Executive function in first-episode schizophrenia: a three-year longitudinal study of an ecologically valid test.
ABSTRACT Executive function impairment is a key cognitive deficit in schizophrenia. However, traditional neuropsychological tests of executive function may not be sensitive enough to capture the everyday dysexecutive problems experienced by patients. Additionally, existing literature has been inconsistent about longitudinal changes of executive functions in schizophrenia. The present study focuses on examining the longitudinal change of executive functions in schizophrenia using the Modified Six Elements Test (MSET) that was developed based on the Supervisory Attentional System model and shown to be sensitive to everyday dysexecutive problems. In the present study, MSET performance was assessed in 31 medication-naïve first-episode schizophrenic patients at four times over a period of three years, while the 31 normal controls were assessed once. Patients demonstrated impairment in MSET as compared to controls. Importantly, the MSET impairment persisted from the medication-naïve state to clinical stabilization and the three years following the first psychotic episode though patients improved in a conventional executive test (Modified Wisconsin Card Sorting Test). Performance was not related to intelligence, educational level, symptom changes, age-of-onset, or duration of untreated psychosis. Better MSET performance at medication-naïve state predicted improvement in negative and positive symptoms over the three-year period. These findings may suggest that MSET impairment is a primary deficit in schizophrenia that occurs early in the course of the illness and remains stable irrespective of clinical state for at least three years following the first episode of schizophrenia.
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ABSTRACT: Effective integration of visual information is necessary to utilize abstract thinking, but patients with schizophrenia have slow eye movement and usually explore limited visual information. This study examines the relationship between abstract thinking ability and the pattern of eye gaze in patients with schizophrenia using a novel theme identification task. Twenty patients with schizophrenia and 22 healthy controls completed the theme identification task, in which subjects selected which word, out of a set of provided words, best described the theme of a picture. Eye gaze while performing the task was recorded by the eye tracker. Patients exhibited a significantly lower correct rate for theme identification and lesser fixation and saccade counts than controls. The correct rate was significantly correlated with the fixation count in patients, but not in controls. Patients with schizophrenia showed impaired abstract thinking and decreased quality of gaze, which were positively associated with each other. Theme identification and eye gaze appear to be useful as tools for the objective measurement of abstract thinking in patients with schizophrenia.Behavioral and Brain Functions 04/2014; 10(1):13. · 2.79 Impact Factor
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ABSTRACT: Objective: To carry out a systematic review of the literature addressing cognitive functions in first-episode psychosis (FEP), divided into domains. Although this is not a full "cognitive-genetics-in-schizophrenia review," we will also include putative ideas of mechanism(s) behind these impairments, focusing on how early stress, and genetic vulnerability may moderate cognitive function in psychosis. Method: Relevant studies were identified via computer literature searches for research published up to and including January 2013, only case-control studies were included for the neurocognitive meta-analysis. Results: Patients with FEP present global cognitive impairment compared to healthy controls. The largest effect size was observed for verbal memory (Cohen's d effect size = 2.10), followed by executive function (effect size = 1.86), and general IQ (effect size = 1.71). However, effect sizes varied between studies. Conclusion: Cognitive impairment across domains, up to severe level based on Cohen's effect size, is present already in FEP studies. However, differences in levels of impairment are observed between studies, as well as within domains, indicating that further consolidation of cognitive impairment over the course of illness may be present. Cognitive abnormalities may be linked to a neurodevelopmental model including increased sensitivity to the negative effect of stress, as well as genetic vulnerability. More research on this field is needed.Frontiers in Psychiatry 01/2014; 4:182.
