Schizophrenia Research 162 (2015) 108–111
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Schizophrenia Research journal homepage: www.elsevier.com/locate/schres
Compensatory cognitive training for people with first-episode schizophrenia: Results from a pilot randomized controlled trial Paul D. Mendella a, Cynthia Z. Burton b, Giorgio A. Tasca c,d, Paul Roy a, Lea St. Louis c, Elizabeth W. Twamley e,f,⁎ a
Ricci & Associates, 1101 Prince of Wales Drive, Suite 110, Ottawa, ON K2C 3W7, Canada San Diego State University/University of California, San Diego Joint Doctoral Program in Clinical Psychology, 140 Arbor Drive (0851), San Diego, CA 92103, United States The Ottawa Hospital, 501 Smyth Road, Ottawa, ON K1G 0H9, Canada d University of Ottawa, 65 Laurier Avenue East, Ottawa, ON K1N 6N5, Canada e University of California, San Diego, Department of Psychiatry, United States f Center of Excellence for Stress and Mental Health, VA San Diego Healthcare System, United States b c
a r t i c l e
i n f o
Article history: Received 3 November 2014 Received in revised form 6 January 2015 Accepted 8 January 2015 Available online 24 January 2015 Keywords: Cognitive remediation Psychosis Cognition Social cognition Functional capacity
a b s t r a c t Cognitive training or remediation now has multiple studies and meta-analyses supporting its efficacy in improving cognition and functioning in people with schizophrenia. However, relatively little is known about cognitive training outcomes in early psychosis. We conducted a pilot randomized controlled trial of Compensatory Cognitive Training (CCT) compared to Treatment as Usual (TAU) in 27 participants with first-episode psychosis who had received treatment for psychosis for less than six months. Assessments of cognition (MATRICS Consensus Cognitive Battery; MCCB) and functional capacity (UCSD Performance-Based Skills Assessment-Brief; UPSA-B) were administered at baseline and following the 12-week treatment. The CCT condition, compared to TAU, was associated with significant improvements on the MCCB composite score, as well as MCCB subtests measuring processing speed (Trail Making) and social cognition (Mayer–Salovey–Caruso Emotional Intelligence Test), with large effects on these three outcome measures. There were no significant CCT-associated effects on the UPSA-B or on positive, negative, or depressive symptoms. CCT treatment of cognitive impairments in first-episode schizophrenia is feasible and can result in large effect size improvements in global cognition, processing speed, and social cognition. Published by Elsevier B.V.
1. Introduction The cognitive impairments associated with schizophrenia and their negative effects on functional outcomes are well-established in the psychiatric literature (e.g., Heinrichs and Zakzanis, 1998; Green et al., 2000). Current efforts are therefore focused on empirically supported treatments to improve cognitive functioning among affected individuals. Cognitive remediation, or cognitive training, is one such treatment and is defined as “a behavioral, training-based intervention that aims to improve cognitive processes (attention, memory, executive function, social cognition, or metacognition) with the goal of durability and generalization” (Wykes et al., 2011). Recent evidence suggests that cognitive remediation has a moderate effect on cognitive measures and psychosocial functioning, and a small effect on psychiatric symptom severity; it has proven more effective in clinically stable patients and when combined with other psychiatric rehabilitation programs (Wykes et al., 2011). On average, however, most published trials of cognitive remediation include middle-aged, chronically ill individuals with ⁎ Corresponding author at: Department of Psychiatry, University of California, San Diego, 140 Arbor Drive (0851), San Diego, CA 92103, United States. Tel.: +1 619 543 6684. E-mail address: [email protected] (E.W. Twamley).
http://dx.doi.org/10.1016/j.schres.2015.01.016 0920-9964/Published by Elsevier B.V.
a confirmed diagnosis of schizophrenia, limiting conclusions about its efficacy for those in the prodromal phase or first-episode of psychotic illness. Few studies have examined cognitive remediation in the early course of schizophrenia, but there are numerous reasons to pursue this line of investigation. Cognitive impairment is evident before the onset of overt psychosis, continues during the early phase of illness, and may even worsen during the first episode (Saykin et al, 1994; Bilder et al., 2006; Eastvold et al., 2007). Further, first episode participants have shown inconsistent trajectories of cognitive performance, where some cognitive abilities improve over time and others deteriorate (Jahshan et al., 2010). At the same time, young individuals early in the course of illness may have greater brain plasticity and more limited structural and functional brain changes than those with chronic psychotic illness, which could lead to better results of cognitive remediation treatment (Keshavan and Hogarty, 1999; Berger et al., 2007). Indeed, there is some evidence to suggest that cognitive remediation may have a neuroprotective effect against gray matter loss in early schizophrenia (Eack et al., 2010a). People enduring a first episode of schizophrenia, therefore, may be uniquely positioned to capitalize on neural plasticity and bypass some cognitive deficits through cognitive remediation treatment.
