Margherita Bechi

The Brief Assessment of Cognition in Schizophrenia. Normative data for the Italian population

ObjectiveTo provide normative values for the Italian population for the Brief Assessment of Cognition in Schizophrenia (BACS), a recent brief neuropsychological instrument for the assessment of cognition in patients with schizophrenia.ParticipantsData were collected from 204 healthy adult Italian subjects, stratified by gender, education and age.Measurements and resultsTests included in the BACS are the following: list learning, digit sequencing, verbal fluency, token motor task, symbol-coding and Tower of London. Normative values were established using the Equivalent Scores method in order to enable comparison with other neuropsychological tasks commonly used in the assessment of the Italian population. Performance on the BACS was influenced by the commonest demographic variables such as age and education.ConclusionsThe availability of normative data for the Italian population will increase the usefulness of this test for both clinical and experimental purposes.SommarioNon esistono ad oggi batterie specifiche brevi e facilmente fruibili in lingua italiana per la valutazione del deficit cognitivo dei pazienti con schizofrenia. Lo scopo di questo studio è di tradurre e tarare sulla popolazione italiana la batteria BACS (Brief Assessement of Cognition in Schizophrenia), un breve strumento di screening creato per indagare in modo specifico gli ambiti cognitivi riconosciuti come quelli con le maggiori disfunzioni e correlati ai sintomi della schizofrenia (memoria verbale, velocità e coordinazione psico-motoria, attenzione, funzioni esecutive e fluenza verbale) e che ha mostrato nella validazione in lingua americana una buona correlazione con batterie neuropsicologiche standard e una buona affidabilità testretest. Il campione è costituito da 204 soggetti italiani stratificati per sesso, età e scolarità. I test inclusi nella BACS sono i seguenti: memoria di lista di parole, riordinamento di cifre, fluenza verbale, compito motorio dei gettoni, associazione simboli-numeri e Torre di Londra. I dati normativi sono stati calcolati con il metodo statistico dei Punteggi Equivalenti, con l’obiettivo di rendere possibile il confronto con altri test neuropsicologici usati comunemente in lingua italiana. Le prestazioni alla BACS sono risultate influenzate da variabili demografiche come età e scolarità, confermando i dati presenti in letteratura. La disponibilità di dati normativi per la popolazione italiana ha la potenzialità di aumentare l’utilità di questo test per scopi sia clinici che di ricerca.

Computer-aided neurocognitive remediation as an enhancing strategy for schizophrenia rehabilitation

Cognitive dysfunction is a chronically disabling feature of schizophrenia, associated with limits in obtaining rehabilitation improvements. The purpose of this study is to assess the effectiveness of intensive computer-aided cognitive remediation treatment (CRT) added to a standard rehabilitation treatment (SRT), in enhancing neuropsychological performances and daily functioning in patients with schizophrenia. A 12-week, randomized, controlled, single-blind trial of neurocognitive remediation was carried out on 86 patients with clinically stabilized DSM-IV schizophrenia. Patients were assessed on cognitive and daily functioning before and after either CRT or placebo training that had been added to their SRT. After 3 months the repeated measure ANOVA showed a significant time x treatment interaction for executive function and attention performances and in daily functioning assessment in favour of patients in the SRT+CRT treatment. Results confirmed that cognitive remediation added to the SRT of schizophrenia enhanced its neuropsychological effects and increased the effects of a long-term rehabilitation programme in terms of functional outcomes.

Influence of catechol-O-methyltransferase Val158Met polymorphism on neuropsychological and functional outcomes of classical rehabilitation and cognitive remediation in schizophrenia.

Neurocognitive deficits are recognized as core features of schizophrenia and have a great impact on functional outcome. Recent reports have suggested that a functional polymorphism, Val158Met, of the catechol-O-methyltransferase (COMT) gene, partially influences cognitive performances (mainly cognitive flexibility and working memory) both in schizophrenic patients and in healthy controls, probably by modulating prefrontal dopamine function. While previous studies focused on single evaluation of cognitive functioning, we aimed to analyse the additive effect of COMT genotype and cognitive exercise on dynamic modulation of cognitive performances. We analysed the COMT Val158Met polymorphism in 50 patients with chronic schizophrenia randomly allocated to two treatment conditions for 3 months: standard rehabilitation treatment (SRT) alone and SRT plus specific cognitive exercise of impaired functions. We then divided our sample in four subgroups on the basis of genotype (Val/Val versus Met carriers) and treatment (placebo versus active). We assessed patients with a neuropsychological battery, the Positive and Negative Symptoms Scale (PANSS) and the Quality of Life Scale (QLS) at enrolment, after 3 months of therapy and after further 3 months of follow-up. We found significantly greater improvement of cognitive flexibility performance and QLS total score for Met carriers on active treatment in comparison to Val/Val on placebo. The findings support the hypothesis that COMT polymorphism influences individual capacity to recover from cognitive deficit through rehabilitation therapy after a wider intervention also including deficit-specific cognitive exercise as a potentiating tool.

