Improving outcome of treatment-resistant schizophrenia: effects of cognitive remediation therapy.

Treatment-Resistant Schizophrenia (TRS) represents a main clinical issue, associated with worse psychopathological outcomes, a more disrupted neurobiological substrate, and poorer neurocognitive performance across several domains, especially in verbal abilities. If cognitive impairment is a major determinant of patients' functional outcomes and quality of life, targeting cognitive dysfunction becomes even more crucial in TRS patients in order to minimize cognitive and functional deterioration. However, although Cognitive Remediation Therapy (CRT) represents the best available tool to treat cognitive dysfunction in schizophrenia, specific evidence of its efficacy in TRS is lacking. Based on these premises, our study aimed at investigating possible differences in CRT outcomes in a sample of 150 patients with schizophrenia, stratified according to antipsychotic response (TRS vs. non-TRS). Subjects were assessed for neurocognition through Brief Assessment of Cognition in Schizophrenia (BACS) and the Wisconsin Card Sorting Test (WCST) at baseline and after CRT. As expected, we observed greater baseline impairment among TRS patients in BACS-Verbal Memory and WCST-Executive Functions. Repeated measures ANCOVAs showed significant within-group pre-/post-CRT differences in the above-mentioned domains, both among non-TRS and TRS subjects. However, after CRT, no differences were observed between groups. This is the first study to indicate that CRT represents a highly valuable resource for TRS patients, since it may be able to fill the cognitive gap between treatment response groups. Our finding further highlights the importance of early implementation of CRT in addition to pharmacotherapy to reduce the cognitive and functional burden associated with the disease, especially for TRS patients.

Theory of mind and stereotypic behavior promote daily functioning in patients with schizophrenia.

OBJECTIVES: Functional disruption is a main feature of schizophrenia and still represents a major treatment challenge. A more in-depth identification of functional predictors is crucial for the creation of individualized rehabilitation treatments, which can translate into better functional outcomes. In this study, we aimed at pinpointing specific domains that affect different functional profiles, using a data-driven approach. METHODS: We included a comprehensive evaluation of functional predictors, namely demographic, cognitive, sociocognitive and clinical variables, with a focus on constituent subdomains of autistic symptoms that have been associated with functioning in the recent literature. RESULTS: In 123 schizophrenia patients, a two-step cluster analysis identified two groups of patients with different functional profiles (low vs high functioning). A backward stepwise logistic regression analysis showed that the odds of being a member of the high functioning group are significantly higher for individuals with (1) more years of education, (2) better Theory of Mind abilities, (3) higher levels of stereotypies/narrowed interests, (4) lower difficulties in social interaction, (5) lower communication difficulties and with (6) being male. CONCLUSION: Findings raise the intriguing possibility that stereotypic behaviors may have a beneficial effect on functioning in schizophrenia. While the underlying mechanism is currently unknown, we hypothesize that patients may benefit from contexts in which more predictive relationships between environmental entities can systematically be established. This study underscores the potential utility of routinely assessing autistic symptomatology in schizophrenia, which can be instrumental in identifying novel therapeutic targets that can be utilized to improve daily functioning.

Cognition in Schizophrenia: Modeling the Interplay between Interleukin-1ß C-511T Polymorphism, Metabolic Syndrome, and Sex.

INTRODUCTION: Cognitive deficits and metabolic disturbances are among the main determinants of functional impairment and reduced life expectancy in patients with schizophrenia, and they may share underlying biological mechanisms. Among these, interleukin-1ß (IL-1ß), a key mediator of inflammatory response, is of particular interest. IL-1ß C-511T polymorphism has been associated with neuropsychiatric conditions and, in the general population, with cognitive and metabolic alterations. This study aims to evaluate the effects of the IL-1ß C-511T polymorphism on both cognition and metabolic syndrome in a sample of patients affected by schizophrenia, with a focus on sex differences. METHODS: 138 patients with schizophrenia were assessed for metabolic parameters and neurocognitive measures by means of the Brief Assessment of Cognition Scale. The effects of IL-1ß C-511T polymorphism on cognition and metabolic syndrome were evaluated in the context of general linear models. RESULTS: The analysis showed a significant interaction between IL-1ß genotype and sex on 2 core cognitive domains. In detail, among CC homozygous, females outperformed males on processing speed, while among T carriers, males outperformed females on executive functions. A significant interaction also emerged between metabolic syndrome, sex, and IL-1ß genotype for executive functions, with worse performance for T carrier females with metabolic syndrome. No significant direct effect was observed for metabolic syndrome on cognition. CONCLUSION: These findings support the hypothesis that IL-1ß polymorphism could play a key role in mediating the complex and refined relationship between metabolic syndrome and cognitive performance.

