Component mechanisms of executive function in schizophrenia and their contribution to functional outcomes

Objective: In schizophrenia, scores reflecting deficits in different cognitive processes are strongly correlated, making it difficult to establish a solid relationship between different cognitive mechanisms and other features of this disorder. The objective of this study was to explore whether three frequently postulated executive functions (updating, shifting, and inhibition) could be compared between groups and considered independently in terms of their respective roles in functional outcome. Methods: This study relied on confirmatory factor analysis of schizophrenia patients (n=141) and healthy controls (n=119). The main analyses examined the degree to which three executive functions (updating, set-shifting, and inhibition) could be separated in schizophrenia and compared this model among groups. Structural equation modeling analysis was also performed to examine the extent to which executive function components contribute to functional outcome in schizophrenia. Results: Multiple-group confirmatory factor analysis with unconstrained model parameters indicated that the full three-factor model may fit the data in both groups (χ2 = 61.48, degrees of freedom = 34, p < 0.001, comparative fit index = 0.95; standardized root mean square residual = 0.037; root mean square error of approximation = 0.04; Akaike's information criteria = 169.49; normed fit index = 0.90), although there was also a good data fit for the patient group with a two-factor model. In the patient group, structural equation modeling suggested that shifting and (principally) updating were associated with the general measure of functional outcome (regression path coefficients: 0.34, p < 0.005; 0.39, p < 0.005, respectively), although when combined the mechanisms fail to contribute. Conclusion: This data suggests that the factor structure may be similar but not identical between groups, and both updating and shifting may play an important role in functional outcome in schizophrenia.

Catechol-O-methyltransferase (COMT) polymorphisms modulate working memory in individuals with schizophrenia and healthy controls

Objective: Cognitive impairment is a core feature of schizophrenia, related to dopaminergic dysfunction in the prefrontal cortex (PFC). It is hypothesized that functional single nucleotide polymorphism (SNP) rs4680 of the catechol-O-methyltransferase (COMT) gene could mediate the relationship between cognition and dopamine activity in the PFC. Other COMT SNPs could also play a role. Methods: We evaluated the role of three COMT SNPs (rs737865, rs165599, and rs4680) in schizophrenia and their impact on three working memory tasks. For genetic association analyses, 212 individuals with schizophrenia and 257 healthy controls (HCs) were selected. The Visual Working Memory (VWM) Task, Keep Track Task, and Letter Memory Task were administered to 133 schizophrenics and 93 HCs. Results: We found a significant association of rs737865, with the GG genotype exerting a protective effect and the GA haplotype (rs4680/rs165599) exerting a risk effect for schizophrenia. COMT rs4680 AA carriers and rs737865 AA carriers scored lowest on the Keep Track Task. When the genotype*group interaction effect was evaluated, rs165599 exerted opposite effects for VWM and Keep Track task performance in patients and controls, with AA carriers scoring lowest on both tests among controls, but highest among patients. Conclusion: These data support the hypothesis that COMT polymorphisms may be associated with schizophrenia and modulate cognition in patients and controls.

Validação da Recovery Assessment Scale (RAS) no Brasil para avaliar a capacidade de superação das pessoas com esquizofrenia / Validation of the Recovery Assessment Scale (RAS) in Brazil in people with schizophrenia

RESUMO Objetivo Adaptar para o Brasil e investigar a confiabilidade e validade da Recovery Assessment Scale (RAS) em pessoas com esquizofrenia. Métodos Etapa 1 – foi realizada tradução profissional para o português, adaptação e retrotradução da RAS. Etapa 2 – estudo-piloto em um grupo de 12 pessoas com esquizofrenia para garantir compreensão dos itens da escala. Etapa 3 – As pessoas com esquizofrenia (N = 104) foram submetidas à versão brasileira da RAS e a instrumentos de funcionalidade, qualidade de vida e sintomas para busca de evidências de validade. Resultados Os resultados revelaram bons índices de consistência interna e de precisão teste e reteste dos instrumentos. Foram estabelecidas evidências de validade convergente entre a RAS e medidas de qualidade de vida (r = 0,58; p < 0,001), funcionamento ocupacional (r = 0,40; p < 0,001), habilidades de vida independente (r = 0,24; p < 0,02), gravidade (CGI, r = -0,31; p < 0,003) sintomas da esquizofrenia: PANSS total (r = -0,21; p < 0,05), PANSS negativa (r = -0,28; p < 0.007), PANSS positiva (r = -0.08; p = 0,437)] e depressão [Calgary (r = -0,27; p < 0,01)]. A análise fatorial exploratória revelou seis fatores, sendo quatro destes similares a estudos prévios. Conclusão A partir deste estudo, considerou-se que a palavra “superação” reflete melhor o conceito de “recovery”. A versão brasileira da escala RAS é um instrumento válido e reprodutível para aferir a capacidade de “superação” das pessoas com esquizofrenia.

