MODELING THE PSYCHOPATHOLOGICAL DIMENSIONS OF SCHIZOPHRENIA This page intentionally left blank MODELING THE PSYCHOPATHOLOGICAL DIMENSIONS OF SCHIZOPHRENIA FROM MOLECULES TO BEHAVIOR Edited by MIKHAIL V. PLETNIKOV Johns Hopkins University School of Medicine Baltimore, MD, USA JOHN L. WADDINGTON Royal College of Surgeons in Ireland Dublin, Ireland AMSTERDAM • BOSTON • HEIDELBERG • LONDON NEW YORK • OXFORD • PARIS • SAN DIEGO SAN FRANCISCO • SINGAPORE • SYDNEY • TOKYO Academic Press is an imprint of Elsevier Academic Press is an imprint of Elsevier 125 London Wall, London EC2Y 5AS, UK 525 B Street, Suite 1800, San Diego, CA 92101-4495, USA 225 Wyman Street, Waltham, MA 02451, USA The Boulevard, Langford Lane, Kidlington, Oxford OX5 1GB, UK Copyright © 2016 Elsevier B.V. All rights reserved. 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ISBN: 978-0-12-800981-9 British Library Cataloguing-in-Publication Data A catalogue record for this book is available from the British Library Library of Congress Cataloging-in-Publication Data A catalog record for this book is available from the Library of Congress For information on all Academic Press publications visit our website at http://store.elsevier.com/ Typeset by TNQ Books and Journals www.tnq.co.in Printed and bound in the United States of America Contents Contributors xi Modeling Dimensions of Psychopathology Preface xv in the Context of the Epidemiology of Psychotic Illness 34 Modeling Dimensions of Psychopathology I in the Context of the Pathobiology of Psychotic Illness 35 FROM CLINICAL DIMENSIONS Conclusions 36 TO ANIMAL MODELS Acknowledgments 37 References 37 Clinical and Pathological Aspects 4. Modeling the Positive Symptoms 1. Overview of Schizophrenia: Dimensions of Schizophrenia of Psychopathology TURSUN ALKAM AND TOSHITAKA NABESHIMA ARSIME DEMJAHA AND ROBIN M. MURRAY Introduction 39 The Inadequacy of Diagnostic Categories 5 Delusions and Hallucinations 40 Psychopathological Dimensions—A Challenge to Neuroimaging Studies on Positive Symptoms 42 Categorical Approach to Diagnosis 5 Delusional and Hallucinogenic Signaling 43 The Need for a Precise Dimensional Model 7 Methods to Investigate Positive Symptom-Related Specificity to Disorder 9 Behaviors in Animal Models 47 Chronological Stability of Dimensions 10 Conclusion 49 Differential Associations of Dimensions with Biological References 49 and Clinical Parameters 10 Categories or Dimensions, or Both? 11 Conclusion 12 5. Animal Models of Psychotic Disorders: References 12 Dimensional Approach Modeling Negative Symptoms 2. A Review of the Epidemiology BRIAN P. KIRBY of Schizophrenia ALAN S. BROWN AND FLORENCE S. LAU Introduction 55 Modeling Symptomatology 55 Introduction 17 Model Validity 57 Evidence for Environmental Factors in Schizophrenia 17 Modeling Techniques 57 Infections after Birth 24 Modeling the Negative Symptoms 58 Gene–Environment Interaction 25 Conclusions 61 Future Directions 26 References 63 Conclusion 27 References 27 6. Modeling Cognitive Impairment Animal Models of Psychotic Disorders: FRANCESCA MANAGÓ, HUIPING HUANG AND PAPALEO FRANCESCO Dimensional Approach Cognitive Dysfunctions in Schizophrenia 3. Modeling Dimensions of Psychopathology: and Mouse Models 69 Integration with the Epidemiology and Executive Control 70 Pathobiology of Psychotic Illness Working Memory 72 JOHN L. WADDINGTON Attention 74 Social Cognition 76 Introduction 33 Conclusions and Future Directions 78 Modeling Dimensions of Psychopathology 34 References 79 v vi CONTENTS 7. Modeling Affective Symptoms 9. Social Isolation Rearing and of Schizophrenia Sensorimotor Gating in Rat Models LUKA CULIG AND CATHERINE BELZUNG of Relevance to Schizophrenia: What We Know, and What We Do Not Know Introduction 85 SUSAN B. POWELL AND NEAL R. SWERDLOW Anhedonia 86 Social Interaction 87 Social Isolation Rearing in Rats 125 Avolition 88 Reduced Prepulse Inhibition after SIR 128 Animal Models of Schizophrenia 90 Relevance to Deficient Sensorimotor Gating in Pharmacological Models 90 Schizophrenia? 