Schizophrenia Bulletin vol. 31 no. 4 pp. 910–921, 2005
doi:10.1093/schbul/sbi035
Advance Access publication on July 27, 2005
Negative Symptoms and Specific Cognitive Impairments as Combined Targets for
Improved Functional Outcome Within Cognitive Remediation Therapy
Kathryn E. Greenwood1,2, Sabine Landau3, and
Til Wykes2
Key words: schizophrenia/cognition/mechanisms/
community function/neurocognitive/interventions
2
Department of Psychology, Institute of Psychiatry, De
Crespigny Park, London SE5 8AF; 3Biostatistics and
Computing, Institute of Psychiatry, London
Introduction
The association between cognition and functioning in
schizophrenia has been widely reported in the last decade,1–2 yet the positive effects of remediation programs
on cognition do not translate directly to improved real-life
functioning.3 The cognitive mechanisms that should be
targeted to achieve the best outcomes are, as yet, only
loosely defined,2 and certain groups of people, such as
those with negative symptoms, may respond better
than others.4 Indeed both cognition and negative symptoms are associated with poor community function in
schizophrenia, yet the role of negative symptoms on
functioning is contentious.1, 5–15 Previous studies have
considered the strong independent associations between
cognition and community functioning, while symptoms
have been assumed to contribute only indirectly through
their link with cognition or through overlaps with definitions of functioning.1, 5 The independent contribution of
symptoms to community functioning has not been fully
explored, however, due to the confounding of negative
symptoms with poor general cognition.16–18 The area is
also complicated by the range of different cognitive measures, the use of global and questionnaire measures of functioning, and the scarcity of theoretical frameworks.1–2
Broad global domains such as IQ, executive function
(Wisconsin Card Sorting Test), vigilance, memory, and
more recently working memory have each been associated with poor function.1, 5–12 Indeed composite executive function scores, in particular, have been associated
with daily living skills, occupation, and community function, as assessed through indirect questionnaire or global
measures.1 The use of these global measures adds little,
however, to our understanding of the mechanisms by
which poor cognition is related to poor function.
Negative symptoms are associated with the same global
cognitive impairments in IQ, executive function, vigilance,
memory, and working memory that predict poor community function.17–26 Negative symptoms have, however,
also been linked theoretically and empirically with specific
Negative symptoms and poor cognition are both associated
with poor functional outcome in schizophrenia. This poor
functional outcome has been attributed to poor cognition
rather than any independent contribution from symptoms.
Identifying target cognitive processes and mechanisms
that predict community function, and possible moderator
effects of negative symptoms, will allow the development
of cognitive remediation programs that are successful in improving functional outcome. A referred sample of 53 in- and
outpatients with schizophrenia with general cognitive
impairment (including 28 with severe negative symptoms)
and 22 healthy controls, balanced for premorbid IQ, were
compared cross sectionally on measures of community shopping skills, executive function, and working memory. Across
the groups, there were direct relationships between community functioning and specific executive functions, and there
were interactions between group membership and the types
of associations found. Working memory was independently
associated with accurate community functioning only in
people with schizophrenia and negative symptoms. This association was not due to the sole presence of working memory impairment or just to negative symptoms. Poor
community function is predicted both by specific cognitive
impairments that are prominent in people with negative
symptoms and through the moderating effect of negative
symptoms on the working memory–community function relationship. This may reflect a synergistic association between symptoms and cognition: negative symptoms arise
from cognitive impairment but also impact detrimentally on
working memory functioning. Both cognitive processes and
negative symptoms should be targeted in cognitive remediation to effect the greatest change in community functions.
1
To whom correspondence should be addressed; tel: þ44 (0)
207 919 2983, fax: þ44 (0) 207 919 2473, e-mail: k.greenwood@
iop.kcl.ac.uk.
Ó The Author 2005. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved.
For permissions, please email: [email protected].
910
Targeting Cognitive Mechanisms to Improve Function
cognitive processes. These processes have included deficits
in the generation of plans and strategies, the initiation
of actions, and the use of immediate working memory,
which result in a restriction in spontaneous activity.27–28
Strategy, response initiation, and working memory impairments may constitute core impairments in schizophrenia
with negative symptoms.29 The strong association between negative symptoms and global poor cognition
has confounded investigations of specific cognition–
function relationships. This confounding has rendered
equivocal the independent effect of negative symptoms
on community function when cognition is included.