P.D. Mendella et al. / Schizophrenia Research 162 (2015) 108–111
In light of this rationale, some researchers have begun to explore cognitive remediation in early schizophrenia. A recent review of eight published manuscripts concluded that preliminary results are positive, but more empirical research is needed to confirm the efficacy of cognitive remediation (Barlati et al., 2012). For example, one study of cognitive remediation in adolescents with early onset psychosis initially found no superior effect of cognitive remediation compared to psychoeducation, but at one year follow-up there appeared to be an effect on early visual information processing (Ueland and Rund, 2004; Ueland and Rund, 2005). Other studies have found positive effects of cognitive remediation for early course schizophrenia on global cognition (Eack et al., 2009; Fisher et al., 2015), learning (Fisher et al., 2015), executive functioning (Wykes et al., 2007; Fisher et al., 2015), social cognition (Eack et al., 2009), psychiatric symptoms (Eack et al., 2009), and social adjustment (Eack et al., 2009, 2010b). A recent comparison of early-course (b 5 years illness duration) and chronic (N15 years illness duration) cognitive remediation participants showed that the early-course participants had larger improvements in processing speed, executive functioning, and functional capacity (Bowie et al., 2014). Overall, cognitive remediation treatment in early schizophrenia shows promise, but more empirical evidence is required. Additionally, the studies of cognitive remediation in early course schizophrenia have all employed restorative, drill-and-practice interventions; compensatory training approaches have not been investigated. This study aimed to pilot-test a manualized Compensatory Cognitive Training (CCT) intervention in a sample of first episode schizophrenia participants. In contrast to restorative approaches to cognitive remediation, which rely on drills and practice to improve cognition, compensatory cognitive training approaches teach cognitive strategies as ways of working around cognitive impairments, with the goal of developing new cognitive habits that generalize to cognitive performance and meaningful real-world outcomes (Wykes et al., 2011). CCT has demonstrated efficacy in participants with chronic schizophrenia (Twamley et al., 2012) and targets cognition in four domains: prospective memory, attention and vigilance, learning and memory, and executive functioning. CCT is a brief (24 h over 12 weeks), groupbased intervention that teaches strategies in the domains above via interactive, game-like activities to maintain interest and increase focus and motivation. Therapists elicit clients' personal goals and link the strategies taught to their specific goals in order to enhance intrinsic motivation (e.g., “You told me that dating is important to you, and these skills for paying attention during conversations will help you have conversations on your dates.”). Home exercises are assigned weekly to promote cognitive habit learning and strategy use in the real world. Each session follows the same general format of reviewing the home exercises, establishing a rationale for new skills to be taught, demonstrating the skill, having participants practice the skill, planning for implementation in daily life, and assigning home exercises for the coming week. The CCT manual is provided free of charge at www. cogsmart.com. It was hypothesized that, compared to a control group receiving treatment as usual (TAU), the CCT participants would demonstrate improvements in a cognitive composite score and functional capacity (co-primary outcomes) at post-treatment. We also examined change on individual cognitive test scores and psychiatric symptom ratings (secondary outcomes). 1.1. Method 1.1.1. Participants Participants were outpatients enrolled at On Track, the Champlain District Regional First Episode Psychosis Program, of The Ottawa Hospital. On Track provides clinical services to individuals who are experiencing their first psychotic episode, and who have received treatment for less than six months prior to enrollment in the program. In addition to
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being enrolled as a patient at On Track, inclusion criteria for enrollment in the study consisted of the following: 1) Individuals must be diagnosed with a primary psychotic disorder (i.e., schizophreniform disorder, schizophrenia, or schizoaffective disorder). Diagnoses were made by the treating psychiatrist on the basis of a clinical interview. 2) Recruitment was limited to individuals between the ages of 18 and 35, in order to increase group homogeneity. 3) Only English speakers were included in the study because the therapist and patient manuals for CCT were available in English only. Potential participants were excluded from the study if: 1) The individual was clinically unstable to the degree that weekly group therapy was not feasible. 2) The individual had previously been diagnosed with an underlying neurological condition affecting cognition (e.g., significant traumatic brain injury; seizure disorder). 3) There was evidence of significant, active substance abuse. Thirty-one participants were enrolled. One was too old to meet inclusion criteria and was dropped; one withdrew consent; two in the TAU group were lost to follow-up. In the final sample, there were 27 participants (16 CCT; 11 TAU). 1.1.2. Procedure Individuals who were identified as potential participants by their On Track psychiatrists, social workers, or nurses were approached for possible enrollment in the study. Written informed consent to participate in the study was obtained from each participant, and the study was approved by the Ottawa Hospital Research Ethics Board. Following informed consent and baseline assessment, participants were randomized into the experimental (Compensatory Cognitive Training; CCT) or control (Treatment as Usual; TAU) group via computerized randomization. The randomization was carried out by an independent staff member who was given subject identification numbers only; thus, the research associate was not aware of the random assignments until after they occurred. After 12 weeks, each participant was re-administered the outcome measures. All participants were compensated for their time during the assessments, but not for attending treatment. The examiner was not blind to group assignment, but was not involved in providing treatment. 1.1.3. Experimental and control conditions Participants in CCT attended a weekly 2-hour group treatment session with 7–8 participants per group. They were also supplied with patient manuals outlining each session. Each session was facilitated by the therapists (PDM and LSL), except on a few occasions when one of the facilitators was not available due to scheduling conflicts or illness. In such cases, the group was led by the remaining facilitator. Participants in the CCT group continued to receive standard treatment at On Track while they were enrolled in the study. Participants in the TAU group received standard treatment during the duration of the study, which included routine psychiatric care provided by a program psychiatrist, as well as regular access to treatment providers from other disciplines represented in the program (e.g. psychology, social work, nursing, occupational therapy). 1.1.4. Measures The following outcome measures were administered to each participant at baseline and post-treatment. The Wechsler Test of Adult Reading was administered only during the baseline assessment, in order to obtain an estimate of general intellectual functioning. 1) Wechsler Test of Adult Reading (WTAR; The Psychological Corporation, 2001): A measure that assesses an individual's ability to read single words. This task is used to estimate pre-morbid, general intellectual functioning.
