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E-raamat: Systems Biology in Psychiatric Research: From High-Throughput Data to Mathematical Modeling

Edited by (Klinikum München Ost, München, Germany), Edited by (Ludwig-Maximilian-University of Munich, Munich, Germany), Edited by (Central Institute of Mental Health, Mannheim, Germany), Edited by (University of Dusseldorf, Germany)
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  • Ilmumisaeg: 30-Mar-2010
  • Kirjastus: Blackwell Verlag GmbH
  • Keel: eng
  • ISBN-13: 9783527630288
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Systems Biology in Psychiatric Research: From High-Throughput Data to Mathematical ModelingSuurem pilt
  • Formaat: PDF+DRM
  • Ilmumisaeg: 30-Mar-2010
  • Kirjastus: Blackwell Verlag GmbH
  • Keel: eng
  • ISBN-13: 9783527630288
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This first book to provide a comprehensive overview of the recent progress made in this break-through approach of systems biology in psychiatric research includes expert contributions from a variety of disciplines. Particular focus is placed on high-throughput methods and the analysis of data thus obtained, as well as their use in silico experiments so as to gain an insight into the complex biological processes in neuronal systems.

A must-have for everyone working in psychiatric research.

This first book to provide a comprehensive overview of the recent progress made in this break-through approach includes expert contributions from a variety of disciplines. Particular focus is placed on high-throughput methods and the analysis of data thus obtained, as well as their use in silico experiments so as to gain an insight into the complex biological processes in neuronal systems.
A must-have for everyone working in psychiatric research.
Foreword v
Preface xv
List of Contributors
xvii
Part One Introduction
1(110)
1 Philosophical Aspects of Neuropsychiatry
3(24)
Felix Tretter
1.1 Development of Research Paradigms and Strategies in Psychiatry
4(1)
1.2 The Mind-Body Problem - Philosophy of Mind
5(6)
1.2.1 Monism and Dualism
8(1)
1.2.2 Correlation
9(1)
1.2.3 Identity Theory and its Problems
9(2)
1.2.4 Causation
11(1)
1.2.5 Supervenience
11(1)
1.3 The Conditions of Scientific Knowledge - Philosophy of Science
11(1)
1.4 Experimental Research - From Observation to Theory
12(5)
1.4.1 Hypotheses and Theory
14(1)
1.4.2 The "Epistemic Cycle"
14(1)
1.4.3 Top-Down Analysis - Reductionism?
15(1)
1.4.4 Bottom-Up Explanations - Holism?
16(1)
1.5 Theoretical (Neuro)psychiatry
17(2)
1.6 Systems Thinking
19(1)
1.7 Perspectives - Towards a "Neurophilosophy"
19(8)
References
22(5)
2 Neuropsychiatry - Subject, Concepts, Methods, and Computational Models
27(54)
Felix Tretter
Peter J. Gebicke-Haerter
2.1 Introduction
27(1)
2.2 Psychiatric Fundamentals of Neuropsychiatry
27(6)
2.2.1 General Psychiatry
27(1)
2.2.2 Psychopathology
28(1)
2.2.2.1 Quantitative Psychopathology
28(1)
2.2.2.2 Theoretical Psychopathology
29(1)
2.2.3 Psychiatric Diagnoses
30(1)
2.2.3.1 Diagnostic Criteria
30(1)
2.2.4 Theoretical Psychiatry
30(1)
2.2.4.1 "Computational Neuropsychiatry"
31(1)
2.2.4.2 "Systems Neuropsychiatry"
32(1)
2.3 Neurobiological Fundamentals of Neuropsychiatry
33(40)
2.3.1 Basic Findings of (Neuro)biological Psychiatry
33(1)
2.3.1.1 Neuropsychopathology
33(1)
2.3.1.2 Neurobiological Methods
34(1)
2.3.1.3 Experimental Paradigms
35(3)
2.3.1.4 Structure and Function of the Brain
38(2)
2.3.1.5 Global Circuits and their Connectivities
40(3)
2.3.1.6 Local Networks of Neurons
43(3)
2.3.1.7 Prefrontal Network in Schizophrenia
46(4)
2.3.2 Neuron
50(2)
2.3.2.1 Electrical Signaling of the Neuron
52(2)
2.3.3 Synapse
54(2)
2.3.3.1 Receptors
56(7)
2.3.4 The Cell as a System of Interacting Molecules
63(1)
2.3.4.1 Intracellular Signal Cascades - From Receptor to Genome
63(1)
2.3.4.2 Modeling Signal Transduction Networks Relevant in Schizophrenia
64(2)
2.3.4.3 Genomics and Proteomics
66(1)
2.3.4.4 Gene Regulation - Circular Signaling Pathways
67(2)
2.3.4.5 Systems Biology of the Neuron
69(1)
2.3.5 The Brain as a Neurochemical Oscillator
70(1)
2.3.5.1 Neurochemical Interaction Matrix
71(1)
2.3.5.2 "Neurochemical Mobile"
72(1)
2.4 Conclusions and Perspectives
73(8)
References
76(5)
3 Introduction to Systems Biology
81(16)
Marvin Schulz
Edda Klipp
3.1 Introduction
81(2)
