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On OCD, Substance Addiction, PG , Behavioral Addiction and what lies between. Joseph Zohar Tel-Aviv University 1 Some basic facts about OCD 2 Diagnoses of anxiety disorders 6 main categories – Panic Disorder (PD) – with/without agoraphobia – Social Anxiety Disorder (SAnD) – Generalized Anxiety Disorder (GAD) – Posttraumatic Stress Disorder (PTSD) – Obsessive-Compulsive Disorder (OCD) – Simple/Specific Phobia Obsessions (DSM 4) • Recurrent and persistent thoughts, impulses, or images that are experienced as intrusive and inappropriate and that cause marked anxiety or distress. 4 Obsessions (DSM 5) • Recurrent and persistent thoughts, urges, or images that are experienced as intrusive and unwanted and that usually cause marked anxiety or distress. 5 DSM 4 DSM 5 Impulses ~ urges 6 8 Compulsions • Repetitive behaviors (e.g. hand washing counting, checking ) that the person feels driven to perform according to rules that must be applied rigidly. 9 Where does OCD belong? 11 Question for DSM V • Is OCD part of Anxiety disorder ? • If it is separate then what disorders should be included ? • What may be the system that we could use to diagnose those disorders ? • OCD in other psychiatric disorders- Is there a case for “schizo-obsessive” subtype ? 12 Current Classification of Anxiety Disorders Posttraumatic Stress Disorder Phobic Disorders Generalized Anxiety Disorder Panic Disorder ObsessiveCompulsive Disorder 13 Is OCD part of Anxiety disorder ? OCD be included under a grouping of Anxiety and Obsessive-compulsive spectrum Disorders. Current Classification of Anxiety Disorders Posttraumatic Stress Disorder Phobic Disorders Generalized Anxiety Disorder Panic Disorder ObsessiveCompulsive Disorder 18 19 26 Core elements • Compulsive engagement or a craving state prior to behavioral engagement. • Impaired Control over behavioral engagement. • Continued behavioral engagement despite adverse consequences. 27 Core elements of addiction. • Compulsive engagement or a craving state prior to behavioral engagement. • Impaired Control over behavioral engagement. • Continued behavioral engagement despite adverse consequences. Shaffer HF; Addiction 99. 28 Repetitive behaviours Symptom OCD Syndrome Behavioural dimension Addiction 29 From a dimensional point of view Addiction is: Craving state prior to behavioral engagement- OCD & Addiction 30 From a dimensional point of view Addiction is: Craving state prior to behavioral engagement Impaired control over behavioral engagement OCD & Addiction 31 From a dimensional point of view Addiction is: Craving state prior to behavioral engagement Impaired control over behavioral engagement Continued behavioral engagement despite adverse consequences OCD & Addiction 32 On OCD, Substance Addiction, PG , Behavioral Addiction 61 Skipper Butterfly 62 What is the connection between Skipper butterfly and Testing the Boundaries of Addiction? 63 The Future of Psychiatric Diagnosis Phenotype vs. Endophenotype 64 The Future of Psychiatric Diagnosis Phenotype vs. endophenotype Ten Species in One. DNA barcoding reveals cryptic species in the 65 neotropical skipper butterfly. Hebert et al, PNAS, 101: 14813-17, 2004 New approach to diagnosis A different approach is to look beyond the symptoms 73 Two types of Age-related Macular Degeneration • Dry AMD - Geographic Atrophy (GA) is a consequence of the degeneration of the photoreceptor cells and the retinal pigment epithelium (RPE). • Wet AMD - Neovascular AMD is characterized by abnormal growth of capillaries from the choroid and by subsequent exudation of fluid, lipid, and blood. 74 75 76 77 … 78 A different approach is to look beyond the symptoms Endophenotype as a Tool for Future Classification of Anxiety Disorders 81 What do we mean when we talk about Endophenotype ? 84 What Are Endophenotypes? Endophenotypes in psychiatry (Gottesman and Gould, 2003) – Define mediating factors between genes and disorders – More genes involved, greater complexities of phenotypes and genetic analyses Potenza MN. Presentation to Ortho-McNeil CAPSS 314 Investigators. January 21, 2004; Gottesman II, Gould TD. Am J Psychiatry. 