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Cognitive Remediation Therapy (CRT): Improving

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 4

Cognitive Remediation Therapy (CRT):

Improving Neurocognition and
Functioning in Schizophrenia
Rafael Penadés and Rosa Catalán
Institute of Clinical Neurosciences, Hospital Clínic de Barcelona,
Department of Psychiatry and Psychobiology, University of Barcelona,
IDIBAPS-CIBERSAM, Barcelona
Spain

1. Introduction
Schizophrenia is generally viewed as a chronic disorder characterized by psychotic symptoms
and relatively stable neurocognitive and interpersonal deficits. According to the revised fourth
edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR), to be
diagnosed with schizophrenia, three diagnostic criteria must be met (APA 2000):
1. Characteristic symptoms: Two or more of the following, each present for much of the
time during a one-month period (or less, if symptoms remitted with treatment).
 Delusions
 Hallucinations
 Disorganized speech, which is a manifestation of formal thought disorder
 Grossly disorganized behaviour (e.g. dressing inappropriately, crying frequently)
or catatonic behaviour
 Negative symptoms: Blunted affect (lack or decline in emotional response), alogia
(lack or decline in speech), or avolition (lack or decline in motivation)
If the delusions are judged to be bizarre, or hallucinations consist of hearing one voice
participating in a running commentary of the patient's actions or of hearing two or more
voices conversing with each other, only that symptom is required above. The speech
disorganization criterion is only met if it is severe enough to substantially impair
communication.
2. Social or occupational dysfunction: For a significant portion of the time since the onset
of the disturbance, one or more major areas of functioning such as work, interpersonal
relations, or self-care, are markedly below the level achieved prior to the onset.
3. Significant duration: Continuous signs of the disturbance persist for at least six months.
This six-month period must include at least one month of symptoms (or less, if
symptoms remitted with treatment).
The primary treatment of schizophrenia is antipsychotic medications, often in combination
with psychological and social supports. Antipsychotic medication has made it possible to
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70 Schizophrenia in the 21 Century

reduce psychotic symptoms and to prevent relapses, but is it expected that antipsychotic
medication could, one day, improve cognition. Frequently, residual cognitive impairments
stand as impediments to full recovery from schizophrenia (Bell and Berson, 2001). A number
of psychosocial interventions may be useful in the treatment of schizophrenia including:
family therapy, supported employment, cognitive remediation, skills training, cognitive
behavioural therapy (CBT), token economic interventions, and psychosocial interventions for
substance use and weight management. Cognitive Remediation Therapy (CRT) is a promising
new treatment designed to improve neurocognitive abilities such as attention, memory and
executive functioning. A large body of data on the efficacy of cognitive remediation therapy
has been produced, and a number of meta-analyses have shown moderate to large effects on
cognitive outcomes. However, experts in the field claim that CRT should not only enhance
cognition but also that the improvement in cognition will affect community functioning.
Consequently, clinicians are now increasingly concerned with identifying appropriate
cognitive targets and ways of promoting secondary improvements in functioning.

2. Neuropsychology in schizophrenia
Current neuropsychological models of schizophrenia assert that cognitive impairments
found in patients are simply the expression of some abnormalities in brain functioning.
These abnormalities are found mainly in the frontal lobe and lead to a reduced capacity to
activate frontal areas when faced with a cognitive challenge. In addition, multiple
connectivity abnormalities between different brain regions have also been described. More
specifically, it seems that the neural circuits interconnecting the limbic, the temporal and the
frontal lobe are irregularly connected (Barch 2005). This model has received considerable
support in empirical studies from various disciplines including neuroimaging,
electrophysiology, neuropsychology and cognitive psychology (Andreasen, 1997). In an
excellent review, Shenton et al. (2001) described the anatomical abnormalities that have been
replicated most consistently in schizophrenia research: cavum septum pellucidum (92%),
amygdala or hippocampus (74%), lateral ventricles (73%), basal ganglia (68%), superior
temporal gyrus (67%), corpus callosum (63%), temporal lobe (61%), thalamus (42%),
cerebellum (31%) and brain volume (22%). Nevertheless, the proposed model goes beyond
the direct relationship between anatomical abnormalities and neurocognitive impairments.
None of the aforementioned brain areas work in isolation. Rather, they work together as a
part of different cortico-subcortical circuits linking the frontal cortex with other brain
regions, such as the limbic system, basal ganglia and thalamus (Pearlson et al., 1996). This
type of "disconnection" between brain areas would involve defective processing of
information and be expressed as cognitive impairment (Weinberger & Lipska 1995).
Thus, due to the heterogeneity of the causes of cognitive impairments, it is more common to
find different cognitive profiles with selective cognitive impairments than homogeneous,
generalized cognitive impairment. Different sorts of dysfunctions have been described in
various domains such as attention, vigilance, verbal memory and working memory.
Additionally, patients with schizophrenia present serious difficulties in executive
functioning: inflexibility, poor self-monitoring, lack of planning, and passive performance
due to a lack of cognitive strategies. Problems with motor skills and difficulty in
suppressing or inhibiting inappropriate responses are also present. Heinrichs & Zakzanis
(1998) conducted a meta-analysis of more than 200 studies and found that between 60-80%
Cognitive Remediation Therapy (CRT): Improving Neurocognition and Functioning in Schizophrenia 71

