On

1

• On
• OCD,
• Substance Addiction,
• PG ,
• Behavioral Addiction
• and what lies between.
• 
  Joseph Zohar
• 
  Tel-Aviv University
• .

2
Some basic facts about OCD
3
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

4
Obsessions (DSM 4)

• Recurrent and persistent thoughts, impulses, or
  images that are experienced as intrusive and
  inappropriate and that cause marked anxiety or
  distress.

5
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.

6
DSM 4 DSM 5

• Impulses urges

7
Obsessions (DSM 4)

• The person attempts to ignore or suppress them or
  to neutralize them with some other thought or
  action..

8
(No Transcript)
9
Compulsions

• Repetitive behaviors (e.g. hand washing counting,
  checking ) that the person feels driven to
  perform according to rules that must be applied
  rigidly.

10
Compulsions

• The behaviors are aimed to reduce distress or
  preventing some dreaded events. However they are
  not connected in realistic way with what they are
  designed to neutralize or prevent or are clearly
  excessive.

11

• Where does OCD belong?

12
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 ?

13
Current Classification of Anxiety Disorders
Posttraumatic Stress Disorder
Generalized Anxiety Disorder
Phobic Disorders
Panic Disorder
Obsessive-Compulsive Disorder
14
Is OCD part of Anxiety disorder ?

• OCD be included under a grouping of Anxiety and
  Obsessive-compulsive spectrum Disorders.

15
Is OCD part of Anxiety disorder ?

• Cortical- Basal circuit abnormalities in OCD
• vs.
• Limbic circuit abnormalities in
• GAD ,SAnD and PD.

16
Insight specificer

• Good or fair insight.
• Poor insight.
• Delusional OCD.
• .

17
Tic related specifier.
18
Current Classification of Anxiety Disorders
Posttraumatic Stress Disorder
Generalized Anxiety Disorder
Phobic Disorders
Panic Disorder
Obsessive-Compulsive Disorder
19
(No Transcript)
20
(No Transcript)
21
(No Transcript)
22
(No Transcript)
23
(No Transcript)
24
(No Transcript)
25
Businessman Howard Hughes

• Was obsessed with avoiding germs since childhood
• Devised insulations of paper towels and tissues
  for protection, and demanded that anything
  brought to him was wrapped in special tissue

• Insisted that doors and windows be sealed
• Was ultimately overwhelmed by his efforts and
  ended his life in filth and neglect

26
(No Transcript)
27
Core elements

• Compulsive engagement or a craving state prior to
  behavioral engagement.
• Impaired Control over behavioral engagement.
• Continued behavioral engagement despite adverse
  consequences.

28
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.

29
Repetitive behaviours
OCD
Behaviouraldimension
Addiction
30
From a dimensional point of view
Addiction is

• Craving state prior to behavioral engagement-
• OCD Addiction

31
From a dimensional point of view
Addiction is

• Craving state prior to behavioral engagement
• Impaired control over behavioral engagement
• OCD Addiction

32
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

33
Some basic facts about OCD
34
Prevalence of OCD Worldwide
Weissman et al (1994), J Clin Psychiatry 55 5-10
35
Prevalence of OCD Worldwide

• Location
• North AmericaUSACanada
• EuropeGermany
• AsiaKoreaTaiwan
• Latin AmericaPuerto Rico
• AustralasiaNew Zealand

Weissman et al (1994), J Clin Psychiatry 55 5-10
36
Prevalence of OCD Worldwide

• Location
• North AmericaUSACanada
• EuropeGermany
• AsiaKoreaTaiwan
• Latin AmericaPuerto Rico
• AustralasiaNew Zealand

• Prevalence
• 2.32.3
• 2.1
• 1.90.7
• 2.5
• 2.2

Weissman et al (1994), J Clin Psychiatry 55 5-10
37
Epidemiology
Anxiety disorders Lifetime () 12-month ()
Panic Disorder 3.5 2.3
Generalised Anxiety Disorder 5.1 3.1
Agoraphobia without panic 5.3 2.6
Simple Phobia 11.3 8.8
Social Anxiety Disorder 13.3 7.9
ObsessiveCompulsive Disorder 1.6 1.0
Any anxiety disorder 29.3 20.3
Kessler et al. Arch Gen Psychiatry 2005
38
How many OCD patients have you seen in the past
two weeks?