Executive function in first-episode schizophrenia: A three-year longitudinal
study of an ecologically valid test
Kristy C.M. Liua, Raymond C.K. Chanb, Kevin K.S. Chana, Jennifer Y.M. Tanga, Cindy P.Y. Chiua,
May M.L. Lama, Sherry K.W. Chana, Gloria H.Y. Wonga, Christy L.M. Huia, Eric Y.H. Chena,⁎
aDepartment of Psychiatry, The University of Hong Kong, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong
bNeuropsychology and Applied Cognitive Neuroscience Laboratory, Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences,
4A Datun Road, Beijing 100101, China
a r t i c l ei n f oa b s t r a c t
Received 16 July 2010
Received in revised form 13 November 2010
Accepted 29 November 2010
Available online 30 December 2010
Executive function impairment is a key cognitive deficit in schizophrenia. However, traditional
neuropsychological tests of executive function may not be sensitive enough to capture the
everyday dysexecutive problems experienced by patients. Additionally, existing literature has
been inconsistent about longitudinal changes of executive functions in schizophrenia. The
present study focuses on examining the longitudinal change of executive functions in
schizophrenia using the Modified Six Elements Test (MSET) that was developed based on the
Supervisory Attentional System model and shown to be sensitive to everyday dysexecutive
problems. In the present study, MSET performance was assessed in 31 medication-naïve first-
episode schizophrenic patients at four times over a period of three years, while the 31 normal
controls were assessed once. Patients demonstrated impairment in MSET as compared to
controls. Importantly, the MSET impairment persisted from the medication-naïve state to
clinical stabilization and the three years following the first psychotic episode though patients
improved in a conventional executive test (Modified Wisconsin Card Sorting Test).
Performance was not related to intelligence, educational level, symptom changes, age-of-
onset, or duration of untreated psychosis. Better MSET performance at medication-naïve state
predicted improvement in negative and positive symptoms over the three-year period. These
findings may suggest that MSET impairment is a primary deficit in schizophrenia that occurs
early in the course of the illness and remains stable irrespective of clinical state for at least three
years following the first episode of schizophrenia.
© 2010 Elsevier B.V. All rights reserved.
Executive impairment is one of the most robust and
central deficits to be associated with schizophrenia and is
seen across stages of the illness (Chan et al., 2006a,b;
Fioravanti et al., 2005; Rund, 2002). Schizophrenic patients
tend to show impairment in tests sensitive to frontal lobe
lesions, including Wisconsin card sorting, verbal fluency and
trail making (Chan et al., 2006b; Liddle and Morris, 1991).
The neuropsychological tests traditionally used in exam-
ining executive functions may not be sufficiently sensitive to
detect the dysexecutive syndrome experienced by patients in
everyday life. Studies have shown that even though people
with frontal lobe lesions exhibit many characteristics of a
dysexecutive syndrome in their daily lives, some may not
demonstrate impairment on performing conventional exec-
utive tests (Shallice and Burgess, 1991). To better capture the
everyday executive functioning in patients, the Modified Six
Elements Test (MSET) was incorporated into the Behavioural
Assessment of the Dysexecutive Syndrome (BADS; Wilson
et al., 1996). In the MSET, subjects have to plan their time so
as to complete at least part of each of the six subtasks while at
Schizophrenia Research 126 (2011) 87–92
⁎ Corresponding author. Tel.: +852 2255 4488; fax: +852 2255 1345.
E-mail address: email@example.com (E.Y.H. Chen).
0920-9964/$ – see front matter © 2010 Elsevier B.V. All rights reserved.
Contents lists available at ScienceDirect
journal homepage: www.elsevier.com/locate/schres
the same time complying with certain simple rules. Unlike
most conventional executive function tests, with provided
goals and defined structure, MSET requires subjects to
structure the tasks themselves. In this respect, MSET
resembles the open-ended nature of problem solving in
everyday life. Indeed, it has been shown to be sensitive to
everyday executive functioning in people with frontal lobe
lesions (Shallice and Burgess, 1991) and patients with
schizophrenia (Chan et al., 2006a,b). Among all the tests in
BADS, MSET has been found to be superior in ecological
validity and sensitivity when applied to people with
schizophrenia (Chan et al., 2006a,b; Evans et al., 1997; Katz
et al., 2007; Krabbendam et al., 1999), and other psychiatric
and neurological disorders (Burgess et al., 1998; Chan and
Manly, 2002; Norris and Tate, 2000). For example, Katz et al.
(2007) found a moderate to strong correlation between MSET
performance and several key areas of daily functioning
(instrumental activities of daily living, communication, and
work readiness) in patients with schizophrenia as measured
by the Routine Task Inventory (Allen, 1989, as cited in Katz
et al., 2007). MSET performance has consistently been
impaired in people with chronic and with first-episode
schizophrenia (Chan et al., 2004, 2006a,b; Evans et al.,
1997; Katz et al., 2007).
