Food for thought: Psychological
approaches to cognitive decline
in schizophrenia
Til Wykes
Institute of Psychiatry
King’s College London
June 2011
What happened in the last
century?
• UK reduced the number of inpatient beds
– 140,000 in 1950s to 40,000 in 1994
• Long stay hospitals closed
– To reduce institutionalism
• Increased care opportunities in the community
– To increase assimilation
• Rehabilitation options
– To improve work outcomes and daily living skills
Where did that leave people with a
diagnosis of schizophrenia?
• Still a high cost of acute care beds in UK
– £652m : 5.4% all UK NHS costs
• No improvements in social outcomes (Mason
et al, 1996)
• Poor employment record
• High re-admission rates, particularly
following a first episode
In the USA
for Serious mental illness
• $193.2 billion in lost earnings
• $100.1 billion in Health care
• $24.3 in disability benefits
• Grand total --- $317.6 billion
Kessler et al, AJP 2008
Aims
• Do people with a diagnosis of schizophrenia
experience cognitive problems?
• Are these cognitive problems important for
recovery?
• How might we treat them?
Between episodes
“My concentration is very poor. I jump
from one thing to another. If I am talking
to someone they only need to cross their
legs or scratch their head and I am
distracted and forget what I was saying.”
McGhie and Chapman, 1961
During an episode
“Where did all this start and could it
possibly have started the possibility
operates some of the time having the
same decision as you and possibility that I
must now reflect or wash out any doubts
that’s bothering me ……”
From Wykes and Leff, 1982
First episode
“I was looking at A or B for some subjects now I’m looking
at C or D if I’m lucky.”
“Memory loss is the new thing that’s bothering me.”
“I have low concentration”
“I’m coming to terms with the fact that I have got a
learning difficulty.”
Michael, Aged 16 years
Inside my head - Channel 4, June 2002
Do cognitive problems predate the
onset of disorder?
• Jones et al (1998, 2000)
– UK Birth cohort
– Cognitive abnormalities in children pre-schizophrenia
• Lewis et al (1998, 1999)
– Conscripts in Denmark
– Lower IQ in conscripts pre-schizophrenia
• Cannon M. et al (2001)
– New Zealand birth cohort
– Cognitive difficulties at all stages pre-schizophrenia
Learning from service users
“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”
Social functioning
“I want to be able to cook and eat when I want”
Life skills
“I want to live in my own place not a hostel”
Dependence on services
Work
From Bell et al (2001)
Work Habits
Personal
presentation
Work Quality
Cognitive variables (in yellow)
Memory, Attention, Flexibility, Learning
What did symptoms add?
Nothing
Social functioning
Social behaviour during recovery
• What effect do
positive symptoms
add?
55
Problem score
• NOTHING
(Smith et al 2002)
50
poor
working
memory
good
working
memory
45
40
35
0
3
6
9
Time in months
12
Life Skills
Velligan et al 1999
Positive
symptoms
Life
skills
Cognition
Negative
symptoms
Life Skills
Velligan et al 1999
Positive
symptoms
Cognition
42%
Negative
symptoms
Life
skills
Dependence on care
The Netherne Series
Wykes, Katz, Hemsley, Dunn & Sturt, 1990 -1994
Thinking flexibility
Positive
symptoms
60%
Negative
symptoms
Length of illness
Previous skills
Dependence on
psychiatric services
Average weekly costs for service users in
SL&M NHS Trust
Wykes, Reeder, Williams, Corner, Rice and Everitt, 2003
250
200
Day care costs
Inpatient costs
Residential costs
Community care
150
100
50
0
Cognitive
All service users
Impairment and
with a Sz
Sz diagnosis
diagnosis
Thinking, symptoms and outcomes
Occupational
Functioning
Cognition
Social
Functioning
Positive and/or
negative symptoms
Life Skills
Dependence on
psychiatric care
Thinking, symptoms and outcomes
Occupational
Functioning
Cognition
Social
Functioning
Positive and/or
negative symptoms
Life Skills
Dependence on
psychiatric care
Perlick et al, 2008
Community activities
Bowie et al 2006
What do we know about
cognition in schizophrenia?
