impaired functioning in schizophrenia: models, mechanisms and measurement
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Impaired Functioning in Schizophrenia: Models, Mechanisms and Measurement. Dr Kathryn Greenwood Department of Psychology, University of Sussex & Sussex Partnership NHS Foundation Trust. Overview. Personal Accounts Theories of symptoms, cognition and function in schizophrenia Studies - PowerPoint PPT PresentationTRANSCRIPT
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Impaired Functioning in Schizophrenia: Models,
Mechanisms and Measurement
Dr Kathryn Greenwood
Department of Psychology, University of Sussex & Sussex Partnership NHS Foundation Trust
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Overview• Personal Accounts• Theories of symptoms, cognition and function in
schizophrenia• Studies
– 1 Executive impairment profiles in Schizophrenia (JINS)– 2 Executive impairments and symptoms models (Schiz
Bull) – (including in materials in preparation)– 3 Cognitive impairments and Awareness (Schiz Bull)– 4 Genes and outcome (Neuroscience letters) – 5 VR as a measurement tool (in preparation)
• Clinical implications and future directions
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Personal Accounts
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“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
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“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 yearsInside my head - Channel 4, June 2002
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Work
“I want to be able to do things that other people do, like have a boyfriend and a job …”
Social Functioning
“I want to have friends”
Community Function
“I want to be able to cook and eat when I want”
“I want to live in my own place not a hostel”
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Theoretical Background
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Crow 1980Type I schizophrenia Type II schizophrenia
Positive symptoms Negative symptoms
Intact cognition Impaired cognition
Dopamine abnormalities Ventricular and other structural abnormalities
Good treatment response Poor treatment response
Good outcome Poor outcome
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Liddle 1987, 1991Reality Distortion Disorganisation Psychomotor
PovertyHallucinations/Delusions
Disorders of thinking and affect
Flat affectPoverty of speech movement, gesture
Impaired figure-ground perception
InitiationOrientation AttentionInhibitionWorking memory
InitiationStrategy use Processing in LTM
Poor self care and occupation fx
Poor poor social and recreational fx
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Baddeley’s Working Memory Model
Central Executive Visuospatial Sketchpad
Phonological
LoopStore
Baddeley and Hitch, 1978; Baddeley and Della Sala 1996
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Goldman-Rakic 1987
Central Executive
sensory
motor
Articulat - ory loop
Object
Features
Visual-
Spatial
Adjacent modality-specific working memory systems in DLPFC with own control systems: a fundamental impairment in schizophrenia
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Shallice’s Supervisory Attentional System
• Automatic contention schedulingUntil• i) novel environment • ii) requirement to inhibit one strong or
several weak competing schema
• New Schema construction• Implementation in working memory• Monitoring and Inhibition
Norman and Shallice 1982; Shallice and Burgess 1992; 1996
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Frith’s Cognitive Neuropsychology of Schizophrenia 1992
Three main (theory of mind) disorders:
1) Disorders of willed intentions (action driven by intention)
2) Disorders of self-monitoring 3) Monitoring the Intentions of others
Negative symptoms = absence of initiation of willed intentions, plans and strategies and impaired monitoring of others so missed communication cues
Thought disorder (incoherence of behaviour/affect) = poor inhibition of stimulus driven responses by intentions, as well as impaired self monitoring of communication goal to output and impaired monitoring of listener’s understanding
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Do Specific Cognitive deficits predict specific domains of function?
Velligan et al. 2000
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Neurocognition and function: Are we measuring the right stuff?
Green 2000
learning potential and skill acquisition as mediators of functional outcome
Card Sort
Immediate verbal memory
Community/daily
activities
Social problem solving/ instrumental skills
Psychosocial skill acquisition
Verbal fluency
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Green’s conclusions 2000‘We have learned whether but not HOWneurcognition is related to functional
outcome?’
Need to know what mediates relation between neurocognition and outcome?
• Processes (learning potential) that underlie the ability to acquire and perform life skills
• Social cognition
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There is a need for new cognitive models of negative
symptoms and function in order to improve functional outcomes
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Lincoln et al. (in press)Negative symptoms associated with Impaired Social
Cognition: difficulties in ToMlower self-esteem less self-serving bias Negative self-concepts related to interpersonal abilitiesDysfunctional acceptance beliefs.
