Psychiatry Research 169 (2009) 191–196

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Psychiatry Research
j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / p s yc h r e s

Computer-aided neurocognitive remediation as an enhancing strategy for

schizophrenia rehabilitation
Roberto Cavallaro a, Simona Anselmetti a,⁎, Sara Poletti a, Margherita Bechi a, Elena Ermoli a,
Federica Cocchi a, Paolo Stratta b, Antonio Vita c, Alessandro Rossi b, Enrico Smeraldi a,d
a
Department of Clinical Neurosciences, San Raffaele Universitary Scientific Institute Hospital, Vita-Salute San Raffaele University, Milano, Italy
b
Department of Experimental Medicine, University of L'Aquila, L'Aquila, Italy
c
Department of Mental Health, University of Brescia, Italy
d
National Institute of Neurosciences, Italy

A R T I C L E I N F O A B S T R A C T

Article history: Cognitive dysfunction is a chronically disabling feature of schizophrenia, associated with limits in obtaining
Received 2 July 2007 rehabilitation improvements. The purpose of this study is to assess the effectiveness of intensive computer-
Received in revised form 18 October 2007 aided cognitive remediation treatment (CRT) added to a standard rehabilitation treatment (SRT), in
Accepted 12 June 2008
enhancing neuropsychological performances and daily functioning in patients with schizophrenia. A 12-
week, randomized, controlled, single-blind trial of neurocognitive remediation was carried out on 86 patients
Keywords:
Schizophrenia
with clinically stabilized DSM-IV schizophrenia. Patients were assessed on cognitive and daily functioning
Rehabilitation before and after either CRT or placebo training that had been added to their SRT. After 3 months the repeated
Treatment outcome measure ANOVA showed a significant time × treatment interaction for executive function and attention
Neuropsychology performances and in daily functioning assessment in favour of patients in the SRT + CRT treatment. Results
Cognition disorders confirmed that cognitive remediation added to the SRT of schizophrenia enhanced its neuropsychological
effects and increased the effects of a long-term rehabilitation programme in terms of functional outcomes.
© 2008 Elsevier Ireland Ltd. All rights reserved.

1. Introduction these deficits would provide benefits to the functioning of patients

Cognitive dysfunction is a common, chronically disabling feature of
schizophrenia. The main domains of cognition, including attention,
executive function, working memory, verbal memory, psychomotor
coordination and learning ability, are significantly disrupted in
schizophrenia (Rund, 1998). Neuropsychological impairments have
been associated with both the heterogeneity of psychosocial outcome
(Green, 2000; Hogarty and Flesher, 1999) and fewer improvements
following rehabilitation (Green, 2000; Bell et al., 2001). Despite
optimistic expectations, the effect sizes of improvements reported
with atypical antipsychotics in the neuropsychological performance of
patients with schizophrenia are limited, perhaps because of metho-
dological flaws in the available research (Harvey and Keefe, 2001).
These findings of limited improvement with atypical antipsycho-
tics have increased interest in experimental approaches based on
cognitive interventions for the rehabilitation of cognitive deficits in
patients with schizophrenia, with the presumption that reducing
⁎ Corresponding author. Department of Clinical Neurosciences, San Raffaele
Universitary Scientific Institute Hospital, Vita-Salute San Raffaele University, Via
Stamira d'Ancona 20, 20127 Milano, Italy. Tel.: +39 0226433218, fax: +39 0226433265.
E-mail address: anselmetti.simona@hsr.it (S. Anselmetti).
(Wykes et al., 1999). During the past few years, many different
cognitive remediation programmes have been developed. Brenner et
al. (1994) were the first to develop a comprehensive therapeutic
programme for patients with schizophrenia, which targeted both
cognition and psychosocial outcome (IPT) This kind of intervention
showed some beneficial effects (Spaulding et al., 1999; Van Der Gaag
et al., 2002), but the effectiveness on the psychosocial outcome was
still limited (Van Der Gaag et al., 2002). Other kinds of cognitive
remediation treatment (CRT) targeted only cognitive function, with
the same core feature: intensive training which included exercises
created to target cognitive function and was aimed at improving
global functioning. Most studies that evaluated the effectiveness of
CRT compared a group treated with CRT with a control group treated
with a standard programme (Kurtz, 2003; Hogarty et al., 2004).
Furthermore, only a few studies investigated the effects of cognitive
remediation as part of a broader rehabilitation treatment programme
while at the same time assessing the effect on a functional measure
(Bell et al., 2001; Mc Gurk et al., 2005, 2007; Vauth et al., 2005; Reeder
et al., 2006). Wykes and Van Der Gaag (2001) suggested that “CRT
should not be a stand-alone therapy in clinical practice, but rather it
should be part of comprehensive programmes for rehabilitation and
recovery so that any improvement following CRT can be exploited in
further training or recovery therapy”.