of patients with schizophrenia have neurocognitive impairments that can be classified as

moderate or severe. However, it was not possible to find a unique cognitive profile for all
patients. Various combinations of impairments including attention, working memory,
verbal or visual learning, psychomotor speed and executive function were described (Table
1). Therefore, heterogeneity across all possible conceivable neurocognitive domains is
perhaps what best describes the pattern of neurocognitive impairment in schizophrenia.
Nevertheless, although the neuropsychological assessment of a patient diagnosed with
schizophrenia may reflect an impaired profile through a number of domains such as
attention, vigilance, verbal memory and working memory, the presence of attention and
executive impairments are the common feature.

MILD IMPAIRMENT MODERATE IMPAIRMENT SEVERE IMPAIRMENT

0.5-1 SD below the mean 1-2 SD below the mean <2 SD below the mean
Perceptual skills Verbal memory Executive function
Speed processing Working memory Verbal fluency
Recognition memory Recall memory Verbal learning
Naming Visuo-motor skills Motor speed
General Intelligence Distractibility Vigilance
Table 1. The severity of cognitive impairments in schizophrenia.

3. Relevance of neurocognition in schizophrenia

Neurocognitive impairments in schizophrenia are not trivial because they are consistently
associated with low social functioning and worse outcomes. Up to 60% of the variance in
social functioning seems to be explained by neurocognitive variables. Performance in tests
of attention, working memory, verbal memory, psychomotor speed and executive functions
have been shown to be selectively related to different aspects of psychosocial functioning
ranging from the level of independence in daily living skills, work performance and use of
psychiatric services to the ability to learn new skills. Green (1996) conducted an important
meta-analytic study attempting to test the aforementioned putative relationship between
neurocognition and functioning. A positive and significant relationship between cognition
and functioning was established through the meta-analysis and the various cognitive
domains showed significant correlations. More specifically, verbal memory acted as the
most robust predictor of functioning including social functioning, social problem solving
and learning new skills. This close relationship has been replicated in other studies.
Additionally, in former studies other variables including attention, processing speed and
executive functions also proved to be strongly related to psychosocial functioning (Table 2).
The presence of impairments in both verbal memory and attention span would affect the
ability to acquire social skills and might be associated with considerable social dysfunctions.

Vigilance Working Memory Verbal Memory Executive Function

Social
+ +
Functioning
Vocational
+ + + +
Functioning
Autonomy + + +
Table 2. Relationship between cognitive performance and functioning.
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72 Schizophrenia in the 21 Century

Furthermore, some specific neuropsychological tests such as the Wisconsin Card Sorting
Test (WCST) can be useful in the prediction of concrete aspects of functioning such as work
performance (Lysaker et al. 1996). This test has shown an acceptable level of prediction
regarding work performance in patients with schizophrenia. Thus, bad performance on the
WCST is associated with fewer working hours in a competitive job, increased likeliness of
emergent symptoms during the workday and the possibility of new hospital admissions.
McGurk & Melter (2003) have pointed to neurocognitive aspects as the most important
factors to be taken into account when attempting to return to work. Finally, it should be
emphasised that cognitive impairments may interact with negative symptoms. Even further,
some authors suggest that the combination of problems, negative symptoms and cognitive
dysfunction would themselves generate pervasive social dysfunction. This is especially
pernicious as some negative symptoms would prevent the patient being involved in
rehabilitation programs.

4. Evidence-based treatments
Initially, neuropsychological rehabilitation programs used in brain injury were the best
option for treating cognitive impairment in patients with schizophrenia. Other interventions
used in degenerative processes and elderly people were also tried. Nowadays, this practice
would not be considered appropriate because cognitive rehabilitation in schizophrenia has
its own peculiarities. Therefore, it is highly advisable to use specific interventions, especially
those that have been proven to be effective in controlled studies. Various approaches seem
to be efficacious and effective alternatives. Interestingly, all these cognitive remediation
therapies for schizophrenia have in common that they are types of behavioural training that
aim to improve cognitive processes (attention, memory, executive function, social cognition
or metacognition) with the goal of durability and generalization (Crew, 2010). Another
important feature of evidence-based cognitive remediation therapies is the aim of enhancing
cognition with the expectation that improved cognition will affect community functioning.

