Computerized Cognitive Remediation Therapy in Adolescents With a First Psychotic Episode

Overview

Cognitive deficits (CD) are considered one of the essential characteristics in psychotic disorders and occur throughout the course of the disease, being a key characteristic in the evolution of the disease and in the functionality and prognosis of patients. Intervening in the early stages of the disease and specifically in adolescence, a period of high brain plasticity can reduce disabilities in adulthood associated with early-onset psychosis. The objective of this study is to assess the efficacy of cognitive rehabilitation therapy in adolescents with a first psychotic episode, comparing two groups of these patients: a first group (CCRT) will carry out 40 sessions of a computerized cognitive remediation therapy with the usual treatment too, and a second group will perform only the usual treatment (TAU). The main hypothesis is that the CCRT group will present a significant improvement in verbal memory, visual attention, executive function, and social cognition and will present better global functioning compared to the TAU group.

Cognitive deficits (DC) are considered one of the essential features in psychotic disorders and occur throughout the course of the disease. Recent meta-analyses have shown that cognitive remediation therapy can reduce DCs in basic cognitive processes such as attention, memory, and problem solving and can have an impact on social functioning. The aim of this study is to evaluate the effectiveness of a computerized cognitive remediation intervention in cognitive and functional improvement in patients with a first psychotic episode that is psychopathologically stable but presents cognitive impairment. The hypotheses that are raised are: 1. In relation to the cognitive field. Participants in the computerized cognitive remediation therapy + treatment as usual (CCRT) group versus the participants in the treatment as usual (TAU) group are expected to improve in (evaluated by MATRICS): 1. Verbal memory 2. Visual attention 3. Executive function 4. Social cognition 2. In relation to other symptoms. Participants in the CCRT group versus the participants in the TAU group are expected to: 1. Present better Global Functioning evaluated through C-GAS. Parallel groups will be compared with patients between 12 and 18 years of age diagnosed with schizophrenia / schizoaffective recruited at the Hospital Sant Joan de Déu Barcelona. A total of 50 randomly distributed patients will be included (n = 25 CCRT; n = 25 TAU). CCRT group will perform a total of 40 computerized cognitive remediation (cCR) sessions through the NeuroPersonalTrainer program in addition to the treatment as usual, and TAU group will perform only the treatment as usual. An evaluation will be performed before the start of treatment, a second evaluation after the end of the 40cCRsessions/ TAU, and a third evaluation (follow-up) 6 months after the end of the 40cCRsessions. Data Management The aforementioned variables will be collected on the one hand in paper format, in a data collection notebook created by ADHOC for the study that will be kept with a key and the data in electronic format, derived from the computerized programs and tests will be stored with a password, all of this under the responsibility of the principal investigator. The monitoring plan consists in that each visit made to carry out the study will be recorded in the participant's clinical history and the variables of clinical or neuropsychological interest will be included in the history and in a way that can be accessed to verify the data. Verification of all the data of each participant will be carried out once the study has been completed by the participant and the data collection has been completed and all the participant's data has been coded. Data that cannot be recovered will be coded as "missing" and participants who could not be tracked as "drop-outs". The data of each participant will be coded and included in a database for later analysis. Data that could lead to the identification of the participant will not be stored in the database. No information of any kind to identify the participants will be included. Only the study doctor and his collaborators will be able to relate the data collected in the study with his medical history. No adverse effects