• Definition of schizophrenia
– Cognition is important (Kraepelin and Bleuler)
– DSMV considering cognition as a diagnostic adjunct
• Cognitive disturbances present
– before onset
– during episodes
– between episodes of acute symptoms
•
•
•
•
•
Effect Size (Cohen's d )
Summary: Cognitive difficulties experienced
by people with schizophrenia
Speed
Memory
Attention
Reasoning
Tact/Social
cognition
• Synthesis
0.2
0
-0.2
-0.4
-0.6
-0.8
-1
-1.2
-1.4
-1.6
-1.8
-2
Memory
ProblemSolving
IQ
Attention
Perspective- Social Cue
taking
Recognition
© Keshavan
About cognitive difficulties in
schizophrenia
•
•
•
•
Start early – before onset
Persist even when symptoms are absent
Interfere with functioning outcomes
Not related to medication (although it can
make them worse)
Effect Size (Cohen's d )
Pharmacological Treatments for
Cognition
1
0.9
(L) 0.8
0.7
0.6
(M) 0.5
0.4
0.3
(S) 0.2
0.1
0
© Keshavan
Antipsychotics d-Cycloserine
(Keefe
(Buchanan et
et al., 2007)
al., 2007)
Glycine
(Buchanan et
al., 2007)
Galantamine Practice Effect
(Buchanan et (Goldberg et
al., 2008)
al., 2007)
The basis of clinical decisions
Isaacs and Fitzgerald BMJ 1999
• Eminence
– seniority of the protagonist with a touching faith in
clinical experience
• Vehemence
– Volume substitutes for evidence
• Eloquence
– Good dress sense and verbal skill
• Confidence
– Only applicable to surgeons
• Evidence
– Randomised controlled trials, meta-analyses
What does this mean for treatments?
• Methodologically rigorous evaluation to assess
success
• Evidence of how to match therapy to patients
• Treatments are feasible and acceptable
• Avoiding:
– Presumptions such as statistical significance is the
same as clinical significance
• Preventing treatment failure
What do we know about the
treatment of cognition?
‘Scientific evidence has shown
that regular brain training, as
offered by the CD, can help defer
the onset of age-related brain decline’
“prevent brain ageing, .. improve memory".
26th Feb 2009
Nintendo brain-trainer 'no better than pencil and paper'
Brain training? Think again, says study
Experts say they are no better than a crossword
'Brain training' claims dismissed
Why?
• Few reports in the peer reviewed literature
• Experimental data was not collected on the specific training
product
• When there was a study
– No independent data
– Studies often had no control group
– Improvements in performance on the task only (practice)
• When there was a comparison group
– No differences between the product and comparison groups
– Comparison group was better
26th Feb 2009
Brain training tested
• 11,000+ participants (normal people?) randomly assigned to:
• 2 Expt groups
– Playing specially designed games for reasoning and problem solving
– Wide range of games similar to commercial software
• Control group
– Surfed the web to answer obscure questions but no games
• at least 10 mins per day 3 times per week for 6 weeks
• Looked at generalisation to other tasks
• RESULTS
• No evidence that brain training worked
• Despite improvements on trained tasks there was no improvement
in the generalisation tasks – more than the control
Owen et al, Nature May 2010
Rate of accumulation of
information on therapies
Cumulative information on psychological therapies
19
60
19
70
19
75
19
80
19
85
19
90
19
95
20
02
20
08
20
09
20
10
800
700
600
500
400
300
200
100
0
Family
Therapy
CBTp
CRT
Can we change cognition?
Cognitive rehabilitation for schizophrenia: Is it
possible? Is it necessary?
Bellack, 1992
Cognitive Remediation in schizophrenia: Proceed …
with caution!
Hogarty and Flesher, 1992
Why was there therapeutic
pessimism?
• Cognitive difficulties are
– part of the diagnosis genesis (Kraepelin and Bleuler)
– apparent before onset (Cannon et al, 2001)
– Cross-sectional studies and longitudinal
studies show few changes over time except in
some elderly patients
• But stability does not mean immutability
What is Cognitive Remediation
Therapy (CRT) ..
• Is a therapy
• Designed to improve cognitive processes
• Such as: attention, memory, executive,
social cognition and metacognition
• Involves training
Cognitive Remediation Experts Workshop (CREW) Florence April 2010
What has been developed?
• Cognitive rehabilitation programmes:
–
–
–
–
–
–
–
–
–
Neurocognitive Enhancement Therapy (NET)
Computer Assisted Cognitive Remediation (CACR)
Brain Fitness
NEAR
REHACOM
COGREHAB
Cognitive enhancement Therapy (CET)
IPT
Cognitive Remediation Therapy - CIRCuiTS
Training usually involves ….