Psychopathological and neuropsychological correlates of source monitoring impairment in schizophrenia

Schizophrenic patients are known to show a deficit in the source monitoring function, which refers to the set of processes involved in the attribution of an origin to memories and beliefs. A failure in source monitoring was found to be associated with Schneiderian delusions in the recent literature. This study aimed to explore in a sample of schizophrenic patients and controls two aspects of the source monitoring process-recognition and source attribution- and their possible correlation with psychopathology and basic neuropsychological performances. A group of 45 stabilized schizophrenic patients and 54 normal volunteers were studied with a Source Monitoring Task and a battery of neurocognitive functions known to be disturbed in schizophrenia. Recognition of self-generated items was significantly worse than control values in Schneiderian delusional patients only, while source attribution of recognized self-generated items was significantly biased towards the external sources in all delusional patients in comparison to controls. Among schizophrenic patients, source misattribution of self-generated items was significantly correlated to an executive, planning performance. Both performances were correlated to verbal memory in controls. Results confirm an impairment of different subcomponents of source monitoring performance in schizophrenia, heterogeneously related to psychopathological features and neuropsychological performances known to be impaired in schizophrenia.

Cognitive dysfunction and glutamate reuptake: Effect of EAAT2 polymorphism in schizophrenia

A disturbance of glutamatergic transmission has been suggested to contribute to the development of schizophrenic pathophysiology, based primarily on the ability of glutamate receptor antagonists to induce schizophrenic-like symptoms. The excitatory amino acid transporter 2 (EAAT2) is responsible for the majority of glutamate uptake. It also contributes to energy metabolism in the brain, by transporting glutamate into astrocytes for conversion into glutamine. A dysregulation of its level of expression has been associated with multiple neurological disorders. Blocking glutamate uptake by EAAT2 in cultured oligodendrocytes leads to cell death, demyelination and axonal damage, suggesting that it is crucial for normal oligodendrocyte function. Different studies focused on EAAT2 alterations among subjects affected by schizophrenia, reporting a decreased expression in the parahippocampal region and in the dorsolateral prefrontal cortex. Moreover, subjects with the high-risk metabotropic glutamate receptor 3 (GRM3) haplotype associated with schizophrenia had lower EAAT2 expression in the prefrontal cortex and also showed impaired cognitive performances for measures of verbal list learning and verbal fluency. EAAT2 protein activity is regulated by a SNP rs4354668 (-181T/G) which falls in the gene promoter region, with the G allele resulting in a lower activity of the transporter. Based on these data, we assessed possible effects of the -181T/G EAAT2 polymorphism on two core prefrontal cognitive performances, known to be impaired in schizophrenia, in a sample of 211 clinically stabilized patients. We observed better executive functions (WCST, no. of categories) and working memory (N-back: 1-back, 2-back) performances in subjects homozygous for the T allele, compared to the G carriers group. These observations suggest that the presence of the G allele is associated, among patients with schizophrenia, with a disadvantageous effect on core cognitive functions that depend on prefrontal cortex activity. These results are preliminary and need to be replicated by future and larger studies, however they suggest that EAAT2 inefficiency may represent a target of interest for development of pharmacological strategies aimed to improve prefrontal performances by compensating the impaired glutamate reuptake.

Computer-aided neurocognitive remediation in schizophrenia: Durability of rehabilitation outcomes in a follow-up study

Cognitive deficits in patients with schizophrenia constitute a limiting factor to the chances of rehabilitation of daily living abilities, like personal and relational autonomy and working ability. Cognitive Remediation Therapy (CRT) is a rehabilitative technique that aims at the recovery of single cognitive functions through the execution of massive exercises of impaired cognitive domains. This study aims to establish if the results achieved through an intensive deficit-specific neurocognitive treatment of three months duration, were maintained over time. The sample consists in 100 patients diagnosed with schizophrenia according to the criteria of DSM IV. Patients were assessed on cognitive and daily functioning at baseline, after 3 months of either CRT or placebo training added to their standard rehabilitation treatment, at 6 month and 12-month follow-up. Results showed significant changes that were maintained at follow-up for executive function, attention and psychomotor coordination. Moreover the significant improvement in daily functioning was maintained at 6 and 12-month follow-up. In conclusion improvements in cognitive functions and daily functioning achieved through the association of CRT and standard rehabilitation treatment persist over time after the conclusion of the training period.