are expected as it is a protocol that does not include drugs or invasive procedures. In the case of detecting an adverse effect, it would be notified and coded in the database. Statistical analysis The group will be randomized as follows: parallel, CCRT Group compared to TAU Group. Randomization will be performed using permuted blocks with a fixed size of 8 patients assigned a 4: 4 ratio according to computerized allocation i is done blindly. Randomization is performed by an outside person to whom the program applies. Following the CONSORT statement for controlled trials (Moher et al. 2010), the intention-to-treat analysis will be used. This consists of the comparison of the CCRT Group, including all patients, as originally assigned after randomization. The analysis of the missing and drop-outs will also be carried out according to the CONSORT statement. An analysis of the descriptive and contingency tables will be carried out. Tests will be carried out to evaluate the normality of the results through the Kolmogorov-Smirnov test. For variables with a normal distribution, Student's t-test will be applied and non-parametric tests (U-Mann Witney) will be applied for results without normal distribution. For the evaluation of the pre-post differences, repeated measures analysis of variance (ANOVA) designed with the CCRT Group versus TAU Group condition will be used as the independent variable and the baseline and post-treatment evaluations as the time points. An analysis of covariance with repeated measures (ANCOVA) will be performed, including potentials as covariates. The effect size for calculating changes in scores will be calculated in 2 complementary groups in two ways. Eta partial squared (h2p) will be used to calculate the effect size of the scores between baseline and post-treatment evaluations. The effect size of the number needed to treat (NNT) will also be calculated since it is a clinically significant measure that indicates the number of people who would need to be treated to achieve a specific therapeutic goal. Furthermore, it will be determined if the cognitive changes are reliable using TAU Group test-re-test reliability coefficients in order to calculate the standard error of measurement according to Medalia (2005). CCRT Group patients whose score changes to a coefficient value of 1.64 or higher (90% CI) will be identified as a reliable improvement. Finally, the use of repeated measures ANOVA will be used to assess changes from baseline to 3-month follow-up in CCRT Group, with baseline and follow-up as time points. Logistic regression models will also be included to study dichotomous variables in the event that the bivariate analysis has been significant. For the statistical analysis, the statistical package STATA 12 will be used. Data codebook Code=RHC\_0XX Age=Date of birth Sex=Sex N\_Sessions=Sessions performed Peduc=paternal education level Meduc=maternal education level Poccup=paternal occupation Moccup=maternal occupation residence=place of residence kindh=kind of house Npobl=nº hab poblacion Npersh=number of persons at home SES=socioeconomic status F\_Psq\_history=Family Psyquiatric History OSC=Obstetric Risk perinatal=perinatal history psychomot=psychomotor development language=language development read\_write=reading and writing development Psq\_history= Personal Psychiatric History Psq\_age=age first contact mental health service Psq\_pharma=history of pharmacological treatment Psq\_psychology=history of psychological treatments Psq\_1HOSP\_age=age of first hospitalization Psq\_1HOSP\_days=days first hospitalization Medical\_history=relevant medical history academic\_rep=repetition of academic year course=academic level freq\_subs\_lifec= maximum frequency of café throughout life freq\_subs\_3m= frequency of café last 3 months K-SADS-PL-5: Psychopathology PANS-PS\_0: Positive symptoms basal PANS-PS\_40s: Positive symptoms 40 sessions follow-up PANS-PS\_6m: Positive symptoms 6 months follow-up PANS-NS\_0: Negative symptoms basal PANS-NS\_40s: Negative symptoms 40 sessions follow-up PANS-DS\_6m: Negative symptoms 6 months follow-up PANS-DS\_0: Disorganization symptoms basal PANS-DS\_40s: Disorganization symptoms 40 sessions follow-up PANS-DS\_6m: Disorganization symptoms 6 months follow-up GAF\_0= Global Functioning basal GAF\_40s= Global Functioning 40 sessions follow-up