132 Lesion Models 91 Conclusions 133 Developmental Models 92 Acknowledgments 133 Genetic Models 93 References 133 Affective Assays in Models of Schizophrenia 95 Conclusion 98 10. Glutamate Pharmacological Models References 99 Relevant to Schizophrenia and Psychosis: Can a Receptor Occupancy Normalization Approach Reduce the Gap between Animal II and Human Experiments? MARK RAFTER, KEVIN CF. FONE AND PAULA M. MORAN NEUROBIOLOGY OF PSYCHOTIC DISORDERS Behavioral Effects in Humans 140 Relating to Negative Symptoms of Schizophrenia 140 Relating to Cognitive Symptoms of Schizophrenia 143 Non-Genetic Models Other Effects 143 Neurobiology of NMDA-R Antagonism 143 8. Dysregulation of Dopamine Systems Linking NMDA-R Hypofunction in a Developmental Disruption Model and Schizophrenia 144 of Schizophrenia: Implications for Rodent Modeling of Human NMDA-R Pathophysiology, Treatment, Antagonism 149 and Prevention Diversity of NMDA-R Antagonists 149 SOFIA M. DIBBLE, YIJUAN DU AND ANTHONY A. GRACE NMDA-R Antagonist Behavioral Effects in Rodents 151 Schizophrenia as a Neurodevelopmental Disorder 107 Representing Positive Symptoms 151 Cellular Mechanisms of Prenatal Representing Negative Symptoms 154 MAM Exposure 108 Conclusion and Synthesis 165 Effects of Prenatal MAM Exposure on Cortical References 166 Development 109 Subcortical Hyperdopaminergia in MAM: 11. Modeling the Maternal Immune Behavioral Correlates, Direct Measures, and Activation Risk Factor for Schizophrenia Hippocampal Involvement 111 NATALIA MALKOVA, WEI-LI WU AND ELAINE Y. HSIAO Prodromal Hypersensitivity to Stress in MAM-17 113 Sensorimotor Gating Deficits in MAM-17 114 Introduction 175 Deficits in Prefrontal-Dependent Behaviors and Maternal Infection Risk Factors for Aberrant Prefrontal Activity 115 Schizophrenia 175 Functional Disconnection within Modeling MIA Using Prenatal Polyinosine-Polycytidylic Limbic Circuits 116 Injections 176 Oscillatory Activities in MAM 117 Gene–Environment Interactions 181 Social Withdrawal in MAM 117 Environment–Environment Interactions 182 Antipsychotic Drug Actions in MAM 118 Neonatal Poly (I:C) Model 182 Testing Novel Treatment in the MAM Model 118 Modeling MIA in Primates 183 MAM-E17 as a Model to Study Developmental MIA as a Risk Factor for Autism Spectrum Disorder Trajectory 120 and Schizophrenia 184 References 120 Potential Mechanisms Underlying the Effects of MIA 185 CONTENTS vii Immune Abnormalities in Schizophrenia 186 15. Maternal Nutritional Deficiencies and Immune-Related Genetic Risk Factors for Schizophrenia: Lessons from Animal Models with Schizophrenia 187 a Focus on Developmental Vitamin D Deficiency Conclusion 187 DARRYL W. EYLES AND ANGELA J. DEAN References 187 Maternal Nutrition and Schizophrenia: Ecological Data 243 12. Etiological Environmental Models: Which Micronutrient Deficiencies Are Most Relevant Virus Infection Models to Schizophrenia? 244 HÅKAN KARLSSON Epidemiology of Maternal Nutritional Risk Factors for Schizophrenia 244 Background 193 Controlled Trials of Nutritional Supplements for Experimental Models Employing Viruses 196 Treatment of Schizophrenia 247 Specific Experimental Infections 197 Maternal Nutritional Deficiencies and Schizophrenia- Concluding Remarks 202 Relevant Phenotypes in Animal Models 249 References 203 The DVD-Deficiency Animal Model of Schizophrenia 251 Maternal Nutritional Deficiencies Produce a Convergent Phenotype in Adult Offspring 255 13. Toward a Diathesis-Stress Model of Are Alterations in the Ontogeny of Developing DA Schizophrenia in a Neurodevelopmental Systems a Convergent Early Mechanism in Models Perspective of Maternal Nutritional Deficiency? 256 A. BERRY AND F. CIRULLI Conclusions 257 Acknowledgments 259 Introduction 209 References 259 Stress as a Risk Factor for Psychopathology 211 An Integrative Neurodevelopmental Genetic Models Approach to the Etiopathogenesis of Schizophrenia 212 Animal Models of Schizophrenia 212 16. Mouse Models of Schizophrenia: Risk Genes Modeling Schizophrenia with Prenatal