1. 0
2. 1-2
3. 3-4
4. 5-6
5. More than 6

39
If OCD is so prevalent why dont we diagnose OCD
more often?
40

• Diagnosis

41
Why dont we diagnose OCD more often?
Many patients try to disguise their symptoms
42

• Ego-dystonic nature

43
What is the prevalence of OCD and OCD comorbidity
in your clinic?

• 0-2
• 2-5
• 5-10
• 10-20
• gt20

44
How we can improve our diagnosis skills in regard
to OCD?
45
Time course of therapeutic intervention in OCD
OCD symptoms start age 1415
Correct diagnosisage 30
Age (years)
0
5
10
15
20
25
30
35
Professionalhelp soughtage 24
Appropriatetreatmentage 31.5
Hollander et al (1996)
46
Five screening questions to identify OCD

• Do you check things a lot?
• Do you wash or clean a lot?
• Is there any thought that keeps bothering you
  that you would like to get rid of but cant?
• Do your daily activities take a very long time to
  finish?
• Are you concerned about orderliness or symmetry?

Zohar Fineberg Screening tool of NICE
Guidelines , 2001
47

• Why is it so important to diagnose OCD ?

48
Why is it so important to diagnose OCD ?

• Common (1.62.2 population)
• Disabling and chronic (life-long)
• Major impact on quality of life
• Effective treatment is available !

49
Why is it so important to diagnose OCD ?

• Common- (1.62.2 population)
• Disabling and chronic (life-long)
• Major impact on quality of life
• Effective treatment is available !

50
Why is it so important to diagnose OCD ?

• Common- (1.62.2 population)
• Disabling and chronic (life-long)
• Major impact on quality of life
• Effective treatment is available !

51

• How disabling is OCD ?

52
The 10 leading causes of disability in the world

• Unipolar depression
• Iron-deficiency anaemia
• Falls
• Alcohol use
• COPD
• Bipolar disorder
• Congenital anomalies
• Osteoarthritis
• Schizophrenia
• ObsessiveCompulsive Disorder

• 10.7
• 4.7
• 4.6
• 3.3
• 3.1
• 3.0
• 2.9
• 2.8
• 2.6
• 2.2

WHO 1997
53

• Why OCD is so disabling ?

54

• Ego-dystonic nature

55
Why dont we diagnose OCD more often?
Many patients try to disguise their symptoms
56
Why is it so important to diagnose OCD ?

• Common (1.62.2 population)
• Disabling and chronic (life-long)
• Major impact on quality of life
• Effective treatment is available !

57
Effective approaches to OCD

• Psychological approach
• Cognitive behavioral therapy (CBT)
• In vivo exposure coupled with response prevention
• Pharmacological approach
• Clomipramine
• Fluoxetine
• Fluvoxamine
• Paroxetine
• Sertraline
• Citalopram
• Escitalopram

58
Effective approaches to OCD

• Psychological approach
• Cognitive behavioral therapy (CBT)
• In vivo exposure coupled with response prevention
• Pharmacological approach
• Clomipramine
• Fluoxetine
• Fluvoxamine
• Paroxetine
  potent serotonin re-uptake inhibitors
• Sertraline
• Citalopram
• Escitalopram

59
Pharmacological specificity of OCD

• Effective
• Potent SSRIs
• Clomipramine
• Fluvoxamine
• Fluoxetine
• Sertraline
• Paroxetine
• Citalopram
• Escitalopram

• Ineffective
• Tricyclics(apart from clomipramine)
• Lithium
• Benzodiazepines
• Buspirone
• Electroconvulsive therapy

• Potentially effective in combination with SRIs
• Conventional antipsychotics (e.g.,
  haloperidol)
• Atypical antipsychotics (e.g., risperidone
  and, quetiapine, olanzapine)

Adapted from Fineberg N, Gale T. Int J
Neuropsychopharmacol 2005 8 (1) 107129
60

• On
• OCD,
• Substance Addiction,
• PG ,
• Behavioral Addiction
• and what lies between.

61
(No Transcript)
62
Skipper Butterfly
63

• What is the connection
• between Skipper butterfly
• and Testing the Boundaries of
• Addiction?

64
The Future of Psychiatric DiagnosisPhenotype vs.
Endophenotype
65
The Future of Psychiatric DiagnosisPhenotype vs.
endophenotype
Ten Species in One. DNA barcoding reveals cryptic
species in the neotropical skipper butterfly.
Hebert et al, PNAS, 101 14813-17, 2004
66
New approach to diagnosis
67
Reliability and Validity in psychiatric nosology

• Before DSM-III, e.g. anxiety neurosis
• Low reliability
• Low validity

68
Reliability and Validity in psychiatric nosology

• Before DSM-III, e.g. anxiety neurosis
• Low reliability
• Low validity
• DSM-III, DSM-IV, e.g. anxiety disorders
• High reliability
• Low validity

69
Reliability and Validity in psychiatric nosology

• Before DSM-III, e.g. anxiety neurosis
• Low reliability
• Low validity
• DSM-III, DSM-IV, e.g. anxiety disorders
• High reliability
• Low validity
• DSM-?,

70
Reliability and Validity in psychiatric nosology

• Before DSM-III, e.g. anxiety neurosis
• Low reliability
• Low validity
• DSM-III, DSM-IV, e.g. anxiety disorders
• High reliability
• Low validity
• DSM-?, e.g. anxiety associated with
  psychobiological markers x, y, and z
• High reliability
• High validity

71
New approach to diagnosis
72

• A different approach is to look beyond
  the symptoms

73
(No Transcript)
74
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.