2003;160:636-645. Expressed Behavior Phenotype Cognitive function Endophenotype Brain Circuitry 86 Genetic Aetiology What are the tools that we use to study endophenotypes ? Possible tools to explore endophenotype Family aggregation Pharmacological dissection Pharmacological challenge Cognitive challenge Brain structure Brain Circuitry Epigenetic tools Possible tools to explore endophenotype Family aggregation Pharmacological dissection Pharmacological challenge Cognitive challenge Brain structure Brain Circuitry Epigenetic tools Possible tools to explore endophenotype Family aggregation Pharmacological dissection Pharmacological challenge Cognitive challenge Brain structure Brain Circuitry Epigenetic tools Brain Circuitry OCD has: a.Specific brain circuitry: Prefrontal cortex - temporal cortex - thalamus - basal ganglia Background OCD has: a. Specific brain circuitry: Prefrontal cortex - temporal cortex - thalamus - basal ganglia b. OCD is stimuli-depended: Background OCD has: a. Specific brain circuitry: Prefrontal cortex - temporal cortex - thalamus - basal ganglia b. OCD is stimuli-depended: The behavioral therapy is based on this phenomenon (exposure) Expressed Behavior Phenotype Cognitive function Endophenotype Brain Circuitry 97 Genetic - Environment Aetiology Possible tools to explore endophenotype Family aggregation Pharmacological dissection Pharmacological challenge Cognitive challenge Brain structure Brain Circuitry Epigenetic tools Researchers identified abnormally reduced activation of several cortical regions, including the orbitofrontal cortex, during reversal learning in OCD patients and their clinically unaffected close relatives, supporting the existence of an underlying this disorder. endophenotype for The Future of Psychiatric Diagnosis To move from phenotype to endophenotype skipper butterfly Diagnostic Schema 112 Obsessive–compulsive related disorders – DSM-V Preoccupations with bodily sensations or appearance • Body Dysmorphic Disorder • Anorexia Nervosa • Hypochondriasis Neurologic disorders OCD • Tourette’s Syndrome • Sydenham’s Chorea • Autism Impulsive disorders • Sexual compulsions • Trichotillomania • Pathological gambling Hollander E, Allen A. Am J Psychiatry, 2006; Zohar et al. CNS Spectrums 2 (suppl 3), 2007 113 Diagnostic option I – OCDs: Part of affective disorders Affective spectrum disorders Depressive disorders ICDs Autism BDD Hypochondriasis Obsessive–compulsive disorders Anxiety disorders OCD Trichotillomania TS Addiction 114 Testing the Boundaries of OCD New tools 115 A dimensional approach as an endophenotype perspective. 116 Repetitive behaviours Symptom OCD Syndrome Behavioural dimension Addiction 118 A dimensional approach to compulsivity and impulsivity Risk aversive Impulsive OCD BDD AN DEP HYP TS PG SIB Sexual BPD Anticomp social KLEP PD TRICH AUTISM Binge eating Compulsive buying 119 Addiction – loss of control, or impaired control 136 Overlap with OCD ? 138 139 SUD PG OCD Interference with major area of life function Tolerance Withdrawal Repeated unsuccessful attempts to cut back or quit 146 SUD Interference with major area of life function + Tolerance + Withdrawal + Repeated unsuccessful attempts to cut back or quit + PG OCD 147 SUD PG Interference with major area of life function + + Tolerance + + Withdrawal + + Repeated unsuccessful attempts to cut back or quit + + OCD 148 SUD PG OCD Interference with major area of life function + + + Tolerance + + + Withdrawal + + + Repeated unsuccessful attempts to cut back or quit + + + 149 Test SUD PG Iowa Gambling Test (assessing risk-reward decision making) Worse performance Worse 5-HIAA in CSF OCD Worse performance performance Decreased Increased mCPP challenge Euphoria Euphoria Increased OCD Brain function Reduced PFC Reduced PFC Increased PFC Nucleus accumbens Decreased activity Decreased activity Decreased activity Cortico-striatal/thalamocortical Decreased activity Decreased activity Increased activity 150 Diagnostic Schema 155 Obsessive–compulsive related disorders – DSM-V Preoccupations with bodily sensations or appearance • Body Dysmorphic Disorder • Anorexia Nervosa • Hypochondriasis Neurologic disorders OCD • Tourette’s Syndrome • Sydenham’s Chorea • Autism Impulsive disorders • Sexual compulsions • Trichotillomania • Pathological gambling Hollander E, Allen A. Am J Psychiatry, 2006; Zohar et al. CNS Spectrums 2 (suppl 3), 2007 156 Diagnostic option I – OCDs: Part of affective disorders Affective spectrum disorders Depressive disorders ICDs Autism BDD Hypochondriasis Obsessive–compulsive disorders Anxiety disorders OCD Trichotillomania TS Addiction 157 Diagnostic option II – OCDs: Between affective disorders and addiction disorders Affective disorders Depressive disorders Addiction ICDs Autism BDD Hypochondriasis Obsessive–compulsive disorders Anxiety disorders OCD Trichotillomania TS PG 158 Conclusions 181 The Future of Psychiatric Diagnosis Phenotype vs. endophenotype Ten Species in One. DNA barcoding reveals cryptic species in the 182 neotropical skipper butterfly. Hebert et al, PNAS, 101: 14813-17, 2004 183 A different approach is to look beyond the symptoms Diagnostic Schema 190 Repetitive behaviours Symptom OCD Syndrome Behavioural dimension Addiction 193 ICD 10 solution…. , “Disorders of Adult Personality and Behavior”. Under the heading of “Habits and Impulse Disorders” 194 Core elements of addiction. Craving state prior to behavioral engagement, or a compulsive engagement. Impaired Control over behavioral engagement. Continued behavioral engagement despite adverse consequences. Shaffer HF; Addiction 99. 