• Errorless learning
– Trying not to allow errors
– Keeps reinforcement high and learning
accurate
• Verbal monitoring
– Overtly then covertly
• Scaffolding
– So that tasks are always a manageable
challenge
What do people think they are
changing?
• The brain
– Neuroplasticity (a bit vague but somehow to
increased the potency of some connections)
• Cognition
– Specifically to increase the use of sustained
attention, cognitive flexibility
• Metacognition
– Increase the use of metacognitive knowledge
or regulation (knowing what you know and how to use this
information)
Does it work?
Meta-analysis of CRT studies
• Studies had a random allocation
procedure
• CRT vs any control
• Contact with all major contributors
• 40 treatments in 39 trials in 109 reports
Til Wykes, Vyv Huddy, Caroline Cellard, Susan McGurk, Pal Czobar (2011)
Global
cognition
effect
sizes
1982
participants
Specific Domains
Attention/Vigilance
Effect size (* significant)
0.250*
Speed of processing
Verbal working memory
Verbal learning and memory
Visual learning and memory
0.258*
0.346*
0.410*
0.150
Reasoning/Problem Solving
Social cognition
Individual tests
0.572*
0.651*
Digit Span
0.422*
Trail making test
WCST
0.319*
0.335*
CPT
0.206
* Significant effects
Is our job done?
Issue date: March 2009
Schizophrenia
Core interventions in the treatment and
management of schizophrenia in
adults in primary and secondary care
This is an update of NICE clinical
guideline 1
www.nice.org.uk
NICE clinical guideline 82
Developed by the National Collaborating Centre for Mental Health
CTAM – total score 100
Thornley & Adams, 1998
Moher et al, 1998, 1995
Marshall et al, 2000
Schultz et al,
Chalmers et al 1981
Jadad et al, 1996
Juni et al, 1999, 2001
Kazdin and Bass, 1989
Sterne et al, 2002
Added
Therapy description
manual
treatment fidelity
•
•
•
•
•
Sample
Allocation
Assessment
Control
Analysis
• Treatment Description
Wykes et al, 2008; Tarrier and Wykes 2004
CTAM Scores for 40 CRT studies
100
90
80
70
60
50
Total CTAM
40
30
20
10
0
Individual Studies
Clinical Trials rating (CTAM*)
40 studies
• CRT mean score 57 (35-87)
• CBTp mean score 61 (27-100)
– Not different from each other
*Tarrier and Wykes, 2004; Wykes et al, 2008
Effect of methodology on CBTp outcome
0.5
0.4
0.3
0.2
0.1
0
M
.
.
m
ng
ni
m
Sy
Sy
d
oo
.
eg
tio
nc
Fu
N
et
rg
Ta
Wykes et al 2008
Effect of methodology on CBTp outcome
0.5
0.4
0.3
0.2
*
Better
method
0.1
0
M
.
.
m
ng
ni
m
Sy
Sy
d
oo
.
eg
tio
nc
Fu
N
et
rg
Ta
* Only target (positive) symptoms show significant effect
Wykes et al 2008
Effect of method on CRT outcome
0.5
0.4
0.3
0.2
0.1
0
C
og
n
iti
on
Fu
nc
tio
Sy
m
n
pt
om
s
Wykes et al 2011
Effect of method on CRT outcome
*
*
Better
method
Wykes et al 2011
Do CRT effects last?
0.5
0.4
0.3
0.2
0.1
0
C
og
n
iti
on
Fu
nc
tio
Sy
m
n
pt
om
s
Wykes et al 2011
Do CRT effects last?
0.5
0.4
0.3
0.2
Durable
change
0.1
0
C
og
n
iti
on
Fu
nc
tio
Sy
m
n
pt
om
s
Wykes et al 2011
Are changes large enough?
Changes from poor to normal performance
45
40
MEMORY
(within one standard deviation
of the normal digit span score)
35
30
CRT
25
Control
20
Numbers of people with poor memory
Baseline N: CRT 21,Control 18,
Post-treatment N: CRT 12 Control 16
Fisher exact test p=0.037,
15
10
5
0
Post-treatment
Number needed to treat = 3.1
Wykes, Reeder, Landau, et al 2007
Tangible effects - Employment
(Bell et al 2005)
Design CRT plus VR vs VR alone
Tangible effects - Reducing failure
People who have already failed in supported
employment
McGurk et al, 2007
Are any CRT differences
important?