4.1 Integrated Psychological Therapy (IPT)

Integrated Psychological Therapy for Schizophrenia (IPT) was probably the first therapy to
include neurocognitive elements specially developed to be used with schizophrenia patients
(Brenner et al., 1992). It was designed by Professor Hans Dieter Brenner and colleagues at
the University of Bern in Switzerland. There are versions in German, English and Spanish,
adapted by Professor Volker Roder. The IPT is a structured intervention program that
prescribes steps for treating cognitive and behavioural dysfunctions (Roder et al. 2007). It
comprises five modules, applied in the following order: cognitive differentiation, social
perception, communication, social skills, and interpersonal problem solving (Table 3).
Although the main objective is the treatment of neurocognitive disorders, it also includes
psychosocial elements, such as social skills training designed to improve social behavior
deficit. The duration of the intervention generally ranges between 8 and 12 months although
it is not established a priori and depends on the needs and progress of the participants
during the course of treatment. It is a group therapy and is implemented twice a week for
between 45 and 90 minutes. Ideally, group size is between four and eight participants.
Support materials are very simple: a room, a blackboard, projector, paper, and pencils or
pens. Learning techniques are frequently used such as token economy, discriminate
Cognitive Remediation Therapy (CRT): Improving Neurocognition and Functioning in Schizophrenia 73

learning, social reinforcement, modelling and shaping. Group dynamic techniques are also
required including sharing, coaching, role playing, reformulation and positive connotation.

INTERVENTION
MODULES TARGETS
TECHNIQUES
Cognitive Differentiation Attention Card Sorting
Concept formation Verbal concept exercises
Abstraction
Social Perception Social cognition Slides depicting social
situations
Collecting information
Interpretation and
discussion
Assigning a title
Verbal Communication Communication skills Literal repetition
Paraphrasing
W-Questions
Topical questions
Focused communication
Social Skills Social Skills Cognitive analysis
Role-playing
Problem solving Interpersonal problem Problem solving technique
solving Generalisation
Table 3. Modules of the Integrated Psychological Treatment (IPT).

The Cognitive Differentiation module seeks to improve attention (selective attention,

focused attention, sustained attention, alternating attention, etc.) and also conceptualization
skills (abstraction, concept formation, conceptual discrimination, etc.). The exercises consist
of sorting cards; managing verbal concepts; elaborating definitions; managing words in
different contextual meanings, and so on. The use of reinforcement is especially important in
this part of the program to overcome motivational problems and negative symptoms. The
Social Perception module seeks to improve the analysis and understanding of psychosocial
information. This is neurocognitive work but focused on the social cognition processes.
Different slides displaying social interaction situations are shown to the patients to be
analyzed and interpreted. Each slide gives the opportunity for some analysis, coding,
integration and understanding of social information. Therapists try to stimulate patients’
abilities to discriminate between relevant and informative parts and the irrelevant stimuli.
To achieve these targets, therapists use a variety of techniques including shaping, modelling
and coaching. The Communication module targets relevant aspects of communication and
interpersonal behavioural skills. It is designed to work with the three basic processes of
language: listening, understanding and speaking. A series of verbal exercises are proposed
in order to determine the effects of cognitive impairment on communication. These move
from the literal repetition of sentences, formulation of questions and answers, to free
communication exercises which gradually involve patients in interactive communication
exercises. The Social Skills module aims to practice the necessary skills that enable patients
to have satisfactory psychosocial functioning. The authors emphasize that learning through
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74 Schizophrenia in the 21 Century

role-play requires memorization and analysis of social behaviour. Both processes may be
altered as a consequence of cognitive impairments. Therapists encouraged the practice of
these skills in real contexts to compensate for cognitive difficulties. Finally, the Problem
Solving module brings the program to an end. The main objective is to increase the
likelihood of solving the typical problems that appear in usual contexts. The intention is to
allow the patient to be able to identify problems, to develop a rational attitude towards them
and to focus on solutions rather than the problem itself so ultimately, fostering a thinking
style that anticipates and takes into account the consequences of the chosen solutions. As is
well known, all of these skills require a high degree of self-management that is not
frequently found in patients suffering from executive dysfunction. A recent meta-analysis
has confirmed the effectiveness of this therapy (Roder et al. 2006).

4.2 Cognitive Enhancement Therapy (CET)

The Cognitive Enhancement Therapy (CET) program was described by Hogarty & Flesher
(1999 a, 1999 b). It was designed to be applied to patients with schizophrenia who show
significant social and functional disability following pharmacological stabilization. CET has
two complementary targets: neurocognitive rehabilitation and improvement of social
cognition. It is intended that patients develop the cognitive and social skills that will be
required for proper functioning in real interpersonal settings. It is primarily based on
cognitive strategy instruction through computer tasks and group socialization experiences.
The program consists of two distinct parts: a neurocognitive training module and a social
cognition module. Neurocognitive training is done individually and assisted with computer
programs. It should be stressed that the exercises are done on the computer with the help of a
peer and guided by a therapist. The social cognition training is done in groups through
structured exercises and the practice of social interactions in real-life situations. Individual
neurocognitive training is done through a series of exercises of increasing difficulty using
computer programs on a PC. The training lasts about 60 hours and in each session
performance on various tasks is discussed with another patient and the therapist who will
carry out the necessary coaching. In terms of content, training is divided into attention,
memory and problem-solving modules. Attention training is performed using computerized
tasks from other programs such as the Orientation Remediation Module Ben-Yishay (1980)
and the Bracy Computer Program (1987). Additionally, memory training aims to practice a
number of skills that are supposed to improve memory performance. Categorization ability,
use of abstract thinking and a flexible cognitive style on spatial and verbal tasks are all
encouraged. Finally, improvement in problem-solving capacity is done through the practice of
analytical thinking, planning, generation of alternatives and social intuition by reading clues.
The other component of the program is training in social cognition. This training is
conducted in groups and aims to improve the cognitive skills required for effective
interpersonal behaviour. Groups consist of 6 to 8 patients participating in 45 weekly sessions
lasting one hour. Examples of the session topics are: understanding the others point of view,
reading nonverbal signals or adjusting personal behaviour to the norms and rules of the
social context. Group exercises are a way of generating real experiences to facilitate the
learning of a variety of skills such as taking others’ perspectives ), interpreting contextual
variables, solving potential social conflicts, and practicing emotion recognition, cognitive
flexibility, abstract thinking and planning. The group exercises include categorization
Cognitive Remediation Therapy (CRT): Improving Neurocognition and Functioning in Schizophrenia 75

