Annotated Bibliography, Introduction, and Summary Paragraph: Seeking the Truth
Is Longer Treatment Better? A Comparison Study of 3 Versus 6 Months Cognitive Remediation in Schizophrenia Mariachiara Buonocore IRCCS San Raffaele Scientific Institute Marta Bosia Universita `Vita-Salute San Raffaele and IRCCS San Raffaele Scientific Institute Margherita Bechi IRCCS San Raffaele Scientific Institute Marco Spangaro Universita `Vita-Salute San Raffaele and IRCCS San Raffaele Scientific Institute Silvia Cavedoni Universita `Vita-Salute San Raffaele Federica Cocchi, Carmelo Guglielmino, Laura Bianchi, and Antonella Rita Mastromatteo IRCCS San Raffaele Scientific Institute Roberto Cavallaro IRCCS San Raffaele Scientific Institute and Universita ` Vita-Salute San Raffaele Objective:Despite its extensive use for treating cognitive deficits in schizophrenia, computer-assisted cognitive remediation (CACR) currently lacks a standardized protocol. Duration is an important feature to be defined, as it may contribute to heterogeneous outcome. This study compares 2 treatment durations, 3 versus 6 months, to analyze their effects on both cognition and daily functioning.Method:Fifty-seven outpatients with schizophrenia received 3 months of CACR and 41 received 6 months of CACR. All patients were assessed at baseline and after 3 and 6 months with the Brief Assessment for Cognition in Schizophrenia and with the Quality of Life Scale (QLS).Results:Repeated measures ANOVA showed significant improvements in all cognitive domains after 3 months. A significant effect of treatment duration was observed only for executive functions, with significantly higher scores among patients treated for 6 months. Significant improvements in QLS were also observed after 6 months in both groups, with a significant time by treatment interaction for QLS Total Score.Conclusions:Results confirm the efficacy of 3-months CACR in terms of both cognitive and functional improvements, suggesting that an extended intervention may lead to further benefits in executive functions and daily functioning.
General Scientific Summary Computer Assisted Cognitive Remediation (CACR) improves cognition in patients with schizophre- nia. It is not clear how long the treatment should be to see significant effects on functioning. Our study compares 2 treatments duration: 3- versus 6-months CACR. Results shows that 3-months CACR seems to be adequate to improve cognitive deficits in patients with schizophrenia, despite executive functions and quality of life might need a longer treatment to improve.
Keywords:daily functioning, executive functioning, psychosis, quality of life, rehabilitation Neurocognitive impairment represents a core feature of schizophrenia and appears to be strongly correlated with global functional outcome (Bowie et al., 2006). Current treatments ofcognitive dysfunction involve both pharmacological and non- pharmacological interventions. Among the latter, research has increasingly studied the effects of computer-assisted cognitive This article was published Online First February 2, 2017.
Mariachiara Buonocore, Department of Clinical Neurosciences, IRCCS San Raffaele Scientific Institute; Marta Bosia, Universita `Vita-Salute San Raffaele and School of Medicine, IRCCS San Raffaele Scientific Institute; Margherita Bechi, Department of Clinical Neurosciences, IRCCS San Raffaele Scientific Institute; Marco Spangaro, Universita `Vita-Salute San Raffaele and School of Medicine, IRCCS San Raffaele Scientific Institute; Silvia Cavedoni, School of Psychology, Universita `Vita-Salute San Raffaele; Federica Cocchi, CarmeloGuglielmino, Laura Bianchi, and Antonella Rita Mastromatteo, Department of Clinical Neurosciences, IRCCS San Raffaele Scientific Institute; Roberto Cavallaro, Department of Clinical Neurosciences, IRCCS San Raffaele Sci- entific Institute, and Department of School of Medicine, Universita `Vita-Salute San Raffaele.
Correspondence concerning this article should be addressed to Marta Bosia, Department of Clinical Neurosciences, IRCCS San Raffaele Scientific Institute, Via Stamira d’Ancona 20, Milan, Italy. E-mail:[email protected] This document is copyrighted by the American Psychological Association or one of its allied publishers.
