BIPOLAR DISORDER – A PORTRAIT OF A COMPLEX MOOD DISORDER Edited by Jarrett Barnhill Bipolar Disorder – A Portrait of a Complex Mood Disorder Edited by Jarrett Barnhill Published by InTech Janeza Trdine 9, 51000 Rijeka, Croatia Copyright © 2012 InTech All chapters are Open Access distributed under the Creative Commons Attribution 3.0 license, which allows users to download, copy and build upon published articles even for commercial purposes, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. After this work has been published by InTech, authors have the right to republish it, in whole or part, in any publication of which they are the author, and to make other personal use of the work. Any republication, referencing or personal use of the work must explicitly identify the original source. 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Publishing Process Manager Dragana Manestar Technical Editor Teodora Smiljanic Cover Designer InTech Design Team First published February, 2012 Printed in Croatia A free online edition of this book is available at www.intechopen.com Additional hard copies can be obtained from orders@intechweb.org Bipolar Disorder – A Portrait of a Complex Mood Disorder, Edited by Jarrett Barnhill p. cm. 978-953-51-0002-7 Contents Preface IX Part 1 Basic Science Issues 1 Chapter 1 Bivalent Cations in Bipolar Disorders 3 Mihai Nechifor, Cristina Vaideanu and Florina Crivoi Chapter 2 Anti-Stress Effects of Mood Stabilizers and Relevance to Their Therapeutic Actions 17 Young-Ki Chung and Seungmin Yoo Chapter 3 Lithium Enhances Synaptic Plasticity: Implication for Treatment of Bipolar Disorder 41 Seong S. Shim Part 2 Neuropharmacological Challenges 55 Chapter 4 Li + in Bipolar Disorder – Possible Mechanisms of Its Pharmacological Mode of Action 57 Carla P. Fonseca, Liliana P. Montezinho and M. Margarida C.A. Castro Chapter 5 Memantine: A New Mood Stabilizer for Treatment-Resistant Bipolar Disorders 99 Gino Serra, Giulia Serra, Alexia E. Koukopoulos, Francesca Demontis and Athanasio Koukopoulos Chapter 6 Bipolar Disorder and Suicide 121 Dagmar Breznoščáková Part 3 Neurodevelopmental Aspects 143 Chapter 7 Correlations Between the Monoaminergic Status and the Psychoneuroendocrine Typology in a Murine Model – Possible Biomolecular Predictions for an Individualized Pharmacotherapy 145 Andreea Letitia Arsene, Niculina Mitrea and Dumitru Lupuliasa VI Contents Chapter 8 Paediatric Bipolar Disorder – Are Attachment and Trauma Factors Considered? 165 Peter I. Parry Part 4 Psychosocial Approaches 191 Chapter 9 Psychosocial Functioning in Bipolar Disorder from a Social Justice Perspective 193 Emily Manove, Lauren M. Price and Boaz Levy Chapter 10 Star Shots: Stigma, Self-Disclosure and Celebrity in Bipolar Disorder 221 Wendy Cross and Ken Walsh Preface This volume addresses the many faces of Bipolar Disorder (BD). To complete this portrait, we need to explore not only clinical symptoms and treatment responses, but also gene-environment interactions, epigenetics, stress response systems, and psychosocial forces that impact mood disorders in general and BD in particular. From a clinical perspective, the age of onset, severity, and patterns of cycling and symptoms influence clinical course, venue, and treatment decision making. In this edition we address the complexity of BD by focusing on basic neurosciences research, especially the role of neuro-plasticity; multiple neurotransmitter systems; first and second messenger systems; the capacity of several mood stabilizers to alter stress response systems, regulators of circadian rhythms, and the underlying neurophysiology of treating BD. The fundamental processes are addressed in depth by Drs Mahai (bivalent cations in mania); Seong (lithium effects on neuroplasticity); Gino (a novel treatment approach to treatment based on modulating glutaminergic activity treatment with Memantine) and Margarida (the effects of lithium on intracellular mechanisms related to phosphoinositol, GSK3 and other messenger systems). Clinical heterogeneity is the most challenging feature of major psychiatric disorders. A significant contributor to this heterogeneity is gene-environmental interactions. In keeping with this challenge, Dr Young-Ki addresses the relationship between stress, BD and the role many mood stabilizers pay in modulating the stress response systems (neuro-immunological and neuro-endocrinological systems). Her