0165-1781/$ – see front matter © 2008 Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.psychres.2008.06.027
192 R. Cavallaro et al. / Psychiatry Research 169 (2009) 191–196
In the last few decades, computer-aided remediation has been used
with increasing frequency due to the advantages of structured, but
flexible, sets of training tasks and immediate feedback (Brieff, 1994;
Burda et al., 1991; Bellucci et al., 2003; Kurtz et al., 2007). Sets have
usually been directed towards a few specific impairments known to be
common in schizophrenia. In some cases, this approach has led to the
generalization of effects to performance areas other than those that
were targeted (Wykes et al., 1999; Kurtz et al., 2007; Medalia et al.,
2001).
Recent studies that have evaluated cognitive deficit distribution
among patients with schizophrenia (Weickert et al., 2000; Ermoli
et al., 2005) have shown heterogeneous patterns of neuropsycholo-
gical impairment in different subjects. These results seem to suggest
the use of a patient-centred personalized cognitive enhancement
strategy (Reeder et al., 2006), aimed to improve performance in areas
of impairment without diverting resources needed to sustain
performance in areas of preserved function. Moreover, several authors
(Green, 2000, Wykes and Van Der Gaag, 2001) addressed the need to
adopt training methods tailored to individual patients. The overall aim
of CRT should be to enhance and strengthen standard simultaneous
clinical interventions to improve social, functional and adaptive
outcome; unfortunately, available studies rarely test this outcome, if
at all. It is still unclear whether cognitive training programmes could
enhance functioning more than psychosocial or cognitive–behavioural
interventions do alone, and which type of programme is best suited to
achieve this goal (Pilling et al., 2002).
Taking these results and speculations into account, we formulated
and tested the hypothesis that the enhancement of cognitive domains
added to standard rehabilitation treatments might potentially
improve functional outcome in patients affected by schizophrenia,
by optimizing the value of rehabilitation programmes. We performed
a randomized, controlled, single-blind trial, in order to evaluate the
ability of intensive CRT to enhance the effects of a standard
rehabilitation treatment (SRT) programme.
2. Methods
The study was a multicentred, single-blind, randomized and controlled comparison
of two rehabilitation strategies in schizophrenia: standard rehabilitation treatment plus
domain-non-specific enhancement treatment (SRT + PBO) and standard rehabilitation
treatment plus domain-specific cognitive remediation (SRT + CRT). A committee for
medical research ethics approved the study.
2.1. Study design
A 3-month, randomized CRT versus PBO treatment programme was administered to
patients attending a standard rehabilitation programme. Performances of interest were
compared before and after the randomized experimental CRT or PBO add-on period as
follows: 1) after 3 months of a ‘run-in’ standard rehabilitation treatment, which was
considered to be a baseline for neuropsychological assessment and daily functioning;
and 2) after 3 months of single-blind add-on treatment with CRT or PBO, which was
considered to be the endpoint for neuropsychological and daily functioning assessment.
Patients were blind to neurocognitive treatment conditions; patients in both
groups had been told that they were going to receive neurocognitive training created to
train cognitive functions using more or less specific exercises, in addition to their
standard rehabilitation treatment. The psychologists who administered the neuropsy-
chological assessment also assisted patients during the cognitive remediation
programme; it was considered that as the neuropsychological battery was strictly
standardized and in part computerized, subjective influence would be limited.
Raters who administered the Positive and Negative Syndrome Scale for Schizo-
phrenia (PANSS) and the Quality of Life Scale for assessment of psychopathology and
quality of life, respectively, were blind to the neurocognitive treatment groups and
neuropsychological assessments.
2.2. Subjects
Subjects were outpatients diagnosed as having schizophrenia, and referred to the
Psychiatric Rehabilitation Unit of San Raffaele Hospital, Milan, the Department of
Experimental Medicine, University of L'Aquila, L'Aquila and the Day Care Center of
Gorgonzola, Milan. All patients were attending a long-term treatment programme
offering medication management, psychiatric evaluation and rehabilitation. All
diagnoses were made by trained psychiatrists (C.F., V.A., S.P. and R.A.), using the DSM-
IV (American Psychiatric Association, 1994).
After informed consent was obtained, patients were tested and randomly allocated
to one of the treatment conditions. To be included, patients had to satisfy DSM-IV
criteria for schizophrenia and:
