Behavioral Neurobiology of Suicide and Self Harm

Preface
Contents
Why Are Suicide Rates Increasing in the United States? Towards a Multilevel Reimagination of Suicide Prevention
	1 Introduction
	2 Recent Trends in Suicide and Nonfatal Self-Harm
		2.1 Global Trends in Suicide and Nonfatal Self-Harm
			2.1.1 Global Trends in Suicide
			2.1.2 Global Trends in Nonfatal Self-Harm
			2.1.3 Global Trends in Mood and Alcohol Use Disorders
		2.2 Trends in Suicide and Nonfatal Self-Harm in the United States
			2.2.1 Trends in Suicide in the United States
			2.2.2 Trends in Nonfatal Self-Harm in the United States
			2.2.3 Trends in Mood and Alcohol Use Disorders in the United States
		2.3 Why Are Suicide Rates Increasing in the United States?
	3 Individual-Level Suicide Prevention
		3.1 Individual-Level Suicide Risk Prediction
			3.1.1 The Role of Clinical Expertise, Risk Factors, Scales, and Computer Science
			3.1.2 When Is Suicide Risk Highest?
		3.2 Individual-Level Interventions for Suicide Risk Prevention
			3.2.1 Brief Contact Interventions
	4 Population-Level Suicide Prevention
		4.1 Population-Level Suicide Risk Factors: The Logic in Ecological
		4.2 Population-Level Suicide Prevention
	5 Conclusion
		5.1 Towards a Multilevel Approach to Suicide Prevention
	References
Barriers for the Research, Prevention, and Treatment of Suicidal Behavior
	1 Introduction
	2 Issues in the Conceptualization of Suicidal Behavior
		2.1 Suicidal Behavior as a Mental Disorder
		2.2 Subgroups of Suicidal Behavior
	3 Social Barriers to Suicide Prevention
	4 Suicide as a Global Challenge
	5 Barriers to the Prediction of Suicide
		5.1 Lack of Short-Term Risk Factors
		5.2 Lack of Protective Factors
		5.3 Lack of Specific Risk Factors
	6 Barriers to the Development of Treatments for Suicidal Behavior
	7 Difficulties in the Management of Suicidal Behavior in the Clinical Practice
		7.1 Suicide Risk Assessment Tools
		7.2 Medicolegal Aspects in Suicide Risk Assessment
		7.3 Healthcare Professionals´ Skills and Attitudes
	8 Conclusions
	References
The Role of Epigenetic Dysregulation in Suicidal Behaviors
	1 Introduction
	2 Stress Response Pathways
	3 Neurotrophic Factor Signaling
	4 Neurotransmitter Systems
	5 Epigenome-Wide Association Studies (EWAS)
	6 Discussion and Conclusions
	References
Suicide: Genetics and Heritability
	1 Biological Correlates of Hopelessness, Impulsivity, and Aggressivity in Suicidal Behavior
		1.1 Heritability in Suicidal Behavior
	2 Genetic Association Studies and Polygenic Risk Scores
	3 Individual Characteristics: The Diathesis-Stress Model
	4 Serotonin as a Biomarker: Why and Why Not?
		4.1 So, How Is It That We Give People with Depression a Medication That Inhibits This Transporter Even Further? And Why Studie...