This article is intended solely for the personal use of the individual user and is not to be disseminated broadly. Neuropsychology© 2017 American Psychological Association 2017, Vol. 31, No. 4, 467– 4730894-4105/17/$12.00http://dx.doi.org/10.1037/neu0000347 467 remediation (CACR), a rehabilitation treatment consisting of computer based cognitive exercises, plus individual or group instructions to improve cognitive deficits, with the goal of durability and generalization to everyday life abilities (Mueller et al., 2015). Several studies showed the effectiveness of this intervention (Cavallaro et al., 2009;Gomar et al., 2015; McGurk et al., 2007;Wykes et al., 2002), although some negative results have also been reported (Dickinson et al., 2010; Gomar et al., 2015). Despite the amount of literature, research methods involving CACR do not follow a standardized proto- col, leading to high heterogeneity and thus difficulties in draw- ing conclusions. Differences between studies might lie in both methodological aspects, such as the use of restorative or com- pensatory strategies, drill-and-practice rather than drill-and- strategy exercises, specific learning strategies, such as fixed versus individually tailored exercises, as well as in patients clinical status (Barlati et al., 2013;Penades et al., 2006; Rauchensteiner et al., 2011;Sartory et al., 2005). Moreover, frequency and duration of treatment are important features that needs to be taken into account, as there is still high heteroge- neity: from 10 –12 sessions delivered over four weeks (Rauchensteiner et al., 2011), to 100 hours, three sessions per week (Kurtz et al., 2009) until up to more than 120 hours over two years (Eack et al., 2013). Although these aspects have been pointed out since early studies, they are still poorly addressed.
To our knowledge, only one study has explicitly questioned how intense CACR should be to be effective (Choi & Medalia, 2005), showing an association between higher treatment inten- sity and greater cognitive improvement, specifically on sus- tained attention. Duration of treatment, in terms of number of weeks, has been analyzed as possible predictor of cognitive improvement in a few meta-analyses (Radhakrishnan et al., 2016;Wykes et al., 2002), with negative results. However, a head-to-head comparison of interventions with different dura- tion is lacking. Moreover, questions about CACR administra- tion are important in light of the relationship between global function and cognitive improvement after CACR. It is not yet clear how extensive the cognitive improvement has to be to support an overall functional enhancement. A stable improve- ment of functional outcome may require a lasting effect of cognitive improvements. We could hypothesize that a longer training may be better to the “restoration”, especially of more complex cognitive functions, such as executive functions. In addition, if the long-term goal is to improve daily functioning, then it could be useful to consider whether the patient’s quality of life may benefit from a longer training and whether there is a relationship between the cognitive improvement and the func- tional outcome. Despite these considerations, CACR duration has so far rarely been in the limelight and there are still open questions: how long should the training last in order to be effective? How long has to be to show an impact on daily functioning?
Our aim is to evaluate whether a longer training may lead to greater improvement in both cognition and daily functioning. To pursue this goal, we compared two CACR protocols with different duration: 36 sessions of computer aided training that lasted three months versus 72 sessions that lasted six months. Method Participants One hundred twenty-nine Caucasian outpatients diagnosed with schizophrenia according to theDiagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision (DSM–IV–TR; American Psychiatric Association, 2000) were recruited at the Psychiatric Rehabilitation Unit of IRCCS San Raffaele Hospital, Milan, Italy. After a complete description of the study, informed consent to participation was obtained. The protocol followed the principles of the Declaration of Helsinki and was approved by the local Ethical Committee.
To be included, patients had to satisfyDSM–IV–TRdiagnostic criteria for schizophrenia and the following conditions: (a) Treat- ment with a stable dose of the same antipsychotic therapy for at least three months, with a good response (30% or more reduction of Positive and Negative Syndrome Scale-PANSS Total score); (b) No evidence of substance dependence or abuse, comorbid diagno- ses on Axis I or II, epilepsy, or any other major neurological illness or perinatal trauma, or mental retardation; and (c) All patients remained on the same antipsychotic medication throughout the course of the study. Patients needing drug or dose changes during the study were excluded.
Study Design In this study, we compared data from two different protocols performed at different time points through a sequential approach.
The first was a randomized single blind trial to analyze the effect of 3-months CACR, as compared to placebo, proving the effec- tiveness of the 3-months intervention (Cavallaro et al., 2009).
Following these results, we designed an open label trial to evalu- ated the effectiveness of 6-months CACR, recruiting a sample of patients matched for age and education. Within the time-frame of this second study, all eligible patients meeting inclusion criteria were assigned to the 6-months CACR protocol.
In particular, all patients followed, for at least six months, a Standard Rehabilitation Treatment (SRT). Then, added to SRT was one of the following protocols: (a) 3-months CACR: 36 computerized sessions that lasted for 3 months. After CACR, this group continued standard rehabilitation (SRT) for 3 months; and (b) 6-months CACR: 72 computerized sessions that lasted for 6 months. CACR sessions had a frequency of three times a week, each one lasted about 45 min.
All patients were assessed at baseline (T0), before starting CACR, within one week after the end of 36 CACR sessions (T1), and within one week after the end of further 36 CACR sessions or three months of SRT alone (T2). All interventions were conducted by trained psychologists.
Assessments Patients were assessed for psychopathology, cognitive perfor- mance and daily functioning before and after CACR. At baseline, IQ was also evaluated and basic information, such as age, sex, education, duration of illness and medication, were collected.