3.1.1 What is Systems Biology?
81(1)
3.1.2 Purpose of Modeling
81(1)
3.1.3 Levels of Modeling
82(1)
3.2 Data Analysis
83(3)
3.2.1 Types of Data
83(1)
3.2.1.1 Purification
83(1)
3.2.1.2 Detection
83(1)
3.2.1.3 Large-Scale Analyses
84(1)
3.2.1.4 Identification of Components
84(1)
3.2.2 Working with Data
84(1)
3.2.2.1 Different Clustering Approaches
85(1)
3.2.2.2 Principal Component Analysis
85(1)
3.3 ODE Modeling
86(5)
3.3.1 Differential Equations
86(1)
3.3.2 Stoichiometric Matrix
86(1)
3.3.3 Reaction Kinetics
87(1)
3.3.4 Steady States
88(1)
3.3.5 Metabolic Control Analysis
88(1)
3.3.6 Simulating Models
89(1)
3.3.7 Parameter Estimation
90(1)
3.4 Results Gained from Systems Biology
91(1)
3.4.1 Just-in-Time Transcription
91(1)
3.5 Standard Formats, Databases, and Tools
91(2)
3.5.1 XML-Based Formats for ODE Models
91(1)
3.5.2 Databases
92(1)
3.5.3 Tools for the Construction, Simulation, and Analysis of ODE Models
93(1)
3.6 Future Directions in Systems Biology
93(4)
References
94(3)
4 Mind Over Molecule: Systems Biology for Neuroscience and Psychiatry
97(14)
Denis Noble
4.1 Introduction: Mind and Molecule Meet
97(1)
4.2 First Steps: Modeling Excitable Cells
98(3)
4.3 Higher-Level Simulation
101(3)
4.4 Genetic Programs?
104(1)
4.5 Programs in the Brain?
105(2)
4.6 Conclusions
107(4)
References
108(3)
Part Two Basics
111(48)
5 Neuropsychiatry, Psychopathology, and Nosology - Symptoms, Syndromes, and Endophenotypes
113(16)
Wolfram Kawohl
Paul Hoff
5.1 Introduction
113(1)
5.2 Conceptual and Historical Introduction
113(3)
5.3 Finding the "Atomic Unit" in Psychopathology: Endophenotypes
116(3)
5.3.1 Susceptibility Genes
117(1)
5.3.2 Requirements for Endophenotypes
118(1)
5.3.3 Identified and Possible Endophenotypes
118(1)
5.3.4 Endophenotypes and the Role of Psychopathology
119(1)
5.4 Basic Methodological Problem: Time/Spatial Resolution
119(3)
5.4.1 An Example: Libet's Experiment
120(1)
5.4.2 The First Problem: The Estimation of W
121(1)
5.4.3 The Second Problem: The Explanatory Power in the Light of a Questionable Time Resolution
121(1)
5.5 Future New Diagnostic Schedules and Research
122(1)
5.6 On the Future Role of Psychopathology
123(6)
References
125(4)
6 System Properties of Populations of Neurons in Cerebral Cortex
129(16)
Walter J. Freeman
6.1 Introduction
129(2)
6.2 Spatial Structure of Brain Waves
131(2)
6.3 Temporal Structure of the EEG/ECoG
133(3)
6.4 Behavioral Correlates in Spatio-Temporal Patterns of the EEG
136(4)
6.5 Synthesis of Two Levels of Function in the Cortical System
140(1)
6.6 Conclusions and Applications
141(4)
References
143(2)
7 Dopamine and the Electrophysiology of Prefrontal Cortical Networks
145(14)
Patricio O'Donnell
7.1 Introduction
145(1)
7.2 Electrophysiological Actions of DA in Prefrontal Cortical Circuits
146(2)
7.3 Changes in DA Modulation of Pyramidal Neurons during Adolescence
148(1)
7.4 Changes in DA Modulation of GABA Interneurons during Adolescence
149(2)
7.5 Abnormal Periadolescent Maturation of DA Actions in Developmental Animal Models of Schizophrenia
151(2)
7.6 Implications for Schizophrenia Pathophysiology and Novel Treatments
153(6)
References
154(5)
Part Three Research in Molecular Psychiatry
159(70)