– Group vs individual
– Paper and pencil vs Computer
– Therapist present vs absent
– Integrated into services or stand alone
– Embedded in skills training vs not
– Type of training employed:
• drill and practice
• practice + strategic learning (use of metacognition)
Metacognition
• Metacognition: ‘thinking about thinking’
– Metacognitive skills: the ability to reflect upon
one’s own thinking
– Metacognitive knowledge: knowledge about
(i) one’s own cognitive abilities
(ii) the sorts of cognitive abilities needed for a
particular task
(iii) knowledge about thinking in general
CRT aimed at meta-cognitive skills should…
KNOWLEDGE ABOUT THINKING
1. Awareness of strengths and
weaknesses
2. Database of strategies
REGULATION
3. When and where to apply strategies
Thrive in Job
Evidence for a role of meta-cognition
and social functioning
Metacognition
measures
Around 0.5 or more ***
Using WCST
Cognition
WCST Categories
and perseverative
errors
Social
Functioning
GAF, Life Skills
Particularly social
contacts and total scores
Stratta et al, 2009
Do the differences really matter?
• Strategic approach only
produced a significant
functional effect
– DP=0.34 (95% CI -0.11, 0.78);
SC+=0.47 (95% CI 0.22, 0.73)
• Adjunctive psychiatric
rehabilitation increases
functional gains
– Rehab=0.59 (95% CI 0.30, 0.88);
CRT only=0.28(95% CI -0.02, 0.58)
1
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
SC+
Rehab
DP+
Rehab
Effect sizes when rehab provided
Does anything predict CRT
response?
• Age
– Older people do not improve as much (Wykes
et al 2010; McGurk et al, 2009; Kontis et al,
2011)
• Stable symptoms
• Cognitive reserve
– grey matter density related to increased effect (Eack
et al, 2010)
– Also premorbid IQ affects outcome (Kontis et al,
submitted)
What predicts response to Cognitive Enhancement Therapy?
More gray and white matter (“brain reserve”) to begin with,
the better is the response to CET
© Keshavan
We need to know more
• How does CRT improve functioning?
• How much improvement is important?
• Which improvements are important?
Does cognitive improvement drive
functioning improvement?
• People receiving cognitive remediation
and supported work (paid or voluntary)
• Measured
– Cognition
– Work quality
A process model
Cognitive
Flexibility
Memory
Planning
CRT
WORK
quality
Til Wykes, Clare Reeder, Vyv Huddy, Christopher Rice, Rumina Taylor,
Helen Wood, Natalia Ghirasim, Dimitrios Kontis and Sabine Landau
So what next?
• A therapy based on metacognition and
strategy use
• Which service users value
• Which is more feasible?
Computerised therapy
CIRCuiTS
Computerised Interactive
Remediation of Cognition –
Training for Schizophrenia
Wykes, Reeder, Bjorkland, 2010
Improving metacognition
• Strategy-use integral to task completion
• Before beginning a task
– Rate expected difficulty
– Rate expected time to complete task
• On completing the task
–
–
–
–
Score given
Rate usefulness of strategies
Rate actual difficulty of the task
Actual time taken shown
Abstract tasks
An exercise
• Ecologically valid – map on to real-life activities
• Mainly reliant upon multiple executive functions
• Fall under functioning categories:
– Work
– Social situations
– Cooking and shopping
– Travelling
Shopping
What now?
• Can health services afford them?
• Our paper and pencil therapy costs about
£580 per person
• Graduate psychologists, clinical
psychology supervision
Adjusted costs
Post-treatment
Costs in £s
10000
8000
Total Health Care
6000
Total Societal costs
4000
2000
0
CRT group
Control group
Baseline adjusted mean costs
Advantage for CRT - £1086 in health care & £1284 in societal costs, adjusted for
baseline costs and PANSS scores: 95% CI skewed but ns
Wykes, Patel, Knapp et al, 2007; Patel et al, 2009
Learning from service users
Wykes et al 2007 study
“When you improved in therapy then you
felt good about yourself but when you
didn’t improve you felt much worse”
• If memory improves at post-treatment then
– self esteem improved (mean change 1.5 points)
• But when no memory improvement
– self esteem got worse (mean change -3.5 points).
Rose et al 2008
Summary
• Cognitive difficulties interfere with
recovery
• Cognitive remediation therapy
– improves cognition and functioning
– but not symptoms after therapy has ceased
• CRT plus rehab gives the best result
Thanks to a little help from my friends
In particular for the CIRCuiTS trial
•
•
•
•
•
Clare Reeder
Kathy Greenwood
Vyv Huddy
Sabine Landau
Rumina Taylor
Happy Birthday
23rd June
Bethan