Certainly, while symptoms have been associated with
poor community function in some first-episode and
chronic schizophrenia studies,11–15 others have described
only limited or indirect links through the association of
symptoms with poor cognition.1, 5
Cognitive and neurocognitive remediation programs
do improve cognition.3, 30–31 Some studies have suggested
selectivity in the response to cognitive remediation therapy, with better effects, for example, for people with negative symptoms of schizophrenia than for those without
these symptoms.4 Few studies have looked at real-world
outcomes, and those that have report mixed results.3
Improved real-life community, occupation, and daily living
skills do occur following remediation programs. The best
effects are limited to comprehensive programs that incorporate a real-life element, such as neurocognitive enhancement with work therapy.32 Certainly it is apparent
that improving cognition does not translate simply to
improved functional outcome.
This study will elucidate the cognitive processes and
mechanisms that result in poor community function in
schizophrenia, particularly for people with negative
symptoms. Executive functions and working memory
are targeted because of their close links both to negative
symptoms and to poor functioning in the community. If
general cognitive functioning is the significant driver of
poor community function, then people with schizophrenia matched for broad general cognition but not
negative symptoms should differ from healthy controls
but not from each other. If, however, the main predictor
of community function is specific executive processes,
then these poorer executive processes would be associated
with poorer community function within each group.
Finally if negative symptoms are important in the prediction of community function, then they should moderate the relationship between executive function and
community function.
Method
Design
The study was cross sectional, with the dependent variables (community function) and the independent vari-
ables (executive function and general cognitive level)
measured in participants who fell into 1 of 3 groups: these
were healthy controls and 2 groups of participants with
schizophrenia defined according to the presence or absence of negative symptoms.
Participants
Participants with DSM-IV schizophrenia were in- or outpatients. They were referred by mental health teams because they demonstrated some problems with cognition
and/or functioning and were deemed suitable candidates
for cognitive remediation therapy. Participants with
schizophrenia were excluded if they demonstrated intact
general memory (a score of 22 or more on the Rivermead
Behavioural Memory Test)33 and intact general executive
function (a score of 4 categories or more on the Wisconsin
Card Sorting Test)34 or intact social behavior function
(a score of 3 or less on the Social Behaviour Scale).35
This enabled the 2 schizophrenia groups to be balanced
for general cognitive level. These 53 participants with
DSM-IV schizophrenia and cognitive impairments were
divided into 2 groups—28 participants with negative symptoms and 25 participants without negative symptoms—
and were compared to 22 healthy control participants.
Participants with negative symptoms additionally fulfilled criteria of at least 2 negative symptoms (score of 3–5)
on the Positive and Negative Syndrome Scale (PANSS),
including at least 1 of the core psychomotor poverty
symptoms of blunted affect and lack of spontaneity
and flow of conversation.36 Healthy control participants
comprised a nonpsychiatric volunteer sample recruited
from within local employment and sheltered work centers
in order to facilitate the balancing of premorbid IQ and
education levels across samples. All participants gave informed consent for participation in this study, and ethical
approval for the work was obtained from the South London
and Maudsley National Health Service Trust Ethical
Committee. All participants were aged 18–65, with premorbid IQ (National Adult Reading Test–Revised)37
above 70, English as a first language, no neurological
problems or head injury, and no current substance abuse.
Measures
Executive Function Measures. Component executive process and task selection were theoretically and empirically motivated. Executive measures were selected that
were specifically impaired in participants with negative
symptoms in a previous study or were theoretically predicted to be specifically impaired in people with negative
symptoms.27, 29
Working Memory. Verbal working memory was assessed using the Letter Number Span Task (scaled
score).38–39 Working memory was defined as the ability
911
K. E. Greenwood et al.
to hold information in memory for conscious processing
and manipulation.40
Response Initiation–Inhibition. Verbal response initiation–inhibition was evaluated using 2 measures. Response
initiation was assessed using the Phonological Fluency
Test (total number of correct words).41 Response inhibition
was assessed using the Hayling task (error scaled score).42
Participants were required to complete sentences presented orally, with a single word that made no sense at
all in the context of the sentence. Meaningful and related
completions contributed to an error score that reflected
poor inhibition.
Strategy Use. Strategy use was assessed using 3 measures. Spatial strategy use was evaluated using the Key
Search Task (profile score) from the Behavioural Assessment of the Dysexecutive Syndrome.43 Participants were
required to draw a spatial search route to ensure finding
lost keys within a paper representation of a field. A poorer profile score reflects a less organized search strategy.
Verbal strategy use was assessed using measures derived from the phonological fluency task (percentage of
words using a phonemic strategy, percentage of words using
a semantic strategy, number of clusters, and mean cluster
length).44–46 Phonemic cluster words included successive
words that differed by 1 letter, began with the same letter
sound or 2 letters, or rhymed. Semantic cluster words are
successive words that are linked by a superordinate semantic category, represent 2 forms of the same word,
or form a common phrase. Verbal strategy use was also
assessed using a strategy assessment from the Hayling
task (strategy score).42 The measure was the percentage
of meaningless sentence completions that encompassed
a strategy of either reporting items visible in the room
or reporting successive semantically related completions.
