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The Brazilian standardization of the MATRICS consensus cognitive battery (MCCB): Psychometric study
SCHRES-07111; No of Pages 6 Schizophrenia Research xxx (2017) xxx–xxx
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The Brazilian standardization of the MATRICS consensus cognitive battery (MCCB): Psychometric study Ana Olívia Fonseca a,⁎,1, Arthur A. Berberian a,b,1, Carolina de Meneses-Gaya a, Ary Gadelha a, Marcella de O. Vicente a, Keith H. Nuechterlein c,d, Rodrigo A. Bressan a, Acioly L.T. Lacerda a a
Universiedade Federal de Sao Paulo (Unifesp), Department of Psychiatry, Interdisciplinary Lab of Clinical Neurosciences (LiNC), and Schizophrenia Program (PROESQ), Brazil Centro Universitário FIEO, Strict Sensu Educational Psychology Program, 300 UCLA Medical Plaza, Room 2240, Los Angeles, CA 90095, USA UCLA, Department of Psychiatry and Biobehavioral Sciences , 300 UCLA Medical Plaza, Room 2240, Los Angeles, CA 90095, USA d UCLA, Department Psychology, 300 UCLA Medical Plaza, Room 2240, Los Angeles, CA 90095, USA b c
a r t i c l e
i n f o
Article history: Received 9 May 2016 Received in revised form 30 December 2016 Accepted 4 January 2017 Available online xxxx Keywords: Schizophrenia Neuropsychology Neurocognitive function Cognitive deficits MATRICS consensus cognitive battery
a b s t r a c t Objective: Translate, adapt, and validate the MATRICS Consensus Cognitive Battery (MCCB) in Brazil. Method: The present study followed three steps: 1) translation to Portuguese, cultural adaptation, and back translation to English; 2) completion of a pilot study (N = 30) conducted with the purpose of assessing whether the general comprehension of the items was clear and all participants adequately responded to the battery; 3) completion of a Reliability and Validation Study of the Brazilian version of the MCCB with 99 individuals with schizophrenia and 99 healthy subjects. All participants were administered the Structured Clinical Interview for DSM-IV (Diagnostic and Statistical Manual of Mental Disorders) and patients were also rated on the Global Assessment of Functioning (GAF) Scale and the Positive and Negative Symptoms Scale (PANSS). Results: The results showed adequate to high levels of baseline and 4-week retest reliability, except the MSCEITME; adequate internal consistency for the MSCEIT-ME for the total sample and patients group, and moderate Alpha for the health control sample; as well as evidence of convergent validity and sensitivity to differentiate performance between the groups. All the 10 MCCB measures showed the lowest learning effects. Conclusion: Overall the Brazilian version of the MCCB showed similar results to the original North American version. Our findings provides reassurance that the MCCB is a reliable and valid measure of cognition across different countries and cultures, which is especially important to the ongoing work in attempting to discover cognitionenhancing drugs and the effects of cognitive interventions for the treatment of schizophrenia. © 2017 Elsevier B.V. All rights reserved.
1. Introduction The cognitive deficits in schizophrenia, originally described by Kraepelin in 1896 (Kraepelin, 1971), and Bleuler in 1911 (Bleuler, 1950), are well documented in the literature (Bowie and Harvey, 2005; Tamminga, 2006) and are considered the core components of the disease (Elvevåg and Goldberg, 2000). These deficits, seen even in the premorbid base, i.e. before the first psychotic episode, are the factors that best predict functional outcome and prognosis of patients and can persist even when other symptoms are remitted or stabilized (Green and Harvey, 2014). In different studies, N80% of patients showed at least one cognitive domain significantly affected and directly impacting on the ability to acquire new skills and perform activities of daily life
⁎ Corresponding author at: Interdisciplinary Lab of Clinical Neurosciences (LiNC) Edifício de Pesquisas II, Rua Pedro de Toledo, 669, 3° andar, fundos, Vila Clementino, 04039-032 São Paulo, SP, Brazil. E-mail address: [email protected] (A.O. Fonseca). 1 Both authors contributed equally to this work.
such as maintaining personal hygiene, attending school or work, and having a social life (Green et al., 2000; Keefe et al., 2005; Kern et al., 2011). This evidence underscores the need for interventions focused on the cognitive aspects of the disease. However, one major gap in this frontier is the paucity of standardized cognitive measures for schizophrenia, which limits the generalization of the results that have been obtained so far (Nuechterlein et al., 2008). The Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery was developed to fill this gap (Marder and Fenton, 2004), based on the following criteria: 1) good baseline and 4-week retest reliability; 2) high utility as a repeated measure; 3) good relationship with functional outcome; 4) potential changeability in response to pharmacological agents; 5) tolerability by the patient and practicality for the administrator (Green et al., 2004; Nuechterlein et al., 2008). Based on the above criteria, 10 tests were selected for the MATRICS Consensus Cognitive Battery (MCCB) (Nuechterlein et al., 2008). Most of these tests already had a normative database from separate normative samples, but it needed to be normed together on the same sample in order to establish a metric that was
http://dx.doi.org/10.1016/j.schres.2017.01.006 0920-9964/© 2017 Elsevier B.V. All rights reserved.
Please cite this article as: Fonseca, A.O., et al., The Brazilian standardization of the MATRICS consensus cognitive battery (MCCB): Psychometric study, Schizophr. Res. (2017), http://dx.doi.org/10.1016/j.schres.2017.01.006
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A.O. Fonseca et al. / Schizophrenia Research xxx (2017) xxx–xxx
equivalent across each test. Kern et al. (2008) obtained normative data for the United States population and, since then, standardization and translation validation studies have been conducted in several other countries, some of which have also obtained normative data, while others are still in progress (Mohn et al., 2012; Rodriguez-Jimenez et al., 2012; Jędrasik-Styła et al., 2015; Shi et al., 2015; see www. matricsinc.org). In order to investigate and stimulate further studies focusing on the cognitive research of schizophrenia in Brazil, this study involved a translation and adaptation of the MCCB and explored its psychometric properties in Brazil. More specifically, there were examined baseline and 4week retest reliability, internal consistency, evidence of validity based on relationships with other variables (convergent validity, cognitive performance differences between groups), and the learning effect of alternative forms of the MCCB, providing an accumulation of different sources of reliability and validity for the MCCB's use in the Brazilian context.
(SCID-I) (Del-Ben et al., 2001), with an average age of 33.13 (SD = 8.02) years and an average education level of 11.47 (SD = 3.27) years. They were matched with 15 healthy controls, chosen by convenience in database of healthy controls from the Federal University of São Paulo, based on age (M = 32.07; SD = 7.85), sex (60% male) and educational level (M = 10.87; SD = 3.87). Between-group comparisons for these variables were all nonsignificant [(age t = 0.37, p = 0.90), (education: t = 0.46, p = 0.73)]. The main purpose of this study phase was to assess the general comprehension of the questions. All participants were able to understand the instructions, respond to all items and answer this version of the MCCB, thus proving it has been comprehensible. Furthermore, data distribution of these two groups was verified using skewness, kurtosis and the Kolmogorov-Smirnov tests. Distribution of the measures was found normal.