Psychopathological assessment.Psychopathology was as- sessed by means of the Positive and Negative Syndrome Scale This document is copyrighted by the American Psychological Association or one of its allied publishers.
This article is intended solely for the personal use of the individual user and is not to be disseminated broadly. 468 BUONOCORE ET AL. (PANSS;Kay et al., 1987), administered by psychiatrists trained on PANSS rating and calibration.
Neuropsychological assessment.Cognitive performance was assessed with the Brief Assessment of Cognition in Schizophrenia (BACS), a broad neuropsychological battery evaluating core cog- nitive domains that are typically impaired in schizophrenia (Keefe et al., 2004). It consists of the following tests: verbal memory (words recall), working memory (digit sequencing), token motor task (psychomotor speed and coordination), speed of processing (symbol coding), verbal fluency (semantic and letter production), and planning (Tower of London). Analyses were performed ont scores for each BACS subtest and on meantscore, as a measure of global cognition. BACStscores were calculated from Italian normative data (Anselmetti et al., 2008).
Intellectual functioning was assessed by means of the Wechsler Adult Intelligence Scale—Revised (WAIS–R), Italian version (Wechsler, 1998).
The scales were administered by trained psychologists.
Daily functioning outcome assessment.Daily functioning was assessed with the Quality of Life Scale (QLS;Heinrichs et al., 1984), a semistructured interview of 21 items evaluating three different areas of social functioning: (a) interpersonal relationships (items 1– 8), assessing the ability of the patient to establish and maintain social relationships; (b) instrumental role (items 9 –12), evaluating the ability to obtain and maintain a job, to study and to collaborate in everyday housework; and (c) self-directedness (items 13–21), assessing planning abilities, personal autonomy, affective and cognitive functioning, and motivation level.
Information on daily functioning was obtained by the patient and reviewed with an informant (typically the patient’s mother or another first-degree relative). The scale was administered by trained rehabilitation therapists.
Treatments Standard rehabilitation program (SRT).The rehabilitation program focused on the main community goals of social abilities, work, and autonomy. The SRT included noncognitive subpro- grams of IPT (Verbal Communication, Social Skill Training and Problem Solving;Brenner et al., 1994), social skills training pro- grams for residential, vocational, and recreational functioning (Roder et al., 2002), and psychoeducation (Bechdolf et al., 2004; Rund et al., 1994).
Computer-aided training.The computer-aided training em- ployed the Cogpack Software (Marker, 1987-2007). This program includes domain-specific neurocognitive exercises, aimed at train- ing specific cognitive areas known to be impaired in schizophre- nia: verbal memory, verbal fluency, psychomotor speed and coor- dination, executive function, working memory, and attention (for more details seeCavallaro et al., 2009).
Analysis Following verification of normal distribution of the assessed variables through Kolmogorov–Smirnov test, analysis of variance (ANOVA) and chi square test (for dichotomic variables) were performed on demographic, clinical, daily functioning, neuropsy- chological, and IQ variables to evaluate differences between groups.The effect of CACR treatment on neuropsychological perfor- mance and daily functioning was evaluated by means of repeated measures ANOVAs.
Pre-to-post treatment changes in cognition, assessed by BACS, were analyzed with repeated measures ANOVA (3 3,p .05, two-tailed) entering BACS subtests and totaltscores as dependent variables, time as fixed factor (with the three levels T0, T1 and T2), and treatment group as independent variable. Fisher LSD post hoc test followed.
Pre-to-post treatment changes in daily functioning, assessed by QLS, were analyzed with repeated measures ANOVA (3 3,p .05, two-tailed) entering QLS subscales and total scores as depen- dent variables, time as fixed factor and treatment group as inde- pendent variable. Fisher LSD post hoc test followed.
Bartlett test was also performed on significant results, to verify homogeneity of variance.
Pre-to-post treatment changes in both cognition and daily func- tioning were also assessed in term of Cohen’sdeffect-sizes for each treatment group.
The STATISTICA Software for Windows, version 8 (StatSoft Inc., Tulsa, OK) was used to perform the statistical analyses. Results A group of 57 patients received 3-months CACR, whereas a group of 41 patients received 6-months CACR intervention. Fif- teen patients (seven in the first group and five in the second one) dropped out. Reasons for dropping out were worsening of symp- toms or change of residence. The dropouts were excluded from analyses. All patients were on antipsychotic monotherapy and treatment was distributed as follow: 29% Risperidone, 13% Hal- operidol, 32% Clozapine, 11% Olanzapine, 7% Aripiprazole, 7% Paliperidone, 1% Fluphenazine. The mean dose, derived from chlorpromazine equivalents (CPZ-eq) using the conversion pro- posed by Davis (Davis & Chen, 2004), was 265.67 182.Table 1shows demographic and clinical characteristics of the sample at baseline. There were no statistically significant differences be- tween groups at baseline observation for any of the variables studied, except for Psychomotor coordination (F 4.63,p .033), with higher scores in patients treated with 3-months CACR.