Community Function Measures. Community function
was assessed directly using a supermarket shopping
task, introduced by Hamera and Brown47–48 and shown
to be reliable and ecologically valid in assessing real-life
community living skills in schizophrenia. The task was
adapted for the United Kingdom, and measures were
taken to reflect those relevant executive processes
thought to underlie performance. Participants were required to select the correct item, size, and cheapest alternative for each of 10 items presented on a shopping list.
All normal shopping strategies, such as requesting help
from staff, were allowed:
Accuracy was assessed through the total number of correct items, correct sizes, and lowest-price items selected.
Efficiency was evaluated using the time taken.
Redundancy of effort was calculated using the number
of aisles entered above the minimum required when
using the most efficient route.
912
Strategy was measured by the number of items selected
when using an ordered progression through the aisles
without entering unnecessary aisles.
Supermarkets were chosen from a single chain of
stores with comparable store layout and selection of
items. Participants were taken to a novel store in order
to provide the greatest test of executive functions.
Allocation of participants to stores was such that group,
gender, IQ, and age distributions were similar across
stores, and confounding of these effects with store effects
was avoided.
Statistical Analyses
The main objective of the statistical analyses was to
identify the differential effects of group membership and specific executive functions on community
function.
Demographics and Clinical Data. One-way analyses of
variance and chi-squared tests (for sex, category of illness
length, proportion of atypical and cholinergic medication
use) were employed to investigate group differences in
sociodemographic and clinical characteristics and cognitive exclusion criteria.
Executive Functions. Group differences in executive
functions were investigated using analyses of variance
for continuous variables and Kruskall Wallis tests for discrete noncontinuous variables (Key Search profile score
and Hayling error scaled score). The Hayling task verbal
strategy score was arcsine transformed to approximate
normality.
Community Functions. Group differences in community
functions were investigated using generalized linear models,49 with group as a between-subject factor and model
distribution specified according to the predetermined nature of the data, which were a 30-trial binomial distribution with logit link for accuracy and an equivalent 10-trial
distribution for the strategy measure, a Poisson distribution with log link for redundancy, and a normal distribution with identity link for efficiency.
Model Building. The associations between community
functions and cognitive measures were analyzed in 3 steps
using generalized linear regression analyses and the distributions described above. Corrections were made for
multiple group comparisons. Premorbid IQ was included
throughout the analyses in order to investigate specific
cognition–function relationships.
Step 1: Determining Which Variables Should Be in the
Model. Relationships were tested across the whole group
Targeting Cognitive Mechanisms to Improve Function
between community function measures and single executive and working memory impairments identified from
the analysis of group differences.
Step 2: Determining Which Executive Process–Group
Interactions Should Be in the Model. To identify
community functions that were differentially predicted
by executive processes in particular groups, individual executive function–group interaction terms were entered
into the regression analyses, in addition to the main effects
of group and of executive processes from previous analyses. Potential moderator effects were thus identified.
Step 3: Final Model With All Significant Process and
Process–Group Interactions Included. The full regression
model was constructed for each community function
measure. All individual executive functions from step
1, and all group–cognitive function interactions identified
at step 2 were included. For interactions between group
and executive function, the associations between community measures and executive functions were further
assessed for each group separately.
Systematic Analysis of Significant Process–Group
Interactions. A possible explanation of the moderating
effect of the negative group could be that executive function affects community function increasingly for more severe levels of executive impairments (a threshold effect).
This was investigated for accuracy and verbal working
memory. The negative group was divided into 2 subgroups with different levels of impairment. This resulted
in 12 participants with severe working memory impairment (at least 2 standard deviations below the average
standard score) and 16 participants with moderate to intact working memory. If the level of impairment affected
the association between working memory and community
function, then this would suggest that the impairment
factor had a moderating effect in the negative group.
Investigations of group differences in all analyses were
adjusted for multiple group comparisons using Holm’s
Multistage Bonferroni procedure: the smallest p values
were compared in series to 0.05/3, 0.05/2, or 0.05/1,
depending on the number of remaining group comparisons.50 Demographic and executive functions were
investigated using the Statistical Package for the
Social Sciences (version 10).51 Community function
and association analyses were investigated in STATA
(version 7).52
total psychopathology. The groups were balanced for
premorbid IQ, age, sex, and years of education and
did not differ clinically or statistically on any other measure. Importantly, the schizophrenia groups were also
balanced for IQ and broad memory, executive, and social
behavior measures.
