Changes in BDNF methylation patterns after cognitive remediation therapy in schizophrenia: A randomized and controlled trial.

Although cognitive remediation therapy (CRT) produces cognitive benefits in schizophrenia, we do not yet understand whether molecular changes are associated with this cognitive improvement. A gene central to synaptic plasticity, the BDNF, has been proposed as one potential route. This study assesses whether BDNF methylation changes following CRT-produced cognitive improvement are detected. A randomized and controlled trial was performed with two groups (CRT, n = 40; TAU: Treatment as Usual, n = 20) on a sample of participants with schizophrenia. CRT was delivered by trained therapists using a web-based computerized program. Mixed Models, where the interaction of treatment (CRT, TAU) by time (T0: 0 weeks, T1: 16 weeks) was the main effect were used. Then, we tested the association between the treatment and methylation changes in three CpG islands of the BDNF gene. CRT group showed significant improvements in some cognitive domains. Between-groups differential changes in 5 CpG units over time were found, 4 in island 1 (CpG1.2, CpG1.7, CpG1.10, CpG1.17) and 1 in island 3 (CpG3.2). CRT group showed increases in methylation in CpG1.2, CpG1.7 and decreases in pG1.10, CpG1.17, and CpG3.2. Differences in the degree of methylation were associated with changes in Speed of Processing, Working Memory, and Verbal Learning within the CRT group. Those findings provide new data on the relationship between cognitive improvement and changes in peripheral methylation levels of BDNF gene, a key factor involved in neuroplasticity regulation. Trial Registration: NCT04278027.

Difficulties during delivery, brain ventricle enlargement and cognitive impairment in first episode psychosis.

BACKGROUND: Patients with a first episode of psychosis (FEP) display clinical, cognitive, and structural brain abnormalities at illness onset. Ventricular enlargement has been identified in schizophrenia since the initial development of neuroimaging techniques. Obstetric abnormalities have been associated with an increased risk of developing psychosis but also with cognitive impairment and brain structure abnormalities. Difficulties during delivery are associated with a higher risk of birth asphyxia leading to brain structural abnormalities, such as ventriculomegaly, which has been related to cognitive disturbances. METHODS: We examined differences in ventricular size between 142 FEP patients and 123 healthy control participants using magnetic resonance imaging. Obstetric complications were evaluated using the Lewis-Murray scale. We examined the impact of obstetric difficulties during delivery on ventricle size as well as the possible relationship between ventricle size and cognitive impairment in both groups. RESULTS: FEP patients displayed significantly larger third ventricle size compared with healthy controls. Third ventricle enlargement was associated with diagnosis (higher volume in patients), with difficulties during delivery (higher volume in subjects with difficulties), and was highest in patients with difficulties during delivery. Verbal memory was significantly associated with third ventricle to brain ratio. CONCLUSIONS: Our results suggest that difficulties during delivery might be significant contributors to the ventricular enlargement historically described in schizophrenia. Thus, obstetric complications may contribute to the development of psychosis through changes in brain architecture.

Use of cognitive remediation to treat negative symptoms in schizophrenia: is it time yet?

Cognitive remediation is currently recommended to treat cognitive and functional impairments in patients with schizophrenia. Recently, treatment of negative symptoms has been proposed as a new target for cognitive remediation. Evidence of reductions in negative symptoms has been described in different meta-analyses. However, treating primary negative symptoms is still an open question. Despite some emerging evidence, more research focused on individuals with primary negative symptoms is indispensable. In addition, more attention to the role of moderators and mediators and the use of more specific assessments is necessary. Nevertheless, cognitive remediation could be considered as one promising option to treat primary negative symptoms.

Patients with Schizophrenia Showed Worse Cognitive Performance than Bipolar and Major Depressive Disorder in a Sample with Comorbid Substance Use Disorders.