1. Have been treated with a stable dose of the same antipsychotic therapy for at least
6 months, and be responsive (30% or more response based on PANSS scores) and
clinically stabilized;
2. Have participated in a rehabilitation programme, including both cognitive–
behavioural and psychosocial programmes, 3 h a day, three times a week, for
3 months; and
3. Show no evidence of substance dependence or abuse, co-morbid diagnosis on Axis I
or II, epilepsy, or any other major neurological illness or perinatal trauma, or mental
retardation.
All potentially eligible patients were systematically screened using the above
criteria.
All patients remained on the same antipsychotic medication throughout the course
of the study. Atypical antipsychotic medications were administered to 26 patients in the
control condition and 37 in the experimental condition; the remaining patients were
taking typical antipsychotic medication. No significant differences were found
regarding antipsychotic distribution between the groups (χ2 = 0.0004, N.S.). Patients
needing drug or dose changes during the study were excluded.
2.3. Assessments
Patients were assessed for psychopathology, neurocognitive performance and daily
functioning before and after 3 months of experimental treatment. Basic information,
such as age, sex, education, duration of illness and medication, was also collected.
2.3.1. Psychopathological assessment
Psychopathology was assessed by means of the PANSS (Kay et al., 1987),
administered by trained psychiatrists (F.C., S.M.A. and R.C.) who were blind to
treatment randomization and neuropsychological testing. Inter-rater reliability for
PANSS total scores and items scores was fairly good, with kappa scores between 0.60
and 0.70. PANSS items were divided into five factors accordingly to Lindenmayer et al.
(1995): positive, negative, depressive, cognitive and excitement/hostility.
2.3.2. Neuropsychological assessment
All subjects received a neuropsychological test battery including the Brief
Assessment of Cognition in Schizophrenia (BACS), Wisconsin Card Sorting Test
(WCST) and Continuous Performance Test (CPT).
2.3.2.1. BACS. The BACS is a battery of neuropsychological tests that must be
completed in a short time (Keefe et al., 2004). It is specifically designed in two versions
(A and B) to evaluate patients before and after rehabilitation programmes, without the
results being influenced by recall. The entire battery lasts approximately 30 min, and
consists of the following tests: verbal memory (words recall); working memory (digit
sequencing); token motor task (psychomotor speed and coordination); selective
attention (symbol coding); semantic fluency; letter fluency; Tower of London. Verbal
memory tasks were adapted to Italian by replacing English words with Italian words
that were matched for frequency and phonemic characteristics. The English letter
fluency tasks were adapted to use letters that were already used in common Italian
clinical tests for letter fluency. Verbal memory and Tower of London tasks consist of two
alternative forms for repeated measures assessment. For a more specific description,
see Keefe et al. (2004).
2.3.2.2. WCST. The Wisconsin Card Sorting Test (Heaton, 1981) is a measure of
executive function (cognitive flexibility). A computerized version was administered
(Stratta et al., 1997). Subjects were required to sort cards according to a rule (e.g., colour,
shape, or number) that was changed after 10 correct answers. The performance on the
WCST in this study was based on the number of perseverative errors. Scores were
adjusted for age and education (Laiacona et al., 2000).
2.3.2.3. CPT. The Continuous Performance Test is a computerized task that measures
sustained attention. We used the A–X version, modified by Stratta (Stratta et al., 2000),
in which letters are shown serially on a display and subjects are instructed to respond
by pressing a key (zero) only when the letter X follows the letter A. Each letter appeared
for 200 ms and the subjects had 1 s to respond. One hundred and fifty stimuli were
presented over a total time of 10 min. Feedback was provided: a low tone for correct
presses; a high one for false alarms or misses; and no sound at all for correct rejection.
In this study, the number of missed targets was used for analysis.
The neuropsychological tasks were administered by a trained psychologist. Each
baseline cognitive performance measured was rated as “good” or “poor” for each
patient. The cut-off value for each performance was the 75th percentile of the
distribution (Ermoli et al., 2005) of 71 healthy controls matched in age and education
and tested with the same battery.
2.3.3. Daily functioning outcome assessment
Daily functioning was assessed by the Quality of Life Scale (QLS) (Heinrichs et al.,
1984), a semi-structured interview made up of 21 items that evaluates three different
areas of social functioning:
 R. Cavallaro et al. / Psychiatry Research 169 (2009) 191–196 193