Some social cognitive impairments (ToM) were associated with negative symptoms only in people with low self-esteem.
So self-concepts related to social abilities, dysfunctional beliefs and global self-worth alone and in interaction with skill-deficits are associated with negative symptoms
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Rector, Beck and Stolar (2005)
• Low expectancies for pleasure, success, acceptance & perception of limited resources play a major role in the formation of negative symptoms
• Dysfunctional performance beliefs (e.g. If I fail partly, it is as bad as being a complete failure) associated with negative symptoms
• Indirect pathways between functional capacity (cognitive impairment), dysfunctional performance beliefs, and negative symptoms and real-world functioning
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Past and current studies
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Research AimsTo understand the mechanisms through
which bio-psychosocial factors including
• Gene markers • Phenomenology of schizophrenia • Cognitive function &• Psychological function (thinking, mood
and behaviour)
Affect functional outcome in schizophrenia
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Study 1 AimsCategorisation of sub-groups by neuropsychological profile in all cases
confounds the relationship between symptoms and chronicity.
AimsTo explore the severity and profile of executive functioning in relation
to disorganisation and psychomotor poverty and simultaneouslyTo investigate the early and late profiles in first episode and chronic
schizophrenia.
Hypothesis Chronicity will associate with similar but more severe impairment Disorganisation will associate with broad executive deficitPsychomotor poverty with impaired working memory and response
initiation
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Study 1 Measures• working memory
– Digit span, word span, executive golf • planning and strategy formation
– Tower of london, hayling and executive golf strategy scores
• response initiation– Verbal fluency
• response inhibition– Hayling test and complex reaction time test
• IQ – WAIS-R and NART-R
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Novel measures – the question
• To assess similar processes in cognitive & function task Working memory example
• 3KA27
• Crunchy Green salad 250g £1.09Crunchy Green salad 500g £1.24Mixed Salad 250g £1.15Caesar Salad 120g £ 1.05
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Example using Search Strategy
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Novel measures – the answer
• Example using Working Memory3KA27 237AK
• Caesar Salad 120g £ 1.05 Crunchy Green salad 250g £1.09Mixed Salad 250g £1.15Crunchy Green salad 500g £1.24
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Example using Search Strategy
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Study 1 AnalysisGroup differences in executive function
MANCOVA’s controlling for WAIS IQ
Executive profiles • Converted to z-scores and compared
using generalised estimating equations (GEE). Group as between and executive function as within subject factor
Specific islets of strength/deficit• Domain score compared to average of all
others while holding IQ constant
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Study 1 Symptom studyControls (n = 28)
Psychomotor Poverty ( n =
29)
Disorganisation(n = 29)
Statistical Test_______________
Test statistic df p
Age (Years) 33.1 (7.34) 33.9 (8.81) 36.2 (8.04) F=1.2 2,83 .31
Sex (%Male) 89 93 86 X2 =.74 2 .69
Parental SES 3/15/10 4/13/9 (n=7) 2/18/8 (n=8) X2 =1.4 4 .48
Education(Yrs) 14.5 (2.81) 12.8 (2.37) 12.1 (2.19) F=7.0 2,83 .00
Premorbid IQ 110.0 (6.54) 97.0 (12.1) 96.8 (11.5) F=14.8. 2,83 .00
Current IQ 113.2 (16.0) 90.0 (17.6) 88.7 (12.7) F=22.2 2,83 .00
Illness Length (Yrs) 7.83 (7.4) 11.9 (8.55) F=3.9 1,56 .05
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Study 1 Chronicity studyControls (n = 28)
First Episode(n = 22)
Chronic(n = 35)
Statistical Test______________
Test statistic df p
Age (Years) 33.1 (7.34) 28.6 (9.9) 38.1 (6.9) *
Sex (%Male) 89 82 94 X2 = 2.2 2 .33
Parental SES 3/15/10 1/12/8 (n=21) 4/19/11 (n=5) X2 = .87 4 .93
Education(Yrs) 14.5 (2.81) 13.1 (2.98) 12.6 (2.25) F=4.1 2,82
.02
Premorbid IQ 110.0 (6.54) 93.7 (8.9) 99.5 (12.4) F=17.8 2,82
.001
Current IQ 113.2 (16.0) 92.2 (17.2) 91.1 (14.1) F=18.3 2,82
.001
Reality Distortion 19.2 (9.19) 16.9 (9.17) F=.78 1,55
.38
Disorganisation 4.5 (5.9) 10.6 (7.6) F=10.5 1,55
.002
Psychomotor Poverty 7.8 (7.9) 11.6 (8.7) F=2.9 1,55
.095
General Negative 11.5 (7.5) 18.7 (4.7) F=19.7 1,55
.001
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-3
-2.5
-2
-1.5
-1
-0.5
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executive process
z-sc
ore
control psychomotor poverty disorganisation
Distinct profiles and poorer performance in schizophrenia/and disorganisation than controls/pp
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-3
-2.5
-2
-1.5
-1
-0.5
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executive process
z-sc
ore
control first episode chronic
Parallel non-flat profiles and poorer performance in chronic schizophrenia (and FE) compared to controls
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-4
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Executive Profile: Controls Age Young vs Older Controls
Age less than 30
Age greater than 30
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-4
-3
-2
-1
0
1
2 z-s
core
Executive Profile: Medication dose Low vs High Dose
Less than 50% of maximum dose
Greater than 50% of maximum dose
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Executive Profile: Medication Group Standard vs Clozapine vs Atypicals
Standardd.