GAF\_6m= Global Functioning 6 months follow-up W\_V\_Pd=Vocabulary direct W\_V\_T= Vocabulary t-score W\_C\_Pd= Block Design direct W\_C\_T= Block Design t-score W\_S\_Pd= Similarities direct W\_S\_T= Similarities t-score W\_M\_Pd=Matrix reasoning direct W\_M\_T Matrix reasoning t-score W\_B\_Pd=Figure Weights direct W\_B\_T=Figure Weights t-score ICV\_Pe= Verbal Comprehension ICV\_CI= Verbal Comprehension Index IFR\_Pe= Fluid Reasoning IFR\_CI= Fluid Reasoning Index ICG\_Pe= General Ability ICG\_CI= General Ability Index W\_DT\_Pd\_0= working memory Digit span direct W\_DT\_T\_0= working memory Digit span t-score W\_Dd\_Pd\_0= working memory direct Digit span direct W\_Dd\_Pd\_0= working memory direct Digit span t-score W\_Di\_Pd\_0= working memory indirect Digit span direct W\_Di\_Pd\_0= working memory indirect Digit span t-score W\_CN\_Pd\_0= Processing Speed coding direct W\_CN\_Pd\_0= Processing Speed coding t-score W\_LN\_Pd\_0= working memory Letter-number sequencing direct W\_LN\_T\_0= working memory Letter-number sequencing t-score W\_DT\_Pd\_40s= working memory Digit span direct 40 sessions follow-up W\_DT\_T\_40s = working memory Digit span t-score 40 sessions follow-up W\_Dd\_Pd\_40s = working memory direct Digit span direct 40 sessions follow-up W\_Dd\_Pd\_40s = working memory direct Digit span t-score 40 sessions follow-up W\_Di\_Pd\_40s = working memory indirect Digit span direct 40 sessions follow-up W\_Di\_Pd\_40s = working memory indirect Digit span t-score 40 sessions follow-up W\_CN\_Pd\_40s = Processing Speed coding direct 40 sessions follow-up W\_CN\_Pd\_40s = Processing Speed coding t-score 40 sessions follow-up W\_LN\_Pd\_40s = working memory Letter-number sequencing direct 40 sessions follow-up W\_LN\_T\_40s = working memory Letter-number sequencing t-score 40 sessions follow-up W\_DT\_Pd\_6m= working memory Digit span direct 6 months follow-up W\_DT\_T\_6m= working memory Digit span t-score 6 months follow-up W\_Dd\_Pd\_6m= working memory direct Digit span direct 6 months follow-up W\_Dd\_Pd\_6m= working memory direct Digit span t-score 6 months follow-up W\_Di\_Pd\_6m= working memory indirect Digit span direct 6 months follow-up W\_Di\_Pd\_6m= working memory indirect Digit span t-score 6 months follow-up W\_CN\_Pd\_6m= Processing Speed coding direct 6 months follow-up W\_CN\_Pd\_6m= Processing Speed coding span t-score 6 months follow-up W\_LN\_Pd\_6m= working memory Letter-number sequencing direct 6 months follow-up W\_LN\_T\_6m= working memory Letter-number sequencing t-score 6 months follow-up CPT\_CI\_0=Attention basal CPT\_CI\_40s=Attention 40 sessions follow-up CPT\_CI\_RP=Attention 6 months follow-up CPT\_O\_0= Attention, omissions basal CPT\_O\_40s =Attention, omissions 40 sessions follow-up CPT\_O\_RP=Attention, omissions 6 months follow-up CPT\_C\_0= Attention, commissions basal CPT\_C\_40s =Attention, commissions 40 sessions follow-up CPT\_C\_RP=Attention, commissions 6 months follow-up CPT\_HRT\_0= Attention, reaction time basal CPT\_HRT\_40s =Attention, reaction time 40 sessions follow-up CPT\_HRT\_RP=Attention, reaction time 6 months follow-up CPT\_D\_0= Attention, detectability basal CPT\_D\_40s =Attention, detectability 40 sessions follow-up CPT\_D\_RP=Attention, detectability 6 months follow-up CPT\_V\_0= Attention, variability basal CPT\_V\_40s =Attention, variability 40 sessions follow-up CPT\_V\_RP=Attention, variability 6 months follow-up TMT-A\_Pd\_0=Processing Speed TMT-A, direct score basal TMT-A\_Pd\_40s=Processing Speed TMT-A, direct score 40 sessions follow-up TMT-A\_Pd\_RP=Processing Speed TMT-A, direct score , 6 months follow-up TMT-A\_T\_0=Processing Speed TMT-A, t-score basal TMT-A\_T\_40s=Processing Speed TMT-A, t-score, 40 sessions follow-up TMT-A\_T\_6m=Processing Speed TMT-A, t-score, 6 months follow-up TMT-B\_Pd\_0=executive functions TMT-B, direct score basal TMT-B\_Pd\_40s=executive functions TMT-B, direct score 40 sessions follow-up TMT-B\_Pd\_RP=executive functions TMT-B, direct score , 6 months follow-up TMT-B\_T\_0=executive functions TMT-B, t-score basal TMT-B\_T\_40s=executive functions TMT-B, t-score, 40 sessions follow-up TMT-B\_T\_6m=executive functions TMT-B, t-score, 6 months follow-up HVLT\_Pd\_0=Long term Verbal Memory, direct, basal HVLT\_Pd\_40s =Long term Verbal Memory, direct, 40 sessions follow-up HVLT\_Pd\_6m =Long term