insights and observations are germane to our understanding of the lifelong changes in the nature and course of BD. One area of intense interest is the boundary and transformation point between high levels of reactivity early in the course of BD to one that seems to be an expression of primarily endogenous events. This “developmental” characteristic of BD is complicated by frequent relapses over time and points us toward kindling, episode sensitization and alterations in neuroplastic responses by recurring symptoms. In recent years, there is growing interest in the relationship between “soft” forms of BD, namely sub-clinical or sub-syndromal forms (BD. NOS). These subsyndromal forms are grouped under BD spectrum disorder. If we turn our attention to prepubertal onset BD we also confront boundary problems associated with atypical or temperamental presentations of ADHD and severe affective instability, irritability, and X Preface explosive behaviors. In this edition Dr Andreea addresses neurobiological features of affect regulation and expression. This chapter dovetails nicely into Dr Peter's review of the problems child psychiatrists encounter, and in some situations create, when dealing with prepubertal onset BD. The boundary between genetic risk for BD and severe temperamental differences, ADHD, abuse and neglect, and affect dysregulation enter into these considerations. These variations in the presentation of classic BD segue into the markedly increased risk for both attempted and completed suicide in the disorder. Factors such as recurring depression in BP II patients, presence of mixed mood states and subtype early age of onset, substance use, and psychiatric comorbidity contribute to potential suicidal behaviors. For example, many individuals with BD.NOS, Bipolar II (recurring depression), and mixed mood states experience longstanding social and occupational morbidity, prolonged periods of mood-related symptoms and increased risk of suicide. Dr Dagmar provides a thorough analysis of epidemiological research and clinical data that addresses the risks for suicidal behavior and completed suicide in BD. Dr Levy addresses the complex psychosocial issues that encompass BD. In our era of psychopharmacological treatments, various psychotherapy formats are often overlooked or underemphasized. The role of psychotherapy in enhancing quality of life, relapse prevention, adjuncts for treatment resistant patients, and a methodology of closely monitoring patients for early relapse at key points in their clinical course, can be critical for successful outcomes. Increased mastery of the psychosocial consequences of BD may also play a key role in suicide prevention by enhancing family functioning as well as cognitive behavioral and interpersonal skill sets. Dr Wendy culminates this volume on a broader medical sociological note. BD is a costly and life-altering disorder that can adversely affect not only quality of life but also occupation, educational, and family functioning. Dr Wendy explores the impact of disclosure on these parameters. In addition, the author investigates the often ambiguous territory of illness disclosure in terms of stigmatization and social role changes due to occupational and family dysfunction and repeated hospitalizations. These psychosocial issues affect one's willingness to accept the diagnosis, comply with treatment recommendations, and levels of subjective distress and morbidity related to a chronic relapsing disorder. The author then turns to the impact of disclosure by celebrities on stigmatization and social acceptance. Even though Dr Wendy focuses on psychosocial factors, these findings can be extrapolated to chapters on neurophysiological parameters associated with occupational distress, social isolation, and sense of alienation, shame/guilt, and other risk factors for both recurrence and treatment resistance. Bipolar Disorder: A Portrait of a Complex Mood Disorder captures only a portion of the variability and heterogeneity of what we call BD. This book begs the question of approaching BD in terms of a combination of descriptive and etiopathogenic . BIPOLAR DISORDER – A PORTRAIT OF A COMPLEX MOOD DISORDER Edited by Jarrett Barnhill Bipolar Disorder – A Portrait of a Complex. Mechanisms of Its Pharmacological Mode of Action 57 Carla P. Fonseca, Liliana P. Montezinho and M. Margarida C .A. Castro Chapter 5 Memantine: A New Mood