2.3.3.1. Interpersonal relations (items 1–8). This subscale consists of eight items that
assess the ability of the patient to establish and maintain social relationships. Each item
score ranges from 0 (absence of any relationship) to 6 (presence of high quality
relationships).
2.3.3.2. Instrumental role (items 9–12). This subscale contains four items that evaluate
the ability to obtain and maintain a job, to study and to collaborate in everyday
housework. Each item score ranges from 0 (absence of any activity) to 6 (full-time
occupation).
2. Patients in the SRT + CRT group received four different sets of domain-specific
exercises organized according to a standardized procedure. Set 1 was made up of
mainly adaptive exercises and administered for the first 3 weeks in order to give
patients a training period with the computer. Sets a, b and c targeted the same
cognitive functions with different exercises and were alternatively administered for
the remaining 27 weeks. The exercises were graded in difficulty, with easier ones
being presented earlier in the programme.
At the end of this experimental treatment phase, both groups of patients continued
with SRT for at least 9 months.

2.3.3.3. Self-directedness, including intrapsychic foundations and common objects and

2.5. Data analysis
activities (items 13–21). This subscale contains nine items that assess planning
abilities, personal autonomy, affective and cognitive functioning, and motivation level.
Demographic, neuropsychological and clinical characteristics at baseline were
The scale was administered by a trained rehabilitation therapist who routinely uses
compared using analysis of variance (ANOVA) or chi-squared tests when appropriate.
all of these measures and who has demonstrated adequate reliability at routine
The effect of CRT treatment on neuropsychological performances and daily
reliability checks. The rehabilitation therapist was blind to the randomization and
functioning was analyzed with repeated measures ANOVAs (time × treatment interac-
neuropsychological assessment.
tion) with treatment groups as the between-subject factor and the two evaluations
(pretest and posttest) as within-subject factors.
2.4. Treatments
Moreover, in order to compare the magnitude of the treatment effects of both
SRT + CRT and SRT + PBO, we calculated for each variable standardized effect sizes,
2.4.1. Standard rehabilitation programme
determined by changes in the test score (subtraction of the posttest score from the
Inclusion criteria for entering the SRT are a DSM-IV diagnosis of schizophrenia, to
pretest score) divided by the standard deviation of the whole sample at baseline.
have been treated with a stable dose of the same antipsychotic therapy for at least
Differences of effect sizes of improvement for each variable between groups were
3 months and be clinically stabilized, and to show no evidence of substance dependence
then analyzed with ANOVAs. Bonferroni correction was applied.
or abuse or any other major neurological illness or perinatal trauma, or mental
retardation.
At the initiation of SRT, patients are evaluated by the treatment team, composed of 3. Results
a psychiatrist, psychologists and rehabilitation therapists with both standardized and
clinical ratings. The rehabilitation programme focuses on the main community goals of Of the 100 subjects randomly assigned to treatment, 14 dropped
social abilities, work and autonomy. The criteria of the patient's discharge are agreed out (eight in the target group and six in the placebo group) during
between the treatment team and the patient during the admission evaluation. The
mean time of SRT is approximately 15 months. The SRT included non-cognitive
the programme. Reasons for the dropping out were worsening of
subprogrammes of IPT (Verbal Communication, Social Skill Training and Problem symptoms for six patients, change of residence for two patients,
Solving) (Brenner et al., 1994), social skills training programmes for residential, withdrawal of consent for four patients and a full-time job for
vocational and recreational functioning (Roder et al., 2002) and psychoeducation two patients, the withdrawal of consent for four patients and a full-
(Rund et al., 1994; Bechdolf et al., 2004). Each patient participates in the programme for
time job for two patients. Among completers, 36 patients received
a total of 3 half-days a week (9 h excluding the CRT or PBO cognitive remediation
therapy; see Section 2.4.2 for more details) and take part in groups of seven-nine SRT + PBO and 50 SRT + CRT. All results shown refer to completers.