Cognitive Remediation for Inpatients With Schizophrenia: Effects of a Brief and Intensive Training.

Computer-assisted cognitive remediation (CACR) is a computer-based rehabilitation treatment aimed at improving cognition and at developing strategies that can be applied to various functional areas. Different protocols are currently used with great variability over the intensity and duration of treatments. In this study, we evaluated the effects of a brief and intensive CACR training (i.e., 15 sessions for 3 weeks) on cognitive domains, as well as the durability of cognitive gains and their generalization to functional areas, 3 months after CACR training. Thirty-eight patients with schizophrenia were recruited and assessed for psychopathology, cognitive performance, and functioning before the rehabilitative intervention. Patients were reassessed for cognition after CACR rehabilitation. Moreover, a subsample of 13 patients was evaluated for cognition and functioning 3 months after CACR completion. Results show significant improvements in multiple cognitive domains after CACR. Furthermore, 3 months after CACR completion, significant improvements were also detected in executive functions and daily functioning. This study suggests that a brief and intense CACR training is effective on cognitive and functional domains and that it could be feasible and affordable for health care services, thus offering patients the best options for fulfilling recovery goals.

The Influence of Premorbid Adjustment and Autistic Traits on Social Cognitive Dysfunction in Schizophrenia.

OBJECTIVES: Premorbid dysfunction during childhood and adolescence is well documented in patients with schizophrenia. Literature pointed out multiple premorbid trajectories leading to different patients' cognitive status, symptomatology, and global functioning after disease onset. This study aimed at identifying groups of premorbid trajectories and disentangling between group differences in clinical and cognitive measures, focusing on theory of mind (ToM) and autistic traits (ATs). METHODS: Ninety-seven patients with schizophrenia were recruited and assessed for cognitive and ToM abilities, psychopathology, and ATs. A two-step cluster analysis identified three different groups of patients based on premorbid adjustment during childhood, adolescence, and late adolescence (i.e., stable-good, stable-poor, and "deteriorating"). RESULTS: Compared to 66 healthy controls, results showed a widespread impairment in cognitive and ToM abilities among all groups of patients, except for affective ToM and executive functions in the stable-good group. Moreover, the stable-poor group exhibited more pronounced ATs and a more severe ToM impairment, compared to the other two groups of patients. CONCLUSIONS: Our findings highlight the existence of a group of patients with poor premorbid adjustment since childhood, more pronounced ATs and a severe ToM impairment affecting those basic mentalizing skills that are usually preserved in schizophrenia. Results might have intriguing implications in identifying underpinning endophenotypes and implementing cutting-edge rehabilitation programs.

Daily Functioning in Schizophrenia: Is There Room for Anxiety?

The present study aims at evaluating the impact of anxiety on functional outcome in patients with schizophrenia, also taking into account the other main predictors of functioning identified by literature, to disentangle specific subcomponents which contribute to functional outcome. One hundred five patients with DSM-IV-TR schizophrenia were recruited and underwent a broad functional, psychopathological, and clinical-neuropsychological battery. A forward stepwise regression model was used to assess the predictive effect of anxiety and other factors on daily functioning, showing significant results only for global neurocognitive status and anxiety. These results confirm the role of neurocognition and are also in line with the hypothesis that trait anxiety has a direct impact on functional outcome. Overall, the findings support the role of anxiety as a core feature of schizophrenia pathology, with important implications for both research and clinical settings.

The role of premorbid adjustment in schizophrenia: Focus on cognitive remediation outcome.