Comorbidity of substance use disorders (SUD) and severe mental illness (SMI) is highly frequent in patients, the most common diagnoses being schizophrenia (SZ), bipolar disorder (BD) and major depressive disorder (MDD). Since comorbidity has its own clinical features, and neurocognitive functioning is not always similar to psychiatric symptoms the present study explores the cognitive performance of patients with dual disorders. A neuropsychological battery of tests was used to assess 120 under treatment male patients, 40 for each group considered (SZ + SUD, BD + SUD and MDD + SUD) who were mainly polyconsumers. Significant differences (with premorbid IQ as a covariate) were found among the groups, with SZ + SUD having a worse performance in attention, verbal learning, short term memory and recognition. The consideration of a global Z score for performance evidenced an impaired neurocognitive pattern for SZ + SUD compared with BD + SUD and MDD + SUD. According to norms, all patients showed difficulties in verbal learning, short-term memory and recognition. Our research indicated that the neurocognitive functioning of dual disorder patients was influenced by the comorbid SMI, with SZ + SUD presenting major difficulties. Future studies should thoroughly explore the role of such difficulties as indicators or endophenotypes for dual schizophrenia disorders, and their usefulness for prevention and treatment.

Obstetric complications and cognition in schizophrenia: a systematic review and meta-analysis.

BACKGROUND: Schizophrenia (SZ) is a complex brain disorder linked to cognitive and neurostructural abnormalities that involves genetic and environmental factors with obstetric complications (OCs) at birth conferring a high risk for the disease. Indeed, current research in the general population describes the deleterious effect of OCs on cognitive performance in adulthood. With this rationale, we aim to review the relationship between OCs and cognition in SZ and related psychotic disorders. METHODS: A systematic review and meta-analysis describing cognitive function and OCs in patients with SZ and related disorders were conducted. PubMed, EmBase, SCOPUS, and the Cochrane Library were systematically searched to identify eligible studies up to January 2022. We calculated the effect sizes (Hedges' g) of cognitive domains within each study and quantified the proportion of between-study variability using the I2 statistic. Homogeneity was assessed using the Q-statistic (X2). The study was registered on PROSPERO (CRD42018094238). RESULTS: A total of 4124 studies were retrieved, with 10 studies meeting inclusion criteria for the systematic review and eight for meta-analysis. SZ subjects with OCs showed poor verbal memory [Hedges' g = -0.89 (95% CI -1.41 to -0.37), p < 0.001] and working memory performance [Hedges' g = -1.47 (95% CI -2.89 to -0.06), p = 0.01] in a random-effect model compared to those without OCs. CONCLUSIONS: OCs appear to have a moderate impact on specific cognitive such as working memory and verbal memory. Our findings suggest that OCs are associated with brain development and might underlie the cognitive abnormalities described at onset of psychosis.

Cognitive dysfunction in schizophrenia: An expert group paper on the current state of the art.

Cognitive impairment in schizophrenia represents one of the main obstacles to clinical and functional recovery. This expert group paper brings together experts in schizophrenia treatment to discuss scientific progress in the domain of cognitive impairment to address cognitive impairments and their consequences in the most effective way. We report on the onset and course of cognitive deficits, linking them to the alterations in brain function and structure in schizophrenia and discussing their role in predicting the transition to psychosis in people at risk. We then address the assessment tools with reference to functioning and social cognition, examining the role of subjective measures and addressing new methods for measuring functional outcomes including technology based approaches. Finally, we briefly review treatment options for cognitive deficits, focusing on cognitive remediation programs, highlighting their effects on brain activity and conclude with the potential benefit of individualized integrated interventions combing cognitive remediation with other approaches.

Terapia de rehabilitación cognitiva para trastornos depresivos: estudio piloto sobre la mejora y mantenimiento del funcionamiento cognitivo y psicosocial / Cognitive remediation therapy for depressive disorders: Pilot study on the improvement and maintenance of cognitive and psychosocial functioning

Los trastornos depresivos son una de las principales causas de discapacidad global y la presencia de déficits cognitivos se relacionan con un peor pronóstico. Dado que la rehabilitación cognitiva en este trastorno está poco estudiada, y menos sus efectos a largo plazo, nuestro objetivo fue investigar sus beneficios en la mejora cognitiva y funcional de estos pacientes. Veintidós participantes fueron asignados aleatoriamente a: a) terapia cognitivo conductual grupal; y b) terapia cognitivo conductual grupal+terapia de rehabilitación cognitiva. Se realizó una evaluación al inicio del tratamiento, a los 3 y 6 meses de la finalización del mismo. Los participantes asignados al grupo con terapia de rehabilitación cognitiva mejoraron más su funcionamiento ejecutivo y estos efectos se mantenían en el tiempo. Sin embargo, no se encontraron diferencias entre ambos grupos en funcionamiento psicosocial. Estos resultados apoyan la importancia de seguir investigando la utilidad de la rehabilitación cognitiva en la recuperación de pacientes con trastornos depresivos