8 Nicotinic Cholinergic Signaling in the Human Brain - Systems Perspective
161(28)
Arian Mobascher
Georg Winterer
8.1 Introduction
161(1)
8.2 Epidemiological Relevance of the Nicotinic Cholinergic System
162(1)
8.3 nAChrRs and the Cellular Effects of Nicotine
163(6)
8.4 Nicotine and Cognition
169(2)
8.5 Nicotine and Reward
171(2)
8.6 Nicotine and Stress Response
173(1)
8.7 Variation in nAChrR Genes and Smoking
174(4)
8.8 Future Perspectives
178(1)
8.9 Role of Systems Neuroscience
179(10)
References
181(8)
9 Progress in Psychopharmacotherapy though Molecular Imaging
189(18)
Ingo Vernaleken
Gerhard Gruender
Paul Cumming
9.1 Optimizing Psychopharmacotherapy through Molecular Imaging
189(5)
9.1.1 Techniques for Molecular Imaging in Living Brain
189(1)
9.1.1.1 Methodologic Background
189(5)
9.2 Characterization of Neurotransmitter Systems with Molecular Imaging
194(2)
9.3 Focus Schizophrenia
196(3)
9.4 Action of Psychopharmaceuticals in Schizophrenia
199(8)
References
203(4)
10 The Marriage of Phenomics and Genetical Genomics: A Systems Approach to Complex Trait Analysis
207(22)
Laura M. Saba
Paula L. Hoffman
Lawrence E. Hunter
Boris Tabakoff
10.1 Introduction and Brief History of Genetical Genomics
207(7)
10.1.1 Characteristics of eQTLs
209(1)
10.1.2 Recent Developments
210(3)
10.1.3 Extension of Genetical Genomics to Include a Systems Approach to Phenomics
213(1)
10.2 Potential Pitfalls in Phenotype Selection and Current Technology
214(4)
10.3 General Strategy for Identifying Candidate Pathways
218(4)
10.4 Conclusions: Contributions of Genetical Genomic Phenomics to Systems Biology and Medicine
222(7)
References
224(5)
Part Four Data Mining and Modeling
229(118)
11 From Communicational to Computational: Systems Modeling Approaches for Psychiatric Research
231(12)
Eduardo R. Mendoza
11.1 Introduction
231(2)
11.2 Steps of the Modeling Process
233(2)
11.3 From Diagrams to Qualitiative Models through Petri Nets
235(2)
11.4 Petri Net Modeling of Apoptosis in Leukemic Cells and Neurons
237(2)
11.5 From Stoichiometric (Qualitative) to Kinetic (Quantitative) Genome-Scale Models
239(1)
11.6 From Diagrams Directly to Quantitative Canonical Models: The Concept Map Method
239(2)
11.7 Summary and Outlook
241(2)
References
242(1)
12 Network Dynamics as an Interface between Modeling and Experiment in Systems Biology
243(34)
James Smith
Marc-Thorsten Hutt
12.1 Introduction
243(2)
12.2 Aspects of Graph Theory
245(6)
12.3 A Network Perspective on Systems Biology
251(9)
12.3.1 Large-Scale Systems
251(2)
12.3.2 TRNs
253(2)
12.3.3 Metabolic Networks
255(5)
12.4 Network Dynamics
260(7)
12.4.1 General Aspects
260(1)
12.4.2 Binary Dynamics and Cellular Automata on Graphs
261(6)
12.5 Applicability in Psychiatry
267(10)
References
270(7)
13 Some Useful Mathematical Tools to Transform Microarray Data into Interactive Molecular Networks
277(24)
Franziska Matthaus
V. Anne Smith
Peter J. Gebicke-Haerter
13.1 Introduction
277(1)
13.2 Microarray Data
278(1)
13.3 Dimensionality Reduction
279(5)
13.3.1 Principal Components Analysis (PCA)
279(2)
13.3.2 Clustering Methods
281(1)
13.3.2.1 Partitional Clustering: k-Means
282(1)
13.3.2.2 Hierarchical Clustering: Bottom-Up and Top-Down Approaches
282(2)