2. Material and methods
Ninety-nine outpatients with schizophrenia and ninety-nine healthy controls were recruited from three different sites in Brazil (São Paulo, Porto Alegre and Goiania). To confirm the schizophrenia diagnosis, all participants were assessed with the Structured Clinical Interview for DSM-IV (SCID-I) performed by trained psychiatrists. The patients were on antipsychotics and their medication dosages had been stable for at least 4-week prior to the cognitive assessment. Healthy participants were matched to the patient group by sex, age, and academic level. Those one's were recruited from a larger database, referring to MCCB's co-normatization project for Brazil based on the Brazilian census. All of them were assessed with SCID-I in order to rule out a history of Axis I psychiatric disorders. Participants in both groups had at least four years of education, were at least 18 years old, spoken Portuguese as native language and were an IQ ≥ 80, based on their score on the shortform of the WAIS-III. All participants also fulfilled the two following inclusion criteria: 1 no evidence of organic brain disease or head injury with loss of consciousness and 2 - no evidence of substance abuse in the last year. At the first session, patients were evaluated by psychiatrists trained in the application of the SCID-I and PANSS (with Kappa intra-rater coefficient ranging from 0.80 to 1.0) to determine study eligibility. Cognitive assessment was performed by trained psychologists in one single session, lasting approximately 90 min, in an appropriate room. After 4week, forty five patients were randomly selected to be retested with the recommended Alternate Forms (http://www.matricsinc.org/? page_id=23). In the 4-week retest, we used Form 4 of the HVLT-R, Form 5 of the BVMT-R and Form 2 of the NAB Mazes. The correlation between the 10 MCCB measures and symptomatology are described in Table 1.
The study was developed in three stages, described below. Stage 1– Translation of the MCCB Two native Portuguese speakers worked independently from one another, this resulted in two different versions, which were later compared to produce a Brazilian-Portuguese consensus version of the MCCB. This version was then back translated, sent to the authors of each test in the MCCB, and approved. This allowed the Brazilian-Portuguese language version being used for academic research purposes. The academic version was converted into a tool to be published and then available for clinical trials and other professional purposes in clinical settings in Brazil, reconciliation by a professional translation company. Finally, the translated and revised version of the MCCB was edited and printed. Of the 10 MCCB tests, three have alternative forms: BVMT-R, HVLT-R and NAB Mazes, which were also translated. The 10 MCCB tests were administered in the same order as in Kern et al. (2008): 1. Trail Making Test: Part A (TMT-A) 2. Brief Assessment of Cognition in Schizophrenia (BACS): Symbol Coding 3. Hopkins Verbal Learning Test—Revised (HVLT-R) 4. Wechsler Memory Scale—Third Edition (WMS-III): Spatial Span 5. Letter-Number Span Test (LNS) 6. Neuropsychological Assessment Battery (NAB): Mazes 7. Brief Visuospatial Memory Test—Revised (BVMT-R) 8. Category Fluency Test: Animal Naming (Fluency) 9. Mayer–Salovey–Caruso Emotional Intelligence Test (MSCEIT-ME): Managing Emotions 10. Continuous Performance Test—Identical Pairs (CPT-IP) 2.1. Current intellectual functioning A short-form WAIS-III (Wechsler, 1997) was used to estimate current intellectual functioning. It combined the vocabulary and matrix reasoning subtests for this purpose. Stage 2– Pilot Study The Ethics Committee of the Federal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil, approved this study protocol and all individuals provided written informed consent before enrollment in the study. The translated and revised version of the MCCB was applied to fifteen subjects with DSM-IV schizophrenia (60% male) as assessed with the Brazilian version of the Semi-Structured Interview for the Diagnostic and Statistical Manual of Mental Disorders, IV edition
Stage 3– Study of psychometric properties
Table 1 Pearson Correlation Coefficients between the 10 MCCB Measures and Symptoms Scales.
TMT Symbol Coding HVLT Spatial Span LNS MAZES BVMT Fluency CPT MSCEIT a b
PANSS Positive
PANSS Negative
PANSS General
PANSS Total
GAF
0.06 0.21
0.19 –0.03
0.18 –0.01
0.16 –0.01
0.10 –0.12
–0.10 –0.15 –0.15 –0.14 –0.02 0.06 –0.09 –0.24b
–0.21 –0.34b –0.33a –0.32b 0.24b –0.06 –0.23b –0.20
–0.16 –0.24b –0.22b –0.21 –0.07 –0.01 –0.17 –0.20
–0.15 –0.26b –0.25b –0.24b –0.11 –0.01 –0.17 –0.22
–0.00 0.04 0.13 –0.09 0,15 0.22b 0.04 0.14
Correlation is significant at the 0.01 level (2-tailed). Correlation is significant at the 0.05 level (2-tailed).
Please cite this article as: Fonseca, A.O., et al., The Brazilian standardization of the MATRICS consensus cognitive battery (MCCB): Psychometric study, Schizophr. Res. (2017), http://dx.doi.org/10.1016/j.schres.2017.01.006
A.O. Fonseca et al. / Schizophrenia Research xxx (2017) xxx–xxx
2.2. Data analysis
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Table 3 MCCB baseline-4 week retest reliability (Schizophrenia patients N = 45).
All statistical procedures were carried out using the Statistical Package for Social Sciences (SPSS), version 20.0. Data distribution was verified using skewness, kurtosis and the Kolmogorov-Smirnov tests. Logarithmic transformations were performed for measures that did not achieve normality in distribution with TMT-A, BVMT-R, Verbal Fluency and CPT-IP. For reliability, a coefficient of stability (Pearson's r) was calculated, using initial and delayed test scores. Cronbach's Alpha was also used to evaluate internal consistency of the MSCEIT-ME test, which could have a cultural influence. Pearson's correlations were used for convergent validity. Thus, for processing speed, for instance, TMT-A, Symbol Coding and Verbal Fluency were used to assess convergent validity. The Student's t-test was used for comparing the average performance between groups (cognitive performance differences between groups). Finally, to ensure that the MCCB in Brazil has high utility as a repeated measure for clinical trials, the paired Student's t-test was used, comparing performances in first and second assessments to assure limited practice effects.
MCCB tests
Pearson's r
TMT-A BACS SC HVLT-R WMS-III SS LNS NAB Mazes BVMT-R Fluency MSCEIT - R CPT – IP
0.85 0.84 0.63 0.79 0.65 0.83 0.79 0.73 0.55 0.88
TMT-A - Trail Making Test Part A; BACS SC - Brief Assessment of Cognition in Schizophrenia Symbol Coding; HVLT-R - Hopkins Verbal Learning Test - Revised; WMS-III SS - Wechsler Memory Scale–Third Edition Spatial Span; LNS - Letter-Number Span Test; NAB; Mazes - Neuropsychological Assessment Battery Mazes; BVMT-R - Brief Visuospatial Memory Test Revised; Fluency - Category Fluency Test Animal Naming; MSCEIT-ME: Mayer-Salovey-Caruso Emotional >Intelligence Test Managing Emotions; CPT-IP - Continuous Performance Test, Identical Pairs Version.
3. Results The demographic data for both groups are shown in Table 2 along with clinical information. Groups were matched for age, years of education, and gender. As expected, significant between-group differences were noted in current IQ scores, as IQ is a measure of global cognitive functioning.