Do the Schizophrenia Groups Differ on
Executive Functions?
Executive measures have been linked to negative symptoms and therefore should be specifically impaired in the
negative group compared to the non-negative group
and healthy controls. The groups differed in verbal working memory performance (F[2,72] = 8.67, p < .001), with
the negative group being significantly impaired compared
to controls (p < .001 compared to 0.05/3). The nonnegative group showed a trend toward greater impairment than controls (p = .026 compared to 0.05/2) and
did not differ significantly from the negative group (p =
.061 compared to 0.05/1). The groups also differed in verbal response initiation (F[2,72] = 3.17, p = .048), with
a trend for impairment in the negative group relative to
controls (p = .022 compared to 0.05/3) and a similar level
of impairment in the non-negative group relative to controls (p = .044 compared to 0.05/2). Finally, the groups
differed in spatial strategy use (X2[2] = 16.3, p < .001),
with greater impairment in the negative group compared
to each other group (for controls, p < .001 compared to
0.05/3; for non-negative, p = .007 compared to 0.05/2) but
no difference between the non-negative group and controls (p = .36; see figure 1). There were no significant group
differences for the remaining executive measures.
Are There Differences in Community Function Between
the Groups?
People with negative symptoms have poor functional outcome and specific impairments in working memory, strategy, and initiation processes that may underlie this poor
function. For these reasons, people with schizophrenia
and negative symptoms were predicted to perform less
well on community function measures than either the comparison schizophrenia group or healthy controls. Table 2
presents the group comparisons on community function
measures adjusted for multiple group comparisons.
Demographics
Accuracy. The negative group was significantly less
accurate in selecting items correctly than either the nonnegative schizophrenia group or healthy controls (see
table 2). The nonnegative group was also significantly
less accurate than controls. Overall, the negative participants were less than half as likely as controls to accurately
select items.
Sociodemographic, clinical, and cognitive data are presented in table 1. By definition, the schizophrenia groups
differed due to group selection on negative, general, and
Efficiency, Redundancy, and Strategy Measures. The negative group also completed the task less efficiently and
Results
913
K. E. Greenwood et al.
Table 1. Sociodemographic, Cognitive, and Clinical Characteristics
Statistical Test
Characteristic
Control,
n = 22
Non-negative,
n = 25
Negative,
n = 28
F/X2
df
p-Value
Age (years)
36.2 (12.9)
35.3 (10.6)
35.1 (8.8)
.09
2,72
.92
Sex (m/f)
16/6
19/6
20/8
.15
2
.93
Premorbid IQ
89.8 (11.3)
91.1 (14.2)
91.4 (13.3)
.10
2,72
.90
Education (years)
12.2 (1.62)
11.9 (1.32)
11.7 (1.36)
.83
2,72
.44
Social Behavior Schedule
Total Score
NA
11.8 (9.4)
14.2 (12.2)
.66
1,51
.42
Rivermead Behavioural Memory
Test Profile Score
NA
15.2 (4.2)
13.5 (4.7)
2.0
1,51
.16
Wisconsin Card Sorting
Test Category Score
NA
2.9 (2.2)
2.0 (1.9)
2.4
1,51
.13
Illness Length (1/2/3/4)*
NA
(3/7/2/8)
(5/1/6/11)
.73
3
.06
Medication Dose**
NA
55.21 (69.7)
53.21 (29.1)
.007
1,51
.94
% on Atypical Neuroleptics
NA
76
89
.85
1
.29
Cholinergic Medication (yes)
NA
5
3
.31
1
.45
Positive and Negative Syndrome
Scale (PANSS) Positive Score
NA
13.2 (4.7)
13.4 (4.8)
.02
1,51
.91
PANSS Negative Score
NA
12.7 (3.1)
19.4 (6.7)
NA
NA
NA
PANSS General Score
NA
25.0 (6.0)
28.9 (6.9)
NA
NA
NA
PANSS Total Score
NA
50.9 (11.1)
61.7 (14.2)
NA
NA
NA
Note: Where appropriate, value is the mean (with SD in parentheses). NA = not applicable either because the variable is not relevant to
the control group or because the statistical test is different by design.
*Category of illness length was defined as 1 = less than 1 year since first psychiatric contact, 2 = 1–5 years, 3 = 5–10 years, and
4 = greater than 10 years.
