List of Contributors xii
Introduction xvii
SECTION 1 ASSESSMENT AND TREATMENT
1 Assessment 3
Jose M. Menchon
Introduction 3
Detecting OCD 5
Screening in clinical interview 7
Structured interviews 8
Clinical assessment of obsessive-compulsive symptoms 9
Yale?brown obsessive-compulsive scale 10
Dimensional yale?brown obsessive-compulsive scale
(DY?BOCS) 11
Leyton obsessional inventory (LOI) 12
Maudsley obsessional-compulsive inventory (MOCI) 13
Padua inventory (PI) 13
Obsessive compulsive inventory (OCI) 14
Insight 14
Rating insight 15
Assessment of the risk of suicide 17
Differential diagnosis, comorbidities and related disorders
18
Organic brain disorders 19
Schizophrenia 20
Depression 20
Hypochondriasis 20
Phobias 21
Tourette disorder and tic disorders 21
Obsessive-compulsive personality disorder (OCPD) 21
Body dysmorphic disorder (BDD) 21
Hoarding 22
Other disorders 22
Conclusions 22
References 23
2 Pharmacotherapy of obsessive-compulsive disorder 31
Eric H. Decloedt and Dan J. Stein
Introduction 31
Placebo-controlled studies of clomipramine 32
Placebo-controlled studies of fluvoxamine 32
Placebo-controlled studies of fluoxetine 33
Placebo-controlled studies of paroxetine 34
Placebo-controlled studies of sertraline 34
Placebo-controlled studies of citalopram/escitalopram 34
Placebo-controlled studies of venlafaxine 35
Improving early response in OCD 35
Special populations: children 36
Clomipramine 36
Fluvoxamine 36
Fluoxetine 36
Paroxetine 37
Sertraline 37
Citalopram 38
Meta-analyses 38
Tolerability of clomipramine and serotonin reuptake inhibitors
40
Optimal dose of treatment 41
Duration of treatment 42
Refractory OCD 43
Increased dose of SSRI 43
Augmentation of SSRI treatment with antipsychotics 44
Other drugs 45
Alternative modes of administration of SSRIs 46
Combining SRIs 46
Switching SSRIs 46
Adding psychotherapy 47
Future therapeutic options 47
Conclusion 48
References 48
3 Cognitive behavioural therapy in obsessive-compulsive
disorder: state of the art 58
Martin E. Franklin, Addie Goss and John S. March
Theoretical models 58
Treatment 60
Exposure plus response prevention (ERP) 60
Cognitive therapies 63
ERP plus medication 63
OCD protocols 64
Assessment 64
Adult ERP protocol 65
Paediatric ERP protocol 67
Dissemination 67
Future research 69
Summary 69
References 70
4 Electroconvulsive therapy, transcranial magnetic
stimulation and deep brain stimulation in OCD 75
Rianne M. Blom, Martijn Figee, Nienke Vulink and Damiaan
Denys
Introduction 75
Electroconvulsive therapy 75
Transcranial magnetic stimulation 76
Mechanism of action 77
Efficacy of rTMS in OCD 77
Side effects and safety 84
Conclusion and future directions 85
Lesioning 85
Deep brain stimulation 86
Efficacy of DBS in OCD 86
Mechanism of action of DBS in OCD 92
Side effects of DBS in OCD 92
Follow-up treatment 94
Conclusions: DBS 94
Conclusion 94
Acknowledgements 95
References 95
5 Approaches to treatment resistance 99
Stefano Pallanti, Giacomo Grassi and Andrea
Cantisani
Terminological problems and operational definitions 100
Pharmacological strategies in resistant OCD 103
Switching 103
Infusion therapy 104
Cognitive behavioural therapy 105
Serotoninergic agents 106
Dopaminergic agents 108
Glutamatergic agents 113
Opioids 115
Physical therapies 115
Electroconvulsive therapy (ECT) 115
Repetitive transcranial magnetic stimulation (rTMS) 116
Deep brain stimulation (DBS) 116
Family intervention 117
Conclusions and future perspectives 117
References 118
SECTION 2 CLINICAL SPOTLIGHTS
6 Subtypes and spectrum issues 135
Eric Hollander, Steven Poskar and Adriel Gerard
The obsessive-compulsive spectrum 135
Introduction 135
Cluster approach 135
Compulsivity and impulsivity 137
Repetitive behaviour domain 138
Determining placement of proposed OCSDs using cross-cutting
domains 139
Obsessive-compulsive spectrum nosology 144
OCD subtypes: understanding the heterogeneity of OCD 148
Dimensional approach 148
Associated symptom domains 150