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P.D. Mendella et al. / Schizophrenia Research 162 (2015) 108–111
2) Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB; Nuechterlein et al., 2008): A battery of cognitive tests that assesses Speed of Processing, Attention/Vigilance, Working Memory, Verbal Learning, Visual Learning, Reasoning and Problem Solving, and Social Cognition. The MCCB was created by an NIMH consensus panel in order to measure cognitive change in schizophrenia treatment trials. Alternate forms are available for the purpose of re-testing, and were used in the current study. The cognitive composite score (primary outcome) and individual test scores (secondary outcomes) were used. 3) University of California, San Diego Performance Based Skill Assessment—Brief Version (UPSA-B; Mausbach et al., 2007): A performance-based measure that assesses an individual's ability to perform various tasks related to everyday functioning (e.g., communicating by telephone; counting money; paying bills). Higher scores indicate better functional capacity. 4) Positive and Negative Syndrome Scale (PANSS; Kay et al., 1987): A clinician rating scale that assesses positive and negative symptom dimensions related to psychosis. Higher scores indicate more severe symptoms. 5) Calgary Depression Scale for Schizophrenia (CDSS; Addington et al., 1990): A clinician rating scale that assesses symptoms of depression. Higher scores indicate more severe symptoms. 1.1.5. Data analyses To assess change over time between the two conditions, we used analysis of covariance (ANCOVA) in which conditions were compared at post-treatment while controlling for pre-treatment levels. Because this was a pilot study to assess the potential value of the intervention with a small clinical sample, the Type I error rate was not adjusted for the number of comparisons and was kept at p b .05 level for each comparison. Effect size for the ANCOVA was assessed by partial η2 in which medium (N.06) and large (N.14) effects were considered clinically meaningful. 2. Results Table 1 indicates the demographic and clinical information for participants in the full sample. The groups did not significantly differ at baseline on any demographic or clinical variables. For the ANCOVA, the data met assumptions of equality of error variances and homogeneity of regression. Table 2 presents the ANCOVA results comparing the two conditions at post-treatment while controlling for baseline scores. The CCT condition, compared to TAU, was significantly associated with improvements on the MCCB composite score, Trail Making, and the Mayer–Salovey–Caruso Emotional Intelligence Test (MSCEIT), with large effects for each. Non-significant, but medium
effect sizes in favor of CCT were noted on Symbol Coding and Mazes (Table 2). There were no significant CCT-associated effects on functional capacity or positive, negative, or depressive symptoms. 3. Discussion We found that CCT, compared to TAU, was associated with cognitive improvements in the areas of global cognition (MCCB composite score), Trail Making, and social cognition (MSCEIT). Trail making is a key component of the processing speed factor of the MCCB, and the processing speed factor correlates strongly (r = .88) with the cognitive measures of the MCCB (Burton et al., 2013), so it is not surprising to see similar effects on these correlated measures. We have not previously used the MSCEIT to measure social cognition outcomes in response to CCT, but it is possible that improved cognitive habits in attention and cognitive flexibility may have led to improvements on this measure. In contrast with our larger trial focusing on chronic schizophrenia patients (Twamley et al., 2012), we did not observe CCT-associated improvements in negative symptoms or functional capacity in the subjects with first-episode schizophrenia. Our brief, strategy-oriented CCT intervention resulted in improvements in similar areas (global cognition, processing speed, and social cognition) as longer, restorative drill-andpractice interventions (Eack et al., 2009; Fisher et al., 2015). A longer, more symptom-focused intervention may be needed to improve psychiatric symptom severity (e.g., Eack et al., 2009), and interventions focused directly on skill performance may be needed to improve functional capacity (e.g., Bowie et al., 2014). From a practical standpoint, the CCT intervention was well-received by the participants, who all completed the intervention with high attendance rates. Thus, CCT was easily incorporated into our first episode outpatient program. Several limitations to our study must be considered. First, our sample size was small, and our results should be considered preliminary until replicated in a larger sample. In this pilot trial, we did not collect data regarding prescribed medications, nor control for medication effects. Secondly, our outcome assessment could not be blinded in this pilot study, raising the possibility of experimenter bias. However, the improvements we observed in the CCT group were performancebased, rather than examiner-rated. Finally, our control group did not control for therapist time and attention, although both groups in our study received comprehensive psychosocial treatment as part of the On Track program. We conclude that CCT treatment of cognitive impairments in first episode schizophrenia is feasible and can result in large effect size improvements in cognition and social cognition. Generalization of these effects to functioning may require specific adjunctive skills training interventions. Further investigations using more rigorous designs are needed to replicate and extend these findings.
Table 1 Demographic and clinical characteristics of the sample.