Effect of 5-HT1A-receptor functional polymorphism on Theory of Mind performances in schizophrenia

Theory of Mind (ToM) abilities are known to be impaired in schizophrenia and data from functional brain imaging studies showed that ToM deficit is correlated to prefrontal cortex (PFC) dysfunction. Moreover, several lines of evidence suggest a critical role for dopaminergic-serotoninergic interactions at the PFC level. In this view, we aimed to analyse the specific effect of the -1019C/G functional polymorphism of the serotonin 1A receptor (5-HT1A-R), involved in both serotonin and dopamine transmission regulation. A total of 118 clinically stabilised schizophrenia patients was assessed with a neuropsychological battery, including evaluation of IQ, verbal memory, attention and executive function and a ToM task; they also underwent 5-HT1A-R genotyping. We observed a significant effect of the 5-HT1A-R genotype on ToM performances, with the CC genotype performing significantly better. The finding suggests an effect of the 5-HT1A-R polymorphism on ToM cognitive performance in schizophrenia patients, probably through complex interactions between dopaminergic and serotoninergic systems, involved in mentalising.

The communicative impairment as a core feature of schizophrenia: Frequency of pragmatic deficit, cognitive substrates, and relation with quality of life

BACKGROUND Impairments in specific aspects of pragmatic competence, supporting the use of language in context, are largely documented in schizophrenia and might represent an indicator of poor outcome. Yet pragmatics is rarely included in clinical settings. This paper aims to promote a clinical consideration of pragmatics as a target of assessment and intervention. We investigated the frequency of the pragmatic deficit, its cognitive substrates, and the relation with quality of life. METHODS Pragmatic abilities were compared in a sample of patients with schizophrenia and healthy controls based on a comprehensive pragmatic test (APACS). We assessed also for psychopathology, cognition, social cognition, and quality of life. We explored the co-occurrence of deficits in different domains, and we used multiple regressions to investigate the effect of cognition and social cognition on pragmatics, and of pragmatics on quality of life. RESULTS Pragmatic abilities, especially comprehending discourse and non-literal meanings, were compromised in schizophrenia, with 77% of patients falling below cutoff. Pragmatic deficit co-occurred with cognitive or socio-cognitive deficits in approximately 30% of cases. Multiple regression analysis confirmed the interplay of cognition and social cognition in pragmatic behavior. Quality of life was predicted by symptoms and by pragmatic abilities. CONCLUSIONS The high frequency of impairment suggests that the pragmatic deficit is a core feature of schizophrenia, associated with quality of life. Cognitive and socio-cognitive abilities might represent necessary though not sufficient building blocks for the acquisition of pragmatic abilities throughout development. Therefore, a more precise incorporation of pragmatics in the description of the pathology is of high clinical and translational relevance.

Combined social cognitive and neurocognitive rehabilitation strategies in schizophrenia: neuropsychological and psychopathological influences on Theory of Mind improvement.

BACKGROUND Neurocognitive and social cognitive impairments represent important treatment targets in schizophrenia, as they are significant predictors of functional outcome. Different rehabilitative interventions have recently been developed, addressing both cognitive and psychosocial domains. Although promising, results are still heterogeneous and predictors of treatment outcome are not yet identified. In this study we evaluated the efficacy of two newly developed social cognitive interventions, respectively based on the use of videotaped material and comic strips, combined with domain-specific Cognitive Remediation Therapy (CRT). We also analysed possible predictors of training outcome, including basal neurocognitive performance, the degree of cognitive improvement after CRT and psychopathological variables. METHOD Seventy-five patients with schizophrenia treated with CRT, were randomly assigned to: social cognitive training (SCT) group, Theory of Mind Intervention (ToMI) group, and active control group (ACG). RESULTS ANOVAs showed that SCT and ToMI groups improved significantly in ToM measures, whereas the ACG did not. We reported no influences of neuropsychological measures and improvement after CRT on changes in ToM. Both paranoid and non-paranoid subjects improved significantly after ToMI and SCT, without differences between groups, despite the better performance in basal ToM found among paranoid patients. In the ACG only non-paranoid patients showed an improvement in non-verbal ToM. CONCLUSION Results showed that both ToMI and SCT are effective in improving ToM in schizophrenia with no influence of neuropsychological domains. Our data also suggest that paranoid symptoms may discriminate between different types of ToM difficulties in schizophrenia.

Exploring functioning in schizophrenia: Predictors of functional capacity and real-world behaviour

Impairment in daily functioning still represents a major treatment issue in schizophrenia and a more in-depth knowledge of underlying constructs is crucial for interventions to translate into better outcomes. This study aims to model factors influencing both functional capacity and real-life behaviour in a sample of outpatients with chronic schizophrenia, through a comprehensive assessment including evaluations of psychopathology, cognitive and social cognitive abilities, premorbid adjustment, family environment and early childhood experiences. No significant correlation was observed between functional capacity and real-life behaviour. Functional capacity was significantly predicted by IQ, while real-life behaviour was significantly predicted by empathy, affect recognition and symptoms. Functional capacity seems mainly related to neurocognition, whereas real-life behaviour appears more complex, requiring the integration of different factors including symptoms, with a major role of empathy. Results thus support a divergence between the two constructs of functioning and their underlying components and highlight the need to target both dimensions through individualized sequential rehabilitation programs in order to optimize functional outcome.