Premorbid adjustment has been associated with several outcomes in schizophrenia and has been proposed as an index of cognitive reserve. This study aims to comprehensively analyse the relation between premorbid adjustment and clinical, neurocognitive, socio-cognitive and functional assessments, as well as to investigate the effect of premorbid adjustment on cognitive improvements after a cognitive remediation therapy protocol. Seventy-nine clinically stabilised outpatients with schizophrenia underwent a combined intervention consisting of cognitive remediation therapy added to standard rehabilitation therapy. All patients were assessed at baseline for psychopathology, premorbid adjustment, intellectual level, cognition and functioning. Cognitive evaluations were also repeated after the intervention. At baseline, significant correlations were observed between premorbid adjustment and working memory. The global cognitive improvement after treatment was significantly predicted by age and premorbid adjustment. This study confirms the association between premorbid adjustment and cognitive impairment and is the first to highlight the possible role of premorbid adjustment on the capacity to recover from cognitive deficits through a cognitive remediation therapy protocol. The data suggest that cognitive remediation may be particularly effective for people in the early course and that the assessment of premorbid adjustment could be of value to design individualised interventions.

Exploring predictors of work competence in schizophrenia: The role of theory of mind.

In schizophrenia employment rate is dramatically low, also among patients receiving job support interventions. Recent studies showed a direct relationship between neurocognitive deficits and work functioning, as well as proving the benefits of combined neurocognitive and work interventions. Current evidence also supports a role of Theory of Mind (ToM), on work functioning. However, the effect of integrated rehabilitation programmes including a social cognitive training on job outcome is still less explored. The aim of this pilot study is to investigate the relationship between work competence and clinical factors, neurocognitive and ToM abilities, as well as to explore the effect of neurocognitive and ToM treatments combined with work therapy. Thirty-seven outpatients with schizophrenia were assigned to either a Computer-assisted Cognitive Remediation (CACR) plus work therapy group (WTG) or to CACR and WTG added to ToM Intervention, both followed by a job support programme. All patients were assessed for psychopathology, neurocognition, ToM and work functioning. Work outcome was significantly predicted by age at onset, neurocognitive abilities and the degree of ToM improvement after the specific intervention. This study provides preliminary insight on predictors of work competence in schizophrenia, highlighting the importance of ToM abilities.

Cognitive Reserve Profiles in Chronic Schizophrenia: Effects on Theory of Mind Performance and Improvement after Training.

OBJECTIVES: Cognitive reserve (CR), defined as individual differences in the ability to cope with brain damage, seem to be associated to the several psychopathological features in psychiatric patients, such as the functional outcome. This study aims to identify different profiles of CR by combining intelligence quotient (IQ) and premorbid functioning, two measures independently associated to CR in previous works, as well as to explore CR effect on both Theory of Mind (ToM) baseline performance and improvement after socio-cognitive trainings. METHODS: Sixty patients with chronic schizophrenia underwent a socio-cognitive rehabilitation. All patients were assessed for psychopathology, neurocognition, and ToM at baseline and post-treatment. CR profiles were explored with K-means cluster analysis, while differences between clusters in both baseline assessments and post-treatment ToM improvement, were analyzed by means of analysis of variance and repeated measures analysis of covariance. RESULTS: The analysis revealed three CR profiles, respectively, characterized by low early premorbid functioning and mild intellectual impairment, average/high early premorbid functioning trend with moderate intellectual impairment and good early premorbid functioning associated to IQ within normal limits. Analyses showed a significant effect of CR on both baseline ToM performance and treatment outcome: patients with higher CR reached significantly better ToM scores. CONCLUSIONS: These results underline the clinical relevance of defining CR profiles of patients to customize trainings: subjects with a lower CR may benefit from more intensive programs. A deeper knowledge about CR may considerably increase our understanding of individual differences and thus potentiate treatment outcome. (JINS, 2018, 24, 563-571).

Achieving recovery in patients with schizophrenia through psychosocial interventions: A retrospective study.

AIM: Recovery, or functional remission, represents the ultimate treatment goal in schizophrenia. Despite its importance, a standardized definition of remission is still lacking, thus reported rates significantly vary across studies. Moreover, the effects of rehabilitative interventions on recovery have not been thoroughly investigated. This study aimed to evaluate recovery in a sample of patients with chronic schizophrenia engaged in rehabilitation programs and to explore contributing factors, with a focus on sociocognitive rehabilitative interventions. METHODS: Data from 104 patients with schizophrenia treated either with a standard rehabilitation program, including cognitive remediation (n = 46), or the latter plus a specific sociocognitive intervention (n = 58), and assessed for psychopathology, cognition, social cognition, and Quality of Life Scale, were retrospectively analyzed for this study. RESULTS: Recovery, evaluated with the Quality of Life Scale, was achieved by 56.76% of patients in our sample. While no effects were observed for clinical, cognitive, or sociocognitive variables, participation in the sociocognitive rehabilitative interventions was positively associated with recovery. CONCLUSION: Our results indicate that high rates of recovery can be achieved in patients treated with psychosocial interventions and suggest that rehabilitative programs targeting social cognition may further facilitate the process of recovery. If confirmed, these results may have relevant implications for daily clinical practice and service provision, allowing clinicians to develop and optimize specific rehabilitation programs in order to promote recovery.