guidelines, construction of verbal messages, initiation and maintenance of a conversation,

and extracting the central message from the opinion pages of a newspaper (the authors used
the online version of USA Today). In other tasks, therapists encourage participants to
interpret ambiguous scenes in interpersonal contexts in terms of social and emotional
content. Participants are asked to interpret the intentions of various actors in a scene and to
produce a written report highlighting the most relevant leading roles. This program was
tested in a methodologically rigorous study, with a 2 year follow-up, and showed
improvements in verbal memory, processing speed, social cognition and social adjustment
(Hogarty et al. 2004).

4.3 Cognitive Remediation Therapy (CRT)

Initially developed in Australia by Ann Delahunty and reformulated by Til Wykes in the
United Kingdom, this rehabilitation program aims to remediate cognitive impairments in
schizophrenia patients by targeting executive functions. The program is applied
individually, using mainly paper and pencil tasks and is based on cognitive strategy
instruction. Ann Delahunty & Morice Rodney (1993) developed the first version of the
program, the Frontal/Executive program, based on the specific process model. The tasks are
designed to directly activate the frontal and prefrontal neural systems of the patient. The
program consists of three modules: cognitive flexibility, working memory and planning
(Delahunty et al. 1993, 2002).
The “Cognitive Shift Module” aims to address flexibility in thinking and information-set
maintenance both of which presumably require the capacity to effectively engage and
disengage activated neural network processing. It consist of a package of 6 to 8 training
sessions of one hour targeting cognitive inflexibility and attention difficulties. Tasks are
designed to provide some practice in exercises that help patients to get used to switching
from one task to another and being able to keep in mind the information relevant to each
task ‘set’. It is practiced with visual, conceptual and motor information (Table 4). To ensure
maintenance and the switch to the appropriate 'set' for each task, the therapist tries to use
verbal instructions as a cue. Rather than performing the tasks themselves, patients should
practice the connection between thought and behaviour. The therapist's task is to force the
patient to pay attention to all stimuli, to ask the patient to identify what the current 'set' is
and to show the patient whether their performance speed is appropriate. Finally, the
therapist should promote open and covert verbal mediation of the task and not allow the
patient to hesitate about what 'set' has to be used.

AREA TARGET INTERVENTION TECHNIQUE

Psychomotor Line bisection
Visual-motor training
coordination Cancelation tasks
Figure/Ground pictures,
Perceptual Flexibility Alternative perceptions
overlapping figures
Card sorting, number shift, visual
Conceptual Flexibility Alternative concepts
illusions, Stroop exercises
Speed
Psychomotor training Finger tap, hand flip, palm lifting.
Accuracy
Table 4. Components of the ‘Cognitive shift’ module.
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76 Schizophrenia in the 21 Century