13.4 Statistical Tests: ANOVA and the Naive Bayes Classifier
284(2)
13.5 Bayesian Networks
286(8)
13.5.1 Definition of a Bayesian Network
286(2)
13.5.2 Learning Bayesian Networks from Data
288(3)
13.5.3 Bayesian Networks and Microarrays
291(3)
13.6 Final Considerations
294(7)
References
295(6)
14 Biochemical Networks in Psychiatric Disease
301(20)
Maria Lindskog
Geir Halnes
Rodrigo F. Oliveira
Jeanette Hellgren Kotaleski
Kim T. Blackwell
14.1 Introduction
301(1)
14.2 The Example of Schizophrenia
301(1)
14.3 Looking for Nodes of Interaction
302(1)
14.4 Dopamine Signaling and DARPP-32
303(2)
14.5 Physiological Role of DARPP-32
305(1)
14.6 DARPP-32 in Psychiatric Disease
306(2)
14.7 Modeling Signaling Pathways with a Deterministic Model
308(1)
14.8 Biological Conclusions from the DARPP-32 Model
309(1)
14.9 Stochastic Models
310(1)
14.10 PKA Activation: A Case Study
311(5)
14.10.1 Conceptual Model
311(1)
14.10.2 Empirical Estimates of Rate Constants
312(1)
14.10.3 Model Validation against Steady-State Data
313(1)
14.10.4 Model Validation against Dynamic Data
314(1)
14.10.5 Deterministic versus Stochastic Algorithms
314(2)
14.11 Conclusions
316(5)
References
316(5)
15 Local Cortical Dynamics Related to Mental Illnesses
321(20)
Marco Loh
Edmund T. Rolls
Gustavo Deco
15.1 Introduction
321(1)
15.2 A Recurrent Neural Network
321(3)
15.3 Concept of an Attractor Network
324(1)
15.4 Noise and Stability
325(3)
15.5 Mental Illnesses
328(6)
15.5.1 Schizophrenia
328(4)
15.5.2 OCD
332(2)
15.6 Outlook
334(7)
References
335(6)
16 Epilogue
341(6)
Peter J. Gebicke-Haerter
16.1 Some General Remarks
341(1)
16.2 Pharmaceutical Discourse
342(1)
16.3 From Molecular to Cellular Networks
342(1)
16.4 Modeling Strategies
343(4)
References
344(3)
Index 347
Dr. F. Tretter is Senior Physician at the Klinikum München-Haar. He studied Psychology, Medicine and social science with separate doctorates. He worked in experimental electrophysiology for several years at Max Planck Institute for Psychiatry. Later, he worked in clinical psychiatry and specialized in addiction. His present research interests are related to withdrawal syndromes and their treatment, systems research in health care delivery systems, computer simulation of neuronal networks in mental disorders and philosophy of science. Dr. G. Winterer is Professor of Psychiatry at the Psychiatric Clinic, University Düsseldorf, and scientific coordinator of DFG research program : "Nicotine: molecular and physiological effects in the central nervous system of humans ". Dr. P. Gebicke-Haerter is Head of the Molecular Biology /DNA Chip Facility in the Dept. of Psychopharmacology at Central Institute of Mental Health, Mannheim. He started his career at the University of Göttingen and the Max-Planck-Institute there, went as a post-doc fellow to Stanford University, Dept. of Neurobiology, and then became a group leader in the Dept. of Pharmacology at the University of Freiburg. After his habilitation, he switched to the Clinic for Psychiatry in Freiburg and in 2000 went to the Central Institute of Mental Health in Mannheim. His CV contains almost 100 original publications, various reviews and/or book chapters.
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