 Conclusion
	6 Future Perspectives
	References
Bidirectional Relations Among Depression, Migraine, and Epilepsy: Do They Have an Impact on Their Response to Treatment?
	1 Introduction
	2 Complex Relation Between Common Psychiatric Comorbidities and Epilepsy
		2.1 Epidemiologic Data
		2.2 Clinical and Therapeutic Implications
	3 Complex Relation Among Epilepsy, Depression, and Migraine
		3.1 Bidirectional Relation Between Migraine and Epilepsy
			3.1.1 Epidemiologic Data
			3.1.2 Clinical and Therapeutic Implications
			3.1.3 Potential Common Pathogenic Mechanisms
		3.2 Bidirectional Relation Between Migraine and Mood Disorders
			3.2.1 Epidemiologic Data
			3.2.2 Clinical Implications
		3.3 Common Pathogenic Mechanisms Operant in Migraines and Depression
		3.4 Additive Interaction Among Migraine, Depression on the Risk of Epilepsy?
	4 Are Bidirectional Relations Among Epilepsy, Depression, and Migraine Demonstrable in Animal Models?
		4.1 Can a Bidirectional Relation Between Depression and Epilepsy Be Identified in Animal Models of Epilepsy?
			4.1.1 Depression Facilitates Epileptogenesis
			4.1.2 Epilepsy Facilitates Depression Phenotype
		4.2 Can a Bidirectional Relation Between Migraine and Epilepsy Be Identified in Animal Models of Epilepsy?
		4.3 Can a Bidirectional Relation Between Migraine and Epilepsy Be Identified in Animal Models of Epilepsy?
	5 Clinical Implications and Consideration of Future Research
	References
Do Psychotropic Drugs Cause Epileptic Seizures? A Review of the Available Evidence
	1 Introduction
	2 Antidepressants
		2.1 Experimental/Pre-clinical Data
		2.2 Human Data
	3 Central Nervous System (CNS) Stimulants
		3.1 Experimental/Pre-clinical Data
		3.2 Human Data
	4 Antipsychotic Drugs
		4.1 Experimental/Pre-clinical Data
		4.2 Human Data
	5 Conclusion
	References
Can We Anticipate and Prevent the Occurrence of Iatrogenic Psychiatric Events Caused by Anti-seizure Medications and Epilepsy ...
	1 Introduction
	2 ASM and Psychiatric Effects
		2.1 Psychotropic Properties of ASM
	3 Forced Normalization: A Pivotal Concept
	4 Psychiatric Adverse Effects Associated with First, Second, and Third Generations OF ASM
		4.1 Classical ASM
		4.2 New ASM
	5 The Other Side of the Coin: Positive Behavioral Effects Associated with ASM
	6 Possible Clinical and Neurobiological Characteristics Associated with ASM Therapy in the Major Psychiatric Syndromes
		6.1 Depression
		6.2 Psychoses
		6.3 Other Behavioral Changes
	7 Can We Anticipate and Prevent the Occurrence of Iatrogenic Psychiatric Events Caused by ASMs?
	8 Epilepsy Surgery and Psychiatric Symptoms: A Complex Association
		8.1 Psychiatric Disorders in Pre-surgical Candidates
		8.2 Psychiatric Evaluation of Pre-surgical Candidates: Current Reality and Challenges
		8.3 The Impact of Epilepsy Surgery on Pre-surgical Psychiatric Disorders
	9 Epilepsy Surgery and Post-surgical Psychiatric Complications
		9.1 De Novo PD
		9.2 Exacerbation/Recurrence of Psychiatric Symptoms
	10 The Impact of Pre-surgical Psychiatric Disorders on Post-surgical Seizure Outcome
	11 Epilepsy Surgery and Psychosocial Outcome
	12 Can We Anticipate and Prevent the Occurrence of Iatrogenic Psychiatric Events Caused by Epilepsy Surgery?
	References
Temporal Lobectomy: Does It Worsen or Improve Presurgical Psychiatric Disorders?
	1 Introduction
	2 Recurrence of Presurgical Mood and Anxiety Disorders
	3 De Novo Mood and Anxiety Disorders
	4 Post-Surgical Remission of Presurgical Mood and Anxiety Disorders
	5 Psychosis after Temporal Lobectomy
	6 Other Psychiatric Symptoms Following Temporal Lobectomy
	7 Personality Changes After Temporal Lobectomy
	8 Psychiatric Aspects of Temporal Lobectomies in Children
	9 Limitations of the Scientific Evidence
	10 Conclusions
	References
Are Functional (Psychogenic Nonepileptic) Seizures the Sole Expression of Psychological Processes?
	1 Introduction
	2 Neuropsychological Constructs in FND-seiz
		2.1 Emotion Processing
		2.2 Attention
		2.3 Interoception
		2.4 Self-Agency and Locus of Control
	3 Functional Seizures as a Multi-Network Brain Disorder
		3.1 Salience and Limbic Networks
		3.2 Sensorimotor Network
		3.3 Other Implicated Networks
	4 Stress Physiology
		4.1 Autonomic and Neuroendocrine Alterations
	5 Bridging Etiology and Pathophysiology
	6 Conclusion
	References