participants lasting 1.5 h each. Therapists are trained clinical psychologists and Table 1 shows demographic and clinical characteristics of the sample
rehabilitation therapists. The CRT and SRT programmes are not explicitly integrated in at baseline. Table 2 shows neuropsychological performances and QLS
this study. measures of patients in the treatment groups at baseline and retest.
All patients had taken part in this standard programme for 3 months before
randomization.
The “baseline” and “retest” columns show the raw scores of
evaluations and the differences between groups at baseline calcu-
2.4.2. Computer-aided training lated with ANOVA. There were no statistically significant differences
The computer-aided training employed the Cogpack Software® (Marker, 1987–2007). between groups at baseline observation for any of the variables
This programme includes different neurocognitive exercises that can be divided into do- studied.
main-specific exercises, aimed at training specific cognitive areas among the ones known to
be impaired in schizophrenia (verbal memory, verbal fluency, psychomotor speed and
coordination, executive function, working memory, attention) and non-domain-specific 3.1. Retest observations
exercises, that do not focus on one specific function but require the use of several functions
at a time and engage functions such as culture, language and simple calculation skills. Most Psychopathology remained unchanged between the two groups
exercises are adaptive and the computer sets the level of difficulty, based on patients'
throughout all the observations.
performances during the course of the session. The programme records the performance of
each patient for every session, so it gives patients the chance to receive feedback on both The repeated measures ANOVA showed a significant time ×
performance during the sessio and over the course of treatment, and it allows the therapist treatment interaction in favour of the SRT + CRT group for the number
to have a course profile of each patient. of CPT targets missed (F = 4.52, P = 0.03) and the number of
perseverative errors on the WCST (F = 4.15, P = 0.04).
2.4.2.1. Experimental conditions. Both experimental and placebo conditions were
added to the unchanged standard rehabilitation programme. Following admission to the
study, computer-generated random number tables allocated each patient to one of the
Table 1
following conditions:
Sociodemographic and clinical data at baseline of patients in the SRT + CRT and SRT +
PBO groups.
1. SRT + CRT. The experimental condition consisted of three 1-h sessions a week of
domain-specific computer-aided exercises, for a period of 12 weeks. This gave a total of SRT + CRT SRT + PBO Statistics
36 h. Sets of exercises were individually created for each patient on the basis of the n = 50 n = 36 (ANOVA)
quality of baseline performances at neuropsychological assessment: for each poor
performance, a domain-specific exercise was included, while for each good Mean (S.D.) Mean (S.D.) F P
performance a non-domain-specific exercise was added. Age 33.2 (9.5) 34.2 (6.8) 0.31 0.58
2. SRT + PBO. The control condition consisted of 1 h a week of computer-aided non- Years of education 12.1 (2.4) 11.2 (3.6) 1.91 0.17
domain-specific activity and 2 extra h a week of SRT (patients were randomly assigned Age of onset 24.3 (8.1) 26.2 (5.7) 1.40 0.23
to one of the non-cognitive groups previously described), for a period of 12 weeks. Duration of illness (years) 8.28 (6.7) 8.08 (5.1) 0.30 0.58
Subjects completed a total of 36 h. PANSS-positive 10.8 (3.8) 10.05 (3.6) 0.72 0.39
PANSS-negative 13.7 (4.5) 14.6 (4.3) 0.86 0.35
Exercises were administered by trained psychologists whose role was to motivate
PANSS-hostility 9.02 (2.7) 9.3 (3.2) 0.21 0.65
patients and assist them in completing exercises and trying different strategies, without
PANSS-depression 13.9 (4.9) 14.7 (4.2) 0.58 0.45
giving them the solutions to the exercises. In order to standardize the treatments,
PANSS-cognitive 17.2 (5.04) 19.1 (5.3) 2.69 0.11
exercises were organized in sets as follows:
IQ total 87.2. (14.8) 83.3 (11.7) 0.74 0.39
IQ verbal 90.3 (15.1) 85.9 (13.5) 0.49 0.48
1. Patients in the SRT + PBO group received the same set of non-domain-specific
IQ performance 85.2 (15.4) 81.6 (14.3) 0.74 0.39
exercises, which varied only in difficulty level, depending on the patient's ability.
194 R. Cavallaro et al. / Psychiatry Research 169 (2009) 191–196

Table 2
Neurocognitive performances and measures of Quality of Life (QLS) in the SRT + CRT and SRT + PBO groups at baseline and retest.

