1;Preface;6 1.1;Acknowledgments;10 1.2;References;10 2;Acknowledgments;10 3;Contents;12 4;Contributors;14 5;Course and Outcome of Bipolar Disorder;18 5.1;1 Historical Legacies;19 5.2;2 The Course of BPD Prior to the Introduction of Modern Psychotropic Agents;19 5.3;3 Methodological Issues;20 5.4;4 Childhood and Adolescent Antecedents of BPD;21 5.5;5 The Onset of BPD: Age;22 5.5.1;5.1 Specific Age-Related Presentations;22 5.5.1.1;5.1.1 Postpartum BPD;22 5.5.1.2;5.1.2 Late-Onset BPD;22 5.6;6 The Onset of BPD: Polarity;23 5.7;7 Subtypes and Patterns of BPD Based on Course of Illness;24 5.7.1;7.1 Bipolar I and II Disorders;24 5.7.2;7.2 Rapid-Cycling Illness;24 5.7.3;7.3 Nature of the Cycle;24 5.7.4;7.4 Predominant Polarity;25 5.8;8 Duration and Outcome of Individual Episodes;26 5.9;9 Recurrence Rates and Clinical Outcomes;27 5.9.1;9.1 Retrospective or Cross-Sectional Studies;27 5.9.2;9.2 Prospective Studies;28 5.10;10 Predictors/Correlates of Recurrence;28 5.11;11 Other Outcomes;30 5.11.1;11.1 Disability;30 5.11.2;11.2 Death Rates;30 5.12;12 Conclusion;31 5.13;References;31 6;Genetics of Bipolar Disorder;36 6.1;1 Introduction;36 6.2;2 Genetic Epidemiology of BPD;37 6.2.1;2.1 Twin Studies;37 6.2.2;2.2 Family Studies;38 6.3;3 Molecular Genetics;38 6.3.1;3.1 Genetic Linkage and Candidate Gene Studies;38 6.3.2;3.2 Genome-Wide Association Studies;39 6.4;4 New Strategies in BPD Genetics Research;40 6.4.1;4.1 Redefining the Phenotype;40 6.4.2;4.2 Novel Molecular Tools;43 6.4.3;4.3 Novel Analytical Tools;44 6.5;5 Summary;44 6.6;References;44 7;Understanding Bipolar Disorder: The Epigenetic Perspective;48 7.1;1 Introduction;49 7.2;2 Concepts in Epigenetics;49 7.3;3 Bipolar Disorder: The Epigenetic Perspective;51 7.4;4 Discordance of Monozygotic Twins;52 7.5;5 Sexual Dimorphism;53 7.6;6 Parent-of-Origin Effects;54 7.7;7 Other Epigenetic Effects That May Be of Relevance to BPD;55 7.8;8 Experimental Approaches to Epigenetic and Epigenomic Studies of BPD;57 7.9;9 Pilot DNA Methylome Study in BPD;57 7.10;10 Methodological and Experimental Complexities in Studying Epigenetic Factors in Psychiatric Disease;58 7.11;11 Summary;59 7.12;References;60 8;Clinical Endophenotypes for Bipolar Disorder;67 8.1;1 Clinical Endophenotypes for Bipolar Disorder;68 8.2;2 Defining Endophenotypes;69 8.3;3 Evidence for Neurocognitive Endophenotypes for Bipolar Disorder;69 8.4;4 Evidence for Temperamental Endophenotypes for Bipolar Disorder;74 8.5;5 Conclusions;78 8.6;References;78 9;Strategies for the Development of Animal Models for Bipolar Disorder: New Opportunities and New Challenges;84 9.1;1 Introduction;85 9.2;2 Animal Models - Basics;85 9.3;3 A Short Summary of What We Have and Use Today;88 9.4;4 Development of Appropriate Tests;90 9.4.1;4.1 Developing Tests for Behavioral Domains of BPD;91 9.4.2;4.2 Models and Tests for Endophenotypes of Disease;92 9.5;5 Identifying the Best Species and the Best Strains;94 9.5.1;5.1 Model Animals Based on Strain Differences;94 9.5.2;5.2 Nontraditional Models;95 9.6;6 Conclusion;97 9.7;References;97 10;Partial Rodent Genetic Models for Bipolar Disorder;103 10.1;1 Introduction;104 10.2;2 Partial Models for Anhedonia and Depression (Table 1);106 10.3;3 Partial Models for Mania and Excessive Behavioral Excitement (Table 2);109 10.4;4 Partial Models for Affective Vulnerability or Resilience (Table 3);113 10.5;5 Cyclicity;115 10.6;6 Closing Remarks;116 10.7;References;116 11;The Role of the Aminergic Systems in the Pathophysiology of Bipolar Disorder;121 11.1;1 Introduction;122 11.1.1;1.1 Neurobiological Methods;123 11.2;2 Serotonin;124 11.2.1;2.1 Cerebrospinal Fluid Studies;124 11.2.2;2.2 Postmortem Studies;125 11.2.3;2.3 5-HT Receptors and Transporters: PET Imaging Studies;125 11.2.4;2.4 Conclusion;126 11.3;3 Norepinephrine;127 11.3.1;3.1 Metabolite Studies;127 11.3.2;3.2 Tyrosine Hydroxylase in Locus Coeruleus NE Neurons;128 11.3.3;3.3 Genetics;128 11.3.4;3.4 Medication for BPD: Mood Stabilizers;128 11.3.5;3.5 Medication for BP