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Systems biology in psychiatric research : from high-throughput data to mathematical modeling / edited by Felix Tretter ... [et al.]. — Weinheim : Wiley-VCH, c2010. – (64.1905/S995) |
Contents
Contents
Foreword V
Preface XV
List of Contributors XVII
Part One Introduction 1
1 Philosophical Aspects of Neuropsychiatry 3
1.1 Development of Research Paradigms and Strategies in Psychiatry
1.2 The Mind-Body Problem - Philosophy of Mind 5
1.3 The Conditions of Scientific Knowledge - Philosophy of Science 11
1.4 Experimental Research - From Observation to Theory 12
1.5 Theoretical (Neuro)psychiatry 17
1.6 Systems Thinking 19
1.7 Perspectives - Towards a "Neurophilosophy" 19
References 22
2 Neuropsychiatry - Subject， Concepts， Methods， and Computational Models 27
2.1 Introduction 27
2.2 Psychiatric Fundamentals
2.3 Neurobiological Fundamentals of Neuropsychiatry 33
2.4 Conclusions and Perspectives 73
References 76
3 Introduction to Systems Biology 81
3.1 Introduction 81
3.2 Data Analysis 83
3.3 ODE Modeling 86
3.4 Results Gained from Systems Biology
3.5 Standard Formats， Databases， and Tools 91
3.6 Future Directions in Systems Biology 93
References 94
4 Mind Over Molecule: Systems Biology for Neuroscience and Psychiatry 97
4.1 Introduction: Mind and Molecule Meet 97
4.2 First Steps: Modeling Excitable Cells 98
4.3 Higher-Level Simulation 101
4.4 Genetic Programs? 104
4.5 Programs in the Brain? 105
4.6 Conclusions 107
References 108
Part Two Basics 111
5 Neuropsychiatry， Psychopathology， and Nosology - Symptoms， Syndromes， and Endophenotypes 113
5.1 Introduction 113
5.2 Conceptual and Historical Introduction 113
5.3 Finding the "Atomic Unit" in Psychopathology: Endophenotypes 116
5.4 Basic Methodological Problem: Time/Spatial Resolution 119
5.5 Future New Diagnostic Schedules and Research 122
5.6 On the Future Role of Psychopathology 123
References 125
6 System Properties of Populations of Neurons in Cerebral Cortex 129
6.1 Introduction 129
6.2 Spatial Structure of Brain Waves 131
6.3 Temporal Structure of the EEG/ECoG 133
6.4 Behavioral Correlates in Spatio-Temporal Patterns of the EEG 136
6.5 Synthesis of Two Levels of Function in the Cortical System 140
6.6 Conclusions and Applications 141
References 143
7 Dopamine and the Electrophysiology of Prefrontal Cortical Networks 145
7.1 Introduction 145
7.2 Electrophysiological Actions of DA in Prefrontal Cortical Circuits 146
7.3 Changes in DA Modulation of Pyramidal Neurons during Adolescence 148
7.4 Changes in DA Modulation of GABA Interneurons during Adolescence 149
7.5 Abnormal Periadolescent Maturation of DA Actions in Developmental Animal Models of Schizophrenia 151
7.6 Implications for Schizophrenia Pathophysiology and Novel Treatments 153
References 154
Part Three Research in Molecular Psychiatry 159
8 Nicotinic Cholinergic Signaling in the Human Brain – Systems Perspective 161
8.1 Introduction 161
8.2 Epidemiological Relevance of the Nicotinic Cholinergic System 162
8.3 nAChrRs and the Cellular Effects of Nicotine 163
8.4 Nicotine and Cognition 169
8.5 Nicotine and Reward 171
8.6 Nicotine and Stress Response 173
8.7 Variation in nAChrR Genes and Smoking 174
8.8 Future Perspectives 178
8.9 Role of Systems Neuroscience 179
References 181
9 Progress in Psychopharmacotherapy though Molecular Imaging 189
9.1 Optimizing Psychopharmacotherapy through Molecular Imaging 189
9.2 Characterization of Neurotransmitter Systems with Molecular Imaging 194
9.3 Focus Schizophrenia 196
9.4 Action of Psychopharmaceuticals in Schizophrenia 199
References 203
10 The Marriage of Phenomics and Genetical Genomics: A Systems Approach to Complex Trait Analysis 207
10.1 Introduction and Brief History of Genetical Genomics 207
10.2 Potential Pitfalls in Phenotype Selection and Current Technology 214
10.3 General Strategy for Identifying Candidate Pathways 218
10.4 Conclusions: Contributions of Genetical Genomic Phenomics to Systems Biology and Medicine 222
References 224
Part Four Data Mining and Modeling 229
11 From Communicational to Computational: Systems Modeling Approaches for Psychiatric Research 231
11.1 Introduction 231
11.2 Steps of the Modeling Process 233
11.3 From Diagrams to Qualitative Models through Petri Nets 235
11.4 Petri Net Modeling of Apoptosis in Leukemic Cells and Neurons 237
11.5 From Stoichiometric (Qualitative) to Kinetic (Quantitative) Genome-Scale Models 239
11.6 From Diagrams Directly to Quantitative Canonical Models: The Concept Map Method 239
11.7 Summary and Outlook 241
References 242
12 Network Dynamics as an Interface between Modeling and Experiment in Systems Biology 243
12.1 Introduction 243
12.2 Aspects of Graph Theory 245
12.3 A Network Perspective on Systems Biology 251
12.4 Network Dynamics 260
12.5 Applicability in Psychiatry 267
References 270
13 Some Useful Mathematical Tools to Transform Microarray Data into Interactive Molecular Networks 277
13.1 Introduction 277
13.2 Microarray Data 278
13.3 Dimensionality Reduction 279
13.4 Statistical Tests: ANOVA and the Naive Bayes Classifier 284
13.5 Bayesian Networks 286
13.6 Final Considerations 294
References 295
14 Biochemical Networks in Psychiatric Disease 301
14.1 Introduction 301
14.2 The Example of Schizophrenia 301
14.3 Looking for Nodes of Interaction 302
14.4 Dopamine Signaling and DARPP-32 303
14.5 Physiological Role of DARPP-32 305
14.6 DARPP-32 in Psychiatric Disease 306
14.7 Modeling Signaling Pathways with a Deterministic Model 308
14.8 Biological Conclusions from the DARPP-32 Model 309
14.9 Stochastic Models 310
14.10 PKA Activation: A Case Study 311
14.11 Conclusions 316
References 316
15 Local Cortical Dynamics Related to Mental Illnesses 321
15.1 Introduction 321
15.2 A Recurrent Neural Network 321
15.3 Concept of an Attractor Network 324
15.4 Noise and Stability 325
15.5 Mental Illnesses 328
15.6 Outlook 334
References 335
16 Epilogue 341
16.1 Some General Remarks 341
16.2 Pharmaceutical Discourse 342
16.3 From Molecular to Cellular Networks 342
16.4 Modeling Strategies 343
References 344
Index 347