**Medication dose was converted to a standard dose by calculating the total percentage of the maximum recommended dose53.
more slowly, with increased redundancy and poorer
strategy use, compared to both the non-negative group
and controls. The non-negative group demonstrated significantly poorer strategy use than controls but showed
less redundancy, in that they entered significantly fewer
aisles above the minimum. Overall, controls were 4 times
more likely and non-negative participants were twice as
likely to use a strategy compared to negative participants.
Fig. 1. Group Differences in Executive Functions. The graphs present the mean score and standard error bars for each group.
914
Note: OR = odds ratio, D = difference, IRR = incidence rate ratio. Significant group differences compared to adjusted significance level a = 0.05/3, 0.05/2, or 0.05/1,
according to order of significance in the Multistage Bonferroni procedure. CI(1–a) denotes intervals at the (1–a) 3 100% confidence level.
*N = 68 for redundancy; n = 52 for strategy.
<.0001
44.54
.006 (CI 0.95
[.29, .81])
2.76
OR = .49
.001 (CI 0.98
[.13, .37])
<.001 (CI 0.97
[.27, .72])
OR = .44
Strategy*
Aisle Strategy
(0–10)
3.66
OR = .22
6.52
2
<.0001
94.97
<.001 (CI 0.98
[.29, .81])
8.75
OR = 2.63
<.001 (CI 0.97
[1.56,2.40])
.013 (CI 0.95
[.31, .47])
IRR = .73
Redundancy*
Aisles Above
Minimum
2.47
OR = 1.93
6.64
2
<.0001
23.06
.001 (CI 0.97
[4.2,19.1])
3.40
D = 11.66
.21
D = 4.56
Efficiency
Time (mins)
1.25
D = 16.22
4.57
<.001 (CI 0.98
[8.0,24.5])
2
<.001
2
40.27
< .001 (CI 0.97
[.52, .84])
3.17
.007 (CI 0.95
[.54, .91])
OR = .571
Accuracy
Total Correct
(0–30)
2.68
OR = .47
6.19
<.001 CI 0.98
[.35, .62]
OR = .466
df
X2
p
z
Effect Size
p
z
Effect Size
p
z
Effect Size
Measure
Negative Versus Control
Non-negative Versus Control
Table 2. Group Differences in Outcome Measures on the Supermarket Shopping Task
Negative Versus Non-negative
Group Effect
p
Targeting Cognitive Mechanisms to Improve Function
Negative participants were likely to enter twice as many
aisles above minimum as controls and nearly 3 times as
many as non-negative participants (see table 2).
Hence, despite similar IQ and general cognitive function, the negative group performed more poorly than the
non-negative group on all community function measures.
General cognitive function cannot, therefore, account for
all the differences between groups in community function. The next set of analyses therefore investigated
whether specific executive functions, which are impaired
in the negative group, can account for these differences.
Model Building
Step 1: Which Executive Impairments Predict Community
Function Impairments? Regressions of single executive
function variables on community function measures
were undertaken across the whole group to identify executive processes that could account for community function impairments. These are shown in table 3. The
direction of the correlations across the groups is as predicted, such that the overall odds ratios predict that higher
cognitive function is associated with better performance.
All individual associations between cognitive and functional measures were significant.
Step 2: Which Executive Impairments Interact With Group
in Predicting Community Function? In order to test
whether executive function measures interact with group,
individual executive function–group interaction terms
were entered into the regression models in addition to significant predictors from step 1. Working memory interacted with group membership for most investigated
measures (accuracy: X2[2] = 22.5, p < .001; redundancy:
X2[2] = 13.0, p = .0015; strategy: X2[2] = 9.2, p =.01) and is
thus a particularly strong contender for a differential
group effect in predicting community function. Premorbid IQ also interacted with group membership for 2 measures (accuracy: X2[2] = 7.9, p = .02; strategy: X2[2] = 6.4,
p = .04), spatial strategy for 1 measure (redundancy:
X2[2] = 6.2, p = .045), and response initiation for 1 measure (redundancy: X2[2] = 32.4, p < .001). These significant interactions between cognitive measures and group
are indicated by a double asterisk in table 3.
Step 3: Which Executive Functions Independently Predict
Community Function Either Differentially Within a
Particular Group or Within All Groups? The final model
for each community function measure included both the
significant predictor main effects from step 1 and the significant interaction terms from step 2. The results are presented in table 4. When a predictor effect interacted with
group, this effect was assessed separately for each group.
Two cognitive processes were each predictive of community functioning across the groups: poor working
memory predicted less efficient community function,
915
916
6.96
.001**
OR = 1.03
3.82
.001
and poor spatial strategy use predicted less accurate community function. These cognitive measures were predictive despite being independent from the real-life
supermarket context.
