Daniel R. Mueller

Social cognition as a mediator variable between neurocognition and functional outcome in schizophrenia: empirical review and new results by structural equation modeling.

Cognitive impairments are currently regarded as important determinants of functional domains and are promising treatment goals in schizophrenia. Nevertheless, the exact nature of the interdependent relationship between neurocognition and social cognition as well as the relative contribution of each of these factors to adequate functioning remains unclear. The purpose of this article is to systematically review the findings and methodology of studies that have investigated social cognition as a mediator variable between neurocognitive performance and functional outcome in schizophrenia. Moreover, we carried out a study to evaluate this mediation hypothesis by the means of structural equation modeling in a large sample of 148 schizophrenia patients. The review comprised 15 studies. All but one study provided evidence for the mediating role of social cognition both in cross-sectional and in longitudinal designs. Other variables like motivation and social competence additionally mediated the relationship between social cognition and functional outcome. The mean effect size of the indirect effect was 0.20. However, social cognitive domains were differentially effective mediators. On average, 25% of the variance in functional outcome could be explained in the mediation model. The results of our own statistical analysis are in line with these conclusions: Social cognition mediated a significant indirect relationship between neurocognition and functional outcome. These results suggest that research should focus on differential mediation pathways. Future studies should also consider the interaction with other prognostic factors, additional mediators, and moderators in order to increase the predictive power and to target those factors relevant for optimizing therapy effects.

Integrated psychological therapy for schizophrenia patients

‘The recovery outcomes (from schizophrenia) are still poor. This indicates heterogeneous course patterns of schizophrenia, demanding multimodal treatments rather than a single intervention.’ Daniel R. Mueller and Volker Roder Author for correspondence University Psychiatric Services Bern, University Hospital of Psychiatry Bolligenstrasse 111, CH-3000 Bern 60, Switzerland Tel.: +41 319 309 915 Fax: +41 319 309 988 volker.roder@spk.unibe.ch Expert Rev. Neurotherapeutics 7(1), 1–3 (2007)

Effectiveness of Integrated Psychological Therapy (IPT) for Schizophrenia Patients: A Research Update

Standardized recovery criteria go beyond symptom remission and put special emphasis on personal and social functioning in residence, work, and leisure. Against this background, evidence-based integrated approaches combining cognitive remediation with social skills therapy show promise for improving functional recovery of schizophrenia patients. Over the past 30 years, research groups in 12 countries have evaluated integrated psychological therapy (IPT) in 36 independent studies. IPT is a group therapy program for schizophrenia patients. It combines neurocognitive and social cognitive interventions with social skills and problem-solving approaches. The aim of the present study was to update and integrate the growing amount of research data on the effectiveness of IPT. We quantitatively reviewed the results of these 36 studies, including 1601 schizophrenia patients, by means of a meta-analytic procedure. Patients undergoing IPT showed significantly greater improvement in all outcome variables (neurocognition, social cognition, psychosocial functioning, and negative symptoms) than those in the control groups (placebo-attention conditions and standard care). IPT patients maintained their mean positive effects during an average follow-up period of 8.1 months. They showed better effects on distal outcome measures when all 5 subprograms were integrated. This analysis summarizes the broad empirical evidence indicating that IPT is an effective rehabilitation approach for schizophrenia patients and is robust across a wide range of sample characteristics as well as treatment conditions. Moreover, the cognitive and social subprograms of IPT may work in a synergistic manner, thereby enhancing the transfer of therapy effects over time and improving functional recovery.

One-Year Randomized Controlled Trial and Follow-Up of Integrated Neurocognitive Therapy for Schizophrenia Outpatients

OBJECTIVE Cognitive remediation (CR) approaches have demonstrated to be effective in improving cognitive functions in schizophrenia. However, there is a lack of integrated CR approaches that target multiple neuro- and social-cognitive domains with a special focus on the generalization of therapy effects to functional outcome. METHOD This 8-site randomized controlled trial evaluated the efficacy of a novel CR group therapy approach called integrated neurocognitive therapy (INT). INT includes well-defined exercises to improve all neuro- and social-cognitive domains as defined by the Measurement And Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative by compensation and restitution. One hundred and fifty-six outpatients with a diagnosis of schizophrenia or schizoaffective disorder according to DSM-IV-TR or ICD-10 were randomly assigned to receive 15 weeks of INT or treatment as usual (TAU). INT patients received 30 bi-weekly therapy sessions. Each session lasted 90min. Mixed models were applied to assess changes in neurocognition, social cognition, symptoms, and functional outcome at post-treatment and at 9-month follow-up. RESULTS In comparison to TAU, INT patients showed significant improvements in several neuro- and social-cognitive domains, negative symptoms, and functional outcome after therapy and at 9-month follow-up. Number-needed-to-treat analyses indicate that only 5 INT patients are necessary to produce durable and meaningful improvements in functional outcome. CONCLUSIONS Integrated interventions on neurocognition and social cognition have the potential to improve not only cognitive performance but also functional outcome. These findings are important as treatment guidelines for schizophrenia have criticized CR for its poor generalization effects.