Posttest Evaluations Treatment effects on cognition.Analyses showed a signifi- cant time effect for all the functions evaluated, as well as a significant time by treatment group interaction only for executive functions in particular planning abilities, evaluated by means of the Tower of London (F 2.65;df 2;p .03, seeTable 2for details).
Specifically, within the 3-months treatment group, post hoc analysis showed a significant improvement from T0 to T1 in the following cognitive functions: verbal memory (p .0001), work- ing memory (p .04), verbal fluency (p .001), processing speed (p .0001), and planning (p .05). Further significant improve- ments in cognitive functions were not observed from T1 to T2.
For the 6-months treatment group, post hoc analysis also showed a significant improvement at three months (T0 –T1) for the following functions: verbal memory (p .0001), working memory (p .0001), verbal fluency (p .04), processing speed (p .03), and planning (p .0001). This document is copyrighted by the American Psychological Association or one of its allied publishers.
This article is intended solely for the personal use of the individual user and is not to be disseminated broadly. 469 DURATION OF COGNITIVE REMEDIATION IN SCHIZOPHRENIA Further significant improvements in cognitive functions were not observed from T1 to T2.
Finally, post hoc analysis showed a significant difference be- tween treatment groups in executive performance at T2, with higher scores among patients treated for 6-months CACR com- pared to the group treated with 3-months CACR (p .03).
Treatment effects on daily functioning.Analysis showed a significant time effect for all the functions evaluated, as well as a significant time by treatment group interaction for QLS Total Score (F 6.89;df 2;p .0001; seeTable 2for details).
Within the 3-months treatment group, post hoc analysis did not show a significant improvement at three months (from T0 to T1) for any QLS subscale, whereas significant improvements at six months (from T0 to T2) were observed for QLS Relationships (p .002); QLS Work (p .04); QLS Self directedness (p .0001); QLS Total score (p .0001).
Within the six months treatment group as well, post hoc analysis did not show any significant improvement at three months, while significant improvements at six months were observed QLS Re- lationships (p .0001), QLS Work (p .0001), QLS Self direct- edness (p .0001), and QLS Total score (p .0001).
Post hoc analysis showed no significant differences between treatment groups.
Effect Sizes of Improvement Within the 3-months treatment group the following effect-sizes of improvement were observed: Verbal memory (0.48), Working memory (0.14), Psychomotor coordination (0.33), Verbal fluency (0.30), Processing speed (0.31), Planning (0.22), BACS Composite Score (0.42), QLS relationships (0.23), QLS work (0.20), QLS self-directedness (0.25) and QLS Total Score (0.30).
Within the 6-months treatment group the following effect-sizes of improvement were observed: Verbal memory (0.57), Working memory (0.28), Psychomotor coordination (0.16), Verbal fluency (0.27), Processing speed (0.23), Planning (0.61), BACS CompositeScore (0.54), QLS relationships (0.45), QLS work (0.52), QLS self-directedness (0.58), and QLS Total Score (0.71). Discussion CACR has been extensively employed as a rehabilitation treat- ment and vast amount of research has been conducted since its first applications (Cella et al., 2015). However, to date CACR admin- istration does not follow a standardized protocol, which, in addi- tion to treatment’s heterogeneous characteristics, might explain uneven results in research (Barlati et al., 2013). This issue high- lights even more the necessity of better defining treatment’s fea- tures to support more standardized protocols for this intervention.
Surprisingly, over the past 10 years only one study has explicitly questioned which characteristics could have made CACR the most effective treatment, in terms of intensity (Choi & Medalia, 2005), whereas duration has been explored only quantitatively through meta-analyses (McGurk et al., 2007).
The present study focuses on CACR duration, investigating whether longer cycles of treatment could further extend the ben- efits of CACR with respect to both cognition and daily function- ing. For this purpose, we compared two groups attending the same CACR rehabilitation, respectively for three and six months, eval- uating both cognitive domains and daily functioning at baseline, three months and six months.