The specific executive components measured by different
conventional executive function tests are still not well
understood, probably due to the lack of theoretical guidance
in the development of these tests (Chan et al., 2008a). The
Supervisory Attentional System (SAS) model (Norman and
Shallice, 1986) proposes a classification of executive function
components and has been useful in explaining the nature of
dysexecutive syndrome (Chan et al., 2004, 2006b). There are
two systems in the SAS model, namely, contention scheduling
and supervisory attention. The former system is responsible
for routine and over-learned behaviours and allows prioriti-
zation of such actions (e.g., making coffee when the phone
rings). The latter system, on the other hand, is responsible for
regulating goal-directed behaviours in non-routine and novel
situations (Norman and Shallice, 1986).The MSET is based on
the latter system. It requires test-takers to attempt at least
part of the six sub-tasks while at the same time complying
with simple rules. To achieve high performance on this test,
test-takers must consistently and optimally mobilize the
most appropriate schemata across the sub-tasks. Therefore, in
terms of SAS systems, MSET was developed to capture the
regulation of the non-routine component of the supervisory
attention system. Moreover, MSET has demonstrated con-
struct validity in measuring the ‘action/attention inhibition’
and ‘output generation’ components of executive functions
proposed in the SAS (Chan et al., 2004).
In the existing literature, studies that provide longitudinal
data of executive functioning in schizophrenia have primarily
utilized conventional executive function measures. These
empirical findings have been inconsistent as some found
longitudinal stability, while others reported decline or im-
provement (e.g. Gold et al., 1999; Hill et al., 2004; Hoff et al.,
possible explanations for the mixed findings include heteroge-
neous patient profiles, varied methodological designs, and
inconsistency of executive tests employed across the studies.
Alternatively, it may be that conventional executive function
tests probe various aspects of executive functions (Evans et al.,
1997) and that the temporal change of these components
differs. In light of the mixed findings, the present study
attempts to elucidate the longitudinal trajectories of the
individual components of executive function through applica-
tion of MSET.
In the present study, longitudinal assessment of MSET
performance was carried out in medication-naïve, first-
episode patients with schizophrenia-spectrum disorders, for
a period of three years after the first presentation of illness.
The present study aims to address the following questions:
(1) whether patients show impairments in MSET perfor-
mance; (2) whether MSET performance improves after
antipsychotic treatment; (3) how MSET performance evolves
over the three years following the first psychotic episode and;
(4) whether MSET performance is related to demographics,
clinical variables, duration of untreatedpsychosis, or outcome
in first-episode schizophrenia.
Participants were 31 medication-naïve patients with first-
episode schizophrenia-spectrum disorders chosen from a
larger cohort recruited for longitudinal studies by our research
team (some of the baseline data has been reported by Chan
et al., 2006b). All patients were Cantonese-speaking, Han
Chinese, and met DSM-IV (American Psychiatric Association,
1994) criteria for schizophrenia, schizophreniform disorder, or
schizoaffective disorder. Consensus clinical diagnoses were
made by two experienced psychiatrists based on DSM-IV.
if they were clinically judged to have high risk of suicidal
behaviour. The healthy control sample consisted of 31
volunteers recruited from the general public and matched
with the patient group for gender, age, and years of education.
Controls were screened with a questionnaire designed by our
team (available upon request) to ensure the absence of
The study was approved by the relevant Institutional Review
Boards and written informed consent was attained from all
subjects prior to participation. Assessment of patients was
the third year. Healthy controls were assessed only once.