Integrated Psychological Therapy: Effectiveness in Schizophrenia Inpatient Settings Related to Patients' Age

OBJECTIVE Elderly people with schizophrenia often suffer from cognitive impairments, which affect their social functioning. Today, only a few therapy approaches for middle-aged and older patients are available. The Integrated Psychological Therapy (IPT) combines neurocognitive and social cognitive interventions with social skills approaches. The aim of this study was to evaluate (1) whether IPT is effective in younger patients (age < 40 years) and middle-aged patients (age ≥ 40 years) and (2) whether control conditions (treatment as usual or unspecific group activities) reveal some change in outcome depending on age. METHOD A total of 15 controlled IPT studies with 632 inpatients with schizophrenia were evaluated in a standard meta-analytic procedure. Studies were categorized into two age categories. RESULTS Significant medium to large effect sizes (ES) were evident for IPT independent of age on the global cognitive score (mean score of all cognitive variables), on neurocognition, social cognition, social functioning, psychopathology, and the global therapy effect (mean of all variables). The IPT effects in middle-aged patients were significantly larger on the global cognitive score, on neurocognition, and on social cognition compared with younger patients. Opposite results could be observed in control conditions. Only younger patients participating in the control conditions showed small but significant ES on these variables, but almost middle-aged control patients did not. However, none of the differences in the control conditions were significant between the two age categories. A moderator analysis obtained no evidence for a strong impact of IPT variations, therapy setting, patient characteristics, and methodologic rigor of the research design. CONCLUSIONS These results support evidence for the efficacy of IPT independent of age. Results further indicate the need of goal-oriented specific psychological interventions for middle-aged and older patients with schizophrenia.

Does Integrated Neurocognitive Therapy (INT) reduce severe negative symptoms in schizophrenia outpatients

Negative symptoms often inhibit the social integration of people suffering from schizophrenia. Reducing severe negative symptoms (SNS) in a clinically relevant way is a major unmet need. The aim of this study was to investigate whether Integrated Neurocognitive Therapy (INT), a group cognitive remediation therapy (CRT), reduces SNS in schizophrenia outpatients. INT was compared with Treatment As Usual (TAU) in a randomized-controlled trial (RCT). A total of 61 SNS outpatients participated in the study, 28 were allocated to the INT group and 33 to the TAU group. A test-battery was used at baseline, post-treatment at 15weeks, and 1-year-follow-up. Remission rates of SNS after therapy were significantly higher for INT compared to TAU. A trend favoring INT was obtained at follow-up. Furthermore, INT showed significantly higher functional outcome during follow-up compared to TAU. Regarding cognition, the strongest significant effect was found in attention post-treatment. No effects between groups on more complex neurocognition and social cognition were evident. SNS outpatients seem to accept INT group intervention as suggested by the high attendance rate.

Efficacy and feasibility of the integrated psychological therapy for outpatients with schizophrenia in greece: final results of a RCT

The goal of this study was to evaluate the efficacy and the feasibility of cognitive remediation group therapy in patients with schizophrenia in Greece. For this purpose, the cognitive part of the Integrated Psychological Therapy (IPT), focusing on neuro- and social cognition, was compared in a randomized controlled trial (RCT) with treatment as usual (TAU). 48 outpatients took part in the study. IPT groups received 20 biweekly 1-h-therapy sessions. A test-battery was assessed at baseline, after therapy, and at a 3-month follow-up. Regarding cognitive functioning, significant effects favouring IPT were found in working memory and social perception during therapy and at follow-up. No effects could be found in verbal memory and vigilance. Significant effects favoring IPT were found in negative symptoms, in insight and in general symptoms during therapy and at follow-up using the Positive and Negative Syndrome Scale (PANSS). No effects were evident in positive symptoms and in psychosocial functioning. Significant effects favoring TAU were found in the quality of life assessment at follow-up. The study supports evidence for the feasibility and efficacy of IPT in psychiatric care in Greece and it hopefully will initiate the broader use of evidenced-based treatments like IPT in Greek Psychiatry.