In analyzing the effect of the two treatment groups (3 vs. 6 months) on cognition, we found a significant improvement in both groups and a significant between-groups difference only for exec- utive functions, in the subcomponent of planning, as evaluated by the Tower of London. Supporting previous literature (Bosia et al., 2007,2014;Cavallaro et al., 2009;Poletti et al., 2010), we ob- served a significant global change in cognition at three months for all patients, thus confirming that 3-months CACR is adequate to strengthen impaired functions. This result is also consistent with previous meta-analyses showing an adequate improvement in cog- nitive functions already after a brief period of CACR, even though Table 1 Sociodemographic and Clinical Data at Baseline of Patients in the 3 Months and 6 Months Treatment Variable3-months treatment (mean SD)6-months treatment (mean SD)ANOVA/ 2 F/ 2 p N57 41 Males/Females 37/20 21/20 Age 33.82 9.89 34.21 9.56 .04 .95 Education (yrs) 11.75 2.30 11.55 2.89 .53 .59 Age of onset 22.98 5.39 24.58 7.06 2.27 .10 Illness duration (yrs) 10.84 5.42 10.20 8.30 .63 .59 Antipsychotic dose (CPZ Eq) 315.15 27.88 222.81 39.42 3.66 .06 PANSS – Total score 50.00 8.84 54.53 7.67 2.76 .06 PANSS – Positive scale 14.78 4.63 15.73 5.13 4.22 .06 PANSS – Negative 20.24 6.33 21.80 5.24 .56 .56 PANSS – General 34.30 8.89 38.60 6.39 2.26 .10 IQ Verbal 91.43 14.35 89.40 10.46 1.11 .33 IQ Performance 84.15 13.52 82.17 12.93 .27 .75 IQ Total 86.95 12.74 85.33 9.25 .74 .47 Note. CPZ Eq chlorpromazine equivalents; PANSS Positive and Negative Syndrome Scale. Degree of freedom 1 for analyses. This document is copyrighted by the American Psychological Association or one of its allied publishers.
This article is intended solely for the personal use of the individual user and is not to be disseminated broadly. 470 BUONOCORE ET AL. the duration is often uneven among the studies (McGurk et al., 2007). When addressing further improvement from three to six months, the analysis showed a significant change only for execu- tive functions in the group of patients treated with 6-months CACR. These patients reached significantly higher scores in ex- ecutive functions at six months than the group treated with 3-months, whereas no significant differences were observed in other cognitive domains at six months.
Beyond further supporting global efficacy of 3-months CACR on cognition, these findings suggest that most cognitive functions, such as verbal memory, working memory, psychomotor coordina- tion, and fluency, do not obtain additional benefit from a training lengthening. We can hypothesize that these skills reach a plateau with a 36-session treatment, and then maintain themselves stable over time, with no significant progressions (Cavallaro et al., 2009; Poletti et al., 2010). Interestingly, the only cognitive function that seems to benefit from a treatment extension is planning ability, as patients receiving the 6-months CACR showed significantly higher scores after 72 CACR sessions, compared to those attending only 36 CACR sessions. Planning, a subcomponent of executive functions, is a complex ability that requires evaluation of a se- quence of thoughts and actions to achieve a goal and thus selection and application of the best strategy. Planning can be defined as a higher cognitive function, relying on a broad neural network that involves also other specific and lower level cognitive functions (i.e., memory and attention), directly trained through CACR. In this view, our result suggests that higher-level functions may need a longer training to be “restructured” and that this further poten- tiation may be boosted by the improvement in lower level func- tions, obtained with 3-months CACR. These findings are particu- larly encouraging: they represent empirical evidence of how a longer treatment can lead to a higher benefit in an important aspect of cognition, such as planning.
Addressing daily functioning, as evaluated by means of QLS, the analysis showed a significant improvement over time for all subscales and Total score, with a significant Time Treatment group interaction for Total Score. In details, we did not observe any significant change in QLS from baseline to T1 (three months), although we detected significant improvements in all QLS sub- scales and Total score at six months among all patients. This result is in line with previous work (Bosia et al., 2007) suggesting that a 3-months treatment is not long enough to see generalization of results on patients’ global functioning, as cognitive exercise may restore the patient’s cognitive scaffold, intended as the target on which classical rehabilitation acts to rebuild skills. Results also showed a significant effect of treatment group on QLS Total Score improvement, with patients treated with 6 months CACR reaching higher scores, although not significantly different from the group treated with 3 months CACR.
In sum, results confirm the efficacy of 3-months CACR in terms of both cognitive and functional improvements, as well as evi- dencing that higher functions, such as planning abilities, may further benefit from an extended intervention with possible impact on daily functioning.
However, there are some limitations to this study that should be pointed out. First of all, this is not a randomized study, which would have been the best design to compare treatment effects.