75
(No Transcript)
76
(No Transcript)
77
(No Transcript)
78

79

• A different approach is to look beyond
  the symptoms

80
Skipper Butterfly
81
Endophenotype as a Tool for Future Classification
of Anxiety Disorders
82
Testing the Boundaries of OCD

• New tools

83
(No Transcript)
84

• What do we mean when we talk about
  Endophenotype ?

85
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. 2003160636-645.
86
Expressed Behavior
Phenotype
Cognitive function
Endophenotype
Brain Circuitry
Genetic
Aetiology
87

• What are the tools that we use to study
  endophenotypes ?

88
Possible tools to explore endophenotype

• Family aggregation
• Pharmacological dissection
• Pharmacological challenge
• Cognitive challenge
• Brain structure
• Brain Circuitry
• Epigenetic tools

89
Possible tools to explore endophenotype

• Family aggregation
• Pharmacological dissection
• Pharmacological challenge
• Cognitive challenge
• Brain structure
• Brain Circuitry
• Epigenetic tools

90
(No Transcript)
91
Possible tools to explore endophenotype

• Family aggregation
• Pharmacological dissection
• Pharmacological challenge
• Cognitive challenge
• Brain structure
• Brain Circuitry
• Epigenetic tools

92
(No Transcript)
93
Brain Circuitry

• OCD has
• Specific brain circuitry
• Prefrontal cortex - temporal
• cortex - thalamus - basal ganglia

94
Background

• OCD has
• Specific brain circuitry
• Prefrontal cortex - temporal
• cortex - thalamus - basal ganglia
• OCD is stimuli-depended

95
(No Transcript)
96
Background

• OCD has
• Specific brain circuitry
• Prefrontal cortex - temporal
• cortex - thalamus - basal ganglia
• OCD is stimuli-depended
• The behavioral therapy is based on this
  phenomenon (exposure)

97
Expressed Behavior
Phenotype
Cognitive function
Endophenotype
Brain Circuitry
Genetic - Environment
Aetiology
98
Possible tools to explore endophenotype

• Family aggregation
• Pharmacological dissection
• Pharmacological challenge
• Cognitive challenge
• Brain structure
• Brain Circuitry
• Epigenetic tools

99

• 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 endophenotype for this
  disorder.

100
The Future of Psychiatric Diagnosis To move from
phenotype to endophenotype
skipper butterfly
101
Questions for DSM V
102
Possible tools to explore endophenotype

• Family aggregation
• Pharmacological dissection
• Pharmacological challenge
• Cognitive challenge
• Brain structure
• Brain Circuitry
• Epigenetic tools

103
Is OCD part of Anxiety disorder ?

• 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.

104
Possible tools to explore endophenotype

• Family aggregation
• Pharmacological dissection
• Pharmacological challenge
• Cognitive challenge
• Brain structure
• Brain Circuitry
• Epigenetic tools

105
Expressed Behavior
Phenotype
Cognitive function
Endophenotype
Brain Circuitry
Genetic - Environment
Aetiology
106
Background

• OCD has
• Specific brain circuitry
• Orbitofrontal cortex ventral caudate nucleus
  (basal ganglia)- thalamus

107

• On
• Substance Addiction
• Behavioral Addiction
• and what lies between.
• 
  Joseph Zohar
• 
  Tel-Aviv University
• .

108
Testing the Boundaries of OCD

• New tools

109
Research planning agenda for DSM-V
obsessivecompulsive related disorders

• At least one of these two biological/
  aetiological findings.
• Family history ()
• Fronto-striatal brain circuitry ()
• 
  i.e., caudate hyperactivity
• At least two of those three criteria.
• 1.Phenomenology Obsessions and/or compulsions
  course
• 2.Co-morbidity
• 3.Treatment response

Zohar et al. CNS Spectrums 2 (suppl 3),
2007
110
DSM-V obsessivecompulsive and related disorders

• OCD ()
• Body Dysmorphic Disorder ()
• Hypochondriasis ()
• Tourettes Syndrome ()
• OC personality disorder ()
• Sydenhams/ PANDAS ()
• Grooming disorders ()
• Trichotillomania (), excoriation (picking)(),
  nail biting ()