Age, years Education, years Male, % Estimated premorbid IQ (WTAR score) MCCB composite t-score UPSA-B total score PANSS positive symptom severity PANSS negative symptom severity CDSS depressive symptom severity
Whole Sample (n = 27)
CCT group (n = 16)
TAU group (n = 11)
Mean (SD) or %
Mean (SD) or %
Mean (SD) or %
t or χ2
df
p
24.9 (3.4) 13.2 (2.4) 74.1 99.4 (13.0) 35.1 (8.5) 72.7 (13.4) 10.1 (4.4) 15.7 (6.4) 4.2 (3.8)
25.0 (3.9) 13.3 (2.6) 68.8 99.9 (14.1) 35.4 (7.0) 73.9 (13.8) 9.7 (3.2) 16.5 (5.4) 3.2 (3.4)
24.8 (2.6) 13.1 (2.3) 81.8 98.6 (11.7) 34.6 (10.6) 71.0 (13.2) 10.8 (5.7) 14.5 (7.7) 5.6 (4.1)
0.13 0.23 0.45 0.24 0.23 0.55 −0.65 0.78 −1.70
25 25 1 24 23 25 25 25 25
.894 .822 .662 .813 .822 .590 .519 .443 .101
Note. CDSS = Calgary Depression Scale for Schizophrenia; MCCB = MATRICS Consensus Cognitive Battery; PANSS = Positive and Negative Syndrome Scale; UPSA-B = UCSD Performance Based Skills Assessment, Brief version; WTAR = Wechsler Test of Adult Reading.
P.D. Mendella et al. / Schizophrenia Research 162 (2015) 108–111
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Table 2 Analysis of covariance results comparing conditions at post-treatment and controlling for baseline scores.
MCCB Composite Trail Making, part A Symbol Coding HVLT-R Spatial Span Letter–Number Sequencing Mazes BVMT-R Category Fluency MSCEIT CPT-IP UPSA-B Total PANSS positive symptom score PANSS negative symptom score CDSS depressive symptom score
Baseline mean (SD) score (CCT; n = 16)
Post-treatment mean (SD) score (CCT; n = 16)
Baseline mean (SD) score (TAU; n = 11)
Post-treatment mean (SD) score (TAU; n = 11)
F(1,24)
p
η2, effect size
35.4 (7.0) 40.6 (9.8) 34.8 (7.9) 41.8 (9.3) 46.7 (6.8) 38.3 (5.2) 42.5 (9.6) 44.9 (9.7) 43.9 (6.5) 42.8 (12.2) 40.9 (12.0) 73.9 (13.8) 9.7 (3.2) 16.5 (5.4) 3.2 (3.4)
41.0 (6.8) 47.3 (11.0) 40.9 (9.2) 41.5 (6.6) 47.6 (10.7) 41.5 (8.2) 46.9 (8.2) 46.9 (7.0) 45.6 (10.0) 47.3 (9.5) 42.7 (9.7) 75.4 (11.8) 8.2 (2.4) 16.1 (8.9) 2.3 (2.4)
34.6 (10.6) 37.4 (12.1) 36.5 (12.1) 39.8 (7.6) 45.0 (11.2) 36.3 (9.0) 42.7 (12.7) 41.5 (11.0) 40.1 (8.2) 46.3 (10.8) 34.0 (6.4) 71.0 (13.2) 10.8 (5.7) 14.5 (7.7) 5.6 (4.1)
34.5 (13.2) 36.6 (15.0) 38.8 (11.8) 37.1 (10.9) 46.7 (7.4) 36.3 (12.1) 42.8 (12.8) 42.3 (14.8) 42.0 (15.4) 42.3 (10.7) 36.2 (7.0) 71.9 (15.6) 8.1 (1.9) 13.5 (7.8) 3.7 (2.7)
11.86 5.20 1.91 1.34 0.01 1.35 1.61 0.41 0.27 4.69 0.76 0.20 0.06 0.17 0.10
.002 .032 .180 .259 .928 .257 .217 .526 .607 .041 .392 .657 .802 .684 .752
.350, large .178, large .074, medium .053, small .000, no effect .055, small .063, medium .017, small −.011, small .170, large −.032, small .008, no effect −.003, no effect −.008, no effect −.005, no effect
Note. p-values in bold indicate p b .05. Effect sizes, partial η2, indicate small N .01, medium N .06, and large N .14 effects. BVMT-R = Brief Visuospatial Memory Test—Revised; CCT = Compensatory Cognitive Training; CDSS = Calgary Depression Scale for Schizophrenia; CPT-IP = Continuous Performance Test—Identical Pairs; HVLT-R = Hopkins Verbal Learning Test —Revised; MCCB = MATRICS Consensus Cognitive Battery; MSCEIT = Mayer–Salovey–Caruso Emotional Intelligence Test; PANSS = Positive and Negative Syndrome Scale; TAU = Treatment as usual; UPSA-B = UCSD Performance-Based Skills Assessment, Brief version.
Role of funding source This work was supported by an Investigator Initiated Research Grant from Pfizer Canada to PDM and by R01MH080150 from the National Institute of Mental Health to EWT. Contributors Paul D. Mendella designed the study, oversaw the study staff and therapists, co-led the treatment groups, contributed to data interpretation, and drafted and edited the manuscript; Cynthia Z. Burton conducted the analyses, contributed to data interpretation, and drafted the introduction section of the manuscript; Giorgio A. Tasca conducted the initial analyses and contributed to data interpretation; Paul Roy contributed to study design and data interpretation; Lea St. Louis served as a study therapist and contributed to data interpretation; Elizabeth W. Twamley assisted with data analyses, contributed to data interpretation, drafted the discussion section, and edited the manuscript. Conflict of interest The authors declare no conflicts of interest. Acknowledgments The authors thank all of the study participants for their participation.