Second, a control computerized condition was not included for patients treated with 3-months CACR, thus we cannot exclude that Table 2 t Score of Neuropsychological and Functional Measures of Patients at T0, T1, and T2, Separated According to Treatment Groups Measure3-months CACR 6-months CACR T G T T0 (mean SD) T1 (mean SD) T2 (mean SD) T0 (mean SD) T1 (mean SD) T2 (mean SD)FpFp BACS Verbal memory 36.01 10.99 40.83 11.45 42.20 12.65 34.78 13.17 40.81 11.43 41.99 11.75 23.17 .0001 1.59 .17 Working memory 35.89 10.09 38.58 10.89 37.94 13.31 33.93 8.80 39.36 9.81 36.52 10.03 5.27 .0001 1.35 .24 Psychomotor coordination 33.76 14.39 35.37 1.65 38.65 12.81 26.57 12.52 27.99 11.11 28.84 14.53 .80 .44 1.64 .16 Verbal fluency 36.84 8.53 39.78 9.5 39.54 10.67 34.68 9.38 36.90 8.0 37.19 9.76 8.04 .0001 .25 .90 Processing speed 29.52 12.76 33.54 11.47 33.03 1.72 28.40 1.71 31.29 10.46 31.17 12.94 7.75 .0001 .52 .72 Planning 34.76 14.31 37.95 12.63 36.91 14.5 33.76 11.35 41.26 12.41 42.97 10.92 7.30 .0001 2.65 .03 Composite Score 34.03 7.54 37.12 7.79 37.99 5.56 32.57 7.25 36.18 6.3 36.54 7.37 31.95 .0001 .50 .60 QLS Relationships 19.25 1.13 19.97 1.15 21.27 1.15 20.53 1.31 23.33 1.33 24.10 1.33 9.53 .0001 2.66 .07 Work 4.00 .85 4.20 .88 5.30 1.00 2.93 .99 4.06 1.02 5.66 1.15 6.55 .0001 1.48 .20 Self-directedness 25.42 1.22 26.05 1.25 27.90 1.22 27.33 1.41 29.46 1.44 31.70 1.41 9.99 .0001 3.20 .05 Total score 48.67 2.83 50.22 2.53 54.47 2.67 50.80 2.83 56.86 2.92 61.46 3.08 15.82 .0001 6.89 .0001 Note. CACR computer-assisted cognitive remediation; BACS Brief Assessment of Cognition in Schizophrenia; QLS Quality of Life Scale. ANOVA effects for time (T) and Time Treatment Group Interaction (G T) are also reported. Degree of freedom 2 for all analyses. This document is copyrighted by the American Psychological Association or one of its allied publishers.
This article is intended solely for the personal use of the individual user and is not to be disseminated broadly. 471 DURATION OF COGNITIVE REMEDIATION IN SCHIZOPHRENIA the differences between the two treatment groups could depend on aspecific effect of “computer exercising.” Third, the QLS scale used for the evaluation of daily functioning was originally created to assess deficit symptoms (Heinrichs et al., 1984), although it could be useful in future studies to use a more performance based scale like the UCSD Performance based Skills assessment (Patter- son et al., 2001). Moreover, it is worth noting that examining individual subtests of the BACS, although allowing a more in- depth evaluation of specific cognitive functions, may hamper the statistical power of results.
This is the first study specifically addressing CACR duration with respect to both cognition and daily functioning. Defining the appropriate CACR duration is of great interest, as it would help the clinician to have a more precise idea of the resources to be invested in each patient to optimize outcome. Although further research is needed to clarify this important issue, including follow-up studies evaluating the maintenance of results over time, these results suggest that 3-months CACR could be proposed as a standard protocol, whereas the 6-months CACR is worth extending to a selected group of patients with more prominent deficit in executive functions persisting after the 3-months CACR. References American Psychiatric Association. (2000).Diagnostic and statistical man- ual of mental disorders(4th ed., revised). Washington, DC: Author.
Anselmetti, S., Poletti, S., Ermoli, E., Bechi, M., Cappa, S., Venneri, A., . . . Cavallaro, R. (2008). The Brief Assessment of Cognition in Schizo- phrenia. Normative data for the Italian population.Neurological Sci- ences, 29,85–92.http://dx.doi.org/10.1007/s10072-008-0866-9 Barlati, S., Deste, G., De Peri, L., Ariu, C., & Vita, A. (2013). Cognitive remediation in schizophrenia: Current status and future perspectives.
Schizophrenia Research and Treatment, 2013,156084.http://dx.doi.org/ 10.1155/2013/156084 Bechdolf, A., Knost, B., Kuntermann, C., Schiller, S., Klosterkötter, J., Hambrecht, M., & Pukrop, R. (2004). A randomized comparison of group cognitive-behavioural therapy and group psychoeducation in pa- tients with schizophrenia.Acta Psychiatrica Scandinavica, 110,21–28.
http://dx.doi.org/10.1111/j.1600-0447.2004.00300.x Bosia, M., Bechi, M., Marino, E., Anselmetti, S., Poletti, S., Cocchi, F.,...