Zohar et al. CNS Spectrums 2 (suppl 3), 2007
111
Testing the Boundaries of OCD

• New tools

112

• Diagnostic Schema

113
Obsessivecompulsive related disorders DSM-V
Hollander E, Allen A. Am J Psychiatry, 2006
Zohar et al. CNS Spectrums 2 (suppl 3), 2007
114
Diagnostic option I OCDs Part of affective
disorders
115
Testing the Boundaries of OCD

• New tools

116
A dimensional approach as an endophenotype
perspective.
117
A dimensional approach
118
Repetitive behaviours
OCD
Behaviouraldimension
Addiction
119
A dimensional approach to compulsivity and
impulsivity
120
DSM 4 DSM 5

• Impulses urges

121
Testing the Boundaries of OCD
122

• On
• Substance Addiction
• Behavioral Addiction
• and what lies between.

123
Addiction

• Addiction comes from the Latin addicere,
  meaning enslaved by, or bound to.
• It is not necessarily related to Substance Abuse
  Disorders (SUD)

124

• Addiction the focus is not on chronic use of a
  substance and the associated physical dependence
  (e.g. coffee), but the harmful effects of the
  addictive process on the individuals
• Shifting from physical dependence to the impact
  of addiction

125

• Addiction Shifting from physical dependence to
  the impact of addiction

126

• Addiction
• and
• Impulsivity

127

• Addiction
• loss of control,
• or
• impaired control

128
Behavioral and substance addictions

• Behavioural addictions
• Pathological gambling
• Pyromania
• Kleptomania
• Compulsive shopping
• Internet addiction
• Sexual Addiction

Zohar et al. Poster presented at SOBP, 2006
129

• From
• Substance Addiction
• to
• Behavioral Addiction

130
Behavioural and substance addictions

• Behavioural addictions
• Pathological gambling

Zohar et al. Poster presented at SOBP, 2006
131
Behavioural and substance addictions

• Behavioural addictions
• Pathological gambling
• Pyromania

Zohar et al. Poster presented at SOBP, 2006
132
Behavioural and substance addictions

• Behavioural addictions
• Pathological gambling
• Pyromania
• Kleptomania

Zohar et al. Poster presented at SOBP, 2006
133
Behavioural and substance addictions

• Behavioural addictions
• Pathological gambling
• Pyromania
• Kleptomania
• Compulsive shopping

Zohar et al. Poster presented at SOBP, 2006
134
Behavioural and substance addictions

• Behavioural addictions
• Pathological gambling
• Pyromania
• Kleptomania
• Compulsive shopping
• Internet addiction

Zohar et al. Poster presented at SOBP, 2006
135
Behavioural and substance addictions

• Behavioural addictions
• Pathological gambling
• Pyromania
• Kleptomania
• Compulsive shopping
• Internet addiction
• Sexual Addiction

Zohar et al. Poster presented at SOBP, 2006
136

• Addiction
• loss of control,
• or
• impaired control

137

• Addiction
• and
• Impulsivity

138

• Overlap
• with OCD ?

139
(No Transcript)
140
Behavioural and substance addictions

• Behavioural addictions
• Pathological gambling
• Pyromania
• Kleptomania
• Compulsive shopping
• Internet addiction
• Sexual behaviours
• Addiction
• Reward circuitry, frontal deficits
• Impulsive choices

Zohar et al. Poster presented at SOBP, 2006
141

• In DSM IV, no Addiction
• But
• Abuse
• Dependence
• Withdrawal
• Intoxication

142
From a dimensional point of view
Addiction is

• Craving state prior to behavioral engagement-
• OCD Addiction

143
From a dimensional point of view
Addiction is

• Craving state prior to behavioral engagement
• Impaired control over behavioral engagement
• OCD Addiction

144
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

145
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.

146
OCD PG SUD
Interference with major area of life function
Tolerance
Withdrawal
Repeated unsuccessful attempts to cut back or quit
147
OCD PG SUD
Interference with major area of life function
Tolerance
Withdrawal
Repeated unsuccessful attempts to cut back or quit
148
OCD PG SUD
Interference with major area of life function
Tolerance
Withdrawal
Repeated unsuccessful attempts to cut back or quit
149
OCD PG SUD
Interference with major area of life function
Tolerance
Withdrawal
Repeated unsuccessful attempts to cut back or quit
150
OCD PG SUD Test
Worse performance Worse performance Worse performance Iowa Gambling Test (assessing risk-reward decision making)
Increased Decreased 5-HIAA in CSF
Increased OCD Euphoria Euphoria mCPP challenge
Increased PFC Reduced PFC Reduced PFC Brain function
Decreased activity Decreased activity Decreased activity Nucleus accumbens
Increased activity Decreased activity Decreased activity Cortico-striatal/thalamo-cortical
151
OCD PG SUD
Genes
? D2A1 allele of D2 receptor gene (DRD2)
Treatment
/- SSRI
- (exacerbates) Naltrexone
? Nalmefene
152
The Future of Psychiatric Diagnosis To move from
phenotype to endophenotype
skipper butterfly
153