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Contents lists available at ScienceDirect
Schizophrenia Research journal homepage: www.elsevier.com/locate/schres
Compensatory cognitive training for people with first-episode schizophrenia: Results from a pilot randomized controlled trial Paul D. Mendella a, Cynthia Z. Burton b, Giorgio A. Tasca c,d, Paul Roy a, Lea St. Louis c, Elizabeth W. Twamley e,f,⁎ a
Ricci & Associates, 1101 Prince of Wales Drive, Suite 110, Ottawa, ON K2C 3W7, Canada San Diego State University/University of California, San Diego Joint Doctoral Program in Clinical Psychology, 140 Arbor Drive (0851), San Diego, CA 92103, United States The Ottawa Hospital, 501 Smyth Road, Ottawa, ON K1G 0H9, Canada d University of Ottawa, 65 Laurier Avenue East, Ottawa, ON K1N 6N5, Canada e University of California, San Diego, Department of Psychiatry, United States f Center of Excellence for Stress and Mental Health, VA San Diego Healthcare System, United States b c
a r t i c l e
i n f o
Article history: Received 3 November 2014 Received in revised form 6 January 2015 Accepted 8 January 2015 Available online 24 January 2015 Keywords: Cognitive remediation Psychosis Cognition Social cognition Functional capacity
a b s t r a c t Cognitive training or remediation now has multiple studies and meta-analyses supporting its efficacy in improving cognition and functioning in people with schizophrenia. However, relatively little is known about cognitive training outcomes in early psychosis. We conducted a pilot randomized controlled trial of Compensatory Cognitive Training (CCT) compared to Treatment as Usual (TAU) in 27 participants with first-episode psychosis who had received treatment for psychosis for less than six months. Assessments of cognition (MATRICS Consensus Cognitive Battery; MCCB) and functional capacity (UCSD Performance-Based Skills Assessment-Brief; UPSA-B) were administered at baseline and following the 12-week treatment. The CCT condition, compared to TAU, was associated with significant improvements on the MCCB composite score, as well as MCCB subtests measuring processing speed (Trail Making) and social cognition (Mayer–Salovey–Caruso Emotional Intelligence Test), with large effects on these three outcome measures. There were no significant CCT-associated effects on the UPSA-B or on positive, negative, or depressive symptoms. CCT treatment of cognitive impairments in first-episode schizophrenia is feasible and can result in large effect size improvements in global cognition, processing speed, and social cognition. Published by Elsevier B.V.
1. Introduction The cognitive impairments associated with schizophrenia and their negative effects on functional outcomes are well-established in the psychiatric literature (e.g., Heinrichs and Zakzanis, 1998; Green et al., 2000). Current efforts are therefore focused on empirically supported treatments to improve cognitive functioning among affected individuals. Cognitive remediation, or cognitive training, is one such treatment and is defined as “a behavioral, training-based intervention that aims to improve cognitive processes (attention, memory, executive function, social cognition, or metacognition) with the goal of durability and generalization” (Wykes et al., 2011). Recent evidence suggests that cognitive remediation has a moderate effect on cognitive measures and psychosocial functioning, and a small effect on psychiatric symptom severity; it has proven more effective in clinically stable patients and when combined with other psychiatric rehabilitation programs (Wykes et al., 2011). On average, however, most published trials of cognitive remediation include middle-aged, chronically ill individuals with ⁎ Corresponding author at: Department of Psychiatry, University of California, San Diego, 140 Arbor Drive (0851), San Diego, CA 92103, United States. Tel.: +1 619 543 6684. E-mail address: [email protected] (E.W. Twamley).
http://dx.doi.org/10.1016/j.schres.2015.01.016 0920-9964/Published by Elsevier B.V.
a confirmed diagnosis of schizophrenia, limiting conclusions about its efficacy for those in the prodromal phase or first-episode of psychotic illness. Few studies have examined cognitive remediation in the early course of schizophrenia, but there are numerous reasons to pursue this line of investigation. Cognitive impairment is evident before the onset of overt psychosis, continues during the early phase of illness, and may even worsen during the first episode (Saykin et al, 1994; Bilder et al., 2006; Eastvold et al., 2007). Further, first episode participants have shown inconsistent trajectories of cognitive performance, where some cognitive abilities improve over time and others deteriorate (Jahshan et al., 2010). At the same time, young individuals early in the course of illness may have greater brain plasticity and more limited structural and functional brain changes than those with chronic psychotic illness, which could lead to better results of cognitive remediation treatment (Keshavan and Hogarty, 1999; Berger et al., 2007). Indeed, there is some evidence to suggest that cognitive remediation may have a neuroprotective effect against gray matter loss in early schizophrenia (Eack et al., 2010a). People enduring a first episode of schizophrenia, therefore, may be uniquely positioned to capitalize on neural plasticity and bypass some cognitive deficits through cognitive remediation treatment.