Clozapine
Atypical
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Study 1 Conclusions• Schizophrenia - characterised by a single executive
profile that reflects the make up of symptoms (psychomotor poverty / disorganisation) but not chronicity
• Parallel but attenuated profile at first episode due to incorporation of those with intact function
• Disorganisation - broad impairment profile incorporating planning and working memory
• Psychomotor poverty - particularly impaired response initiation
• Predictive power of either symptoms or cognition on outcome is short lived but stable symptom-cognition markers should be targets of intervention
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Study 2 • Schizophrenia - characterised by a single executive
profile that reflects the make up of symptoms (psychomotor poverty / disorganisation) but not chronicity
• Parallel but attenuated profile at first episode due to incorporation of those with intact function
• Disorganisation - broad impairment profile incorporating planning and working memory
• Psychomotor poverty - particularly impaired response initiation
• Predictive power of either symptoms or cognition on outcome is short lived but stable symptom-cognition markers should be targets of intervention
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Negative Symptoms matter in the Leap from Cognition to
Community Function in Schizophrenia:
Dr K Greenwood, Dr S Landau, Professor T Wykes
Department of Psychology, Institute of Psychiatry, London, UK.
e-mail: [email protected]
Implications for Intervention
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Introduction• People with schizophrenia and negative
symptoms have poor functioning (occupation, community and daily living skills)
• Poor functioning is a source of distress for both people with schizophrenia and their families
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Negative Symptoms associated with Community Function
• Negative symptoms (flat affect, poverty of speech, apathy) affect function:
• Only Indirectly through link with Cognition
• Independently
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Cognitive Impairments associated with Community
Function• Executive function predicts Community
function, Occupation, Daily living • Working Memory predicts Occupation
• Global cognition predicts Daily living
• Cognition is a stronger predictor than symptoms (Green 2000)
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Cognitive Impairments associated with negative
symptomsNegative symptoms:
Linked theoretically with : Executive function and Working memory
Initiation/generation of strategies (Frith) Working memory (Goldman-Rakic)
Linked Empirically with: Response Initiation (Franke et al. 1993)
Immediate/working memory (Pantelis et al 2001) Focused/switching attention (Buchanan et al 1994)
Initiation/working memory/strategy use (Greenwood 2000)
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Objective • To investigate specific relationships between
negative symptoms, executive/working memory functions and community function and in particular to investigate the independent effect of negative symptoms
• Reducing confounding of negative symptoms and low IQ
• Using process approach and theoretically driven framework
• Also using a novel measure to directly assess community function
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Design• Cross sectional Comparison:
22 Healthy controls 28 Schizophrenia & negative symptoms balanced general22 Schizophrenia & no negative symptoms cognitive impairment
• Balancing: Age, Sex, Premorbid IQ,
• Predictors: working memory, initation, inhibition, strategy, symptoms
• Analysis: Identify individual associations to function, interactions, and final regression model
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The measure A test of supermarket shopping Skills
Participants had to select 10 items from ashopping list. Measures were taken of:
– accuracy (items correct)– Efficiency (time/route length) – Redundancy (no. aisles entered above minimum)– Strategy
(adapted from Test of Grocery Shopping Skills, Hamera and Brown 2000)
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Research Questions• Is directly assessed community function more impaired in
people with schizophrenia and negative symptoms (when directly assessed and without IQ confound)
• Do specific executive processes predict specific community functions (working memory-accuracy; strategy-strategy)
• Do the associations differ in different symptom groups (use of theoretical rationale to investigate moderator effect of negative symptoms)
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Subject Characteristics
Controls Non-negative
Negative
Age (Years)
36.23 35.28 35.07
Sex (M/F) 16/6 19/6 20.8
Premorbid IQ
89.77 91.12 91.36
RBMT Score 15.242-23
13.52 7 – 23
WCST Score 2.88 0 - 6
2.07 0 - 6
Total PANSS 50.88 35 - 76
62.11*42 - 88