• A dimensional approach to compulsivity and
  impulsivityFrom
• Compulsivity (Risk Aversion) to
• Impulsivity (Risk Taking )

154
A dimensional approach to compulsivity and
impulsivity
155

• Diagnostic Schema

156
Obsessivecompulsive related disorders DSM-V
Hollander E, Allen A. Am J Psychiatry, 2006
Zohar et al. CNS Spectrums 2 (suppl 3), 2007
157
Diagnostic option I OCDs Part of affective
disorders
158
Diagnostic option II OCDs Between affective
disorders and addiction disorders
159
(No Transcript)
160
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.

161
(No Transcript)
162
(No Transcript)
163
(No Transcript)
164

165
New approach to diagnosis
166

• A different approach is to look beyond
  the symptoms

167
(No Transcript)
168
Endophenotype as a Tool for Future Classification
of Anxiety Disorders
169
OCD toward DSM V Will it change ?What will
remain
170
Obsessions

• Recurrent and persistent thoughts, impulses, or
  images that are experienced as intrusive and
  inappropriate and that cause marked anxiety or
  distress.

171
Obsessions

• Recurrent and persistent thoughts, urges, or
  images that are experienced as intrusive and
  unwanted and that usually cause marked anxiety or
  distress.

172
Compulsions

• The behaviors are aimed to reduce distress or
  preventing some dreaded events. However they are
  not connected in realistic way with what they are
  designed to neutralize or prevent or are clearly
  excessive.

173
Is OCD part of Anxiety disorder ?

• OCD be included under a grouping of Anxiety and
  Obsessive-compulsive spectrum Disorders.

174
Insight specificer

• good or fair insight.
• B. poor insight.
• C. delusional OCD.
• .

175
Tic related specifier.
176
Research planning agenda for DSM-V
obsessivecompulsive related disorders

• Core repetitive behaviours domain
• Shared brain circuitry
• Familial/genetic factors
• Neurotransmitter/peptide systems
• Targeted treatments for symptom domains
• Phenotype and treatment response
• Shaped by Associated Symptom Domains

Zohar et al. Poster presented at SOBP, 2006
177
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

178
Questions

• Internet addiction and OCD are they
  related?
• How could this be further explored using
  endophenotypical tools?

179
OCD toward DSM V What will change What will
remain
180
(No Transcript)
181
Conclusions
182
The Future of Psychiatric DiagnosisPhenotype vs.
endophenotype
Ten Species in One. DNA barcoding reveals cryptic
species in the neotropical skipper butterfly.
Hebert et al, PNAS, 101 14813-17, 2004
183
(No Transcript)
184

• A different approach is to look beyond
  the symptoms

185
Expressed Behavior
Phenotype
Cognitive function
Endophenotype
Brain Circuitry
Genetic
Aetiology
186

• 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 endophenotype for this
  disorder.

187
Questions for DSM V
188
Research planning agenda for DSM-V
obsessivecompulsive related disorders

• Core repetitive behaviours domain
• Shared brain circuitry
• Familial/genetic factors
• Neurotransmitter/peptide systems
• Targeted treatments for symptom domains
• Phenotype and treatment response
• Shaped by Associated Symptom Domains

Zohar et al. Poster presented at SOBP, 2006
189
Current Classification of Anxiety Disorders
Posttraumatic Stress Disorder
Generalized Anxiety Disorder
Phobic Disorders
Panic Disorder
Obsessive-Compulsive Disorder
190

• Diagnostic Schema

191
Obsessivecompulsive related disorders DSM-V
Hollander E, Allen A. Am J Psychiatry, 2006
Zohar et al. CNS Spectrums 2 (suppl 3), 2007
192
Diagnostic option I OCDs Part of affective
disorders
193
Repetitive behaviours
OCD
Behaviouraldimension
Addiction
194
ICD 10 solution. ,

• Disorders of Adult Personality and Behavior.
• Under the heading of
• Habits and Impulse Disorders

195
A dimensional approach to compulsivity and
impulsivity
196
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.

197
Behavioural and substance addictions

• Behavioural addictions
• Pathological gambling
• Pyromania
• Kleptomania
• Compulsive shopping
• Internet addiction
• Sexual behaviours
• Addiction
• Reward circuitry, frontal deficits
• Impulsive choices

Zohar et al. Poster presented at SOBP, 2006
198
Behavioural addictions

• Behavioural addictions
• Pathological gambling
• Pyromania
• Kleptomania
• Compulsive shopping
• Internet addiction
• Sexual Addiction

Zohar et al. Poster presented at SOBP, 2006
199
Addiction

• Addiction comes from the Latin addicere,
  meaning enslaved by, or bound to.
• It is not necessarily related to Substance Abuse
  Disorders (SUD)

200
Diagnostic option II OCDs Between affective
disorders and addiction disorders
201
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

202
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

203

• On
• Substance Addiction
• Behavioral Addiction
• and what lies between.
• .