The “Working Memory Module” aims to target the executive processes central to memory
control, and has patients work with as many as two to five information sets at a time. It
focuses on variables such as attention, sequencing, working simultaneously with multiple
tasks, and delayed verbal and visual memory information. Working memory is defined as
the ability to maintain or manipulate different sets of data. In schizophrenia, poor
memorization is interpreted as a consequence of executive impairment rather than primary
memory impairment per se. Thus, improving executive functions might be an important
factor in enhancement of memory functioning. The module consists of two parts: A and B.
Both consist of eight sessions of one hour and are designed to be used over several weeks.
Part A introduces a series of working memory tasks ranging from one to four information
sets. Part B provides additional exercises to Part A tasks with special emphasis on
sequencing and dual tasks.
Finally, the primary target of the “Planning Module” is self-ordered, goal-oriented,
set/schema formation and manipulation, that is, the application of the practiced processes,
such as Working Memory, to tasks requiring planning. The goal of the tasks is to improve
cognitive functioning by using active cognitive strategies including active coding,
sequencing and chunking, and using internal and external verbal mediation in multitasking
performance. The Planning Module also includes two parts: A and B. The first is a package
of twelve sessions of one hour and part B involves about eight training sessions. Both
modules provide practical exercises that facilitate the formation and manipulation of sets of
information or goal-oriented schemes, with special emphasis on generating cognitive
strategies and self-control. We work on control processes relating to the skills of attention,
sequencing, organizing information, practical reasoning, formation of sub-objectives, and
self-monitoring. Part B of the Planning Module provides more complex tasks requiring the
application of effective executive skills. All tasks set out in Part B are designed to involve
abstraction with more complex and complementary material. Finally, some everyday tasks
like using a recipe or reading a map are used as complementary exercises.
The theoretical formulation of cognitive remediation therapy by Til Wykes and Clare Reeder
(2005) also represents a major overhaul of the Frontal/Executive program. Although it uses
the same treatment modules, it requires that the therapist proceed in a new way. The most
important innovations are the emphasis on meta-cognition, and the use of techniques such
as errorless learning and scaffolding. Scaffolding is a learning technique in which the
therapist tries to teach the patient to solve problems taking their cognitive limitations into
account. This involves an instructor extending a learner's ability by providing support in
those aspects of a task which the learner cannot accomplish, while removing assistance in
those areas where competence has been achieved. Exercises become an opportunity to
practice cognitive strategies and also to learn new ones. All this learning is done through an
errorless learning approach using tasks of progressive complexity and with the problem
being set, as far as possible, at the subject's own pace. Subsequently, further practice is
necessary to achieve the over-learning of the new cognitive strategies. The same procedure
applied throughout the modules will be used to solve everyday problems of working
memory, planning and, to some degree, cognitive flexibility. All in all, the treatment
guidelines proposed by Wykes (2008) are based on the following principles:
1. Initial assessment
2. Identification of personal goals
Cognitive Remediation Therapy (CRT): Improving Neurocognition and Functioning in Schizophrenia 77

3. Personal therapeutic relationship to promote self-esteem

4. Tailoring of sessions
5. Reflective learning (metacognition)
6. Use of scaffolding
7. Using errorless learning
8. Development of cognitive strategies
9. Generalization to everyday life
This program has been tested in controlled studies and has shown positive effects on
cognition and on some aspects of social functioning (Wykes et al. 1999, 2007; Penadés 2006).

4.4 Studies of efficacy

The first review of cognitive remediation was performed by Kurtz et al. (2001). Because of its
thoroughness and the fact that it was the first review that used meta-analytic methodology, it
can be considered as a pioneering study even though, in this analysis, the authors mixed
results from ‘laboratory’ and clinical studies. The review was conducted on three distinct
cognitive domains according to the target of the neurocognitive intervention: executive
function, attention and memory. Starting with executive function, a fairly statistically
significant (effect size = 0.96) effect was found. Various intervention techniques produced a
reduction in neurocognitive deficits such as committing perseverant errors. Furthermore, the
interventions facilitate cognitive flexibility and improve patients’ categorization ability. This
effect remained similar in other studies despite the differences in intervention strategies.
Although the meta-analysis confirmed these positive findings, the effect size obtained in
clinical settings was always somewhat lower than in research conditions. Additionally, the
meta-analysis showed that both reinforcement learning and teaching cognitive strategies were
effective in improving performance on attention tests. Results regarding the method of
repeated practice were contradictory, so their role in improving performance on attention
tasks is unclear. Finally, the studies focusing on memory impairments showed that cognitive
remediation is capable of enhancing memory function in a clear and consistent way, especially
when the intervention is based on the teaching of coding strategies. In summary, the Kurtz
study was the first to establish that cognitive intervention can produce lasting and valuable
improvements in neurocognition in schizophrenia patients.
The second meta-analysis to be published was conducted by Krabbendam and German (2003).
It differed considerably from the previous one in that it was the first meta-analysis performed
only with controlled trials using standardized intervention protocols, comprehensive
neurocognitive assessment batteries, real patients and healthy controls. The authors conducted
a systematic review and chose 12 of 19 controlled studies. The main result of the analysis was
that cognitive remediation was effective and produced a result considered to be a medium
effect (effect size = 0.45). This finding is more or less the same as that obtained in the other
review. Again, effect size was somewhat smaller in studies performed in clinical settings than
in laboratory studies. Improvements were described in the majority of cognitive domains such
as attention, learning and memory, verbal fluency, abstraction ability, and executive functions.
On the other hand, the results were higher for programs using learning strategies than the
programs using repeated practice only, although this finding did not reach statistical
significance. With the publication of this study, new evidence for the efficacy neurocognitive
rehabilitation was added. Specifically that neurocognitive improvement can also be obtained
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78 Schizophrenia in the 21 Century