2.2.1. Clinical assessments
Positive and Negative Syndrome Scale (PANSS; Kay et al.,
1988) was used to assess symptoms in patients; ratings were
made based on clinical interviews and medical records. The
inter-rater reliability of the three raters was 0.83 for the PANSS
(by intra-class correlation coefficient). The Interview for the
Retrospective Assessment of the Onset of Schizophrenia
(Hafner et al., 1992) was used to assess duration of untreated
psychosis (DUP) and for obtaining information about educa-
tional level. Functioning was measured using the Social and
K.C.M. Liu et al. / Schizophrenia Research 126 (2011) 87–92
Occupational Functioning Scale (SOFAS; American Psychiatric
2.2.2. Cognitive assessments
18.104.22.168. Intelligence. Intelligence was calculated at the first
assessment in both patients and normal controls using the
Information, Arithmetic, Digit Span, Digit Symbol and Block
Design subtests of the Wechsler Adult Intelligence Scale-
Revised for Cantonese speaking populations (Hong Kong
Psychological Society, 1989).
22.214.171.124. Modified Six Elements Test (MSET). The MSET (Burgess
et al., 1996) is a simplified version of the original Six Elements
Test developed by Shallice and Burgess (1991). It consists of
three types of tasks (viz. dictation, simple arithmetic and
picture naming), each having two subtasks. The dictation
task requires participants to tell a story on a specific topic
(‘a holiday’ for subtask A; ‘a happy event’ for subtask B). The
simple arithmetic task consists of 60 simple arithmetic
questions. The picture naming task contains of 60 brightly
colored pictures which must be identified in writing. Each
participant was administered the task individually. Partici-
pants were required to attempt at least part of each subtask
within 10 min; they received instructions that the subtasks of
the same task could not immediately follow each other. They
were also told that the aim of the test was not to finish all the
subtasks as fast as possible. A digital timer was provided for
participants to monitor time. Four scores were calculated for
the MSET: (1) the number of subtasks completed; (2) the
number of rule-breaking behaviour (rule error); (3) the
number of times the subject has spent over 217 s on one
subtask (time error) and; (4) the summary score of the above
three scores (total profile score) (Wilson et al., 1996).
The Chinese version of the task has been adapted to be
used in patients with first-episode and chronic schizophrenia
and healthy adults in Hong Kong, and has been shown to be
sensitive to deficits in attention allocation and planning
(Chan et al., 2004, 2006a,b).
126.96.36.199. Modified Wisconsin Card Sorting Test. The Modified
Wisconsin Card Sorting Test (MWCST: Nelson, 1976) was
chosen as the conventional executive test with which to
compare to MSET. Participants were required to sort 48
stimulus cards according to defined rules. When the partici-
pants had given six correct responses consecutively, a change
of rule occurred. The number of categories completed and
perseverative errors were calculated.
2.3. Data analysis
All statistical analyses were carried out using the Statistical
Packages for Social Sciences (SPSS) version 17.0. To compare
controls, an analysis of covariance (ANCOVA) was carried out
with IQ, age, gender, and educational level as covariates. A
repeatedmeasures ANOVAfor MSET scoresand MWCST scores
with four within-subject levels (medication-naïve, stabilized,
year one, and year three) was performed to investigate the
changes of MSET scores and MWCST scores over time.
Correlational analyses were carried out between MSET scores
and demographic, clinical, and outcome variables.
3.1. Sample characteristics
Participant characteristics are presented in Table 1. There
were no significant differences between patients and normal
controls in age, years of education, or gender ratio (Table 1).
Of the 11 patients with diagnosis of schizophreniform
disorder, nine converted to schizophrenia and two to
schizoaffective disorder within three years. Twenty-nine
patients were medication-naïve in the first assessment and
the majority of patients remained on stable medication
during follow ups, as presented in Table 2. PANSS scores of
patients are presented in Table 3. A repeated measures
ANOVA showed that there were significant changes of PANSS
scores over time.
3.2. MSET and MWCST performance at the first episode
MSET and MWCST scores of patients at initial presentation
were compared to that of healthy controls (Table 4). Results
fromthe ANCOVA,controlling for the effectsof IQ, age,gender
and educational level, showed that patients attempted
significantly fewer subtasks, committed more time errors,
and had lower total profile scores than the normal controls in
Patients (n=31)Controls (n=31)
Age, mean (SD), years
Educational level, mean (SD), years
DUP, median (IQR), days
Diagnoses, number (%)
SD: standard deviation; DUP: duration of untreated psychosis; IQR: inter-quartile range.