204

• Thanks !

205

• What we see is not necessarily a reflection of
  the underlie core infrastructure
• the genome .

206

• Why?

207
(No Transcript)
208
(No Transcript)
209
(No Transcript)
210

• The key is the interaction!

211

• Genes are like the keyboard, but the tune can
  change.

212

• How do we name this phenomena?

213

• Epigenetic-

214

• Epigenetic-
• the interaction between the genes and the
  environment.

215
(No Transcript)
216

• 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.

217

• What is the concept that we use in order to
  explore the epigenetic phenomena?

218
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. 2003160636-645.
219

• A different approach is to look beyond
  the symptoms

220
Epigenetic

• We have moved from determinism to determinability.

221

• Biological markers

222

• What are the tools that we use to study
  endophenotypes ?

223
Possible tools to explore endophenotype

• Pharmacological challenge
• Cognitive challenge (emotion recognition)
• Brain function
• Brain structure
• Genetic tools
• Family aggregation

224
The Future of Psychiatric Diagnosis Phenotype
vs. endophenotype
skipper butterfly
225
Current Classification of Anxiety Disorders
Posttraumatic Stress Disorder
Generalized Anxiety Disorder
Phobic Disorders
Panic Disorder
Obsessive-Compulsive Disorder
226
OCD toward DSM V What will change What will
remain
227
Workshop

• .
• The first question is
• Whether or not OCD should be removed from
  Anxiety Disorders.

228
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 ?

229
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 ?

230
Workshop

• Based on
• Phenomenology,
• Family studies,
• Response to treatment,
• Cognitive function.
• Biological marker,
• Epidemiological findings
• Brain imaging

231
Workshop

• Based on
• Phenomenology,
• Family studies,
• Response to treatment,
• Cognitive function.
• Biological marker,
• Epidemiological findings
• Brain imaging

232

• Research summary from Hermesh

233

• Preferential response to SSRIs and
• SRIs
  in OCD
• but not in other anxiety disorders were
• both SRIs, NARIs and SNRIs were
• found to be equally effective.

234
Workshop

• Based on
• Phenomenology,
• Family studies,
• Response to treatment,
• Cognitive function.
• Biological marker,
• Epidemiological findings
• Brain imaging

235
(No Transcript)
236

• 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.

237
Workshop

• Based on
• Phenomenology,
• Family studies,
• Response to treatment,
• Cognitive function.
• Biological marker,
• Epidemiological findings
• Brain imaging

238

• Male Female ratio
• 11 in OCD
• 2-3 1 in GAD, SAnD and PD

239
Workshop

• Based on
• Phenomenology,
• Family studies,
• Response to treatment,
• Cognitive function.
• Biological marker,
• Epidemiological findings
• Brain imaging

240
(No Transcript)
241
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)

242
SPECT in 32yo male with OCD (99mTc-MHPAO)
PCP a 1.LF UK, J.Kosová a J.Kupka
243
(No Transcript)
244

• CS circuit abnormalities in OCD
• vs.
• Limbic circuit abnormalities in GAD ,
  SAnD and PD.

245
18FDG PET panic disorders vs controls
Pašková B, Praško J, Horácek J, Kopecek M,
Škrdlantová L, Belohlávek O., CNS a PCP 2003
246
PET anxiety PTSDgtcontrols
Person 1
247
Workshop

• Based on
• Phenomenology,
• Family studies,
• Response to treatment,
• Cognitive function.
• Biological marker,
• Epidemiological findings
• Brain imaging
• the group felt that it was justified to
  remove OCD from Anxiety Disorders.

248
DSM-V research planning agenda

• Fear and stress circuitry disorders
• GAD and Major Depressive Disorder
• ObsessiveCompulsive and related disorders

Hollander E, Allen A. Am J Psychiatry, 2006
Zohar et al. CNS Spectrums 2 (suppl 3), 2007
249
Questions for DSM 5

• 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?