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In light of this rationale, some researchers have begun to explore cognitive remediation in early schizophrenia. A recent review of eight published manuscripts concluded that preliminary results are positive, but more empirical research is needed to confirm the efficacy of cognitive remediation (Barlati et al., 2012). For example, one study of cognitive remediation in adolescents with early onset psychosis initially found no superior effect of cognitive remediation compared to psychoeducation, but at one year follow-up there appeared to be an effect on early visual information processing (Ueland and Rund, 2004; Ueland and Rund, 2005). Other studies have found positive effects of cognitive remediation for early course schizophrenia on global cognition (Eack et al., 2009; Fisher et al., 2015), learning (Fisher et al., 2015), executive functioning (Wykes et al., 2007; Fisher et al., 2015), social cognition (Eack et al., 2009), psychiatric symptoms (Eack et al., 2009), and social adjustment (Eack et al., 2009, 2010b). A recent comparison of early-course (b 5 years illness duration) and chronic (N15 years illness duration) cognitive remediation participants showed that the early-course participants had larger improvements in processing speed, executive functioning, and functional capacity (Bowie et al., 2014). Overall, cognitive remediation treatment in early schizophrenia shows promise, but more empirical evidence is required. Additionally, the studies of cognitive remediation in early course schizophrenia have all employed restorative, drill-and-practice interventions; compensatory training approaches have not been investigated. This study aimed to pilot-test a manualized Compensatory Cognitive Training (CCT) intervention in a sample of first episode schizophrenia participants. In contrast to restorative approaches to cognitive remediation, which rely on drills and practice to improve cognition, compensatory cognitive training approaches teach cognitive strategies as ways of working around cognitive impairments, with the goal of developing new cognitive habits that generalize to cognitive performance and meaningful real-world outcomes (Wykes et al., 2011). CCT has demonstrated efficacy in participants with chronic schizophrenia (Twamley et al., 2012) and targets cognition in four domains: prospective memory, attention and vigilance, learning and memory, and executive functioning. CCT is a brief (24 h over 12 weeks), groupbased intervention that teaches strategies in the domains above via interactive, game-like activities to maintain interest and increase focus and motivation. Therapists elicit clients' personal goals and link the strategies taught to their specific goals in order to enhance intrinsic motivation (e.g., “You told me that dating is important to you, and these skills for paying attention during conversations will help you have conversations on your dates.”). Home exercises are assigned weekly to promote cognitive habit learning and strategy use in the real world. Each session follows the same general format of reviewing the home exercises, establishing a rationale for new skills to be taught, demonstrating the skill, having participants practice the skill, planning for implementation in daily life, and assigning home exercises for the coming week. The CCT manual is provided free of charge at www. cogsmart.com. It was hypothesized that, compared to a control group receiving treatment as usual (TAU), the CCT participants would demonstrate improvements in a cognitive composite score and functional capacity (co-primary outcomes) at post-treatment. We also examined change on individual cognitive test scores and psychiatric symptom ratings (secondary outcomes). 1.1. Method 1.1.1. Participants Participants were outpatients enrolled at On Track, the Champlain District Regional First Episode Psychosis Program, of The Ottawa Hospital. On Track provides clinical services to individuals who are experiencing their first psychotic episode, and who have received treatment for less than six months prior to enrollment in the program. In addition to
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being enrolled as a patient at On Track, inclusion criteria for enrollment in the study consisted of the following: 1) Individuals must be diagnosed with a primary psychotic disorder (i.e., schizophreniform disorder, schizophrenia, or schizoaffective disorder). Diagnoses were made by the treating psychiatrist on the basis of a clinical interview. 2) Recruitment was limited to individuals between the ages of 18 and 35, in order to increase group homogeneity. 3) Only English speakers were included in the study because the therapist and patient manuals for CCT were available in English only. Potential participants were excluded from the study if: 1) The individual was clinically unstable to the degree that weekly group therapy was not feasible. 2) The individual had previously been diagnosed with an underlying neurological condition affecting cognition (e.g., significant traumatic brain injury; seizure disorder). 3) There was evidence of significant, active substance abuse. Thirty-one participants were enrolled. One was too old to meet inclusion criteria and was dropped; one withdrew consent; two in the TAU group were lost to follow-up. In the final sample, there were 27 participants (16 CCT; 11 TAU). 1.1.2. Procedure Individuals who were identified as potential participants by their On Track psychiatrists, social workers, or nurses were approached for possible enrollment in the study. Written informed consent to participate in the study was obtained from each participant, and the study was approved by the Ottawa Hospital Research Ethics Board. Following informed consent and baseline assessment, participants were randomized into the experimental (Compensatory Cognitive Training; CCT) or control (Treatment as Usual; TAU) group via computerized randomization. The randomization was carried out by an independent staff member who was given subject identification numbers only; thus, the research associate was not aware of the random assignments until after they occurred. After 12 weeks, each participant was re-administered the outcome measures. All participants were compensated for their time during the assessments, but not for attending treatment. The examiner was not blind to group assignment, but was not involved in providing treatment. 1.1.3. Experimental and control conditions Participants in CCT attended a weekly 2-hour group treatment session with 7–8 participants per group. They were also supplied with patient manuals outlining each session. Each session was facilitated by the therapists (PDM and LSL), except on a few occasions when one of the facilitators was not available due to scheduling conflicts or illness. In such cases, the group was led by the remaining facilitator. Participants in the CCT group continued to receive standard treatment at On Track while they were enrolled in the study. Participants in the TAU group received standard treatment during the duration of the study, which included routine psychiatric care provided by a program psychiatrist, as well as regular access to treatment providers from other disciplines represented in the program (e.g. psychology, social work, nursing, occupational therapy). 1.1.4. Measures The following outcome measures were administered to each participant at baseline and post-treatment. The Wechsler Test of Adult Reading was administered only during the baseline assessment, in order to obtain an estimate of general intellectual functioning. 1) Wechsler Test of Adult Reading (WTAR; The Psychological Corporation, 2001): A measure that assesses an individual's ability to read single words. This task is used to estimate pre-morbid, general intellectual functioning.