Depressive disorders are one of the main causes of global burden disease and cognitive impairment is associated with worse prognosis. Cognitive Remediation Therapy (CRT) and its long-term effects are understudied; our aim is to investigate the benefits of CRT in the cognitive and functional improvement and maintenance of theses patients. Twenty-two participants were randomly assigned to: a) Group Cognitive Behavioral Therapy (CBT-G) and b) CBT-G plus CRT. Patients were evaluated before treatment, at 3 and 6 months after the end of the treatment. Participants assigned to the TRC group improved more in executive function and its effects remain over time. However, no differences were found between groups in psychosocial functioning improving. These results support the relevance of continue investigating the usefulness of CRT in depression patients recovery

Obstetric Complications and Brain Imaging in Schizophrenia: A Systematic Review.

Schizophrenia is a complex disorder in which clinical symptomatology typically reflects underlying brain abnormalities that coalign with multiple physical health comorbidities. The pathogenesis of schizophrenia involves the interplay between genetic and environmental factors, with obstetric complications widely described as key players in elevating the risk of psychosis. In this regard, understanding the anatomical and functional alterations associated with obstetric complications may help to elucidate potential mechanisms through which birth complications could contribute to schizophrenia pathogenesis. We conducted a systematic review of the extant literature describing brain abnormalities and obstetric complications in patients with schizophrenia and related disorders in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines. A total of 471 studies were retrieved and screened, and 33 studies met inclusion criteria for our review. Studies varied considerably in their methods, with 11 studies employing computed tomography, 1 using magnetic resonance spectroscopy, and 21 using magnetic resonance imaging. The scientific quality of the included studies was assessed and documented. Obstetric complications increase the risk of provoking brain abnormalities. These abnormalities range from decreased gray matter volume and abnormal brain-ventricle ratios to a reduction of volume in limbic regions-which relate to what is commonly observed in schizophrenia. However, current evidence from neuroimaging studies remains scant in relation to establishing obstetric complications as an independent risk factor for schizophrenia.

Cognitive remediation and brain connectivity: A resting-state fMRI study in patients with schizophrenia.

Cognitive remediation is able to improve activation patterns in the frontal lobe but only few data on neuroconnectivity has been reported yet. Resting-state approach is a neuroimaging methodology with potentiality for testing neuroconnectivity in the context of cognitive remediation in schizophrenia. A resting-state fMRI data was acquired in part of the sample (n = 26 patients, n = 10 healthy controls) of a partner study (NCT02341131) testing the effects of cognitive remediation. A data-driven approach using independent component analysis (ICA) was used to identify functional brain networks, which were compared between groups and group per time using a dual-regression approach. ICA results revealed reduced functional connectivity between patients and controls in sensorimotor, basal ganglia, default mode and visual networks at baseline (p<0.05 FWE-corrected). After treatment, time per group analyses evidenced increased connectivity in sensorimotor network. Furthermore, group comparison at follow-up showed similar connectivity patterns between patients and healthy controls in sensorimotor network, but also in default mode and basal ganglia networks. No differences between treatment groups were found. Our results add some evidence to the hypothesis of altered connectivity in schizophrenia, and the possibility to modify some aspects of brain connectivity networks after psychological interventions.

Efficacy and Moderators of Cognitive Behavioural Therapy for Psychosis Versus Other Psychological Interventions: An Individual-Participant Data Meta-Analysis.