In addition, numerous cognitive processes were shown
to be independently predictive of community function
only within particular groups. Importantly, poor working
memory was a highly significant independent predictor of
inaccurate community function, and low premorbid IQ
was a specific independent predictor of inefficiency only
in the negative group. Good working memory also significantly predicted better aisle strategy use only in controls,
although the same pattern was found in the negative
group. Response initiation predicted redundancy in controls, with a trend also in the negative group, but the associations were in opposite directions. In the latter
association, the same underlying relationship may have
operated differently in the different groups. In the negative group, whose search strategies were poorer, better response initiation may have contributed to more active
searches and less redundancy, but in controls, whose
search strategies were already superior, better response
initiation may have reflected higher self-motivated sustained attention resulting in longer searches and greater
redundancy. There were no independent cognitive predictors of community function within the non-negative
group.
Are the Associations in the Negative Group due to the
Greater Prevalence of Severe Executive Impairments in
This Group?
Note: OR = odds ratio, IRR = incidence rate ratio, D = difference.
*N = 68 for redundancy; n = 52 for strategy.
**Also interacts with group in predicting community function.
.001
5.89
2.14
OR = 1.02
Strategy*
Aisle Strategy
(0–10)
.03**
OR = 1.46
OR = 1.22
<.001**
–4.32
IRR = .98
<.001**
–7.44
<.001**
–3.62
OR = .89
<.001
–5.02
IRR = .98
Redundancy*
Aisles Above
Minimum
.04
D = –.25
Efficiency
Time (mins)
–2.02
<.001**
5.86
OR = 1.02
Accuracy
(0–30 correct)
z
Effect Size
Shopping
Measure
IRR = .91
.009
–2.63
D = –.34
<.001
–4.82
.004
–2.87
D = –3.17
OR = 1.14
.004
6.99
OR = 1.28
D = –2.07
<.001
6.17
8.81
<.001**
OR = 1.03
z
Effect Size
z
Effect Size
p
Effect Size
z
p
Working Memory
(scaled score: 1–19)
Spatial Strategy
(profile score: 0–4)
Premorbid IQ (National
Adult Reading Test–Revised)
Associated Executive, Memory, and IQ Factors
Table 3. Model Building Steps 1 and 2—Executive and Premorbid Predictors of Community Function in Individual Analyses
p
Response Initiation
(no. correct words)
p
K. E. Greenwood et al.
The possibility of a threshold effect was investigated.
Executive function may be related to community functioning only where these executive impairments are
marked, as in the negative syndrome. Within the negative
group, and for the selected community function measure
(accuracy), the interaction between the impairment factor
(marked versus moderate–intact working memory impairment group) and the working memory–community
function relationship was not significant (z = 0.98, p =
.33). Contrary to the case in a threshold model, the effect
of working memory on community functioning was not
stronger in the marked impairment subgroup compared
to the moderate–intact subgroup. In fact, the odds of accurately selecting an item were estimated to increase by
22% for every unit change in working memory score in
the moderate–intact group but only by 11% in the
marked impairment group. Also counter to a simple
threshold model, 50% of participants with marked impairment but no negative symptoms (n = 8) demonstrated
good community functioning within half a standard deviation of controls and above the negative group mean.
Indeed, the poorest working memory span in the absence
of negative symptoms coincided with intact community
Table 4. Final Model (Step 3)—Core Independent Predictors of Community Function
Associated Executive, Memory, and IQ Factors
Premorbid IQ
(National Adult
Reading Test–Revised)
Shopping
Measure
Effect Size
z
Spatial Strategy
(profile score: 0–4)
p
Effect Size
.13
OR = 1.1
z
Working Memory
(scaled score: 1–19)
p
Effect Size
.013
OR = 1.19
z
Response Initiation
(no. correct words)
p
Effect Size
z
p
.48
<.001 (CI0.99
[1.08,1.3])
OR = .96
.77
.44
.52
.60
D = .005
.03
.98
Accuracy
(0–30 correct)
N
OR = 1.01
1.5
2.48
C
OR = 1.01
.54
.96
OR = 1.03
NN
OR = 1.01
1.92
.06
OR = .98
.60
.55
D = 1.95
3.14
.002
1.4
Efficiency
Time (mins)
N
D = .47
24.8
C
D = .44
1.8
NN
D = .07
.013 (CI0.99
[0.96, 0.02])
D = –1.05
.89
.37
.07
.43
.66
1.21
.23
Redundancy*
Aisles Above
Minimum
N
IRR = .99
IRR = 1.01
.89
IRR = .95
.16
IRR = .98
1.98
.048
.17
IRR = .97
.75
.45
IRR = 1.03
4.02
.001 (CI0.99
[1.01,1.05])
IRR = 1.08
1.19
.23
IRR = .99
.25
.81
IRR = .99
.69
.49
OR = 1.16
1.67
.095
OR = 1.27
1.79
.074
OR = .97
1.90
.058
.006 (CI0.99
[1.01, 1.63])
IRR = .87
NN
Strategy*
Aisle Strategy
(0–10)
N
OR = 1.0
.24
.81
C
OR = .98
.78
.43
OR = 1.29
2.74
NN
OR = .98
1.45
.15
OR = 1.03
.42
.67
Note: N = negative group, C = control group, NN = nonnegative group, OR = odds ratio, D = difference, IRR = incidence rate ratio. Significant associations should be
compared to adjusted significance level a = 0.05/3, 0.05/2, or 0.05/1, according to order of significance in the Multistage Bonferroni procedure. Significant associations are
shaded grey. CI(1–a) denotes intervals at the (1–a) 3 100% confidence level.