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Statistical Analyses • Association Analyses (GLR – with binomial, Poisson, normal
distribution)*
Stage 1: Identify individual associations (cognition x function)
Stage 2: Identify individual interactions (cognition x symptom group x
function)
Stage 3: Conduct final regression model
Premorbid IQ controlled
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Poorer strategy, working memory, initiation
in negative group
0
1
2
3
4
control non-neg neg
Spatial Strategy Score
0
2
4
6
8
10
12
control non-neg neg
Verbal working memory score
05
10152025303540
control non-neg neg
Verbal fluency initiation
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Community function: Poorer accuracy, efficiency and strategy in
negative groupCorrect lowest price
012345678
control non-neg neg
Time Taken
0
10
20
30
40
50
60
control non-neg neg
Tim
e ta
ken
0
2
4
6
8
10
12
1416
control non-neg neg
Aisles above Minimum
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The results
• Some cross group predicted associations between cognition and function (e.g. accuracy and strategy, efficiency and working memory)
• Some executive-function associations only with negative symptoms (working memory and accuracy, IQ and efficiency)
• Not just because of poor general cognition and Not a threshold effect but a true interaction
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Executive & premorbid factors associated with community function• Working memory associated with all
function measures (p = .01- < .001)• Strategy associated with strategy measures
and route length (p = .04- < .001)• Initiation associated with correct items,
efficiency and strategy (p = .02 - <.001)
• Premorbid IQ associated with most measures (p = 0.04-<0.001)
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Independent cognition to community function associations are present only
for specific groups• In Negative group
Working memory associated with size accuracy price accuracy
Verbal fluency associated with aisles above minimumPremorbid IQ associated with correct items
time• In Controls
Working memory associated with aisle strategyVerbal fluency associated with aisles above minimum
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Conclusion so far…
• Community functions are more impaired in schizophrenia with negative symptoms even compared to a group with equivalent general cognitive function
• Executive functions associated with community function only in negative not non-negative schizophrenia
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Negative symptoms moderate the association between impaired
executive and community functions• No significant interaction of working
memory severity factor within negative group
• Moderating effect is not a cognitive threshold effect
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A synergistic cognition-symptom interaction predicts community
function: A working memory model
Core Working Memory
Negative Symptoms
Community
FunctionAbility
Dom
ain
Spec
ific
WMCF
exp.
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Research Question - 2
• Do cognition or symptoms predict changes in community function when investigated longitudinally?
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Design - 2• Longitudinal follow-up of shopping
function (n=43) :
• Comparing baseline (t1) to 6 months (t3)
• Broader range Demographics, Cognition, Symptoms and function
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Influences on recovery Differences in baseline measures between
improvers (n=21) and non-improvers (n=22)– initial community function (p <.001) – self-esteem (p = 0.026)– working memory (p=0.047)
Independent predictors of improvement on– Initial community function (p = 0.004)– Self esteem (p <0.001)– Working memory (p = 0.088)
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A synergistic cognition-symptom interaction predicts community
function: A working memory model
Core Working Memory
Negative Symptoms
Community
FunctionAbility
Dom
ain
Spec
ific
WMCF
Level
Self esteem
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The design III: the relationship of SST to other functions
• Cross sectional comparison of standardised shopping function to other function measures(n=53) :
• Accuracy correlated with social behaviour (SBS) (r = -0.4 p = 0.001) but not level of independence in day care, number of activities or self-reported shopping activities
• Efficiency correlated with level of independence in day care and independence in handling money (Spearman’s rho = -0.4 p = 0.005 and -0.3 p = 0.047) but not with social behaviour, number of activities or other self-reported shopping activities
• The ability to shop accurately seems linked to the appropriateness of other social behaviours and the ability to shop efficiently seems linked to other measures of independence in function. Shopping function is unrelated to activity levels in shopping or other behaviours.