Cavallaro, R. (2007). Influence of catechol-O-methyltransferase Val158Met polymorphism on neuropsychological and functional out- comes of classical rehabilitation and cognitive remediation in schizo- phrenia.Neuroscience Letters, 417,271–274.http://dx.doi.org/10.1016/ j.neulet.2007.02.076 Bosia, M., Zanoletti, A., Spangaro, M., Buonocore, M., Bechi, M., Cocchi, F.,...Cavallaro, R. (2014). Factors affecting cognitive remediation response in schizophrenia: The role of COMT gene and antipsychotic treatment.Psychiatry Research, 217(1–2), 9 –14.http://dx.doi.org/10 .1016/j.psychres.2014.02.015 Bowie, C. R., Reichenberg, A., Patterson, T. L., Heaton, R. K., & Harvey, P. D. (2006). Determinants of real-world functional performance in schizophrenia subjects: Correlations with cognition, functional capacity, and symptoms.The American Journal of Psychiatry, 163,418 – 425.
http://dx.doi.org/10.1176/appi.ajp.163.3.418 Brenner, H. D., Roder, V., Hodel, B., Kienzle, N., Reed, D., Liberman, R. P. (1994).Integrated psychological therapy for schizophrenic pa- tients. Seattle, WA: Hogrefe & Huber Publishers Press.
Cavallaro, R., Anselmetti, S., Poletti, S., Bechi, M., Ermoli, E., Cocchi, F., . . . Smeraldi, E. (2009). Computer-aided neurocognitive remediation as an enhancing strategy for schizophrenia rehabilitation.Psychiatry Re- search, 169,191–196.http://dx.doi.org/10.1016/j.psychres.2008.06.027Cella, M., Reeder, C., & Wykes, T. (2015). Lessons learnt? The importance of metacognition and its implications for Cognitive Remediation in schizophrenia.Frontiers in Psychology, 6,1259.http://dx.doi.org/10 .3389/fpsyg.2015.01259 Choi, J., & Medalia, A. (2005). Factors associated with a positive response to cognitive remediation in a community psychiatric sample.Psychiatric Services, 56,602– 604.http://dx.doi.org/10.1176/appi.ps.56.5.602 Davis, J. M., & Chen, N. (2004). Dose response and dose equivalence of antipsychotics.Journal of Clinical Psychopharmacology, 24,192–208.
http://dx.doi.org/10.1097/01.jcp.0000117422.05703.ae Dickinson, D., Tenhula, W., Morris, S., Brown, C., Peer, J., Spencer, K., . . . Bellack, A. S. (2010). A randomized, controlled trial of computer- assisted cognitive remediation for schizophrenia.American Journal of Psychiatry, 167,170 –180.http://dx.doi.org/10.1176/appi.ajp.2009 .09020264 Eack, S. M., Mesholam-Gately, R. I., Greenwald, D. P., Hogarty, S. S., & Keshavan, M. S. (2013). Negative symptom improvement during cog- nitive rehabilitation: Results from a 2-year trial of Cognitive Enhance- ment Therapy.Psychiatry Research, 209,21–26.http://dx.doi.org/10 .1016/j.psychres.2013.03.020 Gomar, J. J., Valls, E., Radua, J., Mareca, C., Tristany, J., del Olmo, F.,...
the Cognitive Rehabilitation Study Group. (2015). A multisite, random- ized controlled clinical trial of computerized cognitive remediation therapy for schizophrenia.Schizophrenia Bulletin, 41,1387–1396.
http://dx.doi.org/10.1093/schbul/sbv059 Heinrichs, D. W., Hanlon, T. E., & Carpenter, W. T. Jr. (1984). The Quality of Life Scale: An instrument for rating the schizophrenic deficit syndrome.Schizophrenia Bulletin, 10,388 –398.http://dx.doi.org/10 .1093/schbul/10.3.388 Kay, S. R., Fiszbein, A., & Opler, L. A. (1987). The positive and negative syndrome scale (PANSS) for schizophrenia.Schizophrenia Bulletin, 13, 261–276.http://dx.doi.org/10.1093/schbul/13.2.261 Keefe, R. S., Goldberg, T. E., Harvey, P. D., Gold, J. M., Poe, M. P., & Coughenour, L. (2004). The Brief Assessment of Cognition in Schizo- phrenia: Reliability, sensitivity, and comparison with a standard neuro- cognitive battery.Schizophrenia Research, 68, 283–297.http://dx.doi .org/10.1016/j.schres.2003.09.011 Kurtz, M. M., Seltzer, J. C., Fujimoto, M., Shagan, D. S., & Wexler, B. E.