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2) Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB; Nuechterlein et al., 2008): A battery of cognitive tests that assesses Speed of Processing, Attention/Vigilance, Working Memory, Verbal Learning, Visual Learning, Reasoning and Problem Solving, and Social Cognition. The MCCB was created by an NIMH consensus panel in order to measure cognitive change in schizophrenia treatment trials. Alternate forms are available for the purpose of re-testing, and were used in the current study. The cognitive composite score (primary outcome) and individual test scores (secondary outcomes) were used. 3) University of California, San Diego Performance Based Skill Assessment—Brief Version (UPSA-B; Mausbach et al., 2007): A performance-based measure that assesses an individual's ability to perform various tasks related to everyday functioning (e.g., communicating by telephone; counting money; paying bills). Higher scores indicate better functional capacity. 4) Positive and Negative Syndrome Scale (PANSS; Kay et al., 1987): A clinician rating scale that assesses positive and negative symptom dimensions related to psychosis. Higher scores indicate more severe symptoms. 5) Calgary Depression Scale for Schizophrenia (CDSS; Addington et al., 1990): A clinician rating scale that assesses symptoms of depression. Higher scores indicate more severe symptoms. 1.1.5. Data analyses To assess change over time between the two conditions, we used analysis of covariance (ANCOVA) in which conditions were compared at post-treatment while controlling for pre-treatment levels. Because this was a pilot study to assess the potential value of the intervention with a small clinical sample, the Type I error rate was not adjusted for the number of comparisons and was kept at p b .05 level for each comparison. Effect size for the ANCOVA was assessed by partial η2 in which medium (N.06) and large (N.14) effects were considered clinically meaningful. 2. Results Table 1 indicates the demographic and clinical information for participants in the full sample. The groups did not significantly differ at baseline on any demographic or clinical variables. For the ANCOVA, the data met assumptions of equality of error variances and homogeneity of regression. Table 2 presents the ANCOVA results comparing the two conditions at post-treatment while controlling for baseline scores. The CCT condition, compared to TAU, was significantly associated with improvements on the MCCB composite score, Trail Making, and the Mayer–Salovey–Caruso Emotional Intelligence Test (MSCEIT), with large effects for each. Non-significant, but medium
effect sizes in favor of CCT were noted on Symbol Coding and Mazes (Table 2). There were no significant CCT-associated effects on functional capacity or positive, negative, or depressive symptoms. 3. Discussion We found that CCT, compared to TAU, was associated with cognitive improvements in the areas of global cognition (MCCB composite score), Trail Making, and social cognition (MSCEIT). Trail making is a key component of the processing speed factor of the MCCB, and the processing speed factor correlates strongly (r = .88) with the cognitive measures of the MCCB (Burton et al., 2013), so it is not surprising to see similar effects on these correlated measures. We have not previously used the MSCEIT to measure social cognition outcomes in response to CCT, but it is possible that improved cognitive habits in attention and cognitive flexibility may have led to improvements on this measure. In contrast with our larger trial focusing on chronic schizophrenia patients (Twamley et al., 2012), we did not observe CCT-associated improvements in negative symptoms or functional capacity in the subjects with first-episode schizophrenia. Our brief, strategy-oriented CCT intervention resulted in improvements in similar areas (global cognition, processing speed, and social cognition) as longer, restorative drill-andpractice interventions (Eack et al., 2009; Fisher et al., 2015). A longer, more symptom-focused intervention may be needed to improve psychiatric symptom severity (e.g., Eack et al., 2009), and interventions focused directly on skill performance may be needed to improve functional capacity (e.g., Bowie et al., 2014). From a practical standpoint, the CCT intervention was well-received by the participants, who all completed the intervention with high attendance rates. Thus, CCT was easily incorporated into our first episode outpatient program. Several limitations to our study must be considered. First, our sample size was small, and our results should be considered preliminary until replicated in a larger sample. In this pilot trial, we did not collect data regarding prescribed medications, nor control for medication effects. Secondly, our outcome assessment could not be blinded in this pilot study, raising the possibility of experimenter bias. However, the improvements we observed in the CCT group were performancebased, rather than examiner-rated. Finally, our control group did not control for therapist time and attention, although both groups in our study received comprehensive psychosocial treatment as part of the On Track program. We conclude that CCT treatment of cognitive impairments in first episode schizophrenia is feasible and can result in large effect size improvements in cognition and social cognition. Generalization of these effects to functioning may require specific adjunctive skills training interventions. Further investigations using more rigorous designs are needed to replicate and extend these findings.
Table 1 Demographic and clinical characteristics of the sample.