Baseline Statistics Retest

SRT + CRT n = 50 SRT + PBO n = 36 (ANOVA) SRT + CRT n = 50 SRT + PBO n = 36
Mean (S.D.) Mean (S.D.) F P Mean (S.D.) Mean (S.D.)
Verbal memory (mean of 5 trials) 7.4 (2.4) 6.6 (2.4) 2.98 0.09 8.5 (1.9) 7.5 (2.3)
Working memory (n corr sequences) 17.3 (4.5) 16.6 (5.3) 0.7 0.4 18.7 (4.1) 17.1 (5.3)
Psychomotor coordin (n of tokens) 72.4 (18.4) 70.6 (14) 0.63 0.43 762 (15.8) 71.2 (11.3)
Letter fluency (n words generated) 11.2 (3.7) 9.9 (4.5) 0.31 0.57 12.3 (4.4) 11.5 (4.3)
Semantic fluency (n words generated) 18.3 (5.3) 15.5 (6.7) 1.9 0.16 19.2 (5.6) 16.9 (5.7)
Selective attention (n correct items) 39.6 (11.9) 35.2 (10.7) 3.8 0.06 432 (11.8) 38.06 (13.1)
Planning (Tower of London: n correct responses) 13.8 (4.2) 12.7 (3.9) 1.61 0.21 14.5 (3.6) 13.7 (4.2)
Sustained attention (CPT: n missed) 26.1 (24.8) 30.5 (34.5) 1.1 0.29 12.8 (13.9) 28.1 (34.3)
Cognitive flexibility (n persever err) 19.1 (9.1) 16.5 (10.5) 0.13 0.71 9.5 (7.7) 14.5 (11.4)
QLS-relationships 20.9 (8.9) 19.9 (8.5) 0.47 0.99 21.5 (8.2) 19.2 (8.6)
QLS-work 3.7 (5.7) 3.9 (6.1) 0.02 0.88 3.8 (6.2) 4.1 (6.1)
QLS-self directness 26.1 (9.7) 25.2 (7.9) 0.33 0.57 27.4 (9.6) 23.9 (8.2)
QLS-total score 47.7 (20.1) 46.1 (18.3) 0.28 0.59 52.8 (19.4) 47.2 (19.2)