3.1. Reliability 3.1.1. Analysis I: baseline and 4-week retest reliability Forty-five patients with schizophrenia were retested thirty days later by the same examiner. All Pearson's correlations were in the .70s and .80s except for the LNS and HVLT-R, which were in the .60s, and MSCEIT-ME, which was 0.55 These results are summarized in Table 3.
3.1.2. Analysis II: internal consistency Considering the total sample, MSCEIT-ME showed a Cronbach's alpha of 0.71. When analyzed separately, by group, the alpha was 0.72 for patients and 0.63 for the control group.
3.2. Analysis III: convergent validity Support for convergent validity was found in significant correlations among all measures that assessed the same construct for the total sample (Table 4). For processing speed, we observed a significant negative correlation of a strong magnitude between Symbol Coding (SC) score and the TMT-A completion time and a positive moderate correlation between SC and Animal Verbal Fluency. The correlation between the TMTA and verbal Fluency was significant but weaker. When Pearson's correlations was calculated separately for the groups, the TMT-A showed a strong negative correlation with SC and a significant but weak correlation with verbal Fluency for the patient group. For controls, we found a strong negative correlation between TMT-A and SC and a moderate correlation between TMT-A and verbal Fluency. SC showed a significant but weak correlation with Fluency for patients and a moderate correlation for controls. For working memory, we found strong positive correlations between WMS-III Spatial Span (SS) and the Letter-Number Test (LNS) for the total sample. WMS-III SS also showed a strong correlation with LNS for patients and for controls separately.
Table 2 Demographic data of the participants and summary of the cognitive performance differences between groups. Domain
Age Education (years) Current IQ PANSS
GAF Male (%) Trail making test, part A Symbol coding HVLT-R Spatial span Number letter span Mazes BVMT-R Fluency MSCEIT-ME CPT-IP
Variable
Positive Symptoms Negative Symptoms Total score
Schizophrenia group (N = 99)
Control Group (N = 99)
Mean (SD) (raw scores)
Mean (SD) (raw scores)
F
t
df
p
Cohen's d
37.57 (10.26) 10.74 (3.66) 91.03 (12.05) 13.16 (4.71) 17.58 (6.92) 60.12 (15.88) 49.86 (13.17) 52.5 54.19 (36.58) 33.25 (13.04) 19.88 (5.01) 11.86 (4.12) 10.03 (4.02) 12.03 (7.43) 13.02 (8.28) 15.47 (5.68) 95.29 (12.21) 1.60 (0.77)
37.55 (10.59) 11.12 (3.62) 101.28 (14.58)
0.182 0.009
–0.014 –0.523
196 196
0.989 0.601
0.00 0.07
16.58 1.038 2.264 0.001 0.579 2.393 0.022 0.119 0.684 1.442
3.942 –6.961 –8.144 –5.332 –4.888 –4.238 –6.938 –6.262 –4.475 –5.712
196 196 196 196 196 196 196 196 196 196
b0.001 b0.001 b0.001 b0.001 b0.001 b0.001 b0.001 b0.001 b0.001 b0.001
0.56 0.99 1.15 0.75 0.69 0.60 0.98 0.89 0.64 0.81
52.5 38.55 (14.86) 46.86 (14.42) 25.30 (4.33) 15.11 (4.45) 12.97 (4.43) 16.27 (6.62) 21.15 (8.21) 20.44 (5.48) 103.11 (12.37) 2.24 (0.80)
Please cite this article as: Fonseca, A.O., et al., The Brazilian standardization of the MATRICS consensus cognitive battery (MCCB): Psychometric study, Schizophr. Res. (2017), http://dx.doi.org/10.1016/j.schres.2017.01.006
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A.O. Fonseca et al. / Schizophrenia Research xxx (2017) xxx–xxx
Table 4 Pearson Correlation Coefficients for the 10 MCCB Measures (N = 99).
TMT Symbol coding HVLT_R Spatial span Number letter span Mazes BVMT_R Fluency CPT_IP MSCEIT-ME
TMT
Symbol Coding
HVLT_R
Spatial Span
Number Letter Span
Mazes
BVMT_R
Fluency
CPT_IP
MSCEIT_ME
– –0.682a –0.440a –0.504a –0.629a –0.588a –0.536a –0.514a –0.588a –0.179
–0.610a – 0.539a 0.598a 0.705a 0.577a 0.627a 0.586a 0.676a 0.279a
–0.393a 0.356a – 0.471a 0.555a 0.442a 0.545a 0.499a 0.512a 0.297a
–0.508a 0.541a 0.466a – 0.651a 0.656a 0.651a 0.471a 0.615a 0.326a
–0.536a 0.608a 0.521a 0.634a – 0.659a 0.550a 0.617a 0.752a 0.401a
–0.558a 0.500a 0.302a 0.554a 0.472a – 0.612a 0.528a 0.576a 0.240b
–0.406a 0.616a 0.502a 0.635a 0.566a 0.449a – 0.416a 0.519a 0.258a
–0.257b 0.343a 0.377a 0.367a 0.437a 0.372a 0.300a – 0.596a 0.270a
–0.574a 0.575a 0.394a 0.577a 0.646a 0.472a 0.399a 0.265a – 0.319a
–0.226b 0.417a 0.288a 0.309a 0.382a 0.277a 0.362a 0.338a 0.355a –
Correlations in patients above the diagonal and correlations in controls below the diagonal. a Correlation is significant at the 0.01 level (2-tailed). b Correlation is significant at the 0.05 level (2-tailed).
3.3. Analysis IV: cognitive performance differences between groups
4.1. Reliability studies
Diagnosis of schizophrenia was used as an external criterion, comparing the average performance between groups. All 10 MCCB measures were sensitive to discriminate performance between that of patients and controls (Table 2). The TMT-A presented the lowest effect size and the HVLT-R presented the highest.
The MSCEIT-ME test showed adequate internal consistency, based on Cronbach's Alpha, suggesting homogeneity in their items. With this, interpretations regarding results are relatively free of biases determined by particularities of specific items. When considering only the sample of the healthy controls, the MSCEIT-ME items showed a moderate alpha. The MSCEIT-ME test had the lowest baseline and 4-week retest correlation, even though it showed moderate coefficients. Different studies, including MCCB translation studies in other countries, have reported that social cognition is a factor partially separable from the other six cognitive domains, depending more on the interpretation of emotions and perceptions of others and therefore being more affected by cultural influences (Adolphs, 2010; Mason and Morris, 2010). The fact that the scores for this test were obtained through a scoring system developed for South American population (International MSCEIT™ scoring system by Multi-Health Systems, Inc.) may explain at least part of this finding (Rodriguez-Jimenez et al., 2012). South America covers a wide range of countries, with different mores, which Brazil is the only one that uses the Portuguese language.
3.4. Analysis V: utility as a repeated measure The initial assessment was compared with 4-week retest scores. These results are summarized in Table 5. No significant changes in test scores across two occasions were observed for 9 out of 10 tests, the exception being BVMT-R. The BVMT-R scores showed significant improvement but with a small effect size (0.30). There were no detectable floor or ceiling effects.
4. Discussion The current results provide solid data regarding the psychometric properties of the Brazilian version of the MCCB. Two main aspects can be emphasized. First, the steps taken to achieve an appropriate translation were strictly observed, including the translation of the original tests to the Portuguese language and the analysis of their back translation. A pilot study was conducted in which it was possible to note that all participants, both patients and healthy controls, understood the instructions and performed the tasks as requested. Second, this study demonstrates several aspects of reliability and validity for the MCCB in Brazil, that is, baseline and 4-week retest reliability, internal consistency, convergent validity and cognitive performance differences between groups. Data on practice effects are also provided.