196 Behavioural addictions Behavioural addictions: Pathological gambling Pyromania Kleptomania Compulsive shopping Internet addiction Sexual Addiction ; Zohar et al. Poster presented at SOBP, 2006 198 Addiction Addiction comes from the Latin “addicere”, meaning “enslaved by”, or “bound to”. It is not necessarily related to Substance Abuse Disorders (SUD) 199 Diagnostic option II – OCDs: Between affective disorders and addiction disorders Affective disorders Depressive disorders Addiction ICDs Autism BDD Hypochondriasis Obsessive–compulsive disorders Anxiety disorders OCD Trichotillomania TS PG 200 •Thanks ! 204 • What we see is not necessarily a reflection of the underlie core infrastructure – the genome . 205 •Why? 206 The key is the interaction! Genes are like the keyboard, but the tune can change. How do we name this phenomena? Epigenetic- Epigeneticthe interaction between the genes and the environment. Individuals with one or two copies of the short allele of the 5-HTT promoter polymorphism exhibited more depressive symptoms, diagnosable depression, and suicidality in relation to stressful life events than individuals homozygous for the long allele. What is the concept that we use in order to explore the epigenetic phenomena? What Are Endophenotypes? Endophenotypes in psychiatry (Gottesman and Gould, 2003) mediating factors between genes and disorders – Define – More genes involved, greater complexities of phenotypes and genetic analyses Potenza MN. Presentation to Ortho-McNeil CAPSS 314 Investigators. January 21, 2004; Gottesman II, Gould TD. Am J Psychiatry. 2003;160:636-645. A different approach is to look beyond the symptoms What are the tools that we use to study endophenotypes ? Possible tools to explore endophenotype Pharmacological challenge Cognitive challenge (emotion recognition) Brain function Brain structure Genetic tools Family aggregation The Future of Psychiatric Diagnosis Phenotype vs. endophenotype skipper butterfly Current Classification of Anxiety Disorders Posttraumatic Stress Disorder Phobic Disorders Generalized Anxiety Disorder Panic Disorder ObsessiveCompulsive Disorder 225 OCD toward DSM V: What will change What will remain 226 Question for DSM V Is OCD part of Anxiety disorders ? If it is separate then what disorders should be included ? What system could we use to diagnose those disorders ? OCD in other psychiatric disorders- Is there a case for “schizo-obsessive” subtype ? Question for DSM V Is OCD part of Anxiety disorders ? If it is separate then what disorders should be included ? What system could we use to diagnose those disorders ? OCD in other psychiatric disorders- Is there a case for “schizo-obsessive” subtype ? Workshop Based on Phenomenology, Family studies, Response to treatment, Cognitive function. Biological marker, Epidemiological findings Brain imaging 235 Decreased cognitive flexibility and Cognitive inhibition were found to be present in OCD but not in other anxiety disorders such as SAND, PD and GAD. Addiction ? 267 Compulsive-Impulsive Dimension DSM IV – ICD Pathological Gambling Kleptomania Pyromania Trichotillomania To be added: Compulsive shopping Compulsive computer use Compulsive sexual behavior Internet addiction Intermittent explosive behavior 269 Conclusions It is important to screen for OCD New approaches to OC-related disorders are being considered in the DSM-V process Consensus on treatment of OCD with SSRIs 289 OCD - 1st ‘Revolution’ Over the past 25 years, OCD has moved from being viewed as a rare refractory disorder of psychological origin to a fairly prevalent disorder w with two effective therapeutic strategies (SSRIs and cognitive-behavioural therapy[CBT]), a and a solid neuroscientific conceptualisation OCD -2nd ‘revolution’ 1. OCD is a distinct disorder, separate from anxiety disorders. 2. OCD should be expanded from a single disorder to multiple disorders (OCDs), including trichotillomania, body dysmorphic disorder, etc. 3. Two-step diagnosis - the addition of a dimensional profile to diagnostic work-up. 4. The addition of the dopaminergic angle to serotoninergic formulation of OCD is recommended for OC disorders especially with a motor dimension or reward sensitivity. •Thanks ! 300 •Teşekkür ederim! 301