K.C.M. Liu et al. / Schizophrenia Research 126 (2011) 87–92
MSET, and completed fewer categories and committed more
perseverative errors in MWCST.
3.3. Longitudinal change of MSET and MWCST scores
A repeated measures ANOVA showed that there was no
significant longitudinal change for any MSET score (Table 5).
To exhaustively explore the possible changes of MSET scores
between time points, in particular that from medication-
naïve state to clinical stabilization, paired sample t-tests were
used to compare MSET scores for all combinations of time
point pairs. Again, for all MSET scores, no significant changes
were observed between any time points. In contrast, results
of repeated measures ANOVA showed that there were
significant changes in the two MWCST scores.
3.4. Demographic and clinical correlates of MSET performance
In patients, females committed more time errors than
males (t=−2.567, p=.016); amongst controls, there was no
gender difference in MSET scores. Neither IQ nor educational
level was correlated with MSET scores in patients or normal
controls. Age of onset and DUP were not correlated with
MSET scores in patients, and MSET scores did not differ
significantly between patients with different diagnoses. At
initial presentation, positive symptoms were correlated with
time errors (r=.443, p=.013), but there was no significant
correlation between change in MSET performance and
change in negative or positive symptoms.
3.5. MSET performance and outcome
MSET scores at initial presentation were not correlated
with change in SOFAS score, while rule error scores at initial
presentation correlated negatively with changes in negative
symptoms (r=−.362, p=.046), and time error scores at
initial presentation correlated negatively with changes in
positive symptoms (r=−.453, p=.010).
The current study provided longitudinal data on an
ecologically valid measure of executive dysfunction in a
medication-naïve cohort of first-episode schizophrenic
patients. We found that first-episode patients exhibited
impairment in MSET performance at medication naïve state
regardless of DUP, age of onset, IQ or educational level.
Stability of MSET impairment was observed longitudinally
from the medication-naïve state through the first three years
of illness which contrasted with the improvement seen in the
patients' performance on a conventional executive test
(MWCST). Importantly, better MSET performance at the
initial medication-naïve state predicted greater improvement
in symptoms at the end of the third year, but was not related
to three-year functional outcome.
Drug treatment of patients.
Year 1Year 3
CPZ equivalent doses,
Concurrent drugs, numbers (%):
PANSS scores of patients.
Year 1Year 3
Overall score, mean (SD)
Positive scale, mean (SD)
Negative scale, mean (SD)
General psychopathology scale, mean (SD)
1N2, 3, 4
1N2, 3, 4; 2N3, 4
1N2, 3, 4; 2N3
1N2, 3, 4; 2N3, 4
PANSS: Positive and Negative Syndrome Scale; SD: standard deviation.
aAs measures by LSD comparisons, significance value at pb.05. For simplification, numbers are used to denote the different clinical stage: 1: initial presentation,
2: clinical stabilization, 3: Year 1, 4: Year 3.
MSET and MWCST performance of patients at the first episode.
Rule error, mean (SD)
Time error, mean (SD)
Total profile score,
5.19 (1.20)5.90 (0.40)9.33.004
3.70 (2.10)5.35 (1.14)9.38.003
6.43 (5.39)1.80 (2.40)11.55.001
MSET: Modified Six Elements Test; MWCST: Modified Wisconsin Card
Sorting Test; SD: standard deviation.
K.C.M. Liu et al. / Schizophrenia Research 126 (2011) 87–92
The impairment in MSET performance, as found in the
present study, is consistent with previous findings of chronic
and medicated first-episode patients (Chan et al., 2004; Evans
et al., 1997; Katz et al., 2007). It also adds to the scarce data
concerning medication-naïve patients (Chan et al., 2006b)
and is consistent with the findings of impairments in
conventional executive functions tasks in medication-naïve
patients (Mohamed et al., 1999). The presence of MSET
impairment early in the course of illness, before the effects of
medication or progression of illness, suggests that it is a
deficit fundamental to schizophrenia.