in clinical settings and is detectable not only in the laboratory but also in clinical
neuropsychological testing. However, it still left the open question of the relevance of this
improvement to daily functioning and the durability of the improvements achieved.
Almost simultaneously, Twamley et al. (2003) published another important study. These
authors conducted a systematic review and decided to include only protocol-controlled
studies, involving formalized intervention protocols and preferably studies carried out in
clinical settings. They added another important inclusion criterion; the studies should to be
randomized and assessment of the outcomes should be performed in masked conditions.
Thus, it became the first meta-analysis of cognitive rehabilitation in schizophrenia with all the
features of evidence-based medicine. A systematic search was conducted using these criteria
with only 17 studies being selected among all studies published. In addition to efficacy on
neurocognition, they compared other interesting aspects such as the type of intervention
(repeated practice versus learning strategies) or whether the intervention was assisted by
computer or only with paper and pencil tasks. The authors found that different types of
rehabilitation were effective in improving cognitive performance and they were able to
improve not only cognitive functioning but also some of the negative symptoms and daily
functioning of patients. On the other hand, the programs based on computer tasks did not add
better results to the use of paper and pencil tasks. However, remediation programs based on
teaching strategies were more efficacious that those based only on repeated practice. As such,
this meta-analysis added support to the reported efficacy of cognitive remediation programs
in patients with schizophrenia, and this time the analysis was done with high-quality studies.
Unfortunately, the question of whether the improvement following cognitive remediation was
clinically or functionally relevant to the patient still remained an open question.
The most recent meta-analytic study was conducted by Susan McGurk et al. (2007), adding
important secondary analysis to the more general analysis. It included only randomized and
controlled trials, and the authors monitored neurocognition outcomes as well as clinical
symptoms and psychosocial functioning. In addition, questions concerning the characteristics
of rehabilitation programs were also analyzed, such as the required number of hours of
intervention, the usefulness of cognitive rehabilitation programs with broader psychosocial
intervention, and the importance of the patients’ demographic characteristics. Other technical
issues, such as the kind of control group (active or passive), were also analyzed. A total of 26
controlled studies were selected, including 1,151 patients with a diagnosis of schizophrenia.
The authors underline the need for a new meta-analytic study stating that apart from the
inclusion of new studies published since the last meta-analysis, previous reviews paid little
attention to the effects of neurocognitive rehabilitation on psychosocial functioning.
The study confirms that cognitive remediation is effective in improving cognitive
impairments in schizophrenic patients, obtaining a robust effect size (0.51), which can be
considered a medium effect. This is consistent with previous studies; additionally it
concluded that cognitive remediation produced an improvement in social functioning.
Although the effect size was a somewhat smaller change (0.36), it can be still considered
significant and medium in size. Finally, a positive effect on symptoms was also found,
suggesting that there is a reduction in symptoms after rehabilitation, although the effect size
is now considered only small (0.28). Thus, the study provided the first meta-analytic evidence
for the impact of cognitive remediation in domains other than neurocognition. Improvements
in various factors such as social functioning, quality of life, and personal autonomy were the
Cognitive Remediation Therapy (CRT): Improving Neurocognition and Functioning in Schizophrenia 79

main results. Moreover, an intuitive but previously undemonstrated hypothesis was

confirmed. By adding cognitive remediation therapy to psychosocial rehabilitation, functional
outcomes improved significantly. For instance, by adding cognitive remediation to vocational
rehabilitation work, performance was improved and a higher level of work performance and
longer-lasting jobs were generally achieved. By and large, cognitive remediation impacts on
functioning only when the intervention is part of a broader psychosocial rehabilitation
program. In other words, the effects of cognitive remediation therapy are higher (0.47) when
acting as a part of a broader psychosocial rehabilitation than when applying cognitive
remediation therapy as an isolated intervention (0.05). On the other hand, other studies have
shown that cognitive remediation is clearly superior to other interventions such as
occupational therapy, vocational rehabilitation programs, leisure groups, supportive therapy,
watching videos, and treatment as usual. More specifically, cognitive remediation programs
were more efficacious (0.62) when based on cognitive learning strategies (coaching strategy)
than when the programs were based on progressive exercises or repeated practice (0.24).
Learning strategies are usually based on the learning of memory strategies and cognitive
abilities such as solving problems. Finally, it also was noted the improvements were shown to
be maintained over periods ranging from six months to two years.
To sum up, taking into account all the current scientific evidence, we may conclude that
cognitive remediation therapy is an effective treatment tool for psychiatric rehabilitation. It
has been established that neurocognitive impairments can be ameliorated and some
improvement in social functioning can also be expected. To achieve these results it is
necessary that cognitive remediation therapy is based on the teaching of cognitive strategies
and also involves some cognitive practice. Cognitive remediation therapy needs to be
carried out in the context of broader psychosocial rehabilitation involving the learning of
other communication, social, and self-control skills.