Visual and audio emotion processing training for outpatients with schizophrenia: an integrated multisensory approach.

Deficits in emotion processing (EP) represent a target of rehabilitation in schizophrenia, as they have been related to poor personal and social functioning. To date neither the relationship between these deficits and the generalised cognitive impairment, nor the involvement of specific mechanisms of perception (visual or auditory) are fully comprehended. We developed two treatments targeting EP, through visual or auditory channels, with the aim of disentangling possible differences and/or interactions between the two modalities in schizophrenia-related impairments, also taking into account the role of cognition and social functioning. Thirty five outpatients with schizophrenia were assessed for neurocognition, social functioning and EP (visual and auditory channel) and participated in either visual or auditory EP training or in an active control group. Results showed a significant improvement in EP through the specific channel trained for both groups, with an extended effect also on vocal stimuli for the visual training group. Positive correlations were found between working memory, social functioning and EP. Our findings help to shed light on the possible different involvement of perceptual channels in schizophrenia, as well as supporting previous evidence that emotion recognition may be inter-related but does not overlap with neurocognition and can be specifically trained.

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.

COMT and STH polymorphisms interaction on cognition in schizophrenia.

Catechol-O-methyltransferase (COMT) gene, a key regulator of prefrontal cortex (PFC) dopamine (DA) availability, has been extensively studied in relation to cognitive domains, mainly executive functions, that are impaired in schizophrenia, but results are still controversial. Since recent studies in patients affected by neurodegenerative and psychiatric disorders suggested a role of saitohin (STH) gene as a concurring factor in hypofrontality, we hypothesize that STH and COMT polymorphisms could have an additive effect on cognition in schizophrenia. Three forty three clinically stabilized patients with schizophrenia were assessed with a broad neuropsychological battery including the Brief Assessment of Cognition in Schizophrenia, the Wisconsin Card Sorting Test and the Continuous Performance Test and were genotyped for COMT Val108/158Met and STH Q7R polymorphisms. We observed the effects of COMT on speed of processing and executive functions, as well as a significant effect of STH on executive functions performances. Moreover, a significant interaction between COMT and STH polymorphisms was found on executive functions, with COMT Val/Val and STH R carriers performing worse. Our results showed a significant interaction effect of COMT and STH polymorphisms on cognitive performances, strengthening the involvement of STH in cognitive impairments, especially in the domains commonly impaired in schizophrenia.

The kynurenine pathway in treatment-resistant schizophrenia at the crossroads between pathophysiology and pharmacotherapy.

Two cardinal elements in the complex and multifaceted pathophysiology of schizophrenia (SCZ) are neuroinflammation and dysregulation of glutamatergic neurotransmission, with the latter being especially involved in treatment-resistant schizophrenia (TRS). Interestingly, the Kynurenine (KYN) pathway (KP) is at the crossroad between them, constituting a potential causal link and a therapeutic target. Although there is preclinical and clinical evidence indicating a dysregulation of KP associated with the clinical phenotype of SCZ, clinical studies investigating the possible relationship between changes in biomarkers of the KP and response to pharmacotherapy are still limited. Therefore, we have studied possible differences in the circulating levels of biomarkers of the metabolism of tryptophan along the KP in 43 responders to first-line treatments (FLR) and 32 TRS patients treated with clozapine, and their possible associations with psychopathology in the two subgroups. Plasma levels of KYN were significantly higher in TRS patients than in FLR patients, indicating a greater activation of KP. Furthermore, the levels of quinolinic (NMDA receptor agonist) and kynurenic acid (NMDA negative allosteric modulator) showed a negative and a positive correlation with several dimensions and the overall symptomatology in the whole sample and in FLR, but not in TRS, suggesting a putative modulating effect of clozapine elicited through the NMDA receptors. Despite the cross-sectional design of the study that prevents us from demonstrating causation, these findings show a significant relationship among circulating KP biomarkers, psychopathology, and response to pharmacotherapy in SCZ. Therefore, plasma KP biomarkers should be further investigated for developing personalized medicine approaches in SCZ.