ABSTRACT Objective To adapt and investigate the validity reliability study of the Brazilian version of the Recovery Assessment Scale-RAS in people with schizophrenia. Methods Stage 1 – professional translation to Portuguese, adaptation, and back-translation of the RAS; Stage 2 – RAS was presented to 12 outpatients with schizophrenia to evaluate if they would be able to understand and respond to the instrument; Stage 3 – patients with schizophrenia (n = 104) were assessed with the Brazilian version of the RAS, functional outcomes measures, quality of life and symptoms scales. Results Results showed good internal consistency and retest reliability, and convergent validity between the RAS and quality of life measures (r = 0.58; p < 0.001), occupational functioning (r = 0.40; p < 0.001), independent living skills (r = 0.24; p < 0,02), functionality (CGI, r = -0.31; p < 0.003) and symptoms of schizophrenia, including PANSS total score total (r = -0.21; p < 0.05), PANSS negative (r = -0.28; p < 0.007), PANSS positive (r = -0.08; p = 0.48), and Calgary Depression Scale (r = -0.27; p < 0.01)]. Exploratory factor analysis yielded six factors, four of these very similar to previous studies. Conclusion This study suggests that the word “superação” (“overcome”) better reflects the concept of “recovery” in Brazilian Portuguese. The Brazilian version of RAS is a valid and reliable instrument to evaluate the process of recovery in people with schizophrenia.

Is semantic verbal fluency impairment explained by executive function deficits in schizophrenia?

Objective: To investigate if verbal fluency impairment in schizophrenia reflects executive function deficits or results from degraded semantic store or inefficient search and retrieval strategies. Method: Two groups were compared: 141 individuals with schizophrenia and 119 healthy age and education-matched controls. Both groups performed semantic and phonetic verbal fluency tasks. Performance was evaluated using three scores, based on 1) number of words generated; 2) number of clustered/related words; and 3) switching score. A fourth performance score based on the number of clusters was also measured. Results: SZ individuals produced fewer words than controls. After controlling for the total number of words produced, a difference was observed between the groups in the number of cluster-related words generated in the semantic task. In both groups, the number of words generated in the semantic task was higher than that generated in the phonemic task, although a significant group vs. fluency type interaction showed that subjects with schizophrenia had disproportionate semantic fluency impairment. Working memory was positively associated with increased production of words within clusters and inversely correlated with switching. Conclusion: Semantic fluency impairment may be attributed to an inability (resulting from reduced cognitive control) to distinguish target signal from competing noise and to maintain cues for production of memory probes.

Investigation of cognition in schizophrenia: psychometric properties of instruments for assessing working memory updating / Investigação da cognição na esquizofrenia: propriedades psicométricas de instrumentos para avaliação de atualização da memória de trabalho

Objective This study describes the development of two updating measures of working memory (WM): Letter Updating Test (LUT) and Word Updating Test (WUT). Methods In stage 1, items were created and the instruments were assessed by experts and laymen. In stage 2, tests were given to 15 patients with schizophrenia and 15 paired controls. All were able to understand and respond to the instruments. In stage 3, 141 patients with schizophrenia and 119 healthy controls aged 18 to 60 took part; they were assessed on WM, processing speed (PS) and functional outcome. Results The results showed adequate rates of internal consistency for both measures developed, for both the total sample and each group separately, as well as evidence of convergent validity, discriminant validity and sensitivity to differentiate performance among the groups. Principal component analysis yielded two components, one for updating tests and other for PS measures, indicating factorial validity. Positive and significant, yet low, correlations were found with functionality measures. Conclusion These results provide adequate psychometric parameters for the measures developed, applicable to cognitive research settings in schizophrenia.