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Implications• Synergistic interaction between negative
symptoms and working memory impairments may contribute to progressively poorer community function
• Remediation programmes that employ CBT/ CRT to target negative symptoms/ low self esteem AND domain specific cognition/working memory may break the reciprocal link, enhance generalisation and improve functional outcome
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Why consider a VR assessment of function?
• Most commonly used measures are the GAF and employment status (recent review Greenwood et al. unpublished data)
• Rehabilitation may be maximised by identifying cognitive targets for intervention through refined assessment (Greenwood et al. 2005)
• But few brief direct standardised assessments (McKibbin et al. 2004)
• Need for brief, easily administered community function assessments in schizophrenia, validated against real life functions and underlying cognitive processes
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The Use of Virtual Reality in Assessment and Intervention
• VR apartment for medication management and adherence • VR functional skills assessment for social competence• VR avatar for assessment of social approach and anxiety • VR street, tube train and library for understanding thinking
patterns underpinning to psychosis• VR Park and Maze for real world navigation (allocentric and
egocentric memory)• VR maze for real world sensory integration in working memory• VR supermarket to assess executive function in different clinical
groups BUT no studies in schizophrenia have compared RL and VR
performance on same task and some suggest differential performance in VR dependent on environment and associated cognitive processes
Freeman et al. 2003;2005; Jang et al. 2005; Baker et al 2006; Sorkin et al. 2006; 2008; Kurtz et al. 2007; Ku et al. 2007; Weniger et al 2008; Kim et al. 2008; Park et al. 2009; Zanyi et al. 2009; Josman et al. 2009; Landgraf et al. 2010
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The research questions1. Does performance in VR relate to
the same in RL? 2. Do they share common or distinct
cognitive processes?3. Do these processes differ in different
symptom groups?
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Community Function Measure • Supermarket Shopping Task
(adapted from TOGSS: Hamera and Brown, 2000)
• Virtual Reality Shopping Taskpresented on flat screen computer with joystick(RG Morris et al.)
In each task participants had to select 10 items from a shopping list. Measures were taken of:
– accuracy (items correct)– time – redundancy (no. aisles entered above minimum)
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Cognitive measures
• Memory and Working Memory – Visual Reproduction and Letter-Number Span
• Executive function – BADS- key search & Verbal fluency
• Social Cognition– Intention Inference Test (Sarfarti et al. 1997)
(IQ NART-R and WASI also assessed)
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Participant Demographics
Participants (n=43)Mean (n) s.d. range
Age (Years) 39.5 11.9 21-63 Sex (M/F) 23/21 - -
PANNS positive 14.6 6.5 7 – 28PANSS negative 13.4 5.5 8-27
PANSS total 57.8 18.6 32-103
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Participant Cognition
Participants (n=43)Mean (n) s.d. range
Premorbid IQ 103.6 11.9 74-129mean scaled score
(WASI) 9.2 3.3 3-16
Verbal Fluency 33.2 12.2 8-62Strategy (BADS KS) 2.0 1.1 0-4
Working Memory (L-N) 8.3 3.3 2-16Spatial Memory (Vis
Rep)6.3 4.7 0-17
Social Cognition(comic strip
20.2 5.8 5-27
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Does performance in VR relate to the same in RL?
RL accuracy RL time RL aisles VR accuracy VR time VR aisles
RL accuracy \ -.21 p=.20 -.18 p=.27 .30 p=.05 -.18 p=.25 -.08 p=.61
RL time \ .69 p<.001 -.58 p<.001 .35 p=.02 .45 p= .003
RL aisles \ -.42 p=.006 .65 p<.001 .75 p<.001
VR accuracy \ -.26 p=.087 -.21 p=.19
VR time \ .81 p<.001
VR aisles \
*Significance remained (except trend for RL/VR accuracy) when IQ controlled **No correlations with symptom measures
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Does performance in VR relate to the same in RL?