4.2. Validity studies 4.2.1. Convergent validity To verify whether the results presented here were compatible with the MCCB theoretical framework, convergent validity analyses were performed, showing convergence among the tests that assessed the same construct, especially when assessing the potential for learning and working memory abilities. For processing speed tests (Trail Making Test, BACS Symbol Coding and Animal Fluency), adequate correlations were also found, except for the Trail Making Test and Animal Fluency, which showed low correlations. Our findings are in line with Knowles
Table 5 MCCB Utility as a Repeated Measure: Performance Levels at Baseline and 4-week Retest. Schizophrenic patients (n = 45)
Trail making test, part A Symbol coding HVLT-R Spatial span Number letter span Mazes BVMT-R Fluency MSCEIT-ME CPT-IP
Mean (SD) baseline
Mean (SD) 4-week retest
t
df
p
Cohen's d
Floor/ceiling effect (n out of 61 in T1/T2)
61.71 (45.08) 34.18 (14.75) 20.31 (5.56) 5.02 (2.61) 10.20 (4.03) 9.96 (6.99) 12.60 (8.24) 15.80 (6.17) 96.20 (11.70) 1.62 (0.83)
57.58 (44.96) 35.47 (14.23) 19.13 (5.32) 5.31 (2.65) 10.36 (3.79) 10.73 (7.51) 15.16 (8.62) 16.24 (4.63) 96.60 (12.17) 1.66 (0.98)
1.70 –1.04 1.70 –1.13 –0.32 –1.22 –3.09 –0.71 –0.24 –0.63
44 44 44 44 44 44 44 44 44 44
0.114 0.305 0.098 0.315 0.752 0.230 0.003 0.483 0.815 0.532
0.09 0.09 0.21 0.11 0.04 0.10 0.30 0.08 0.03 0.04
0/0 0/0 0/0 0/0 0/0 0/0 0/0 0/0 0/0 0/0
t = (t-value); dF = degrees of freedom; p = statistical significance (p-value).
Please cite this article as: Fonseca, A.O., et al., The Brazilian standardization of the MATRICS consensus cognitive battery (MCCB): Psychometric study, Schizophr. Res. (2017), http://dx.doi.org/10.1016/j.schres.2017.01.006
A.O. Fonseca et al. / Schizophrenia Research xxx (2017) xxx–xxx
et al. (2012), who reported weak correlations among the tests assessing processing speed, with the lower correlations between the Trail Making Test and the Animal Fluency Test. Those results suggest that, as a multidimensional ability, processing speed consists of at least two or three subcomponents. One possible explanation for this result, is that verbal Fluency is a cognitive function that allows retrieval of information from memory. Despite of the Fluency task version used by the MCCB provides to the participants specific guidelines on how to conduct the search and/or word production within the semantic network, in order to facilitate search and retrieval of words, some authors have suggested a change over the activation flow through the semantic network in schizophrenia (Bokat and Goldberg, 2003; Bozikas et al., 2005; Berberian et al., 2016), which might affect the patient's performance in a distinct way. 4.2.2. Cognitive performance differences between groups Based on the comparison of results of patients and healthy controls, the Brazilian MCCB was sensitive to discriminate performance between that of patients and controls, as there was a consistent performance difference for all MCCB tests. Patients obtained lower scores than healthy controls. These findings corroborate several important studies in the area that showed that schizophrenia patients have lower results than those reported by healthy controls in the MCCB. (Kern et al., 2008; Keefe et al., 2011; August et al., 2012; McCleery et al., 2014). 4.2.3. Utility as repeated measures Because an individual is assessed several times in studies examining cognitive change, measures with small practice effects are useful. All the MCCBs had low levels of practice effects with no statistical significance except the BVMT-R (0.30), which had a small practice effect. Similar results have also been reported in the BVMT-R test, with minimum practice effects (Keefe et al., 2011). Other studies have also shown a significant practice effect in both verbal and visual tests when the same versions are applied. However, for verbal tests, this effect becomes statistically insignificant when different versions of the word list are presented. For the BVMT-R results differ from those described in the North American trial (Nuechterlein et al., 2008; Cohen's d = 0.02). In order to avoid practice effects, there were used alternate forms of the BVMT-R, but the scores increased from baseline to the 4-week retest. Despite of small practice the gains might remain (Benedict and Zgaljardic, 1998; Zgaljardic and Benedict, 2001; Sithinamsuwan et al., 2014), the scores usually did not meet statistical significance. Different factors may influence the degree of learning effects, including age and education (Dikmen et al., 1999; Sithinamsuwan et al., 2014) More controlled studies could investigate the impact of these variables on learning effects. Also, normative data for neuropsychological testing in Brazil is still increasing, and more data would provide information regarding changes due to practice effect among clinical samples and healthy individuals as it would be needed to interpret scores from longitudinal studies. Finally, none of the MCCB measures showed ceiling or floor effects. Thus, the Brazilian MCCB can be considered a feasible instrument for the assessment of cognitive change with treatment over time. 4.3. Limitations of the present study Inter-rater reliability was not explored in the present study. In clinical trials, a degree of consistency in their observations and scoring is desirable. However, only the BVMT-R involves any judgement on the part of scorers. Also, we did not evaluate the practicality ratings (of administrators) and tolerability ratings (of participants). 5. Conclusion Although the social cognition measure did not show the desired level of baseline and 4-week retest reliability (at least using the original
5
scoring system for English-speaking populations), in general the Brazilian version of the MCCB demonstrated several different types of reliability and validity (adequate baseline and 4-week retest reliability and internal consistency, convergent validity, sensitivity to discriminate performance between that of patients with schizophrenia and controls, and small practice effects). This study provides essential data for developing cognitive studies in Brazil and becoming part of an international investigational effort to find interventions that improve cognition in schizophrenia. Conflict of interest Rodrigo A. Bressan has received research grants from AstraZeneca, Janssen Cilag, Novartis, Roche and the governmental funding agencies: CAPES, CNPq and FAPESP; has been a forum consultant for Eli Lilly, Janssen, Novartis and Roche; and has participated in speaker bureaus for Ache, Janssen, Lundbeck and Novartis, in the last five years. Dr. Nuechterlein is a non-compensated officer of MATRICS Assessment, Inc., he has received unrelated research support from Janssen Scientific Affairs, Genentech, and Posit Science, Inc., and he has consulted to Genentech, Otsuka, Janssen, and Takeda. The other authors report no conflicts of interest to disclose. Contributors Bressan and Berberian conceived the study, Vicente assessed the patients, Fonseca and Berberian assessed the patients, wrote the paper, participated in the design of the study, participated in the analysis of the data and coordinated the team. Lacerda supervised the manuscript and participated in the design of study. Meneses-Gaya, Gadelha and Nuechterlein supervised and commented on the manuscript. All authors approved the final manuscript. Role of the funding source The study sponsor (FAPESP) had no role in study design, collection, analysis or interpretation of data. Acknowledgement We thank Mr. Richard Keefe, who assisted with the proof-reading of the manuscript.