Verbal Memory, direct, 6 months follow-up HVLT\_T\_0=Long term Verbal Memory, t-score basal HVLT\_T\_40s =Long term Verbal Memory t-score 40 sessions follow-up HVLT\_T\_6m =Long term Verbal Memory t-score 6 months follow-up HVLT\_Pd\_0=Verbal Memory Learning, direct, basal HVLT\_Pd\_40s =Verbal Memory Learning, direct, 40 sessions follow-up HVLT\_Pd\_6m =Verbal Memory Learning, direct, 6 months follow-up HVLT\_T\_0=Verbal Memory Learning, t-score basal HVLT\_T\_40s =Verbal Memory Learning, t-score 40 sessions follow-up HVLT\_T\_6m =Verbal Memory Learning, t-score 6 months follow-up Rey\_CQ\_0= Copy Quality Visual Memory basal Rey\_CQ\_40s = Copy Quality Visual Memory 40 sessions follow-up Rey\_CQ\_6m = Copy Quality Visual Memory 6 months follow-up Rey \_CA\_0= Copy Accuracy Visual Memory basal Rey\_CA\_40s = Copy Accuracy Visual Memory 40 sessions follow-up Rey\_CA\_6m = Copy Accuracy Visual Memory 6 months follow-up Rey \_MQ\_0= Memory Quality Visual Memory basal Rey\_MQ\_40s =Memory Quality Visual Memory 40 sessions follow-up Rey\_MQ\_6m =Memory Quality Visual Memory 6 months follow-up Rey\_MA\_0= Memory Accuracy Visual Memory basal Rey\_MA\_40s =Memory Accuracy Visual Memory 40 sessions follow-up Rey\_MA\_6m =Memory Accuracy Visual Memory 6 months follow-up WSCT\_E\_0= executive functions, WSCT total errors basal WSCT\_E\_40s = executive functions, WSCT total errors 40 sessions follow-up WSCT\_E\_6m = executive functions, WSCT total errors 6 months follow-up WSCT\_PE\_0= executive functions, WSCT percentage errors basal WSCT\_PE\_40s = executive functions, WSCT percentage errors totals 40 sessions follow-up WSCT\_PE\_6m = executive functions, WSCT percentage errors totals 6 months follow-up WSCT\_persev\_0= executive functions, WSCT persevering responses basal WSCT\_persev\_40s = executive functions, WSCT persevering responses 40 sessions follow-up WSCT\_persev\_6m = executive functions, WSCT persevering responses 6 months follow-up WSCT\_Epersev\_0= executive functions, WSCT persevering errors basal WSCT\_Epersev\_40s = executive functions, WSCT persevering errors 40 sessions follow-up WSCT\_Epersev\_6m = executive functions, WSCT persevering errors 6 months follow-up WSCT\_PEpersev\_0= executive functions, WSCT percentage persevering errors basal WSCT\_PEpersev\_40s = executive functions, WSCT percentage persevering errors 40 sessions follow-up WSCT\_PEpersev\_6m = executive functions, WSCT percentage persevering errors 6 months follow-up WSCT\_ENopersev\_0= executive functions, WSCT non-persevering errors basal WSCT\_ENopersev\_40s = executive functions, WSCT non-persevering errors 40 sessions follow-up WSCT\_ENopersev\_6m = executive functions, WSCT non-persevering errors 6 months follow-up WSCT\_PENopersev\_0= executive functions, WSCT percentage non-persevering errors basal WSCT\_PENopersev\_40s = executive functions, WSCT percentage non-persevering errors 40 sessions follow-up WSCT\_PENopersev\_6m= executive functions, WSCT percentage non-persevering errors 6 months follow-up WSCT\_categories\_0= executive functions, WSCT categories basal WSCT\_categories\_40s = executive functions, WSCT categories non-persevering errors 40 sessions follow-up WSCT\_categories\_6m= executive functions, WSCT categories 6 months follow-up FAS\_Pd\_0=Processing Speed FAS Word Fluency, direct scores basal FAS\_Pd\_40s=Processing Speed FAS Word Fluency, direct scores 40 sessions follow-up FAS\_T\_6m=Processing Speed FAS Word Fluency, direct scores 6 months follow-up FAS\_T\_0=Processing Speed FAS Word Fluency, t-scores basal FAS\_T\_40s=Processing Speed FAS Word Fluency, t-scores40 sessions follow-up FAS\_T\_6m=Processing Speed FAS Word Fluency, t-scores 6 months follow-up Semantic\_Pd\_0=Processing Speed Semantic Word Fluency, direct scores basal Semantic\_Pd\_40s=Processing Speed Semantic Word Fluency, direct scores 40 sessions follow-up Semantic \_Pd\_6m=Processing Speed Semantic Word Fluency, direct scores 6 months follow-up Semantic \_T\_0=Processing Speed Semantic Word Fluency, t-scores basal Semantic \_T\_40s=Processing Speed Semantic Word Fluency, t-scores 40 sessions follow-up Semantic \_T\_6m=Processing Speed Semantic Word Fluency, t-scores 6 months follow-up FACES\_Pd\_0= Social Cognition basal FACES\_Pd\_40s= Social Cognition 40 sessions follow-up FACES\_Pd\_6m= Social Cognition 6 months follow-up