250
OCD subtypes and OC spectrums

• The dimensional approach may be useful in
  supplementing categorical diagnosis
• OCD subtype and related disorders may have unique
  psychobiological features
• Tics and change in reward processing may reflect
  DA dysfunction
• Impulsive aggression may reflect 5-HT dysfunction
• OCD subtype and spectrum dimensions may represent
  unique treatment targets

251
Part I Diagnosis and dimensions

• Should OCD be diagnosed as an anxiety disorder?
• What are the major subtypes and specifiers of
  OCD?
• Which disorders should be included in the OCD
  spectrum?

252
Part I Diagnosis and dimensions

• Should OCD be diagnosed as an anxiety disorder?
• What are the major subtypes and specifiers of
  OCD?
• Which disorders should be included in the OCD
  spectrum?

253
Subtypes

• Tic related
• Childhood onset/pre-puberty
• Symmetry
• Hoarding
• Gender (post-partum)
• Poor insight (delusional OCD)
• Impulsive
• Inattentive
• PANDAS

Zohar et al. CNS Spectrums 2 (suppl 3), 2007
254
OCD subtypes and OC spectrums

• The dimensional approach may be useful in
  supplementing categorical diagnosis
• OCD subtype and related disorders may have unique
  psychobiological features
• Tics and change in reward processing may reflect
  DA dysfunction
• Impulsive aggression may reflect 5-HT dysfunction
• OCD subtype and spectrum dimensions may represent
  unique treatment targets

255
Part I Diagnosis and dimensions

• Should OCD be diagnosed as an anxiety disorder?
• What are the major subtypes and specifiers of
  OCD?
• Which disorders should be included in the OCD
  spectrum?

256

• OCD specifiers
• Symmetry/ordering
• Washing/contamination
• Checking/doubt
• Aggressive/sexual obs.

257
Research planning agenda for DSM-V
obsessivecompulsive related disorders
Obsessions and/or compulsions 3 of 5 criteria 1
of aetiology/pathophysiology

• Phenomenology
• Obsessions and/or compulsions course
• Co-morbidity
• Family history ()
• Fronto-striatal brain circuitry ()
• i.e., caudate
  hyperactivity
• Treatment response

Zohar et al. Poster presented at SOBP,
2006
258
Questions for DSM 5

• 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?

259
Research planning agenda for DSM-V
obsessivecompulsive related disorders
Obsessions and/or compulsions 3 of 5 criteria 1
of aetiology/pathophysiology

• Phenomenology
• Obsessions and/or compulsions course
• Co-morbidity
• Family history ()
• Fronto-striatal brain circuitry ()
• i.e., caudate
  hyperactivity
• Treatment response

Zohar et al. CNS Spectrums 2 (suppl 3),
2007
260
Research planning agenda for DSM-V
obsessivecompulsive related disorders

• Core repetitive behaviours domain
• Shared brain circuitry
• Familial/genetic factors
• Neurotransmitter/peptide systems
• Targeted treatments for symptom domains
• Phenotype and treatment response
• Shaped by Associated Symptom Domains

Zohar et al. Poster presented at SOBP, 2006
261
Research planning agenda for DSM-V
obsessivecompulsive related disorders

• At least one of these two biological/
  aetiological findings.
• Family history ()
• Fronto-striatal brain circuitry ()
• 
  i.e., caudate hyperactivity
• At least two of those three criteria.
• 1.Phenomenology Obsessions and/or compulsions
  course
• 2.Co-morbidity
• 3.Treatment response

Zohar et al. CNS Spectrums 2 (suppl 3),
2007
262
DSM-V obsessivecompulsive and related disorders

• OCD ()
• Body Dysmorphic Disorder ()
• Hypochondriasis ()
• Tourettes Syndrome ()
• OC personality disorder ()
• Sydenhams/ PANDAS ()
• Grooming disorders ()
• Trichotillomania (), excoriation (picking)(),
  nail biting ()

Zohar et al. CNS Spectrums 2 (suppl 3), 2007
263
Cross talk with obsessivecompulsive related
disorders

• Autism
• Eating disorders
• Huntingtons/Parkinsons
• Schizo-obsessive

Zohar et al. Poster presented at SOBP, 2006
264
Repetitive behaviours
OCD
Behaviouraldimension
Autism
265
If it is separate then what disorders should be
included?

• Phenomenology
• Co-morbidity
• Family History,
• Frontal. Striated Circuitry,
• Treatment response
• In order to be included 3 need to be and at
  least one of them need to be etiology related.

266
A dimensional approach as an endophenotype
perspective.
267

• Addiction ?

268
Behavioural and substance addictions

• Behavioural addictions
• Pathological gambling
• Pyromania
• Kleptomania
• Compulsive shopping
• Internet addiction
• Sexual behaviours
• Addiction
• Reward circuitry, frontal deficits
• Impulsive choices

Zohar et al. Poster presented at SOBP, 2006
269
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

270
Questions for DSM V

• Is OCD part of Anxiety disorder ?
• 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?