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Please cite this article as: Fonseca, A.O., et al., The Brazilian standardization of the MATRICS consensus cognitive battery (MCCB): Psychometric study, Schizophr. Res. (2017), http://dx.doi.org/10.1016/j.schres.2017.01.006
Contents lists available at ScienceDirect
Schizophrenia Research journal homepage: www.elsevier.com/locate/schres
The Brazilian standardization of the MATRICS consensus cognitive battery (MCCB): Psychometric study Ana Olívia Fonseca a,⁎,1, Arthur A. Berberian a,b,1, Carolina de Meneses-Gaya a, Ary Gadelha a, Marcella de O. Vicente a, Keith H. Nuechterlein c,d, Rodrigo A. Bressan a, Acioly L.T. Lacerda a a
Universiedade Federal de Sao Paulo (Unifesp), Department of Psychiatry, Interdisciplinary Lab of Clinical Neurosciences (LiNC), and Schizophrenia Program (PROESQ), Brazil Centro Universitário FIEO, Strict Sensu Educational Psychology Program, 300 UCLA Medical Plaza, Room 2240, Los Angeles, CA 90095, USA UCLA, Department of Psychiatry and Biobehavioral Sciences , 300 UCLA Medical Plaza, Room 2240, Los Angeles, CA 90095, USA d UCLA, Department Psychology, 300 UCLA Medical Plaza, Room 2240, Los Angeles, CA 90095, USA b c
a r t i c l e
i n f o
Article history: Received 9 May 2016 Received in revised form 30 December 2016 Accepted 4 January 2017 Available online xxxx Keywords: Schizophrenia Neuropsychology Neurocognitive function Cognitive deficits MATRICS consensus cognitive battery
a b s t r a c t Objective: Translate, adapt, and validate the MATRICS Consensus Cognitive Battery (MCCB) in Brazil. Method: The present study followed three steps: 1) translation to Portuguese, cultural adaptation, and back translation to English; 2) completion of a pilot study (N = 30) conducted with the purpose of assessing whether the general comprehension of the items was clear and all participants adequately responded to the battery; 3) completion of a Reliability and Validation Study of the Brazilian version of the MCCB with 99 individuals with schizophrenia and 99 healthy subjects. All participants were administered the Structured Clinical Interview for DSM-IV (Diagnostic and Statistical Manual of Mental Disorders) and patients were also rated on the Global Assessment of Functioning (GAF) Scale and the Positive and Negative Symptoms Scale (PANSS). Results: The results showed adequate to high levels of baseline and 4-week retest reliability, except the MSCEITME; adequate internal consistency for the MSCEIT-ME for the total sample and patients group, and moderate Alpha for the health control sample; as well as evidence of convergent validity and sensitivity to differentiate performance between the groups. All the 10 MCCB measures showed the lowest learning effects. Conclusion: Overall the Brazilian version of the MCCB showed similar results to the original North American version. Our findings provides reassurance that the MCCB is a reliable and valid measure of cognition across different countries and cultures, which is especially important to the ongoing work in attempting to discover cognitionenhancing drugs and the effects of cognitive interventions for the treatment of schizophrenia. © 2017 Elsevier B.V. All rights reserved.
1. Introduction The cognitive deficits in schizophrenia, originally described by Kraepelin in 1896 (Kraepelin, 1971), and Bleuler in 1911 (Bleuler, 1950), are well documented in the literature (Bowie and Harvey, 2005; Tamminga, 2006) and are considered the core components of the disease (Elvevåg and Goldberg, 2000). These deficits, seen even in the premorbid base, i.e. before the first psychotic episode, are the factors that best predict functional outcome and prognosis of patients and can persist even when other symptoms are remitted or stabilized (Green and Harvey, 2014). In different studies, N80% of patients showed at least one cognitive domain significantly affected and directly impacting on the ability to acquire new skills and perform activities of daily life
⁎ Corresponding author at: Interdisciplinary Lab of Clinical Neurosciences (LiNC) Edifício de Pesquisas II, Rua Pedro de Toledo, 669, 3° andar, fundos, Vila Clementino, 04039-032 São Paulo, SP, Brazil. E-mail address: [email protected] (A.O. Fonseca). 1 Both authors contributed equally to this work.
such as maintaining personal hygiene, attending school or work, and having a social life (Green et al., 2000; Keefe et al., 2005; Kern et al., 2011). This evidence underscores the need for interventions focused on the cognitive aspects of the disease. However, one major gap in this frontier is the paucity of standardized cognitive measures for schizophrenia, which limits the generalization of the results that have been obtained so far (Nuechterlein et al., 2008). The Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery was developed to fill this gap (Marder and Fenton, 2004), based on the following criteria: 1) good baseline and 4-week retest reliability; 2) high utility as a repeated measure; 3) good relationship with functional outcome; 4) potential changeability in response to pharmacological agents; 5) tolerability by the patient and practicality for the administrator (Green et al., 2004; Nuechterlein et al., 2008). Based on the above criteria, 10 tests were selected for the MATRICS Consensus Cognitive Battery (MCCB) (Nuechterlein et al., 2008). Most of these tests already had a normative database from separate normative samples, but it needed to be normed together on the same sample in order to establish a metric that was
http://dx.doi.org/10.1016/j.schres.2017.01.006 0920-9964/© 2017 Elsevier B.V. All rights reserved.
Please cite this article as: Fonseca, A.O., et al., The Brazilian standardization of the MATRICS consensus cognitive battery (MCCB): Psychometric study, Schizophr. Res. (2017), http://dx.doi.org/10.1016/j.schres.2017.01.006
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equivalent across each test. Kern et al. (2008) obtained normative data for the United States population and, since then, standardization and translation validation studies have been conducted in several other countries, some of which have also obtained normative data, while others are still in progress (Mohn et al., 2012; Rodriguez-Jimenez et al., 2012; Jędrasik-Styła et al., 2015; Shi et al., 2015; see www. matricsinc.org). In order to investigate and stimulate further studies focusing on the cognitive research of schizophrenia in Brazil, this study involved a translation and adaptation of the MCCB and explored its psychometric properties in Brazil. More specifically, there were examined baseline and 4week retest reliability, internal consistency, evidence of validity based on relationships with other variables (convergent validity, cognitive performance differences between groups), and the learning effect of alternative forms of the MCCB, providing an accumulation of different sources of reliability and validity for the MCCB's use in the Brazilian context.
(SCID-I) (Del-Ben et al., 2001), with an average age of 33.13 (SD = 8.02) years and an average education level of 11.47 (SD = 3.27) years. They were matched with 15 healthy controls, chosen by convenience in database of healthy controls from the Federal University of São Paulo, based on age (M = 32.07; SD = 7.85), sex (60% male) and educational level (M = 10.87; SD = 3.87). Between-group comparisons for these variables were all nonsignificant [(age t = 0.37, p = 0.90), (education: t = 0.46, p = 0.73)]. The main purpose of this study phase was to assess the general comprehension of the questions. All participants were able to understand the instructions, respond to all items and answer this version of the MCCB, thus proving it has been comprehensible. Furthermore, data distribution of these two groups was verified using skewness, kurtosis and the Kolmogorov-Smirnov tests. Distribution of the measures was found normal.