Neuroinflammation and kynurenines in schizophrenia: Impact on cognition depending on cognitive functioning and modulatory properties in relation to cognitive remediation and aerobic exercise.

Background: In the last decade, the kynurenine pathway (KP) has gained attention in the pathogenesis of cognitive impairment in schizophrenia being at the croassroad between neuroinflammation and glutamatergic and cholinergic neurotransmission. However, clinical findings are scarse and conflicting, and the specific contributions of these two systems to the neurobiology of cognitive symptoms are far from being elucidated. Furthermore, little is known about the molecular underpinnings of non-pharmacological interventions for cognitive improvement, including rehabilitation strategies. Methods: The current study examined 72 patients with schizophrenia, divided in two clusters depending on the severity of the cognitive impairment, with the aim to evaluate the impact of inflammatory biomarkers and KP metabolites depending on cognitive functioning. Moreover, we studied their possible link to the cognitive outcome in relation to sessions of cognitive remediation therapy (CRT) and aerobic exercise (AE) in a longitudinal arm of 42 patients. Results: Neuroinflammation appeared to exert a more pronounced influence on cognition in patients exhibiting a higher cognitive functioning, contrasting with the activation of the KP, which had a greater impact on individuals with a lower cognitive profile. Cognitive improvements after the treatments were negatively predicted by levels of TNF-α and positively predicted by the 3-hydroxykynurenine (3-HK)/kynurenine (KYN) ratio, an index of the kynurenine-3-monooxygenase (KMO) enzyme activity. Conclusion: Overall, these findings add novel evidence on the biological underpinnings of cognitive impairment in schizophrenia pointing at a differential role of neuroinflammation and KP metabolites in inducing cognitive deficits depending on the cognitive reserve and predicting outcomes after rehabilitation.

Theory of Mind intervention for outpatients with schizophrenia.

Social disability is one of the critical areas known to be a predictor of daily functioning in schizophrenia. Recent studies showed that impairments in Theory of Mind (ToM) contribute to real-world social functioning and are more strongly associated with community outcomes than other neuropsychological domains of cognition. Several experiments revealed an improving potential of social cognition targeted training, particularly through introduction of verbalisation and explicit manipulation of information about others' mental states. Based on these data, we evaluated longitudinally, with a controlled trial, the feasibility and efficacy of ToM training and the possible influences of daily functioning and IQ on the enhancement of ToM abilities. Thirty outpatients with schizophrenia were recruited and randomly allocated to two groups: ToM Intervention (ToMI), based on verbalisation of selected comic strips representing ToM scenarios, or active control group (ACG). Results showed a significant improvement of ToM abilities among subjects allocated to ToMI compared to ACG, confirming the hypothesis of the enhancing potential of training methods targeting ToM functions. Moreover, we observed no influences of neuropsychological and functional variables on ToM improvement. Development of future studies should take into account possible effects of ToM training on functional outcome, according to the strong associations between ToM abilities and real-world social functioning.

Saitohin polymorphism and executive dysfunction in schizophrenia.

Saitohin (STH) is an intronless gene nested within the human tau gene, which contains a single nucleotide polymorphism (A/G), suggested to be involved in the physiopathology and clinical course of several neurodegenerative and neuropsychiatric diseases. Recently, an association between this polymorphism and frontal hypoperfusion and clinical prognosis in frontotemporal dementia was reported. The present study sought to evaluate the possible role of the STH polymorphism as a concurring factor of cognitive decline in schizophrenia, a disease sharing both early psychotic manifestations, a core deficit of executive functions and hypofrontality with frontotemporal lobe dementia. 220 clinically stabilized patients with schizophrenia were assessed with the Wisconsin Card Sorting Test (WCST) for evaluation of executive functions and compared for STH allele frequency with 48 patients affected by frontotemporal dementia and 47 healthy subjects. There was no significant difference in allelic distribution between the healthy controls and all other groups, while we observed a significantly greater frequency of G allele among both patients with frontotemporal dementia (p = 0.037) and schizophrenia patients with poor performances of WCST (p = 0.044), compared to schizophrenia patients with best WCST performances. Among the patients with schizophrenia, stratified for age and gender, the STH polymorphism resulted in a significant predictor of WCST performance (p = 0.007). These results suggest a possible contribution of STH gene products on the heterogeneity of core frontal executive functions deterioration, probably through complex interactions with mechanism involved in neurodevelopment and neurodegeneration.