Compulsive hoarding: OCPD, OCD subtype, dimension, OCSD or
something else? 151
Conclusion 154
References 154
7 Paediatric OCD: developmental aspects and treatment
considerations 160
Daniel A. Geller, Alyssa L. Faro, Ashley R. Brown and Hannah
C. Levy
Introduction 160
Epidemiology 160
Aetiological considerations 161
Genetic factors 161
Non-genetic factors 164
Aetiology: summary 167
Clinical features 167
Gender and age at onset 168
Elaboration of phenotypic dimensions 168
Comorbid conditions 169
Neuropsychological endophenotypes 170
Clinical features: summary 170
Clinical assessment 171
Differential diagnosis 172
Normal development 172
Other psychiatric disorders 172
Treatment 173
Pharmacotherapy 174
Moderating effect of comorbid conditions 175
Multimodal treatment 176
Medication augmentation strategies in treatment resistance
177
Safety and tolerability 178
Treatment: summary 178
Course and prognosis 179
Conclusions and future research 179
Acknowledgements 180
References 180
SECTION 3 RESEARCH SPOTLIGHTS
8 Methodological issues for clinical treatment trials in
obsessive-compulsive disorder 193
Samar Reghunandanan and Naomi A. Fineberg
Introduction 193
Randomized controlled trials 194
The rationale of placebo 196
Recruitment criteria 199
Diagnosis 199
OCD dimensions and subtypes 200
The problem of comorbidity 201
Rating scales for OCD trials 203
Evaluating anxiety and depression in OCD 204
Measuring response and remission 205
Relapse prevention 207
Treatment-resistant OCD 208
Psychological treatment trials 209
Integrated pharmacological and psychological treatments in OCD
210
Health-related quality of life 211
Summary 211
References 212
9 Serotonin and beyond: a neurotransmitter perspective of OCD
220
Anat Abudy, Alzbeta Juven-Wetzler, Rachel Sonnino and Joseph
Zohar
Serotonin 221
Serotonin and metabolite concentrations in OCD ? 30 years
later 222
Pharmacological challenge tests 224
Pharmacotherapy 225
Animal models and the role of serotonin 226
Dopamine 227
Dopamine and metabolite concentrations in humans 227
Pharmacological challenge tests 228
Pharmacotherapy 229
Animal models and the role of dopamine 231
Glutamate 232
The glutamatergic influence 232
Glutamate and metabolite concentrations in humans 232
Animal models and the role of glutamate 233
Serotonin: is it the one to blame? 233
The puzzle of antipsychotics and OCD: Is dopamine the answer?
234
So, is it a question of location? (Or . . . location, location,
location?) 234
References 235
10 Brain imaging 244
David R. Rosenberg, Phillip C. Easter and Georgia
Michalopoulou
Neuroimaging modalities 244
Structural assessment 244
Functional neurochemical assessment 245
Structural assessment of OCD 246
Total brain volume/ventricles 246
Basal ganglia 246
Prefrontal cortex 248
Medial temporal-limbic cortex 252
Pituitary 253
Supramarginal gyrus 253
White matter 254
Functional neuroimaging studies of OCD 255
Neurochemistry 258
Serotonin 258
N-acetyl-aspartate 258
Choline 259
Creatine/phosphocreatine 262
Glutamate 262
Conclusion 266
Acknowledgements 267
References 268
11 The genetics of obsessive-compulsive disorder: current
status 277
David L. Pauls
Introduction 277
Twin studies 277
Family studies 279
Family history studies 280
Family interview studies 280
Segregation analyses 284
Candidate gene studies 285
Genetic linkage studies 290
Future work 291
Acknowledgements 292
References 292
12 Neurocognitive angle: the search for endophenotypes
300
Samuel R. Chamberlain and Lara Menzies
Introduction 300
Heritability of OCD 301
The concept of an endophenotype 302
Applying the endophenotype construct to OCD 305
Domains of interest in hierarchical modelling of OCD 307
Cognition 307
Neuroimaging 308
Searching for endophenotypes of OCD 311
Cognition 311
Neuroimaging 313
Other potential endophenotypes 316
Summary 317
Acknowledgements and disclosures 319
References 320
13 Conclusion and future directions 327
Joseph Zohar
References 329
Index 331