5. The Neuro-cognitive-behavioural approach

The majority of empirical findings, including the meta-analysis, challenge the assumption
that simply improving cognitive functioning in schizophrenia will spontaneously lead to
better psychosocial outcomes. Moreover, the results of previous studies suggest that
cognitive remediation is probably the best option to optimize the response of some patients
to psychiatric rehabilitation programs. So CRT is not likely to be implemented as a stand-
alone therapy but as a part of a broader psychosocial rehabilitation program. Unfortunately,
little is known about how to integrate the different rehabilitation tools in a broader
rehabilitation program. Furthermore, even though these interventions show good efficacy in
increasing the chances of functional improvement, only few specialized centres offer these
interventions. Regrettably, they are neither standardized nor available in routine care in the
majority of clinical settings.
Taking into account the published data, an evidence-based guideline for delivering
cognitive remediation with other psychological treatments is presented in Figure 1. This
guideline is based on the principals of the neuro-cognitive-behavioural approach
established elsewhere by Penadés & Gastó (2010):
 It is an empirical approach that incorporates any sort of methodologies, learning
techniques, rehabilitation programs, software or paper and pencil tasks provided that
their efficacy has previously been demonstrated in controlled studies
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80 Schizophrenia in the 21 Century

 Rehabilitation treatment should focus on improving neurocognition but the main target
is to ameliorate associated psychosocial disability
 Rehabilitation treatment must be customized for each patient and should focus on those
targets considered to be important by the patient
 Rehabilitation targets should be agreed with the patient based on their capabilities, their
needs and their current social environment
 This approach is called "neuro-cognitive-behavioural" since it proposes comprehensive
treatment of neurocognitive aspects but does not overlook emotional, functional and
psychological ones
Thus, in order to implement integrated psychosocial rehabilitation programs including CRT
and evidence-based psychological therapies a flowchart has been proposed (Figure 1).

Fig. 1. Flowchart for the Neuro-cognitive-behavioural approach.

6. Improving outcomes and promoting recovery with CRT

As has been suggested before, we have some evidence that improved cognitive function can
lead to improved social functioning in the context of psychological interventions. However,
another concern is the identification of the cognitive domains that need to be targeted to
improve functioning. In a pioneering study, Spaulding et al. (1999) investigated Integrated
Psychological Therapy (IPT) (Brenner et al., 1994) and found some improvements in
attention, memory, and executive function as well as improvements in social competence.
However, as IPT is a multimodal program with cognitive-oriented modules and
psychosocial-oriented modules, the exact role of cognitive change in overall functional
Cognitive Remediation Therapy (CRT): Improving Neurocognition and Functioning in Schizophrenia 81

improvement was not clear. In order to clarify the specific impact of cognitive change on
social functioning, a controlled trial was designed (Penadés et al., 2003) using only the
cognitive modules (cognitive differentiation and social perception). In this trial, memory,
executive functions and social functioning showed improvement. Interestingly, changes in
neurocognition were associated with changes in functional outcome, particularly in personal
autonomy and general functioning.
More specifically, a number of Cognitive Remediation Therapy (CRT) studies have shown
that neurocognitive improvements are associated with improvement in functioning
(McGurk et al., 2007). In one of the first randomized, controlled trials comparing CRT with a
control therapy, Wykes et al. (1999) found differential improvements in cognitive flexibility
and memory in favour of the CRT group. When these cognitive changes reached a certain
threshold, a reduction in social problems was also apparent. Furthermore, other
randomized, controlled trials with CRT have shown various improvements in functioning
ranging from improvements in obtaining and keeping competitive jobs (McGurk et al., 2005;
Vauth et al., 2005), to the quality of, and satisfaction with, interpersonal relationships
(Hogarty et al., 2004; Penadés et al., 2006) and the ability to solve interpersonal problems
(Spaulding et al., 1999). These findings reinforce the assumption that neurocognition and
functioning are strongly related and that CRT is useful in improving functioning.
The impact of CRT on functioning is important because the primary rationale for cognitive
remediation in schizophrenia is to improve psychosocial functioning (Wykes and Reeder,
2005). Surprisingly, the majority of clinical studies of CRT did not test this hypothesis until
recently and focused primarily on cognitive performance (McGurk et al., 2007). Studies have
rarely investigated specific treatment mechanisms or the particular cognitive targets that are
related to social improvements. Obviously, an understanding of the links between cognitive
change and functional improvement is crucial in identifying appropriate cognitive targets
for treatment leading to functional improvement.
In two studies, Reeder et al. (2004) published some surprising results. Cognitive functions
which usually show significant cross-sectional associations with social functioning are not
the same as those associated with improvement in functioning in the context of CRT. In the
first study, it was found that while the “response inhibition speed” factor was associated
with social functioning at baseline, change in a different factor predicted social functioning
change following Cognitive Remediation Therapy (CRT). In the second study (Reeder et al.,
2006), a relationship at baseline was found between social functioning and various cognitive
domains such as verbal working memory, response inhibition, verbal long-term memory
and visual-spatial long-term memory, but not schema generation. Surprisingly, it was the
improvement in schema generation which predicted improved social functioning.
From the two studies, it can be concluded that cross-sectional associations between cognitive
functions and social functioning may not be an appropriate approach for selecting cognitive
targets for intervention. Even though selecting the cognitive targets of CRT on the basis of
cognitive skills that appear to predict functional outcome in schizophrenia sounds logical, it
could be misleading. Thus, while it has been generally assumed that improved cognition will
lead to improved functional outcome, the nature of this putative link is far from clear.
Penadés et al. (2010) conducted research to investigate the neurocognitive changes occurring in
the context of CRT and tried to identify which of those changes led to improvements in daily
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82 Schizophrenia in the 21 Century