S41-03 - A broad-based remediation approach: The integrated neurocognitive therapy (INT)

Objective Cognitive functions have a decisive influence and prognostic value for functional recovery. The NIMH MATRICS initiative established a consensus on neuro-cognitive and social cognitive domains relevant for the treatment of schizophrenia. Against this background we developed the Integrated Neurocognitive Therapy (INT) covering all MATRICS domains. INT is strongly based on therapeutic principles of the Integrated Psychological Therapy (IPT) designed by our research team several years ago. INT is partly computer based and intends to restitute and compensate neuro-cognitive and social cognitive functions. Methods INT was evaluated in an international multi-cite RCT with centers in Switzerland, Germany, and Austria. The Swiss National Science Foundation supported this study. INT was compared with a treatment as usual control condition (TAU). INT patients received 30 therapy sessions twice a week. 169 schizophrenia outpatients participated in the study. Results Using an ANOVA model, INT groups show superior effects after therapy and 1-year follow-up in proximal outcomes of neuro- and social cognition. Significant effects are evident in most of the MATRICS-domains. Additionally, significant effects in more distal outcomes are evident for INT patients in psychosocial functioning and negative symptoms after therapy and at follow-up. A low drop-out rate of 12% of the INT patients indicates a high acceptance by the patients. Conclusions Results support evidence for the efficacy of INT in proximal and distal outcome dimensions. Further evaluations on INT have to investigate its relevance for different psychotic populations such as young early psychotics and more chronic older patients.

F51. INTEGRATED COGNITIVE REMEDIATION THERAPY PREVENTS RELAPSES IN SCHIZOPHRENIA OUTPATIENTS DURING 8-YEARS FOLLOW-UP

Abstract Background Relapse prevention is a major aim of any treatment for schizophrenia patients. In general, recent meta-analyses showed that one third of schizophrenia patients relapse in the first year after treatment, which corresponds with rehospitalization. Since years, study data support evidence for successful relapse prevention of psycho-educative and family therapy approaches in combination with pharmacological treatment. So far little is known about the impact of Cognitive Remediation Therapy (CRT) on relapse prevention. Methods The purpose of this RCT was to investigate whether additional CRT could prevent relapses compared to treatment as usual (TAU) defined as pharmacological and other psychosocial treatments. The CRT approach of choice was the Integrated Neurocognitive Therapy (INT) developed in our lab. INT is a group approach consisting of 4 modules including interventions on all the neuro- and social cognitive domains, defined by the MATRICS initiative, as well as educational, emotion regulation and stress reduction tasks. In this international multicenter study, a total of 156 stabilized schizophrenia outpatients, diagnosed with DSM-IV, participated. From this sample, 71 participants of two out of eight centers could be observed during a follow-up of 1, 5 and 8 years, regarding number of relapses and days of rehospitalization. Relapses were defined as increased symptoms followed by rehospitalization. Results One year after therapy, no marked differences between INT and TAU groups in relapse rates were evident. But during 5- and 8-year follow-up, 78% and 83% of TAU patients relapsed compared to 48% and 52% of INT patients suggesting a significant benefit of INT. TAU patients suffered from more than 2 relapses after 5 years and 2.5 relapses after 8 years. In comparison, INT patients showed 0.9 relapses after 5 and 1.4 relapses after 8 years. After the 5 years follow-up there was a highly significant difference between INT and TAU, and after the 8-years a statistical tendency favoring INT could be found. Regarding the days of hospitalization, TAU patients presented a mean value of 8 days during 1 year after treatment, 90 days after 5 years and 105 days after 8 years compared to INT patients with 1.2 days after 1 year, 19 days after 5 years and 35 days after 8 years. The comparison after 1 year was close to significant, the other ones were clearly significant favoring again the INT intervention. Discussion These data on INT intervention support evidence for an impact of CRT on relapse prevention in a 1, 5 and 8 years follow-up. However, the identification of mechanisms of change within INT treatment needs further research.

FC16-05 - Efficacy of social cognitive remediation in schizophrenia patients: a meta-analysis including 22 RCTS

Introduction Today there is an increased interest from clinicians and researchers in social cognition as a treatment objective for schizophrenia patients. Objectives During the last years, several new Social Cognitive Remediation (SCR) approaches were developed. SCR directly intervene in individual or multiple social cognitive domains declared by the NIMH-MATRICES-Initiative. Some of these approaches integrate social cognitive interventions with therapeutic components intended to ameliorate neurocognitive and social skills or with work rehabilitation. Aims Until today no quantitative review to evaluate the efficacy of SCR has been presented. Methods 22 randomized-controlled trials (RCTs) were identified and included in a meta-analysis. Based on the outcome variables from each study, effect sizes (ES) between SCR and control groups were calculated. Results Over an average length of more than 20 weeks a significant global therapy effect of SCR compared to controls was evident (average ES of all conducted variables). Significant effects were found in the proximal outcome addressing social cognition and specifically in the domains of emotional processes, social perception and ToM. Additionally, the neurocognitive area showed significant evidence of amelioration compared with the control groups. More distal effects were found for psychopathology and social functioning. The global therapy effect could be maintained during a mean follow-up period of 10 months. The setting, the type of control groups and the type of intervention in the experimental group were identified as moderators. Conclusions The results support strong empirical evidence that SCR has a broad effect on various areas of functioning and symptoms relevant in schizophrenia.