Cover

Contents

Preface

Antidepressants: Past and Present

Antidepressant Compounds: A Critical Review

Abstract

Traditional Paths for Development of Antidepressant Compounds

Current Antidepressant Drugs: Are They More Similar than Different?

Other Central Nervous System Drugs Exploited as Antidepressant Drugs or Augmentation Agents

Role of Brain-Derived Neurotrophic Factor and Neurogenesis in Antidepressant Action

Discussion

References

Basic and Clinical Aspects of Depression Research

The Hypothalamic-Pituitary-Adrenal Axis inDepression

Abstract

Corticotropin-Releasing Hormone (Corticotropin-Releasing Factor) in Depression

Vasopressin in Depression

Secretion of Adrenocorticotropin and Cortisol in Depression

Dexamethasone Suppression Test

Adrenocorticotropin Stimulation Test

Serotonergic Stimulation

Early-Life Stress and the Hypothalamic-Pituitary-Adrenal Axis

Effects of Antidepressants on the Hypothalamic-Pituitary-Adrenal Axis

Cortisol Synthesis Inhibitors in the Treatment of Depression

Conclusions

References

Dysfunctional Circadian Rhythms and Mood Disorders: Opportunities for Novel Therapeutic Approaches

Abstract

Circadian Rhythms

Circadian Rhythms and Major Depression

Circadian Rhythms and Bipolar Disorder

The Molecular Clock and Bipolar Disorder

Circadian Genes and Bipolar Disorder

Therapeutic Options Based on Circadian Manipulation

Conclusions

References

The Concept of Depression as a Dysfunction of the Immune System

Abstract

Interrelationship between Cytokines and Brain Function: Relevance to Depression?

The Effect of Inflammatory Changes on Mood

The Role of Stress and Pro-Inflammatory Cytokines

Serotonin, Stress and Depression

Stress, Depression and Neurodegeneration

Antidepressants and Immune Regulation

Could the Inflammation Hypothesis of Depression Contribute to the Development of Novel Antidepressants?

References

The Role of Polyunsaturated Fatty Acids in the Pathology and Treatment of Depression

Abstract

n–3 and n–6 Fatty Acids and Their Functions in the Brain and Immune System

Changes in n–3 and n–6 Fatty Acid Contents in Different Types of Depressed Patients

n–3 Fatty Acids in the Treatment of Depression: Evidence from Clinical Trials

The Pharmacological and Therapeutic Mechanism of n–3 Fatty Acids for Treating Depression

Limitations and Future Research Directions

References

Overcoming Antidepressant Treatment Resistance: Focus on Glutamate

Abstract

Evidence of Glutamatergic Dysfunction in Major Depressive Disorder

Ketamine as a Proof-of-Concept Glutamatergic Antidepressant

Conclusions and Future Directions

References

Neuroimaging and the Pathophysiology and Treatment of Depression: Recent Advances and Future Needs

Abstract

The Pathophysiology of Depression: Imaging Studies

Combining Neuroimaging and Genotyping in the Study of Depression

Neuroimaging and the Treatment of Depression

The Future of Neuroimaging in Benefiting Individuals with Depression

References

Experimental Models of Depression and the Mechanisms of Action of Antidepressants

Animal Models of Depression – Where Are We Going?

Abstract

Traditional Animal Models of Depression

Endophenotype-Style Approaches

Depression and Comorbid Indications

Social Stress-Based Models

Genetic Predisposition

Incorporation of Human Findings

Conclusions and Outlook

References

Genetic Models of Depression and Antidepressant Response

Abstract

Rat Strains Showing Exaggerated Stress-Induced Behavioral Depression

Response to Antidepressant Drugs in Wistar-Kyoto Rats

Mouse Strains Showing Increased Depressive Behaviors

Measuring Antidepressant Responses in Different Mouse Strains

Murine Models of Deficient Monoamine Synthesis

Acknowledgements

References

The Role of 5-HT2C Receptors in the Antidepressant Response: A Critical Review

Abstract

The Relevance of 5-HT2C Receptors in Depression

Antidepressant Drugs Acting at 5-HT2C Receptors Moderate Stress and Anxiety

Implication of 5-HT2C Receptor Desensitization in the Effects of Antidepressant Drugs

Overview and Perspectives

Acknowledgements

References

Chromatin-Based Treatments for Affective Disorders – Insight or Utopia

Abstract

An Introduction to Epigenetics and Chromatin Modifications

DNA Methylation and Affective Disorders

Covalent Modifications of Histones and Affective Disorders

Conclusion

References

Neurotrophic Factors and Antidepressant Action: Recent Advances

Abstract

Neurotrophins: Brain-Derived Neurotrophic Factor, Nerve Growth Factor, Neurotrophin 3 and Neurotrophin 4/5

Fibroblast Growth Factors

Insulin-Like Growth Factor 1

Vascular Endothelial Growth Factor

Transforming Growth Factor Family

Neuropoietic Cytokines

Conclusions

References

Neurogenic Basis of Antidepressant Action: Recent Advances

Abstract

Hippocampal Dysfunction in Depression

Hippocampal Neurogenesis: Background

Stress, Depression and Neurogenesis: Common Regulation Factors

Are Antidepressants Required for Antidepressant Efficacy?

Is Neurogenesis Crucial for All Aspects of the Antidepressant Action?

Key Factors Involved in the Neurogenic Effects of Antidepressants

Neurogenesis as an Etiological Factor of Depression

Conclusion

References

The Future of Antidepressants

The Nature and Treatment of Therapy-Resistant Depression

Abstract

Defining Therapy-Resistant Depression

Prevalence and Risk Factors for Therapy-Resistant Depression

Current State of Pharmacotherapy for Therapy-Resistant Depression

Advances in Neurostimulation Therapies

Conclusions

References

Optimizing Antidepressant Management o fDepression: Current Status and Future Perspectives

Abstract

Making Good with What Is Available…

Basic Psychopharmacology Principles

Making Good on the Future…

Conclusion

Acknowledgement

References

Author Index

Subject Index