(2009). Predictors of change in life skills in schizophrenia after cognitive remediation.Schizophrenia Research, 107,267–274.http://dx.doi.org/ 10.1016/j.schres.2008.10.014 Marker K. R. (1987–2007).COGPACK: The Cognitive Training Package Manual. Marker Software: Heidelberg & Ladenburg, Germany. Re- trieved fromhttp://www.markersoftware.com McGurk, S. R., Twamley, E. W., Sitzer, D. I., McHugo, G. J., & Mueser, K. T. (2007). A meta-analysis of cognitive remediation in schizophrenia.
The American Journal of Psychiatry, 164,1791–1802.http://dx.doi.org/ 10.1176/appi.ajp.2007.07060906 Mueller, D. R., Schmidt, S. J., & Roder, V. (2015). One-year randomized controlled trial and follow-up of integrated neurocognitive therapy for schizophrenia outpatients.Schizophrenia Bulletin, 41,604 – 616.http:// dx.doi.org/10.1093/schbul/sbu223 Patterson, T. L., Goldman, S., McKibbin, C. L., Hughs, T., & Jeste, D. V.
(2001). UCSD Performance-Based Skills Assessment: Development of a new measure of everyday functioning for severely mentally ill adults.
Schizophrenia Bulletin, 27,235–245.http://dx.doi.org/10.1093/ oxfordjournals.schbul.a006870 Penadés, R., Catalán, R., Salamero, M., Boget, T., Puig, O., Guarch, J., & Gastó, C. (2006). Cognitive remediation therapy for outpatients with chronic schizophrenia: A controlled and randomized study.Schizophre- nia Research, 87,323–331.http://dx.doi.org/10.1016/j.schres.2006.04 .019 Poletti, S., Anselmetti, S., Bechi, M., Ermoli, E., Bosia, M., Smeraldi, E., & Cavallaro, R. (2010). Computer-aided neurocognitive remediation in This document is copyrighted by the American Psychological Association or one of its allied publishers.
This article is intended solely for the personal use of the individual user and is not to be disseminated broadly. 472 BUONOCORE ET AL. schizophrenia: Durability of rehabilitation outcomes in a follow-up study.Neuropsychological Rehabilitation, 20,659 – 674.http://dx.doi .org/10.1080/09602011003683158 Radhakrishnan, R., Kiluk, B. D., & Tsai, J. (2016). A meta-analytic review of non-specific effects in randomized controlled trials of cognitive remediation for schizophrenia.Psychiatric Quarterly, 87,57– 62.http:// dx.doi.org/10.1007/s11126-015-9362-6 Rauchensteiner, S., Kawohl, W., Ozgurdal, S., Littmann, E., Gudlowski, Y., Witthaus, H.,...Juckel, G. (2011). Test-performance after cognitive training in persons at risk mental state of schizophrenia and patients with schizophrenia.Psychiatry Research, 185,334 –339.http://dx.doi.org/10 .1016/j.psychres.2009.09.003 Roder, V., Brenner, H. D., Müller, D., Lächler, M., Zorn, P., Reisch, T.,...
Schwemmer, V. (2002). Development of specific social skills training programmes for schizophrenia patients: Results of a multicentre study.
Acta Psychiatrica Scandinavica, 105,363–371.http://dx.doi.org/10 .1034/j.1600-0447.2002.1o214.x Rund, B. R., Moe, L., Sollien, T., Fjell, A., Borchgrevink, T., Hallert, M., & Naess, P. O. (1994). The Psychosis Project: Outcome and cost-effectiveness of a psychoeducational treatment programme for schizo- phrenic adolescents.Acta Psychiatrica Scandinavica, 89,211–218.
http://dx.doi.org/10.1111/j.1600-0447.1994.tb08094.x Sartory, G., Zorn, C., Groetzinger, G., & Windgassen, K. (2005). Com- puterized cognitive remediation improves verbal learning and processing speed in schizophrenia.Schizophrenia Research, 75,219 –223.http://dx .doi.org/10.1016/j.schres.2004.10.004 Wechsler, D. 1998.Wechsler Adult Intelligence Scale Revised (WAIS-R).
Versione Italiana a cura di Laicardi e Orsini. Firenze, Italy: O.S. Firenze.
Wykes, T., Brammer, M., Mellers, J., Bray, P., Reeder, C., Williams, C., & Corner, J. (2002). Effects on the brain of a psychological treatment:
Cognitive remediation therapy: Functional magnetic resonance imaging in schizophrenia.The British Journal of Psychiatry, 181,144 –152. Received September 29, 2016 Revision received November 25, 2016 Accepted December 6, 2016 This document is copyrighted by the American Psychological Association or one of its allied publishers.
This article is intended solely for the personal use of the individual user and is not to be disseminated broadly. 473 DURATION OF COGNITIVE REMEDIATION IN SCHIZOPHRENIA