271

• Two steps Diagnosis
• Threshold
• And
• Dimensions.

272
Obsessive Compulsive Disorders Dimensions
Diagnostic Threshold
Obsessions and/or Compulsions
Zohar et al. CNS Spectrums 2 (suppl 3), 2007
273
Obsessive Compulsive Disorders 8 Dimensions
Insight Impulsivity Tics/Motor/Sensory Reward
Sensitivity Attention Mood Anxiety Social
Low Low Low Low Low Unstable Low Unstable
High High High High High Stable High Stable
Diagnostic Threshold
Obsessions and/or Compulsions
Zohar et al. CNS Spectrums 2 (suppl 3), 2007
274

• In cases of OCD tic disorder

275
Obsessive Compulsive Disorders 8 Dimensions
Insight Impulsivity Tics/Motor/Sensory Reward
Sensitivity Attention Mood Anxiety Social
Low Low Low Low Low Unstable Low Unstable
High High High High High Stable High Stable
Diagnostic Threshold
Obsessions and/or Compulsions
Zohar et al. CNS Spectrums 2 (suppl 3), 2007
276
Treatment of OCD Subtypes

• In cases of OCD tic disorder
• is
• the addition of neuroleptics
• the treatment of choice?

277
(No Transcript)
278
Treatment of OCD Subtypes

• In cases of OCD tic disorder
• the addition of neuroleptics
• is the treatment of choice.

279

• The group suggested also that the
• reward impulse control related disorders
• should not be included in the OCD
• spectrum

280
Conclusions
281
Reasons to establish OCRDs
Advantages
Help screening
Enhance treatment
Access to insurance a serious and persistent disorder
Influence research funding agencies
Enhance endophenotyping effort
Facilitate drug development (larger market)
Decrease concerns regarding off-label prescribing
Disadvantages
Anxiety is a target for CBT
Fragmentation of anxiety clinics
Decrease use of anti-anxiety drugs for OCD
282
DSM-V obsessivecompulsive related disorders
workgroup conclusions

• Clarify OCD symptom dimensions
• Clarify inclusion OCRD criteria weight aetiology
• Determine which disorders are in the spectrum
• Clarify subtypes
• Define relationship to ICD/addictions
• Utilize existing databases (NCSR, MECA)
• Define associated symptom domains
• Construct endophenotype battery
• Develop self-administered scale for threshold
  diagnosis, that is sensitive to change

Hollander E, Allen A. Am J Psychiatry, 2006
Zohar et al. Poster presented at SOBP, 2006
283
Research planning agenda for DSM-V
obsessivecompulsive related disorders

• Core repetitive behaviours domain
• Shared brain circuitry
• Familial/genetic factors
• Neurotransmitter/peptide systems
• Targeted treatments for symptom domains
• Phenotype and treatment response
• Shaped by Associated Symptom Domains

Zohar et al. Poster presented at SOBP, 2006
284
DSM-V obsessivecompulsive related disorders

• Examined for
• Phenomenology
• Comorbidity
• Course of illness
• Family history
• Genetic factors
• Brain circuitry
• Pharmacological
• dissection

• Discussed by
• Cross species/animal models
• Immune function
• Interventional treatment
• CBT issues
• Cross national/ethnic issues

Hollander E, Allen A. Am J Psychiatry, 2006
Zohar et al. Poster presented at SOBP, 2006
285
A dimensional approach as an endophenotype
perspective.
286
Repetitive behaviours
OCD
Behaviouraldimension
Autism
287
A dimensional approach to compulsivity and
impulsivity
288
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
• Remission is a realistic goal with SSRIs
  Long-term relapse prevention study suggests that
  the dose that makes you well, keeps you well

289
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

290
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
  therapyCBT),
• a and a solid neuroscientific
  conceptualisation

291
(No Transcript)
292
Effective approaches to OCD

• Psychological approach
• Cognitive behavioral therapy (CBT)
• In vivo exposure coupled with response prevention
• Pharmacological approach
• Clomipramine
• Fluoxetine
• Fluvoxamine
• Paroxetine
• Sertraline
• Citalopram
• Escitalopram

293
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.

294
Obsessive Compulsive Disorders 8 Dimensions
Insight Impulsivity Tics/Motor/Sensory Reward
Sensitivity Attention Mood Anxiety Social
Low Low Low Low Low Unstable Low Unstable
High High High High High Stable High Stable
Diagnostic Threshold
Obsessions and/or Compulsions
295
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.

296
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.
• Treatment with SSRIs at higher doses and longer
  duration than with anxiety