Regarding the QLS data, the repeated measures ANOVA showed a treatment effect was expected, due to the clinical stabilization of
significant time×treatment interaction, also in favour of the SRT + CRT patients, even for the cognitive factor. In fact, some authors have
group for the total score (F = 4.93, P = 0.03) and for the self- argued that the sensitivity of this factor is too low to determine
directedness subscore (F = 8.4, P = 0.004). cognitive functioning, in comparison to performance-based tasks
(Ehmann et al., 2005; Good et al., 2004). The repeated measures
3.1.1. Effect sizes of improvement ANOVA showed a significant differential improvement in cognitive
Table 3 shows the effect sizes of improvement for each group and the flexibility and attention performances and quality of life measures in
differences between groups. Analysis of variance regarding the effect favour of the SRT + CRT group. Also the effect sizes of improvement,
sizes of improvement of significant variables confirm the significant calculated post hoc in order to compare the magnitude of improve-
difference between CRT + SRT and SRT + PBO groups, respectively, for ment between groups, were significantly higher in the SRT + CRT
WCST performances (F = 11.02, P = 0.001), CPT performances (F = 8.8, group. The findings in the present study confirm previous positive
P = 0.004) and QLS total score (F = 4.9, P = 0.02). reports on the effect of CRT on these cognitive functions (Bell et al.,
2001; Wykes et al., 1999; Kurtz et al., 2007), even when added to a
4. Discussion standard rehabilitation programme. The observed improvements
could not be attributed to a difference in the stimulation and/or
The present study was designed to test whether cognitive increased therapeutic contact as both groups of patients spent the
remediation could enhance the effect of evidence-based treatments same number of hours in the standard programme and received the
such as IPT (Brenner et al., 1994), social skills training (Roder et al., same number of rehabilitation activities. As the Cogpack© exercises do
2002) and psychoeducation (Rund et al., 1994). This design is not resemble the cognitive assessment tasks, the improvements in test
advanced in comparison to previous studies, which have typically performance cannot be due to a practice effect. Nevertheless,
compared the effects of cognitive remediation with a control group after 3 months, some patients in the SRT + PBO group also obtained
receiving standard care (Kurtz et al., 2007; Fiszdon et al., 2005; Sartory an improvement in some domains, as had been expected from the
et al., 2005). The fact that psychopathology didn't show any time × ecological stimulation of neuropsychological performances (Bell et al.,
2001; Spaulding et al., 1999; Lauriello et al., 1999).
These results can be brought back to two hypotheses. The first is that,
Table 3 according to the results of Kurtz et al. (2007), due to the large restrictions
Effect size of improvement for SRT + CRT and SRT + PBO groups for neuropsychological on the social and occupational lives of schizophrenic patients, even a
and daily functioning variables. non-specific but sustained cognitive stimulation could elevate neurop-
Effect size of improvement
sychological functioning. The second is that a structured SRT could
SRT + CRT SRT + PBO Statisticsa
significantly reduce cognitive impairments in specific areas, as a
n = 50 n = 36 (ANOVA) growing number of studies indicate (Spaulding et al., 1999; Brenner,
Mean (S.D.) Mean (S.D.) F P 2000). Nevertheless, our study supported the enhancing role of CRT;
Verbal memory (mean of 5 trials) 0.52 (0.88) 0.42 (0.65) 0.38 0.53 when added to SRT, it helped patients to achieve significantly better
Working memory (n correct sequences) 0.28 (0.90) 0.05 (0.76) 1.51 0.22 outcomes in terms of both cognitive and everyday life functioning.
Psychomotor coordin (n of tokens) 0.26 (0.95) −0.01 (0.76) 1.9 0.16 Regarding individualization of CRT, descriptive analysis of those
Letter fluency (n words generated) 0.27 (0.75) 0.34 (0.72) 0.21 0.64 performances, categorized with the control population-derived cut-
Semantic fluency (n words generated) 0.14 (0.83) 0.23 (0.95) 0.18 0.67
offs, showed a heterogeneous pattern of individual neuropsychologi-
Selective attention (n correct items) 0.35 (0.91) 0.21 (0.84) 0.50 0.47
Planning (Tower of London: n correct 0.17 (0.83) 0.25 (0.99) 0.15 0.69 cal impairment at baseline, as expected (Weickert et al., 2000; Ermoli
responses) et al., 2005). This heterogeneity has led different authors to debate the
Sustained attention (CPT: n missed) 0.56 (0.83) 0.13 (1.03) 4.15 0.04a need for an individualized form of therapy that takes into account the
Cognitive flexibility (WCST: 0.53 (1.22) 0.08 (0.53) 4.52 0.03a
patient's resources and that is directed toward the patient's specific
n perseverative errors)
QLS-relationships 0.11 (0.53) − 0.07 (0.32) 3.18 0.07 impairments (Green, 2000, “learning potential”; Wykes and Van Der
QLS-work 0.06 (0.61) 0.08 (0.48) 0.03 0.85 Gaag, 2001; Wykes et al., 2007). Accordingly, sets of exercises were
QLS-self directness 0.14 (0.37) − 0.12 (0.45) 8.4 0.004a intensive both in terms of the concentration of sessions within a few
QLS-total score 0.29 (0.42) 0.09 (0.38) 4.9 0.02a weeks, and in terms of their specificity for impaired performances
a
Pretest–posttest score divided by standard deviation of the pooled sample. (Reeder et al., 2006), enabling patients to use their motivation and
 R. Cavallaro et al. / Psychiatry Research 169 (2009) 191–196
attentional resources optimally. With more generalized approaches,
patients would have divided their resources between useful and
useless exercises, reducing therefore the ‘best use’ of motivational and
attentional resources. A further advantage of individualize therapy