	5 Epigenetics: When Nature Meets Nurture
		5.1 So What Are These Changes ``Produced by the Environment´´ That We Have Been Talking About?
		5.2 How Are Cortisol Levels a Demonstration of Environmental Influence?
		5.3 Timing and Epigenetic Studies
	6 Prefrontal Cortex: (Maybe) the Most Important Correlate
	7 BDNF: Further Evidence of Cognitive Impairment in Suicide?
	8 Clinical Implications of an Impaired-Cognition Approach to Suicidal Behavior
		8.1 Why Are We Talking About Mindfulness?
	9 Conclusions
	References
Toward a Biosignature of Suicide Reattempt
	1 Background
	2 Definition of Biomarker
	3 Biomarkers of SB
	4 Biomarkers of Repeated SB
	5 Conclusions
	References
Sex, Gender, and Suicidal Behavior
	1 Introduction
	2 Terminology
		2.1 Suicidal Behavior
		2.2 Sex and Gender
	3 Worldwide Suicide Rates by Gender
	4 Gender Differences in Suicide Methods
	5 Gender Differences in Suicide Risk and Protective Factors
		5.1 Demographics Risk Factors
		5.2 Sexual Orientation
		5.3 Religiosity
		5.4 Family History
		5.5 Previous Suicide Attempts
		5.6 Mental Disorders
		5.7 Medical Conditions
		5.8 Childhood Trauma and Stressful Life Events
		5.9 Coping Strategies and Help-Seeking
		5.10 Biological Risk Factors
	6 Toward a Tailored Prevention According to Gender
	References
Neurocognition and the Suicidal Process
	1 Suicide and Cognition: An Introduction
		1.1 History
		1.2 Current Theoretical Perspectives
			1.2.1 Hopelessness Theory of Suicide
			1.2.2 Rational Emotive Behavior Therapy: Theoretical Implications
			1.2.3 Biosocial Theory
			1.2.4 Separation Theory
			1.2.5 Personal Construct Psychology: Theoretical Implications
			1.2.6 Interpersonal Theory of Suicide
			1.2.7 Ideation to Action Theories of Suicide
			1.2.8 Summary and Current Theoretical Perspectives
	2 Suicide and Neurocognition in Psychiatric Disorders
		2.1 Mood Disorders
			2.1.1 Depression and Neurocognition
			2.1.2 Bipolar Disorder (BD) and Neurocognition
		2.2 Schizophrenia and Related Disorders
		2.3 Borderline Personality Disorder
		2.4 Transdiagnostic Effect of Cognition on Suicide
	3 Cognitive Domains and Suicide
		3.1 Overall Cognitive Ability
		3.2 Intelligence
		3.3 Executive Function
		3.4 Processing Speed
		3.5 Memory
		3.6 Attention
		3.7 Social Cognition
	4 Neurocognition and Specific Suicidal Behaviors
		4.1 Comparing Ideators and Attempters
			4.1.1 Attempters vs. Ideators
			4.1.2 Ideators vs. Non-suicidal Controls
			4.1.3 Attempters vs. Non-suicidal Controls
		4.2 First-Degree Relatives of Suicide Attempters
	5 Conclusions
	References
Lipids and Suicide Risk
	1 Introduction
	2 Lipid Classes
		2.1 Polyunsaturated Fatty Acids (PUFAs)
		2.2 Sterols
	3 Evidence Linking Lipids and Suicide Risk
		3.1 Cholesterol Levels and Suicide Risk
		3.2 Neuroactive Steroids and Suicide Risk
		3.3 Polyunsaturated Fatty Acid (PUFA) Dietary Intake and Suicide-Related Outcomes
	4 Potential Mechanisms of Action
		4.1 Inflammation
		4.2 Lipid Raft-Mediated Effects
			4.2.1 Lipid Rafts and PUFAs
			4.2.2 Lipid Rafts and Sterols
		4.3 Bioenergetics
		4.4 Receptor-Mediated Androgen Effects in the Brain
	5 Conclusions
	References
Glutamine and New Pharmacological Targets to Treat Suicidal Ideation
	1 The Glutamate-Glutamine Cycle
	2 Glutamate-Glutamine Cycle and Psychopathology of Suicide
	3 Evidence of Glutamate-Glutamine Cycle Changes in Suicidal Behaviours
		3.1 Glutamine Synthetase
			3.1.1 Glutamine Synthetase and Inflammation
		3.2 Phosphate-Activated Glutaminase
		3.3 Glutamate Receptors
			3.3.1 NMDA Receptors
			3.3.2 AMPA Receptors
			3.3.3 Kainate Receptors
			3.3.4 Metabotropic Receptors
		3.4 Glutamate Transporters
	4 Glutamine-Glutamate as the Target of New Anti-suicide Drugs
		4.1 Glutamine Synthetase
		4.2 NMDA Receptor
			4.2.1 Ketamine (NMDA Receptor Antagonist)
			4.2.2 Esketamine (NMDA Receptor Antagonist)
			4.2.3 Rapastinel (NMDA Receptor Modulator)
			4.2.4 Lanicemine (NMDA Channel Blocker)
			4.2.5 Other NMDA Receptor Targeting Drugs
	5 Conclusion
	References
The Role of Opiates in Social Pain and Suicidal Behavior
	1 Introduction
	2 Physical and Social Pains Are Sharing Common Pathways
		2.1 Social Pain and Opioid System
		2.2 Social Pain and Suicidal Risk
		2.3 Opioid Consumption in Relation to Suicidal Behavior
	3 Suicidal Behavior and Opioid System
	4 To New Pharmacological Treatments for SB
	5 Conclusions
	References
Sleep Disturbances and Suicidal Behavior
	1 Introduction
	2 Method
	3 Sleep Complaints in the General Population
		3.1 Insomnia
		3.2 Excessive Daytime Sleepiness
		3.3 Nightmares
	4 Sleep Disturbances in Psychiatric Conditions
	5 Effects of Insomnia on SIB
	6 Effects of Nightmares on Suicidality
	7 Effects of Excessive Daytime Sleepiness on Suicidality
	8 Role of Confounders in the Relationship Between Sleep Disturbances and SIB
	9 Mechanisms Underlying the Association Between Sleep Disturbances and SIB
	10 Perspectives
	References
Ecological Momentary Assessment for Monitoring Risk of Suicide Behavior
	1 Suicidal Risk Behavior Assessment
		1.1 Assessment
		1.2 Ecological Momentary Assessment
		1.3 Digital Phenotype
	2 Continuous and Objective Monitoring: eB2 System
		2.1 Description and Structure
		2.2 Data Sources
		2.3 Data Consolidation
	3 Digital Biomarkers
		3.1 Behavioral Changes
		3.2 Behavior Stability
		3.3 Disability Assessment
		3.4 Synchronic Indicators
	4 Conclusions
	References