What Patients
Patients Want………
Want………
What
………
Want
“I want to be able to do things that other
people do, like have a boyfriend and a job …”
Vocational functioning
“I want to have friends”
friends”
Social functioning
“I want to be able to cook and eat when I
want”
want”
Life skills
Liège, 15-10-2010
Prof. dr. J. van Os
“I want to live in my own place not a hostel”
hostel”
Independent living
Symptoms, Remission
Remission and
and Recovery
Recovery
Symptoms,
The Mediation
Mediation Theory
Theory
The
Pos Symptoms
Neg Symptoms
Social cognition
Information
bias
NeuroNeurocognition
Social Cognition
Remission
Functional recovery
Neurocognition
Societal
participation
Outcome
Existential recovery
The Brain
Brain is
is Sensitive
Sensitive to
to Social
Social Context
Context
The
Top-down cortical processing
Definition: ability to plan, sequence, selfself-monitor,
comprehend, and implement rules
“Expectation”
Representation
social world
Affectively
meaningful
Neurocognition –– Problem
Problem Solving
Solving
Neurocognition
Motivation
Example:
Wisconsin Card
Sorting Test
“Facts”
Bottom-up sensory input
Interaction
Activities of daily living: planning a meal, using
public transportation, following steps for a job task
Van Os et al, Nature, in press
1
Neurocognition –– Sustained
Sustained Attention
Attention
Neurocognition
Neurocognition –– Working
Working Memory
Memory
Neurocognition
Definition: ability to hold information “on line”
line” in
a temporary store and/or to manipulate the
information
Example: Letter Number Sequencing Test
Definition: ability to respond to targets, not respond to
nontargets,
nontargets, over a period of time
Example: Continuous Performance Test
“Press when you see a 7 preceded by a 3”
1 second
100 ms
Stimulus
Response
6
5
7
4
3
7
9
hold
hold
hold
hold
hold
press
hold
K3B4
____
R8C3G5
______
Time
Activities of daily living: carrying on a social
conversation, switching between different tasks
Activities of daily living: identifying relevant information
in a social interaction, discussions with a doctor
Information BiasBias-Social Cognition
Conclusion 1:
Oops! Somebody in
audience angry….
Salient perception
Conclusion 2:
Thinks my lecture is
boring….
Theory of mind
Conclusion 3:
I am a poor speaker
Reasoning/Attributional style
Conclusion 4:
I’d better do
something else…
Behaviour
False-Positive
Salience:
False
-Positive Salience:
White Noise
Noise Task
Task
White
“Voice in the Noise”
Noise”
?
VIP Study,
Study, Bilbao,
Bilbao, Spain
Spain
VIP
Adolescent Psychotic Disorder
n=42
Controls
n=342
Reference sample
n=97
Galdos, Simons et al, 2009
2
jo
Ma
fe
fe
r li
r li
jo
Ma
s
es
str
s
es
str
Hearing aa Voice
Voice in
in the
the Noise
Noise
Hearing
Illness episode 1
Illness episode 2
Recognise more signal in noise, not mediated by neurocognition
Patients:
Controls:
44%
24%
OR=3.6
Stressreactivity
p=0.003
Reward reactivity
reference
[Ref sample: 24%]
Association positive psychotic
experiences (SIS-R): p=0.003
Galdos, Simons et al, Schiz Bull, 2010
month1
month12
Salience
reactivity
Van Os et al, Nature, in press
PSYMATE
Electronic Epidemiology
Epidemiology
Electronic
Negative Affect:
Delusion factor:
uncertain
thoughts rapid
anxious
paranoid
depressed
l
can’t
express
thoughts
I feeguilty
can a
letdthoughts go
lonely
s
thoughts influenced
unreal
7 Affect:
afraid
losing control
1 Positive
Cheerful
relaxed
Hallucination factor:
happy
hearing
voices
satisfied
seeing things
feeling well
Random event
sampling
10 times per day
Positive Stress
Affect (1(1-7)?
Company
Negative
Affect (1(1-7)?
6 days per week
Experience Sampling
Sampling
Experience
GxE == Familial
Familial Psychotic
Psychotic Reactivity
Reactivity
GxE
Minor stress
Negative affect
Day 2
Day 3
Positive
Social
Minor stress
events
Abberant
Negative
Positive salience
affect
affect
Day 4
Day 5
Day 6
Psychotic Reaction
0,8
Day 1
Delespaul, 1995; MyinGermeys et al, 2001
Controls (n=50)
Relatives (n=50)
Psychosis (n=50)
0,7
0,6
P trend <0.001
0,5
0,4
0,3
0,2
0,1
0
-0,1
Delespaul, 1995; Myin
Germeys et al, 2001
1
2
3
4
Stress
5
6
7
Myin Germeys et al, Psychol Med, 2005
3
UK-700
Study
UK-700 Study
UK
Symptoms Impact
Impact Outcome?
Outcome?
Symptoms
Aberrant
salience
Symptoms
Functional outcome
t0
Psychopathology
Subjective measures
Service use
Self-harm
Social disability
t1
Psychopathology
Subjective measures
Service use
Self-harm
Social disability
t2
Psychopathology
Subjective measures
Service use
Self-harm
Social disability
Burns T et al. Lancet. 1999;353(9171):2185-2189. Van Os J et al. Psychol Med. 1999;29(3):595-606.