was that targeting the specific profile of cognitive impairment allowed
better data analysis: for each performance we could compare the
outcome only of those subjects with a poor baseline performance,
avoiding the bias of a possible performance ceiling effect.
The main result of our study is, in our opinion, the improved
outcome on the Quality of Life Scale evaluation for the SRT + CRT
group, as the improvement in daily functioning is the main target of
rehabilitation in schizophrenia patients, and the final goal of any
therapeutic enhancement strategy (Wykes and Van Der Gaag, 2001).
Among the different areas of functioning assessed with the QLS
(interpersonal relations, instrumental role and self-directedness
(Bobes et al., 2005; Bow-Thomas et al., 1999), we found a significant
time × treatment interaction for the self-directedness subscale. This
scale included items concerning the sense of purpose and motivation,
and items about common possessed objects and participation in a
range of activities, which are both measures of social engagement
(Bow-Thomas et al., 1999). We could argue that, because of the
improvement achieved, patients in the SRT + CRT group may have
learned to spend their time more effectively in basic daily activities
(i.e., reading the newspaper, travelling by public transportation), and
this increased the degree of motivation and sense of purpose. We
expect an improvement of the instrumental role and interpersonal
relations subscales at the follow-up retest, when patients will have had
more time to apply those cognitive functions already taught by CRT to
a more ecological context (during SRT).
According to these results, a treatment period of a maximum
length of 3 months may have been too short to rate certain functioning
differences between treatment groups, as some changes in the QLS
factors (e.g., employment status and relationships) may take a
relatively long time before becoming apparent.
The differential rates of improvement, the improved core deficit
areas, and the functional outcome all support the hypothesis that the
interaction between CRT and SRT is responsible for this favourable
outcome (Bell et al., 2001). More precisely, CRT seemed to stimulate
mental activity and was shown to reduce cognitive limiting factors,
whereas SRT provided an ecological context in which to use and
reinforce mental activity.
In conclusion, despite the need for confirmation in independent
samples, our data seem to suggest that improved cognitive functions
may help patients with schizophrenia to benefit from other SRT and
psychosocial interventions. The long-term enhancement effects of
cognitive remediation on SRT and the progress of cognitive function-
ing in patients with schizophrenia after its withdrawal need further
investigation. Such data are being collected in order to investigate the
outcomes 6 and 12 months after the end of the CRT programme.
This study appears to have some limitations. Firstly, as previously
stated, a longer period of treatment could be more effective to reduce
cognitive deficit and improve social functioning. Secondly, the 1 h a
week of non-domain-specific computer activity introduced to leave
the patients blind about their experimental condition could have had
some effects on cognitive functions, at least for the exposure to
computer activity. This could be the reason for the improvements
found in the SRT + PBO group, and the reduced differential effect on
cognitive functions such as psychomotor coordination between
groups. Considering this plausible, we cannot exclude the hypothesis
that CRT is effective only with 3 h a week training, while it is not
effective with less exposure to computer activity. Nevertheless, this
hypothesis cannot be applied to the results for executive function, as
none of the PBO exercises even marginally address the use of this
cognitive function.
Another caveat could be the single-blinding: there could be a
subjective influence of BACS ratings, even if limited by the strict
195
standardization of the task. Moreover, the QLS scale used for the
evaluation of daily functioning was originally created to assess deficit
symptoms (Heinrichs et al., 1984), though it could overlap in some
areas with an evaluation of negative symptoms. It could be useful in
future studies to use a more performance-based scale like the UCSD
Performance-based Skills assessment (Patterson et al., 2001).
Further studies may be necessary in order to discriminate between
the effect of domain-specific, individualized cognitive remediation and
more general forms of cognitive training that target all cognitive
functions known to be impaired in patients affected by schizophrenia.
Moreover, SRT and CRT were not explicitly integrated in this study,
as previously stated, in order to estimate the ecological enhancement of
cognitive remediation therapy on standard rehabilitation therapy. Efforts
are proceeding in our group to integrate SRT with the inclusion of more
“cognitive stimulation” during rehabilitation groups, with the hypoth-
esis that it could strengthen the cognitive enhancement of CRT.
4.1. Significant outcomes
1. Domain-specific CRT improved cognitive flexibility and sustained
attention performances.
2. Changes in neurocognitive functioning improved functional out-
come, increasing the benefits of SRT.
3. The clinical use of CRT, in addition to SRT, in patients with
schizophrenia is suggested.
4.2. Limitations
1. Longer periods of treatment could be more effective.
2. Non-domain-specific computer activity may have some effects on
psychomotor and attentional performances.
3. The trial was only single- but not double-blind.
Acknowledgement
This work was supported by the Italian Ministry of University and Scientific
Research grant no. 2001064198.
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