0
5
10
15
20
25
RL VR
Accuracy
0
1
2
3
4
5
6
7
8
9
10
RL VR
Aisles
**
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Do RL and VR shopping share the same cognitive
underpinnings?Accuracy
Time
EfficiencyVerbal Fluency
Verbal Fluency
Verbal Fluency
Verbal Fluency
Working Memory
Strategy
Spatial Memory
Social Cognition
R=0.35 p=0.02
R=0.29 p=0.06
R=-0.26 p=0.09
R=0.29 p=0.058
R=-0.27 p=0.08
R=-0.32 p=0.05
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Do Cognitive underpinnings of RL and VR differ in Negative
symptom groupAccuracy
Time
EfficiencyVerbal Fluency
Verbal Fluency
Verbal Fluency
Verbal Fluency
Working Memory
Strategy
Spatial Memory
Social Cognition
R=0.47 p=0.04*
R=0.57 p=0.013
R=-0.52 p=0.02
R=0.47 p=0.05*
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Do Cognitive underpinnings of RL and VR differ in Negative
symptom groupAccuracy
Time
EfficiencyVerbal Fluency
Verbal Fluency
Verbal Fluency
Verbal Fluency
Working Memory
Strategy
Spatial Memory
Social Cognition
R=0.47 p=0.04*
R=0.57 p=0.013
R=-0.52 p=0.02
R=0.47 p=0.05*
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Conclusions 1. Does performance in VR relate to the same in RL? Yes
2. Do they share common or distinct cognitive processes?
Some shared (WM and strategy) but some distinct underlying cognitive processes
3. Do these processes differ in different symptom groups?
Some different and some similar cognitive underpinnings, greater overlap of VR and RL and stronger correlations in Negative symptom sub-group
Particular role for Social Cognition in RL where the social environment is
more important (and in VR with negative symptoms where avatars treated as real) and for spatial memory in VR
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Conclusions and Limitations VR may be seen as an intermediate assessment between cognition
and RL but care should be taken in considering the nature of the VR environment, the underlying cognitive processes, and the clinical presentation of the client group
• Risk of type 1 errors with current comparatively small sample
• Participants had a wide range of cognitive performance with mean cognitive function largely in the average range and with mild-moderate negative symptoms.
• A greater contribution of cognition to community function may
occur when cognition is impaired and symptoms greater (Greenwood, Landau & Wykes 2005)
• Future study will consider the validity of VR assessments of community function within a cognitively impaired sample for whom interventions are developed
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Executive functionA variety of fractionated cognitive processes concerned with the control, organisation and sequencing of higher cognition.
27-46% of people with schizophrenia have selective ‘executive’ profiles and 54-90% have at least one executive impairment (Johnson-Selfridge and Zalewski, 2001; Kremen et al. 2004; Chan et al. 2006a & b). Executive dysfunction is associated with poor social outcome (Kopelowicz et al. 2005, Laes and Sponheim 2006) . In studies of single symptoms, both syndromes have been associated with impaired verbal initiation and working memory and disorganisation also with attention, inhibition, discourse planning and monitoring (Liddle and Morris 1991; Hoffman et al. 1986; Pantelis et al 2001). First episode schizophrenia shows executive dysfunction at this early stage, with some degree of clinical heterogeneity (Joyce et al. 2005; 2007; Chan et al 2006b), but less impairment than is found in chronic schizophrenia (Saykin et al. 1994; Chan et al 2006b). Profiles have varied between studies, with parallel flat profiles of diffuse general impairment, parallel non-flat profiles with selective impairments, and selective impairments specific to chronic schizophrenia (Saykin et al. 1994, Blanchard and Neale 1994; Albus et al. 1996; Chan et al. 2006 a & b). These variations might result from studies that collapse test scores across broad domains.
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Frith Disorganisation symptoms arise from impaired inhibition of habitual responses when plans must be constructed and implemented using working memory, whilst psychomotor poverty results from deficits in the initiation of activities due to impaired initiation of plans.
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Conclusions
• Theoretical understanding of function can provide target cognitive processes for remediation
• Individual approach is important because of complex relationship between symptoms, cognition and function
• Remediation should link to day-to-day function ti improve outcome