New Genetics of Mental Illness (eBook)

Front Cover 1
The New Genetics of Mental Illness 
4 
Copyright Page 5
Table of Contents 6
Contributors 8
Preface 11
Chapter 1. The cell, molecular biology and the new genetics 
14 
THE STRUCTURE AND FUNCTION OF CHROMOSOMES 14
GENETICS AND THE MOLECULAR BASIS OF HEREDITY 19
THE NEW GENETICS 24
THE APPLICATION OF MOLECULAR GENETICS TO THE STUDY OF DISEASE 
28 
THE STUDY OF GENE EXPRESSION 35
CONCLUSIONS 37
REFERENCES 38
Chapter 2. Genetic models of madness 40
SIMPLE GENETIC MODELS AND IRREGULAR TRAITS 42
MULTIFACTORIAL MODELS 45
ITERATIVE MODEL FITTING 49
SEGREGATION ANALYSIS 51
THE BENEFITS AND LIMITATIONS OF QUANTITATIVE MODELS 
53 
REFERENCES 54
Chapter 3. The uses and abuses of linkage analysis in neuropsychiatric disorder 
57 
INTRODUCTION 57
LINKAGE STUDIES 58
ILLUSTRATION AND INTERPRETATION 63
CONCLUSION 66
REFERENCES 67
Cgapter 4. The formal problems of linkage 71
THE APPLICATION OF NEW METHODS 72
THE PROBLEMS OF STUDYING THE PSYCHOSES 73
GENES RELATED TO BRAIN FUNCTION 73
THE NATURE OF LINKAGE 74
THE BASIS OF LINKAGE ANALYSIS 75
PROCEDURES FOR INCREASING THE YIELD OF LINKAGE DATA 
79 
REFERENCES 82
Chapter 5. Schizophrenia: How far can we go in defining the phenotype? 
84 
WHICH CRITERIA ARE THE 'MOST VALID' FOR GENETIC RESEARCH? 
85 
THE LIMITATIONS OF OPERATIONAL CRITERIA 86
A POLYDIAGNOSTIC APPROACH TO THE CLASSIFICATION OF PSYCHOTIC ILLNESS 
88 
CONCLUSIONS 95
REFERENCES 95
Chapter 6. Schizophrenia: Classical approaches with new twists and provocative results 
98 
HISTORICAL DEMOGRAPHY AND CONTEMPORARY EPIDEMIOLOGY 
98 
FAMILIAR FAMILIAL RISKS AS CLUES TO MODE OF TRANSMISSION 
102 
UNEXPRESSED GENOTYPES, PATHOPLASTIC PHENOTYPES, AND COMPLEXITY 
105 
CONCLUSIONS 108
REFERENCES 108
Chapter 7. Genetic linkage studies of schizophrenia 
111 
INTRODUCTION 111
GENETICS AND SCHIZOPHRENIA 111
CONCLUSIONS 119
ACKNOWLEDGEMENTS 120
REFERENCES 120
Chapter 8. Aberrant neurodevelopment as the expression of the schizophrenia genotype 
125 
NEURO-IMAGING STUDIES 126
EARLY DEVELOPMENTAL FACTORS 127
NEURODEVELOPMENT AND NEUROPATHOLOGY 128
GENETIC SPECIFICATION OF NEURODEVELOPMENT 133
CONCLUSION 135
ACKNOWLEDGEMENTS 136
REFERENCES 136
Cha[pter 9. The familial aggregation of affective disorders: relation to symptom severity and social provocation 143
CASE DEFINITION AS A PREREQUISITE OF GENETIC EPIDEMIOLOGY 
143 
EPIDEMIOLOGICAL PITFALLS IN GENETIC RESEARCH 144
STRATEGIC APPROACHES TO THE GENETICS OF AFFECTIVE DISORDERS 
145 
THE CAMBERWELL DEPRESSION STUDY 149
REFERENCES 156
Chapter 10. Life events and depressive symptoms: a twin study perspective 
159 
INTRODUCTION 159
METHODS 160
RESULTS 162
DISCUSSION 172
ACKNOWLEDGEMENTS 176
REFERENCES 176
Chapter 11. Genetic markers and affective disorder 
178 
THE EVIDENCE FOR GENETIC INFLUENCES 179
MODE OF INHERITANCE 182
GENETIC MARKERS 184
CONCLUSIONS AND FUTURE PROSPECTS 190
REFERENCES 191
Chapter 12. The genetics of vulnerability to alcoholism 
195 
CLASSICAL GENETIC STUDIES 195
HIGH RISK STUDIES 201
ALCOHOL CHALLENGE STUDIES IN TWINS 202
GENETIC MARKERS 203
ALCOHOL-METABOLIZING ENZYMES 204
MAPPING ALCOHOL-RELATED BEHAVIOURAL TRAITS IN MICE 
205 
CONCLUSIONS 206
REFERENCES 207
Chapter 13. Genes and the aetiology of eating disorders 
211 
RECENT EVIDENCE FOR FAMILIAL FACTORS IN THE AETIOLOGY OF ANOREXIA NERVOSA 
212 
ACKNOWLEDGEMENTS 221
REFERENCES 221
Chapter 14. Growing together and growing apart: the non-genetic forces on children in the same family 
225 
DOES SHARED ENVIRONMENT MATTER? 227
THE ROLE OF CHANCE IN BRAIN DEVELOPMENT 228
MEASUREMENT ERROR 232
POLARIZING AND EQUALIZING EFFECTS 233
REFERENCES 236
Chapter 15. Autism as a genetic disorder 238
TWIN STUDIES 239
FAMILY STUDIES 242
ASSOCIATED SINGLE-GENE CONDITIONS AND CHROMOSOME ANOMALIES 
248 
DILEMMAS AND PROSPECTS 250
REFERENCES 253
Chapter 16. Learning disability and psychiatric/behavioural disorders: a genetic perspective 
258 
INTRODUCTION 258
DOWN'S SYNDROME AND ALZHEIMER'S DISEASE 260
THE PRADER-WILLI SYNDROME, OBESITY ANDOVER-EATING 263
FUTURE DEVELOPMENTS 265
CONCLUSIONS 267
ACKNOWLEDGEMENTS 268
REFERENCES 268
Chapter 17. The genetics of the commonforms of dementia 272
INTRODUCTION 272
TWIN AND FAMILY STUDIES IN ALZHEIMER'S DISEASE 273
AGEING IN ALZHEIMER'S DISEASE 276
GENETIC LINKAGE STUDIES IN ALZHEIMER'S DISEASE 278
CONCLUSIONS 279
REFERENCES 283
Chapter 18. The molecular basis ofAlzheimer's-type dementia 287
WHAT IS THE AETIOLOGY OF LATE-ONSET, FAMILIALALZHEIMER'S DISEASE? 289
WHAT IS THE AETIOLOGY OF ALZHEIMER'S DISEASE INTHE VOLGA GERMAN POPULATION? 289
INTERPRETATION OF RECOMBINANTS: GOING FROMLINKAGE TO GENE 290
IS ALZHEIMER'S DISEASE HETEROGENEOUS AT THEMOLECULAR LEVEL? A UNIFYING HYPOTHESIS 291
REFERENCES 292
Chapter 19. Prediction and prevention inHuntington s disease 294
INTRODUCTION 294
PREVALENCE 294
EARLY ATTEMPTS AT PREDICTION 296
GENE MAPPING 298
PREDICTIVE TESTING 299
PROGRESS TOWARDS IDENTIFICATION OF THE HUNTINGTON'S DISEASE GENE 
304 
ACKNOWLEDGEMENTS 305
REFERENCES 306
Index 312