Van Os J et al. Psychol Med. 1999;29(5):1183-1195.
Disability and
and CrossCross-sectional
Symptoms
Disability
-sectional Symptoms
Cross
0.45
Disability
Effect Size
Positive
Negative
Depressive
Disability and
and Symptom
Symptom Persistence
Persistence
Disability
0.45
Manic
0.4
0.4
0.35
0.35
0.3
Disability
Effect Size
0.25
Positive
Negative
Depressive
Manic
0.3
0.25
0.2
0.2
0.15
0.15
0.1
0.1
0.05
0.05
0
0
Symptom Persistence
Baseline Symptom Score
Van Os J et al. Psychol Med. 1999;29(5):1183-1195.
Van Os J et al. Psychol Med. 1999;29(5):1183-1195.
Information Bias - Social Cognition
Conclusion 1:
Oops! Somebody in
audience angry….
Salient perception
Conclusion 2:
Thinks my lecture is
boring….
Theory of mind
Conclusion 3:
I am a poor speaker
Reasoning/Attributional style
Conclusion 4:
I’d better do
something else…
Theory of Mind
Behaviour
4
Theory of
of mind
mind
Theory
How Does
Does ToM
ToM Affect
Affect Outcome?
Outcome?
How
First order false belief
Neurocognition ToM
John has five cigarettes left in his packet.
packet. He
puts his packet on the table and goes out of
the room. Meanwhile,
Meanwhile, Janet comes in and takes
one of John’
’s cigarettes and leaves the room
John
John’s
without John knowing.
knowing.
ToM question:
question: When
cigarettes
When John
John comes
comes back
back for
for his
his cigarettes,
cigarettes,, how
many does he think he has left?
left?
Functional outcome
Memory question:
question: How many cigarettes are really left in
John’
’s packet?
John
packet?
John’s
Frith & Corcoran,
Corcoran, 1996
Emotional Appraisal
Appraisal of
of Social
Social World
World Test
Test
Emotional
Patients:: Blunted
Blunted Appraisal
Appraisal Social
Social World
World
Patients:
Patients
Positive
appraisal
7
Controls
Patients
6
5
4
0
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16 17
18
19
20
21
22
23
24
25
neutral
3
2
Feels
negative 1
2
3
4
5
Feels
7 positive
6
Patients:: Blunted
Blunted Appraisal
Appraisal Social
Social World
World
Patients:
Patients
Positive
appraisal
Negative
appraisal
1
Galdos et al, in press
How Does
Does ToM
ToM Affect
Affect Outcome?
Outcome?
How
21/24 ctrl>
ctrl>pt
7
Controls
Patients
Neurocognition ToM
6
5
4
0
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
neutral
Blunted emotional understanding
of the social world
3
Functional outcome
2
Negative
appraisal
1
Galdos et al, in press
5
Meta-analysis
of neurocognition
neurocognition vs.
vs. social
social
Meta-analysis of
Meta
cognition impact
impact on
on outcome
outcome
cognition
Meta-analysis
of neurocognition
neurocognition vs.
vs. ToM
ToM
Meta-analysis of
Meta
impact on
on outcome
outcome
impact
ToM
CrossCross-sectional associations between neurocognition,
neurocognition, social cognition and
functional outcome in individuals with nonnon-affective psychosis.
psychosis. Of 285 studies
identified,
identified, 52 studies comprising 2692 subjects met all inclusion criteria.
Fett et al, Neurosci Biobeh.
Biobeh. Rev. 2010
Fett et al, Neurosci Biobeh.
Biobeh. Rev. 2010
Information Bias - Social Cognition
Conclusion 1:
Oops! Somebody in
audience angry….
Conclusion 2:
Thinks my lecture is
boring….
Theory of mind
Conclusion 3:
I am a poor speaker
Reasoning/Attributional style
Conclusion 4:
I’d better do
something else…
A
Salient perception
B
Behaviour
85
15
15
85
Do the following beads come from
container A or container B?
6
Another one,
please
I know the
answer
Another one,
please
I know the
answer
Method: Procedure & sample
Another one,
please
I know the
answer
4 groups,
groups, f(degree
f(degree of vulnerability to psychosis):
psychosis):
Group
0 Average schizotypy (CAPE pct. 4040-60)
1 High schizotypy (CAPE pct. >75)
2 Relatives
3 Patients (schizophrenia + schizoaffective)
schizoaffective)
n
53
41
46
44
7
Data Gathering
Gathering Bias
Bias and
and Psychosis
Psychosis Risk
Risk
Data
Data Gathering
Gathering Bias
Bias and
and Psychosis
Psychosis Risk
Risk
Data
5
4
4
3
Odds ratio
Odds ratio
2
3
2
1
r
cont
Delusion Delusion +
1
y
ols
otyp
schiz
ive
relat
nt
patie
r
cont
Van Dael et al, 2005
y
ols
otyp
schiz
ive
relat
nt
patie
Van Dael et al, 2006
Symptoms, Remission
Remission and
and Recovery
Recovery
Symptoms,
Pos Symptoms
Neg Symptoms
Social cognition
Information
bias
NeuroNeurocognition
The Mediation
Mediation Theory
Theory
The
Social Cognition
Remission
Functional recovery
Neurocognition
Societal
participation
Outcome
Existential recovery
Fin
8