2. Material and methods
Ninety-nine outpatients with schizophrenia and ninety-nine healthy controls were recruited from three different sites in Brazil (São Paulo, Porto Alegre and Goiania). To confirm the schizophrenia diagnosis, all participants were assessed with the Structured Clinical Interview for DSM-IV (SCID-I) performed by trained psychiatrists. The patients were on antipsychotics and their medication dosages had been stable for at least 4-week prior to the cognitive assessment. Healthy participants were matched to the patient group by sex, age, and academic level. Those one's were recruited from a larger database, referring to MCCB's co-normatization project for Brazil based on the Brazilian census. All of them were assessed with SCID-I in order to rule out a history of Axis I psychiatric disorders. Participants in both groups had at least four years of education, were at least 18 years old, spoken Portuguese as native language and were an IQ ≥ 80, based on their score on the shortform of the WAIS-III. All participants also fulfilled the two following inclusion criteria: 1 no evidence of organic brain disease or head injury with loss of consciousness and 2 - no evidence of substance abuse in the last year. At the first session, patients were evaluated by psychiatrists trained in the application of the SCID-I and PANSS (with Kappa intra-rater coefficient ranging from 0.80 to 1.0) to determine study eligibility. Cognitive assessment was performed by trained psychologists in one single session, lasting approximately 90 min, in an appropriate room. After 4week, forty five patients were randomly selected to be retested with the recommended Alternate Forms (http://www.matricsinc.org/? page_id=23). In the 4-week retest, we used Form 4 of the HVLT-R, Form 5 of the BVMT-R and Form 2 of the NAB Mazes. The correlation between the 10 MCCB measures and symptomatology are described in Table 1.
The study was developed in three stages, described below. Stage 1– Translation of the MCCB Two native Portuguese speakers worked independently from one another, this resulted in two different versions, which were later compared to produce a Brazilian-Portuguese consensus version of the MCCB. This version was then back translated, sent to the authors of each test in the MCCB, and approved. This allowed the Brazilian-Portuguese language version being used for academic research purposes. The academic version was converted into a tool to be published and then available for clinical trials and other professional purposes in clinical settings in Brazil, reconciliation by a professional translation company. Finally, the translated and revised version of the MCCB was edited and printed. Of the 10 MCCB tests, three have alternative forms: BVMT-R, HVLT-R and NAB Mazes, which were also translated. The 10 MCCB tests were administered in the same order as in Kern et al. (2008): 1. Trail Making Test: Part A (TMT-A) 2. Brief Assessment of Cognition in Schizophrenia (BACS): Symbol Coding 3. Hopkins Verbal Learning Test—Revised (HVLT-R) 4. Wechsler Memory Scale—Third Edition (WMS-III): Spatial Span 5. Letter-Number Span Test (LNS) 6. Neuropsychological Assessment Battery (NAB): Mazes 7. Brief Visuospatial Memory Test—Revised (BVMT-R) 8. Category Fluency Test: Animal Naming (Fluency) 9. Mayer–Salovey–Caruso Emotional Intelligence Test (MSCEIT-ME): Managing Emotions 10. Continuous Performance Test—Identical Pairs (CPT-IP) 2.1. Current intellectual functioning A short-form WAIS-III (Wechsler, 1997) was used to estimate current intellectual functioning. It combined the vocabulary and matrix reasoning subtests for this purpose. Stage 2– Pilot Study The Ethics Committee of the Federal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil, approved this study protocol and all individuals provided written informed consent before enrollment in the study. The translated and revised version of the MCCB was applied to fifteen subjects with DSM-IV schizophrenia (60% male) as assessed with the Brazilian version of the Semi-Structured Interview for the Diagnostic and Statistical Manual of Mental Disorders, IV edition
Stage 3– Study of psychometric properties
Table 1 Pearson Correlation Coefficients between the 10 MCCB Measures and Symptoms Scales.
TMT Symbol Coding HVLT Spatial Span LNS MAZES BVMT Fluency CPT MSCEIT a b
PANSS Positive
PANSS Negative
PANSS General
PANSS Total
GAF
0.06 0.21
0.19 –0.03
0.18 –0.01
0.16 –0.01
0.10 –0.12
–0.10 –0.15 –0.15 –0.14 –0.02 0.06 –0.09 –0.24b
–0.21 –0.34b –0.33a –0.32b 0.24b –0.06 –0.23b –0.20
–0.16 –0.24b –0.22b –0.21 –0.07 –0.01 –0.17 –0.20
–0.15 –0.26b –0.25b –0.24b –0.11 –0.01 –0.17 –0.22
–0.00 0.04 0.13 –0.09 0,15 0.22b 0.04 0.14
Correlation is significant at the 0.01 level (2-tailed). Correlation is significant at the 0.05 level (2-tailed).
Please cite this article as: Fonseca, A.O., et al., The Brazilian standardization of the MATRICS consensus cognitive battery (MCCB): Psychometric study, Schizophr. Res. (2017), http://dx.doi.org/10.1016/j.schres.2017.01.006
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2.2. Data analysis
3
Table 3 MCCB baseline-4 week retest reliability (Schizophrenia patients N = 45).
All statistical procedures were carried out using the Statistical Package for Social Sciences (SPSS), version 20.0. Data distribution was verified using skewness, kurtosis and the Kolmogorov-Smirnov tests. Logarithmic transformations were performed for measures that did not achieve normality in distribution with TMT-A, BVMT-R, Verbal Fluency and CPT-IP. For reliability, a coefficient of stability (Pearson's r) was calculated, using initial and delayed test scores. Cronbach's Alpha was also used to evaluate internal consistency of the MSCEIT-ME test, which could have a cultural influence. Pearson's correlations were used for convergent validity. Thus, for processing speed, for instance, TMT-A, Symbol Coding and Verbal Fluency were used to assess convergent validity. The Student's t-test was used for comparing the average performance between groups (cognitive performance differences between groups). Finally, to ensure that the MCCB in Brazil has high utility as a repeated measure for clinical trials, the paired Student's t-test was used, comparing performances in first and second assessments to assure limited practice effects.
MCCB tests
Pearson's r
TMT-A BACS SC HVLT-R WMS-III SS LNS NAB Mazes BVMT-R Fluency MSCEIT - R CPT – IP
0.85 0.84 0.63 0.79 0.65 0.83 0.79 0.73 0.55 0.88
TMT-A - Trail Making Test Part A; BACS SC - Brief Assessment of Cognition in Schizophrenia Symbol Coding; HVLT-R - Hopkins Verbal Learning Test - Revised; WMS-III SS - Wechsler Memory Scale–Third Edition Spatial Span; LNS - Letter-Number Span Test; NAB; Mazes - Neuropsychological Assessment Battery Mazes; BVMT-R - Brief Visuospatial Memory Test Revised; Fluency - Category Fluency Test Animal Naming; MSCEIT-ME: Mayer-Salovey-Caruso Emotional >Intelligence Test Managing Emotions; CPT-IP - Continuous Performance Test, Identical Pairs Version.
3. Results The demographic data for both groups are shown in Table 2 along with clinical information. Groups were matched for age, years of education, and gender. As expected, significant between-group differences were noted in current IQ scores, as IQ is a measure of global cognitive functioning.
3.1. Reliability 3.1.1. Analysis I: baseline and 4-week retest reliability Forty-five patients with schizophrenia were retested thirty days later by the same examiner. All Pearson's correlations were in the .70s and .80s except for the LNS and HVLT-R, which were in the .60s, and MSCEIT-ME, which was 0.55 These results are summarized in Table 3.