The lack of correlation of MSET performance with both IQ
previous empirical findings about the consistency of MSET
impairment in intellectually intact psychosis patients (Chan
et al., 2006b; Evans et al., 1997), suggests that MSET
impairment is unlikely to be entirely a consequence of general
intellectual impairment in schizophrenia, and instead may
To the best of our knowledge, the present study is the first
to provide data about the longitudinal change in MSET
performance of schizophrenic patients. Our results indicate
stability of MSET impairment in a group of medication-naïve
first-episode patients alongside improvement in performance
on a conventional executive test, suggesting that the two
tasks measure different components of executive functioning.
In particular, MSET impairment was already present in the
medication-naïve state and persisted through clinical stabi-
lization, suggesting that the impairment was not alleviated by
antipsychotic medication. The relative temporal stability of
MSET performance, together with the present findings that
MSET performance is not dependent on symptom changes,
suggests that MSET deficit in first-episode schizophrenia is
not likely to be state-dependent. However, this postulation is
tentative and further evidence is needed from replications of
the present findings.
The lack of correlation between MSET performance and
DUPandage of onsetraises the questionof whenMSETdeficit
in schizophrenia occurs. The present findings indicate that
deficits precede the commencement of antipsychotic medi-
cation. Other evidence has shown that deterioration in
cognitive functioning occurs well in advance of clinical
symptoms (e.g. Cannon et al., 2000; Chan et al., 2008b;
Laws et al., 2008), even among individuals who are in the
prodromal stage of psychosis (e.g. Brewer et al., 2005).
However with respect to MSET impairment, the exact period
when the impairment commences is yet to be determined.
Katz et al. (2007) have found that BADS was a significant
predictor for two outcome areas (instrumental activities of
daily living and communication) within a sample of chronic
schizophrenic patients. In the present study, we found that
MSET performance was correlated with clinical outcomes
over a three-year period following a first episode. With a
prospective longitudinal design, the present study provides
valuable data about the relationship of executive functions
(as measured by MSET) early in the course of the illness and
later clinical outcome. It also suggests the importance of
measuring executive functions for rehabilitation of patients.
Severallimitationsshould beaddressed beforedrawingany
of the BADS. Thus, results can only be applicable to the specific
components of executive functions measured by MSET, and
generalization of thepresentfindings remained to beexplored.
Second, although the present study provided valuable data
about executive functions at the early course of first-episode
schizophrenia, the study duration was three years preventing
detection of developmentofexecutivefunctioningover a more
extended period. Indeed, prospective longitudinal studies of
cognitive functions that follow psychosis patients for longer
than 5 years have been scarce (Gold et al., 1999; Hoff et al.,
2005; Stirling et al., 2003) despite the invaluable information
they would contribute to the field. Third, this study has
established that MSET deficit occurred at the early stage of
psychosis prior to the intervention with antipsychotic medica-
tion. However, ascertaining the exact onset of this deficit was
beyond the scope of the study; greater understanding of the
onset is important as it could guide early intervention efforts.
Further longitudinal studies of people at high risk of psychosis
are needed to address this issue.
By using an ecologically valid measure of executive
functions, the present study has shown that executive
deficit in schizophrenia that occurs early in the course of the
illness. More importantly, such deficits remain stable irrespec-
psychosis,whichsuggeststhat the MSETdeficit in first-episode
schizophrenia is not likely to be state-dependent.
Role of funding source
MSET and MWCST performance of patients in the 3 years following a first psychotic episode.
Initial presentation Clinical stabilizationYear 1Year 3
Subtasks attempted, mean (SD)
Rule error, mean (SD)
Time error, mean (SD)
Total profile score, mean (SD)
Categories completed, mean (SD)
Perseverative errors, mean (SD)
MSET: Modified Six Elements Test; WCST: Modified Wisconsin Card Sorting Test; SD: standard deviation.
K.C.M. Liu et al. / Schizophrenia Research 126 (2011) 87–92
Eric Chen and Raymond Chan designed the study. Kristy Liu managed
literature searches and analyses, and wrote the first draft of the manuscript.
Kristy Liu, Raymond Chan, Kevin Chan, Jennifer Tang and Eric Chen
contributed to data analysis. All authors contributed to interpretation of
results, participated in critical revisionof manuscript drafts and approved the
Conflict of interest
All authors declare that they have no conflicts of interest.
There are no further acknowledgements.
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