Download Treating Anxiety and OCD: Past, Present and Future

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