3.1.2. Analysis II: internal consistency Considering the total sample, MSCEIT-ME showed a Cronbach's alpha of 0.71. When analyzed separately, by group, the alpha was 0.72 for patients and 0.63 for the control group.
3.2. Analysis III: convergent validity Support for convergent validity was found in significant correlations among all measures that assessed the same construct for the total sample (Table 4). For processing speed, we observed a significant negative correlation of a strong magnitude between Symbol Coding (SC) score and the TMT-A completion time and a positive moderate correlation between SC and Animal Verbal Fluency. The correlation between the TMTA and verbal Fluency was significant but weaker. When Pearson's correlations was calculated separately for the groups, the TMT-A showed a strong negative correlation with SC and a significant but weak correlation with verbal Fluency for the patient group. For controls, we found a strong negative correlation between TMT-A and SC and a moderate correlation between TMT-A and verbal Fluency. SC showed a significant but weak correlation with Fluency for patients and a moderate correlation for controls. For working memory, we found strong positive correlations between WMS-III Spatial Span (SS) and the Letter-Number Test (LNS) for the total sample. WMS-III SS also showed a strong correlation with LNS for patients and for controls separately.
Table 2 Demographic data of the participants and summary of the cognitive performance differences between groups. Domain
Age Education (years) Current IQ PANSS
GAF Male (%) Trail making test, part A Symbol coding HVLT-R Spatial span Number letter span Mazes BVMT-R Fluency MSCEIT-ME CPT-IP
Variable
Positive Symptoms Negative Symptoms Total score
Schizophrenia group (N = 99)
Control Group (N = 99)
Mean (SD) (raw scores)
Mean (SD) (raw scores)
F
t
df
p
Cohen's d
37.57 (10.26) 10.74 (3.66) 91.03 (12.05) 13.16 (4.71) 17.58 (6.92) 60.12 (15.88) 49.86 (13.17) 52.5 54.19 (36.58) 33.25 (13.04) 19.88 (5.01) 11.86 (4.12) 10.03 (4.02) 12.03 (7.43) 13.02 (8.28) 15.47 (5.68) 95.29 (12.21) 1.60 (0.77)
37.55 (10.59) 11.12 (3.62) 101.28 (14.58)
0.182 0.009
–0.014 –0.523
196 196
0.989 0.601
0.00 0.07
16.58 1.038 2.264 0.001 0.579 2.393 0.022 0.119 0.684 1.442
3.942 –6.961 –8.144 –5.332 –4.888 –4.238 –6.938 –6.262 –4.475 –5.712
196 196 196 196 196 196 196 196 196 196
b0.001 b0.001 b0.001 b0.001 b0.001 b0.001 b0.001 b0.001 b0.001 b0.001
0.56 0.99 1.15 0.75 0.69 0.60 0.98 0.89 0.64 0.81
52.5 38.55 (14.86) 46.86 (14.42) 25.30 (4.33) 15.11 (4.45) 12.97 (4.43) 16.27 (6.62) 21.15 (8.21) 20.44 (5.48) 103.11 (12.37) 2.24 (0.80)
Please cite this article as: Fonseca, A.O., et al., The Brazilian standardization of the MATRICS consensus cognitive battery (MCCB): Psychometric study, Schizophr. Res. (2017), http://dx.doi.org/10.1016/j.schres.2017.01.006
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Table 4 Pearson Correlation Coefficients for the 10 MCCB Measures (N = 99).
TMT Symbol coding HVLT_R Spatial span Number letter span Mazes BVMT_R Fluency CPT_IP MSCEIT-ME
TMT
Symbol Coding
HVLT_R
Spatial Span
Number Letter Span
Mazes
BVMT_R
Fluency
CPT_IP
MSCEIT_ME
– –0.682a –0.440a –0.504a –0.629a –0.588a –0.536a –0.514a –0.588a –0.179
–0.610a – 0.539a 0.598a 0.705a 0.577a 0.627a 0.586a 0.676a 0.279a
–0.393a 0.356a – 0.471a 0.555a 0.442a 0.545a 0.499a 0.512a 0.297a
–0.508a 0.541a 0.466a – 0.651a 0.656a 0.651a 0.471a 0.615a 0.326a
–0.536a 0.608a 0.521a 0.634a – 0.659a 0.550a 0.617a 0.752a 0.401a
–0.558a 0.500a 0.302a 0.554a 0.472a – 0.612a 0.528a 0.576a 0.240b
–0.406a 0.616a 0.502a 0.635a 0.566a 0.449a – 0.416a 0.519a 0.258a
–0.257b 0.343a 0.377a 0.367a 0.437a 0.372a 0.300a – 0.596a 0.270a
–0.574a 0.575a 0.394a 0.577a 0.646a 0.472a 0.399a 0.265a – 0.319a
–0.226b 0.417a 0.288a 0.309a 0.382a 0.277a 0.362a 0.338a 0.355a –
Correlations in patients above the diagonal and correlations in controls below the diagonal. a Correlation is significant at the 0.01 level (2-tailed). b Correlation is significant at the 0.05 level (2-tailed).
3.3. Analysis IV: cognitive performance differences between groups
4.1. Reliability studies
Diagnosis of schizophrenia was used as an external criterion, comparing the average performance between groups. All 10 MCCB measures were sensitive to discriminate performance between that of patients and controls (Table 2). The TMT-A presented the lowest effect size and the HVLT-R presented the highest.
The MSCEIT-ME test showed adequate internal consistency, based on Cronbach's Alpha, suggesting homogeneity in their items. With this, interpretations regarding results are relatively free of biases determined by particularities of specific items. When considering only the sample of the healthy controls, the MSCEIT-ME items showed a moderate alpha. The MSCEIT-ME test had the lowest baseline and 4-week retest correlation, even though it showed moderate coefficients. Different studies, including MCCB translation studies in other countries, have reported that social cognition is a factor partially separable from the other six cognitive domains, depending more on the interpretation of emotions and perceptions of others and therefore being more affected by cultural influences (Adolphs, 2010; Mason and Morris, 2010). The fact that the scores for this test were obtained through a scoring system developed for South American population (International MSCEIT™ scoring system by Multi-Health Systems, Inc.) may explain at least part of this finding (Rodriguez-Jimenez et al., 2012). South America covers a wide range of countries, with different mores, which Brazil is the only one that uses the Portuguese language.
3.4. Analysis V: utility as a repeated measure The initial assessment was compared with 4-week retest scores. These results are summarized in Table 5. No significant changes in test scores across two occasions were observed for 9 out of 10 tests, the exception being BVMT-R. The BVMT-R scores showed significant improvement but with a small effect size (0.30). There were no detectable floor or ceiling effects.
4. Discussion The current results provide solid data regarding the psychometric properties of the Brazilian version of the MCCB. Two main aspects can be emphasized. First, the steps taken to achieve an appropriate translation were strictly observed, including the translation of the original tests to the Portuguese language and the analysis of their back translation. A pilot study was conducted in which it was possible to note that all participants, both patients and healthy controls, understood the instructions and performed the tasks as requested. Second, this study demonstrates several aspects of reliability and validity for the MCCB in Brazil, that is, baseline and 4-week retest reliability, internal consistency, convergent validity and cognitive performance differences between groups. Data on practice effects are also provided.