*N = 68 for redundancy; n = 52 for strategy.
917
Targeting Cognitive Mechanisms to Improve Function
.14
1.39
C
K. E. Greenwood et al.
Model 1: Symptoms Independent e.g.14
Cognition
Community Function
Negative
Symptoms
Model 2: Symptoms Indirect e.g.5
Cognition
Community Function
Negative Symptoms
Model 3: Symptoms as predictors of cognition e.g.5
Negative Symptoms
Community Function
Cognition
Model 4: Synergistic interaction of negative symptoms and cognition in moderating
community function
Cognition
Community Function
Negative
Symptoms
Fig. 2. Models of Hypothetical Relationships Among Cognitive
Function, Negative Symptoms, and Community Function.
functioning above the control mean. Negative symptoms
alone with intact working memory (n = 6) were also associated with good community functioning above the
negative group mean and within half a standard deviation of the control group mean. Hence, working memory
impairment in the absence of negative symptoms did not
necessarily confer poor outcome, and many of those with
marked working memory impairment alone performed
well on the community functioning task.
Discussion
This study revealed 2 distinct and important mechanisms
through which cognition and/or symptoms are related to
poor community function in schizophrenia. These are,
first, direct associations between specific cognitive impairments and community functions and, second, a synergistic
interaction between negative symptoms and cognition in
predicting community function. The negative group was
associated both with specific verbal working memory and
executive impairments and with impairments in a direct
and ecologically valid measure of real-life community
function when compared to non-negative schizophrenia
and healthy controls. These impairments were independent of global cognitive deficits, as, on the whole, they
918
were not present in the non-negative group despite the
equivalent IQ, general memory, and general executive
function in this group. The results pave the way for
a more refined consideration of the mechanism by which
negative symptoms and executive processes contribute to
community functioning.
In the first mechanism, specific cognitive impairments
were directly associated with specific aspects of poor
community function. People who had trouble in an empirical task with drawing a spatial search strategy to locate a hypothetical lost item within a designated space
were also less accurate in a real-life supermarket environment in locating and selecting items correctly. In addition, people who were less accurate at holding and
manipulating information in working memory were
less efficient and took significantly longer to complete
the community function task. While numerous studies
have demonstrated links between cognition and community function1–2 and even between cognition and real-life
skills such as grocery shopping,48 this study is unique in
demonstrating such close links between similar underlying processes on both empirical and real-life tasks. Both
working memory and strategic processes would appear to
be ideal candidates for cognitive remediation therapy, in
order to enhance generalization to the real world.
In terms of mechanisms derived from the literature
(see figure 2), cognition and negative symptoms may contribute to community function independently (model 1).14
Cognition may contribute to community functioning directly, while symptoms are associated only indirectly
through their link with cognition (model 2), or indeed
the reverse may occur so that cognition only associates
indirectly to community functioning through symptoms
(model 3).5 The mechanism thus far is similar to that
reported by previous researchers, in that a direct association is demonstrated across all groups between cognition and community function. This study extends
current knowledge, however, by demonstrating that
this mechanism occurs for cognitive predictors that are
theoretically and empirically linked to negative symptoms. Since impairments in these processes are greater
in people with negative symptoms, these people are
significantly less skilled in the cognitive processes that
underlie community functioning and so do less well
(model 2 or 3).
However, the second and perhaps more important
mechanism is the previously undocumented role of negative symptoms as a moderator of the relationship between
cognitive impairments (particularly working memory)
and poor community functioning in schizophrenia. The
moderator effect reflected the specific association between
cognition and community function only in people with
negative but not non-negative schizophrenia. The interaction between working memory and symptoms in the
current study is not consistent with independent contributions from cognition and symptoms to community
Targeting Cognitive Mechanisms to Improve Function
function (model 1). Neither is it consistent with indirect
contributions of symptoms or cognition to community
function (models 2–3).