Age, years Education, years Male, % Estimated premorbid IQ (WTAR score) MCCB composite t-score UPSA-B total score PANSS positive symptom severity PANSS negative symptom severity CDSS depressive symptom severity
Whole Sample (n = 27)
CCT group (n = 16)
TAU group (n = 11)
Mean (SD) or %
Mean (SD) or %
Mean (SD) or %
t or χ2
df
p
24.9 (3.4) 13.2 (2.4) 74.1 99.4 (13.0) 35.1 (8.5) 72.7 (13.4) 10.1 (4.4) 15.7 (6.4) 4.2 (3.8)
25.0 (3.9) 13.3 (2.6) 68.8 99.9 (14.1) 35.4 (7.0) 73.9 (13.8) 9.7 (3.2) 16.5 (5.4) 3.2 (3.4)
24.8 (2.6) 13.1 (2.3) 81.8 98.6 (11.7) 34.6 (10.6) 71.0 (13.2) 10.8 (5.7) 14.5 (7.7) 5.6 (4.1)
0.13 0.23 0.45 0.24 0.23 0.55 −0.65 0.78 −1.70
25 25 1 24 23 25 25 25 25
.894 .822 .662 .813 .822 .590 .519 .443 .101
Note. CDSS = Calgary Depression Scale for Schizophrenia; MCCB = MATRICS Consensus Cognitive Battery; PANSS = Positive and Negative Syndrome Scale; UPSA-B = UCSD Performance Based Skills Assessment, Brief version; WTAR = Wechsler Test of Adult Reading.
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Table 2 Analysis of covariance results comparing conditions at post-treatment and controlling for baseline scores.
MCCB Composite Trail Making, part A Symbol Coding HVLT-R Spatial Span Letter–Number Sequencing Mazes BVMT-R Category Fluency MSCEIT CPT-IP UPSA-B Total PANSS positive symptom score PANSS negative symptom score CDSS depressive symptom score
Baseline mean (SD) score (CCT; n = 16)
Post-treatment mean (SD) score (CCT; n = 16)
Baseline mean (SD) score (TAU; n = 11)
Post-treatment mean (SD) score (TAU; n = 11)
F(1,24)
p
η2, effect size
35.4 (7.0) 40.6 (9.8) 34.8 (7.9) 41.8 (9.3) 46.7 (6.8) 38.3 (5.2) 42.5 (9.6) 44.9 (9.7) 43.9 (6.5) 42.8 (12.2) 40.9 (12.0) 73.9 (13.8) 9.7 (3.2) 16.5 (5.4) 3.2 (3.4)
41.0 (6.8) 47.3 (11.0) 40.9 (9.2) 41.5 (6.6) 47.6 (10.7) 41.5 (8.2) 46.9 (8.2) 46.9 (7.0) 45.6 (10.0) 47.3 (9.5) 42.7 (9.7) 75.4 (11.8) 8.2 (2.4) 16.1 (8.9) 2.3 (2.4)
34.6 (10.6) 37.4 (12.1) 36.5 (12.1) 39.8 (7.6) 45.0 (11.2) 36.3 (9.0) 42.7 (12.7) 41.5 (11.0) 40.1 (8.2) 46.3 (10.8) 34.0 (6.4) 71.0 (13.2) 10.8 (5.7) 14.5 (7.7) 5.6 (4.1)
34.5 (13.2) 36.6 (15.0) 38.8 (11.8) 37.1 (10.9) 46.7 (7.4) 36.3 (12.1) 42.8 (12.8) 42.3 (14.8) 42.0 (15.4) 42.3 (10.7) 36.2 (7.0) 71.9 (15.6) 8.1 (1.9) 13.5 (7.8) 3.7 (2.7)
11.86 5.20 1.91 1.34 0.01 1.35 1.61 0.41 0.27 4.69 0.76 0.20 0.06 0.17 0.10
.002 .032 .180 .259 .928 .257 .217 .526 .607 .041 .392 .657 .802 .684 .752
.350, large .178, large .074, medium .053, small .000, no effect .055, small .063, medium .017, small −.011, small .170, large −.032, small .008, no effect −.003, no effect −.008, no effect −.005, no effect
Note. p-values in bold indicate p b .05. Effect sizes, partial η2, indicate small N .01, medium N .06, and large N .14 effects. BVMT-R = Brief Visuospatial Memory Test—Revised; CCT = Compensatory Cognitive Training; CDSS = Calgary Depression Scale for Schizophrenia; CPT-IP = Continuous Performance Test—Identical Pairs; HVLT-R = Hopkins Verbal Learning Test —Revised; MCCB = MATRICS Consensus Cognitive Battery; MSCEIT = Mayer–Salovey–Caruso Emotional Intelligence Test; PANSS = Positive and Negative Syndrome Scale; TAU = Treatment as usual; UPSA-B = UCSD Performance-Based Skills Assessment, Brief version.
Role of funding source This work was supported by an Investigator Initiated Research Grant from Pfizer Canada to PDM and by R01MH080150 from the National Institute of Mental Health to EWT. Contributors Paul D. Mendella designed the study, oversaw the study staff and therapists, co-led the treatment groups, contributed to data interpretation, and drafted and edited the manuscript; Cynthia Z. Burton conducted the analyses, contributed to data interpretation, and drafted the introduction section of the manuscript; Giorgio A. Tasca conducted the initial analyses and contributed to data interpretation; Paul Roy contributed to study design and data interpretation; Lea St. Louis served as a study therapist and contributed to data interpretation; Elizabeth W. Twamley assisted with data analyses, contributed to data interpretation, drafted the discussion section, and edited the manuscript. Conflict of interest The authors declare no conflicts of interest. Acknowledgments The authors thank all of the study participants for their participation.
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