4.2. Validity studies 4.2.1. Convergent validity To verify whether the results presented here were compatible with the MCCB theoretical framework, convergent validity analyses were performed, showing convergence among the tests that assessed the same construct, especially when assessing the potential for learning and working memory abilities. For processing speed tests (Trail Making Test, BACS Symbol Coding and Animal Fluency), adequate correlations were also found, except for the Trail Making Test and Animal Fluency, which showed low correlations. Our findings are in line with Knowles
Table 5 MCCB Utility as a Repeated Measure: Performance Levels at Baseline and 4-week Retest. Schizophrenic patients (n = 45)
Trail making test, part A Symbol coding HVLT-R Spatial span Number letter span Mazes BVMT-R Fluency MSCEIT-ME CPT-IP
Mean (SD) baseline
Mean (SD) 4-week retest
t
df
p
Cohen's d
Floor/ceiling effect (n out of 61 in T1/T2)
61.71 (45.08) 34.18 (14.75) 20.31 (5.56) 5.02 (2.61) 10.20 (4.03) 9.96 (6.99) 12.60 (8.24) 15.80 (6.17) 96.20 (11.70) 1.62 (0.83)
57.58 (44.96) 35.47 (14.23) 19.13 (5.32) 5.31 (2.65) 10.36 (3.79) 10.73 (7.51) 15.16 (8.62) 16.24 (4.63) 96.60 (12.17) 1.66 (0.98)
1.70 –1.04 1.70 –1.13 –0.32 –1.22 –3.09 –0.71 –0.24 –0.63
44 44 44 44 44 44 44 44 44 44
0.114 0.305 0.098 0.315 0.752 0.230 0.003 0.483 0.815 0.532
0.09 0.09 0.21 0.11 0.04 0.10 0.30 0.08 0.03 0.04
0/0 0/0 0/0 0/0 0/0 0/0 0/0 0/0 0/0 0/0
t = (t-value); dF = degrees of freedom; p = statistical significance (p-value).
Please cite this article as: Fonseca, A.O., et al., The Brazilian standardization of the MATRICS consensus cognitive battery (MCCB): Psychometric study, Schizophr. Res. (2017), http://dx.doi.org/10.1016/j.schres.2017.01.006
A.O. Fonseca et al. / Schizophrenia Research xxx (2017) xxx–xxx
et al. (2012), who reported weak correlations among the tests assessing processing speed, with the lower correlations between the Trail Making Test and the Animal Fluency Test. Those results suggest that, as a multidimensional ability, processing speed consists of at least two or three subcomponents. One possible explanation for this result, is that verbal Fluency is a cognitive function that allows retrieval of information from memory. Despite of the Fluency task version used by the MCCB provides to the participants specific guidelines on how to conduct the search and/or word production within the semantic network, in order to facilitate search and retrieval of words, some authors have suggested a change over the activation flow through the semantic network in schizophrenia (Bokat and Goldberg, 2003; Bozikas et al., 2005; Berberian et al., 2016), which might affect the patient's performance in a distinct way. 4.2.2. Cognitive performance differences between groups Based on the comparison of results of patients and healthy controls, the Brazilian MCCB was sensitive to discriminate performance between that of patients and controls, as there was a consistent performance difference for all MCCB tests. Patients obtained lower scores than healthy controls. These findings corroborate several important studies in the area that showed that schizophrenia patients have lower results than those reported by healthy controls in the MCCB. (Kern et al., 2008; Keefe et al., 2011; August et al., 2012; McCleery et al., 2014). 4.2.3. Utility as repeated measures Because an individual is assessed several times in studies examining cognitive change, measures with small practice effects are useful. All the MCCBs had low levels of practice effects with no statistical significance except the BVMT-R (0.30), which had a small practice effect. Similar results have also been reported in the BVMT-R test, with minimum practice effects (Keefe et al., 2011). Other studies have also shown a significant practice effect in both verbal and visual tests when the same versions are applied. However, for verbal tests, this effect becomes statistically insignificant when different versions of the word list are presented. For the BVMT-R results differ from those described in the North American trial (Nuechterlein et al., 2008; Cohen's d = 0.02). In order to avoid practice effects, there were used alternate forms of the BVMT-R, but the scores increased from baseline to the 4-week retest. Despite of small practice the gains might remain (Benedict and Zgaljardic, 1998; Zgaljardic and Benedict, 2001; Sithinamsuwan et al., 2014), the scores usually did not meet statistical significance. Different factors may influence the degree of learning effects, including age and education (Dikmen et al., 1999; Sithinamsuwan et al., 2014) More controlled studies could investigate the impact of these variables on learning effects. Also, normative data for neuropsychological testing in Brazil is still increasing, and more data would provide information regarding changes due to practice effect among clinical samples and healthy individuals as it would be needed to interpret scores from longitudinal studies. Finally, none of the MCCB measures showed ceiling or floor effects. Thus, the Brazilian MCCB can be considered a feasible instrument for the assessment of cognitive change with treatment over time. 4.3. Limitations of the present study Inter-rater reliability was not explored in the present study. In clinical trials, a degree of consistency in their observations and scoring is desirable. However, only the BVMT-R involves any judgement on the part of scorers. Also, we did not evaluate the practicality ratings (of administrators) and tolerability ratings (of participants). 5. Conclusion Although the social cognition measure did not show the desired level of baseline and 4-week retest reliability (at least using the original
5
scoring system for English-speaking populations), in general the Brazilian version of the MCCB demonstrated several different types of reliability and validity (adequate baseline and 4-week retest reliability and internal consistency, convergent validity, sensitivity to discriminate performance between that of patients with schizophrenia and controls, and small practice effects). This study provides essential data for developing cognitive studies in Brazil and becoming part of an international investigational effort to find interventions that improve cognition in schizophrenia. Conflict of interest Rodrigo A. Bressan has received research grants from AstraZeneca, Janssen Cilag, Novartis, Roche and the governmental funding agencies: CAPES, CNPq and FAPESP; has been a forum consultant for Eli Lilly, Janssen, Novartis and Roche; and has participated in speaker bureaus for Ache, Janssen, Lundbeck and Novartis, in the last five years. Dr. Nuechterlein is a non-compensated officer of MATRICS Assessment, Inc., he has received unrelated research support from Janssen Scientific Affairs, Genentech, and Posit Science, Inc., and he has consulted to Genentech, Otsuka, Janssen, and Takeda. The other authors report no conflicts of interest to disclose. Contributors Bressan and Berberian conceived the study, Vicente assessed the patients, Fonseca and Berberian assessed the patients, wrote the paper, participated in the design of the study, participated in the analysis of the data and coordinated the team. Lacerda supervised the manuscript and participated in the design of study. Meneses-Gaya, Gadelha and Nuechterlein supervised and commented on the manuscript. All authors approved the final manuscript. Role of the funding source The study sponsor (FAPESP) had no role in study design, collection, analysis or interpretation of data. Acknowledgement We thank Mr. Richard Keefe, who assisted with the proof-reading of the manuscript.
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Please cite this article as: Fonseca, A.O., et al., The Brazilian standardization of the MATRICS consensus cognitive battery (MCCB): Psychometric study, Schizophr. Res. (2017), http://dx.doi.org/10.1016/j.schres.2017.01.006