Executive function needs to be targeted to improve social functioning with Cognitive Remediation Therapy (CRT) in schizophrenia

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Abstract

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. The current paper tries 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. In a previous work, Cognitive Remediation Therapy (CRT) was 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 [Schizophrenia Research, 87 (2006) 323–331]. 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. Although verbal memory, but not executive functioning, was associated with functioning at baseline, it was the improvement in executive functioning that predicted improved daily functioning. Verbal memory played a mediator role in the change process. Consequently, in order to improve daily functioning with CRT, executive function still needs to be targeted in despite of multiple cognitive impairments being present.

Introduction

Links between neurocognition and functioning have encouraged efforts to develop new pharmacological agents (Green et al., 2004) and novel psychological interventions (Wykes and van der Gaag, 2001) 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 (Green, 1999). 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 (Kurtz et al., 2008, Puig et al., 2008).

In addition, it has been suggested that the association between cognition and social functioning could be determined by how social functioning is conceptualized and assessed (Addington and Addington, 2008). More specifically, different domains of functional capacity (i.e., social and living skills) seem to have different correlates in cognition. Processing speed, episodic memory, and executive functions might be associated with everyday living skills, while working memory and verbal fluency might be associated with social competence (McClure et al., 2007). Furthermore, discrete cognitive domains have been found to be differential predictors of functional competence and performance. For instance, verbal memory and executive functions have been showed to be important for functional competence but not for social skills (Bowie et al., 2008).

However, all these studies are mainly based on correlational studies. Unfortunately, results from such studies cannot be used as evidence of a causal relationship. An alternative strategy to partially clarify this problem is to test the impact of cognitive change on functioning in longitudinal studies (Wykes et al., 1990, Green et al., 2000). Cognitive function seems to remain relatively stable throughout the course of schizophrenia (Kurtz et al., 2005, Klingberg et al., 2008) so that studies investigating changes in cognition through treatments can be a useful strategy. Regrettably, the specific cognitive improvements which predict social functioning are not well known and have hardly been tested in the context of treatments.

There is some evidence that improved cognitive function may lead to improved social functioning in the context of psychological interventions. 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 programme with cognitive-oriented modules as well as psychosocial-oriented modules, the exact role of cognitive change in overall functional 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 and controlled trials with CRT have shown different 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 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, clinical studies of CRT have not tested this hypothesis until recently and have focused primarily on cognitive performance (McGurk et al., 2007). Studies have rarely investigated the specific mechanisms of treatment or the specific cognitive targets that are related to social improvements. Obviously, an understanding of the links between cognitive change and functional improvement can be crucial in identifying appropriate cognitive targets for treatment leading to functional improvement.

In two studies, Reeder et al. (2004) have 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 different cognitive domains such as verbal working memory, response inhibition, verbal long-term memory and visuo-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 to select 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. This paper investigates the neurocognitive changes occurring in the context of CRT and tries to identify which of those changes lead to improvements in daily functioning. Particularly, the study aimed to investigate (1) the baseline associations between cognition and functioning, (2) the links between changes in cognition and daily functioning, and (3) the moderating role of change in different cognitive domains and symptoms affecting functioning.

Section snippets

Methods

This study uses data collected as part of a randomized and controlled trial investigating a CRT programme 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 touch with psychiatric services for at least 10 years; composing a truly chronic schizophrenia sample with predominant negative symptoms and cognitive impairments (Table 1). Of these participants, 40 were randomized to receive either CRT or a control

Baseline associations

Cross-sectional associations between cognitive functions, symptoms and social functioning expressed with Pearson's correlations are shown in Table 2.

Links between changes in cognition, symptoms and social functioning

No significant interactions between the group variable and different cognitive scores were found. Then, when the interaction term was removed, improvement in executive function (F(1/25) = 5.85, P = 0.023) was related with social functioning improvement. However, none of the other cognitive scores was significantly predictive of improvement in LSP

Discussion

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

Acknowledgment

Supported in part by “Instituto de Salud Carlos III”, “Fondo Investigaciones Sanitarias (FIS)” project: PI 070258.

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