Several mechanisms may explain the interaction between cognition and the negative symptom group. Working memory impairments may be particularly marked in
schizophrenia with negative symptoms, and only these
marked impairments then predict poor community function (an adaptation of model 2). This explanation seems
unlikely, however, as there was no interaction between
the severity of impairment (marked versus moderate–
intact) and cognition on community function in the negative group. In fact, cognition was a somewhat stronger
predictor of community function in the group with moderate–intact cognition. This suggests that, if anything,
symptoms play a greater role where impairments are
milder. So, the effect was not a simple threshold effect,
since the most cognitively impaired people in the negative group did not perform the least well on community
functions.
Negative symptoms may, instead, bestow some additional contribution to the relationship between cognition
and function found in this group. A mechanism for this
interaction is suggested by a consideration of working
memory capacity and function, which are governed
both by general ability and by domain-specific experience.
Domain-specific experience enhances working memory
capacity in experts compared to novices, across such
spheres as professional chess and academic performance.54–57 Experience may increase working memory
capacity by providing a broader knowledge base and
so promoting enhanced ‘‘chunking’’ and organization of
domain-specific information in working memory through
the development of new cognitive schemata.58 Reduced active participation across a varied array of community, social, and occupational experiences, as a result of negative
symptoms, may create exactly this division in ‘‘expertise’’
between negative and non-negative schizophrenia and
controls. This will, in turn, lead to even poorer domainspecific working memory and community function.
The significant association between good working
memory and good strategy use only in the control
group may reflect the opposite ‘‘expert’’ end of this
continuum.
Hence, the current data are consistent with symptoms
acting as a true moderator of the relationship between
cognition and community functioning (model 4). It is
proposed that a synergistic interaction between working
memory and negative symptoms arrests the normal development of working memory mechanisms within particular domains, through the curtailing of appropriate
domain-specific experiences. This synergy between symptoms and working memory impairment produces the
poorest community functioning. It may also have the
greatest impact where the core impairment is milder and
where environmental effects can have a greater effect.
This second mechanism provides further significant
clinical implications. The interaction of negative symptoms with poor working memory may gradually expand
the divide between novice and expert working memory,
leading to a progressive disruption of community and
other functional domains and a more chronic disorder.
According to this mechanism, programs that address
poor functional outcome should target both cognition
and negative symptoms early in the disorder. A wider
and more immersed experience of community function
may break the synergistic link between negative symptoms and cognition to promote a more adaptive functional outcome.
There are several limitations to the current study.
Supermarket shopping is a narrow domain of community
function, and the target processes for remediation may
not generalize to other aspects of community living.
Furthermore, the current cognitive processes predict
baseline function. It is unclear whether change in these
cognitive processes will predict change in functioning.
Both cognitive processes and mechanisms are identified,
however, which are specific to a particular target group
and which can be investigated further. The dynamic nature of the interaction model, in particular, provides both
a process and a mechanism by which change may occur.
The study controlled for multiple group comparisons but
not for multiple correlations between cognition and community function. This was deliberate in order to capture
all valid mechanisms, but the possibility of Type I errors
is thus greater. The findings require replication, but, nevertheless, many of the results including the moderating
effect of negative symptoms on the working memory–
community function relationship were particularly robust and were highly significant.
In conclusion, this study provides strong evidence that
influencing real-world community function in schizophrenia may require a more complex approach than simple remediation of cognition in general across all people.
Rather, the study supports several distinct cognitive processes and mechanisms, moderated by negative symptoms, which may be active simultaneously and which
predict the exceptionally poor community function in
people with schizophrenia and negative symptoms.
Targeting these processes and mechanisms in conjunction
with their moderating symptoms will provide the greatest
opportunity for cognitive remediation therapy to improve community function in the real world.
Acknowledgments
This study was supported by a grant, RFG 757, from
the Department of Health. We would like to thank
Dr. Pall Matthiasson, M.D., MRCPsych, Division
of Psychological Medicine, Institute of Psychiatry,
London, for his diagnosis and symptom assessments
919
K. E. Greenwood et al.
for people with schizophrenia. Earlier forms of this work
have been presented at the Society for Research in
Psychopathology, San Francisco, September 2002; the
International Congress of Schizophrenia Research and
Sixth Biennial Mt. Sinai Conference on Cognition in
Schizophrenia, Colorado Springs, Colo., April 2003;
and the Fifth International Conference on
Psychological Treatments for Schizophrenia, Oxford,
September 2003.
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