Objetivo O estudo descreve o desenvolvimento de duas medidas de atualização da memória de trabalho (MT): Teste de Atualização de Letras (TAL) e Teste de Atualização de Palavras (TAP). Métodos Na etapa 1 foram criados itens e os instrumentos foram analisados por experts e leigos. Na etapa 2, os testes foram aplicados em 15 pacientes com esquizofrenia e 15 controles pareados. Todos foram capazes de compreender e responder aos instrumentos. Na etapa 3, participaram 141 pacientes com esquizofrenia e 119 controles saudáveis com idades entre 18 e 60 anos, avaliados em MT, velocidade de processamento (VP) e funcionalidade. Resultados Os resultados revelaram bons índices de consistência interna para ambas as medidas desenvolvidas, tanto para a amostra total como para cada grupo separadamente, bem como evidências de validade convergente com medidas de MT, validade discriminante com medidas de VP e sensibilidade para discriminar o desempenho entre os grupos. Análise de componentes principais revelou que os testes de atualização apresentaram altas cargas e um fator separado das medidas de VP. Relações positivas, significativas, porém baixas, foram encontradas com medidas de funcionalidade. Conclusão Esses resultados fornecem bons parâmetros psicométricos para as medidas desenvolvidas, aplicáveis em contextos de pesquisa cognitiva da esquizofrenia.

Factor structure of the Positive and Negative Syndrome Scale (PANSS) in Brazil: convergent validation of the Brazilian version

Objectives: The Positive and Negative Syndrome Scale (PANSS) was developed to assess the symptoms of schizophrenia dimensionally. Although it is widely used in clinical trials in Brazil, it is not fully validated. The aim of this study is to assess the factor structure of the Brazilian PANSS and generate validation data for its current version. Methods: A total of 292 patients diagnosed with schizophrenia were enrolled. Results: Principal component analysis suggested a forced five-factor final model that accounted for 58.44% of the total variance, composed of negative, disorganization/cognition, excitement, positive, and depression/anxiety. Conclusion: The Brazilian PANSS has a similar factor structure and internal consistency compared to its other country versions.

Working memory assessment in schizophrenia and its correlation with executive functions ability / Avaliação da memória de trabalho na esquizofrenia e sua correlação com habilidades de funções executivas

OBJECTIVE: Working memory impairment is common in schizophrenia and is possibly a cause of multiple features of the disorder. However few studies have replicated such findings of impairment patterns in Brazilian samples. The main target of this study was to assess auditory and visual working memory in patients with schizophrenia, to assess if they work as separate systems, and to correlate working memory deficits with executive functions. METHOD: Twenty subjects with schizophrenia and twenty healthy subjects matched by gender, age, and schooling have participated. The abilities assessed were auditory and visual working memory, selective attention, inhibitory control, cognitive flexibility, and planning. RESULTS: Patients showed declines in all measures evaluated, except for a measure reaction time of inhibitory control. Auditory working memory was correlated to selective attention, inhibition, flexibility and planning while Visual working memory to planning and flexibility. CONCLUSION: The present study suggests that working memory and executive functions deficits are present in patients with schizophrenia in the Brazilian sample evaluated. Alterations in executive functions may lead to incapacity of operation of processes of working memory. These findings may contribute to delineate and develop new strategies of schizophrenia treatment in the Brazilian population.

OBJETIVO: Prejuízos em memória de trabalho são comuns na esquizofrenia e possíveis causas de múltiplas características do transtorno. Entretanto, poucos estudos reproduziram achados de padrões específicos de déficits em amostras brasileiras de pacientes com esquizofrenia. O objetivo desta pesquisa foi avaliar a memória de trabalho auditiva e visual na esquizofrenia, verificar se estas habilidades operam como dois sistemas separados, e relacionar possíveis déficits de memória de trabalho com habilidades de funções executivas. MÉTODO: Foram incluídos 20 indivíduos com esquizofrenia e 20 indivíduos saudáveis pareados quanto a sexo, idade e escolaridade. As habilidades avaliadas foram memória de trabalho auditiva e visual, atenção seletiva, controle inibitório, flexibilidade cognitiva e planejamento. RESULTADOS: Os pacientes demonstraram prejuízos em todas as medidas dos testes, exceto em tempo de reação de controle inibitório. Pacientes apresentaram significante correlação entre MT auditiva com medidas de atenção seletiva, controle inibitório, flexibilidade e planejamento. Memória de trabalho visual apresentou correlações com planejamento e flexibilidade. CONCLUSÃO: Este estudo sugere que déficits em memória de trabalho e funções executivas estão presentes em pacientes esquizofrênicos na amostra brasileira avaliada. Alterações nas funções executivas podem levar a incapacidade de adequadas operações de memória de trabalho. Esses achados podem contribuir no delineamento de novos procedimentos de intervenção na esquizofrenia em populações brasileiras.