functioning. This study used data collected as part of a randomized, controlled trial
investigating a CRT program in a partner study (Penadés et al., 2006). The trial recruited 52
schizophrenia patients between the ages of 27 and 42 who had been in contact with psychiatric
services for at least 10 years; composing a truly chronic schizophrenia sample with
predominant negative symptoms and cognitive impairments. Of these participants, 40 were
randomized to receive either CRT or control psychological treatment (Cognitive Behavioral
Therapy; CBT) where neurocognition was not targeted. CRT was based on the
Frontal/Executive program (Delahunty and Morice, 1993). At baseline, daily functioning was
significantly associated with verbal memory. Surprisingly, improvement in executive function,
but not in verbal memory, predicted improved daily functioning among those with chronic
schizophrenia who had current negative symptoms and evidenced neuropsychological
impairments. Notwithstanding, the statistical mediation model found that social improvement
caused by executive changes is expressed indirectly through improvement in verbal memory.
The direct model, as the name suggests, represents the prediction of social improvement
from the change in executive function directly. The mediated model indicates that social
improvement caused by executive changes is expressed indirectly through improvement in
verbal memory. All variables were correlated and reached statistical significance (α > 0.05),
as can be seen in Fig. 2. None of the executive other cognitive measures, such as change in
psychomotor speed (t=0.846, P=0.405), change in nonverbal memory (t=0.934, P=0.358), or
change in working memory (t=1.402, P=0.172) add significant explanatory power to the
effect of executive change in the social improvement function equation.

Fig. 2. Diagrams of direct and mediated models of change in daily functioning after the CRT
intervention.
Cognitive Remediation Therapy (CRT): Improving Neurocognition and Functioning in Schizophrenia 83

Thus, it was found that improvements in cognitive functions that were not significantly
associated with daily functioning at baseline led to improved daily functioning. These
results confirm that there is no evidence for a simple direct relationship between cognition
and the different aspects of social functioning. Consequently, even if people have
impairments in multiple cognitive domains, executive functioning still needs to be the
intervention target. Data are consistent with findings from previous studies (Reeder et al.,
2004, 2006) where it is concluded that baseline correlations may not therefore provide basic
targets for intervention and may fail to highlight potential targets. In these studies, where
improvements in a number of aspects of executive functioning are present, such as schema
generation or response inhibition, CRT leads to improvements in social functioning
regardless of baseline cognitive associations. Furthermore, it is suggested that verbal
memory changes are associated with social improvements when they mediate the executive
improvements. Not surprisingly, memory impairment in long-term schizophrenia can be
considered as a consequence of executive impairment and not necessarily more severe
cognitive impairment (Bryson et al., 2001).

7. Conclusion
Links between neurocognition and functioning have encouraged efforts to develop new
pharmacological agents and novel psychological interventions targeting these variables
directly. These interventions rely on the assumption that changes in neurocognition will
simply improve life skills in patients with schizophrenia. This assumption is strengthened
by the results of numerous studies showing that neurocognitive impairments can produce
impaired social functioning. Many of these studies even suggest that neurocognitive deficits,
particularly verbal memory and executive functions, are more closely linked to functional
outcome than psychiatric symptoms.
However, while the role of impaired cognition in accounting for functional outcome in
schizophrenia is generally established, the relationship between cognitive and functional
change in the context of treatments is far from clear. In a recent study we tried to identify
which cognitive changes lead to improvements in daily functioning among persons with
chronic schizophrenia who had current negative symptoms and evidenced
neuropsychological impairments. Cognitive Remediation Therapy (CRT) had been
compared with a control therapy, involving similar length of therapist contact but different
targets. At the end of treatment, CRT conferred a benefit to people with schizophrenia in
cognition and functioning. Subsequently, analyses of covariance (ANCOVA) were
conducted with baseline and cognitive change scores as covariates to test whether cognitive
change predicted change in functioning. Additionally, statistical tests to establish the
mediation path with significant variables were performed.
At baseline, daily functioning was significantly associated with verbal memory.
Surprisingly, improvement in executive function, but not in verbal memory, predicted
improved daily functioning among persons with chronic schizophrenia who had current
negative symptoms and evidenced neuropsychological impairments. Notwithstanding, the
statistical mediation model found that social improvement caused by executive changes is
expressed indirectly through improvement in verbal memory. Thus, we have found that
improvements in cognitive functions that were not significantly associated with daily
functioning at baseline led to improved daily functioning. These results confirm that there is
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84 Schizophrenia in the 21 Century

no evidence for a simple direct relationship between cognition and the different aspects of
social functioning. Consequently, in order to improve daily functioning through CRT it is
crucial to target executive function even if persons have more severe impairments in other
cognitive domains. Additionally, it is important to remark that in order to achieve
generalization of the CRT effects to daily functioning it is necessary to include CRT in
broader programs in conjunction with other psychosocial interventions.

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