Modeling the interplay of age at onset and sex on cognition in Schizophrenia.

Cognition remains one of the most critical features of the schizophrenia. A wide range of factors has been associated to neurocognition and, among these, sex and age of onset are two of the most consistently reported to influence the functional and cognitive outcome. This work aims to evaluate the effects of sex and age of onset and their interaction on cognition in 419 subjects with schizophrenia. Analyses of variance and analyses of covariance were performed to evaluate the effect of sex and age at onset on cognition. To model the possible interaction sex-onset on cognition, a separate slope regression analysis was performed. Analyses of variance showed significant differences between sexes for age and age at onset, both significantly higher among females, as well as for Executive Functions, with higher performance among males. When compared according to age at onset, late-onset patients performed better than both early- and intermediate-onset ones in Verbal Memory subtest, with a significant effect of length of illness. Moreover, early-onset patients showed a significantly lower IQ compared to both intermediate and late-onset ones, with no significant effect of length of illness. Finally, the separate slope regression revealed a significant interaction between sex and age at onset, with early-onset being associated to a worse global cognition only among male patients. Our finding of a significant sex-onset interaction effect on neurocognition sheds new light on the complex issue of cognitive heterogeneity in schizophrenia. Our data may help towards the development of personalized programs for preventive and rehabilitative purposes.

It is time to address language disorders in schizophrenia: A RCT on the efficacy of a novel training targeting the pragmatics of communication (PragmaCom).

INTRODUCTION: Language and communication disruptions in schizophrenia are at the center of a large body of investigation. Yet, the remediation of such disruptions is still in its infancy. Here we targeted what is known to be one of the most damaged language domains in schizophrenia, namely pragmatics, by conducting a pragmatics-centered intervention with a randomized controlled trial design and assessing also durability and generalization. To the best of our knowledge, this is the first study with these characteristics. METHODS: Inspired by the Gricean account of natural language use, we tailored a novel treatment addressing the pragmatics of communication (PragmaCom) and we tested its efficacy in a sample of individuals with schizophrenia randomized to the experimental group or to an active control group. The primary outcome with respect to the efficacy of the PragmaCom was measured by changes in pragmatic abilities (as evaluated with the global score of the Assessment of Pragmatic Abilities and Cognitive Substrates test) from baseline to 12 weeks and at 3-month follow-up. The secondary outcome was measured by changes in metaphor comprehension, abstract thinking, and global functioning from baseline to 12 weeks and at 3-month follow-up. RESULTS: Relative to the control group, at post-test the PragmaCom group showed greater and enduring improvement in global pragmatic skills and in metaphor comprehension. At follow-up, these improvements persisted and the PragmaCom exerted beneficial effects also on functioning. CONCLUSIONS: Despite the limited sample size, we believe that these findings offer initial yet encouraging evidence of the possibility to improve pragmatic skills with a theoretically grounded approach and to obtain durable and clinically relevant benefits. We argue that it is time that therapeutic efforts embrace communicative dysfunctions in order to improve illness outcome.

Cognitive remediation in schizophrenia: What happens after 10 years?

Cognitive Remediation Therapy (CRT) represents the gold standard treatment for cognitive impairment in schizophrenia, but the permanence of its effects over time have been poorly investigated. Our study aims to evaluate long lasting cognitive and functional effects of CRT together with standard rehabilitation interventions (SRT) in a group of patients diagnosed with schizophrenia, 10 years after the end of the treatment. Forty patients, previously included in a 5-year follow-up study evaluating the effects of CRT combined with SRT, were revalued 10 years after the complete of the intervention. Results revealed that cognitive and functional improvements of combined CRT/SRT interventions are still preserved 10 years after the end of the treatments, with the only exception of psychomotor speed and coordination cognitive subdomain. Moreover, investigating persistence of the influence of SRT, patients that underwent a shorter SRT following CRT (six months vs one year) showed worsened processing speed abilities. This is the first study confirming that cognitive and functional improvements of joint CRT/SRT interventions are still conserved 10 years after the end of the treatments. Preliminary datas suggest that a longer SRT following CRT may lead to significant benefits, in terms of cognitive gains, in patients affected by schizophrenia.