BACKGROUND: Study-level meta-analyses have demonstrated the efficacy of cognitive-behavioural therapy for psychosis (CBTp). Limitations of conventional meta-analysis may be addressed using individual-participant-data (IPD). We aimed to determine a) whether results from IPD were consistent with study-level meta-analyses and b) whether demographic and clinical characteristics moderate treatment outcome. METHODS: We systematically searched PubMed, Embase, PsychInfo and CENTRAL. Authors of RCTs comparing CBTp with other psychological interventions were contacted to obtain original databases. Hierarchical mixed effects models were used to examine efficacy for psychotic symptoms. Patient characteristics were investigated as moderators of symptoms at post-treatment. Sensitivity analyses were conducted for risk of bias, treatment format and study characteristics. RESULTS: We included 14 of 23 eligible RCTs in IPD meta-analyses including 898 patients. Ten RCTs minimised risk of bias. There was no significant difference in efficacy between RCTs providing IPD and those not (p >0.05). CBTp was superior vs. other interventions for total psychotic symptoms and PANSS general symptoms. No demographic or clinical characteristics were robustly demonstrated as moderators of positive, negative, general or total psychotic symptoms at post-treatment. Sensitivity analyses demonstrated that number of sessions moderated the impact of treatment assignment (CBTp or other therapies) on total psychotic symptoms (p = 0.02). CONCLUSIONS: IPD suggest that patient characteristics, including severity of psychotic symptoms, do not significantly influence treatment outcome in psychological interventions for psychosis while investing in sufficient dosage of CBTp is important. IPD provide roughly equivalent efficacy estimates to study-level data although significant benefit was not replicated for positive symptoms. We encourage authors to ensure IPD is accessible for future research.

Cognitive remediation for schizophrenia: An expert working group white paper on core techniques.

Cognitive remediation is now widely recognized as an effective treatment for cognitive deficits in schizophrenia. Its effects are meaningful, durable, and related to improvements in everyday functional outcomes. As with many therapies, the evolution of cognitive remediation has resulted in treatment programs that use a variety of specific techniques, yet share common core principles. This paper is the product of a cognitive remediation expert working group consensus meeting to identify core features of the treatment and produce recommendations for its design, conduct, reporting, and implementation. Four techniques were identified as core features of cognitive remediation: facilitation by a therapist, cognitive exercise, procedures to develop problem-solving strategies, and procedures to facilitate transfer to real world functioning. Treatment techniques within each of these core features are presented to facilitate decisions for clinical trials and implementation in clinical settings.

The role of genetics in cognitive remediation in schizophrenia: A systematic review.

The role of genetics in cognitive remediation therapies in schizophrenia has not been completely understood yet. Different genes involved in neurotrophic, dopaminergic and serotonin systems have reported to influence cognitive functioning in schizophrenia. These genetic factors could also be contributing to the variability in responsiveness to cognitive treatments. No comprehensive synthesis of the literature of the role of genetics in the context of cognitive remediation has been conducted until now. We aimed to systematically review the published works through three electronic database searches: PubMed, Scopus, and the Cochrane Library. Eligible studies revealed a rising interest in the field although the number of published studies was rather small (n = 10). Eventually, promising results showing a relationship between some phenotypic variations based on different polymorphisms and different levels of responsivity to cognitive remediation therapies have been described although results are still inconclusive. In case those findings will be replicated, they could be guiding future research and informing clinical decision-making in the next future.

A pharmacogenetic intervention for the improvement of the safety profile of antipsychotic treatments.

Antipsychotic drugs fail to achieve adequate response in 30-50% of treated patients and about 50% of them develop severe and lasting side effects. Treatment failure results in poorer prognosis with devastating repercussions for the patients, carers and broader society. Our study evaluated the clinical benefits of a pharmacogenetic intervention for the personalisation of antipsychotic treatment. Pharmacogenetic information in key CYP polymorphisms was used to adjust clinical doses in a group of patients who started or switched treatment with antipsychotic drugs (PharmG+, N = 123), and their results were compared with those of a group of patients treated following existing clinical guides (PharmG-, N = 167). There was no evidence of significant differences in side effects between the two arms. Although patients who had their antipsychotic dose adjusted according to CYPs polymorphisms (PharmG+) had a bigger reduction in side effects than those treated as usual (PharmG-), the difference was not statistically significant (p > 0.05 for all comparisons). However, PharmG+ patients treated with CYP2D6 substrates that were carriers of CYP2D6 UMs or PMs variants showed a significantly higher improvement in global, psychic and other UKU side effects than PharmG- patients (p = 0.02, p = 0.05 and p = 0.01, respectively). PharmG+ clozapine treated patients with CYP1A2 or CYP2C19 UM and PMs variants also showed higher reductions in UKU scores than PharmG- clozapine patients in general. However, those differences were not statistically significant. Pharmacogenetic interventions may improve the safety of antipsychotic treatments by reducing associated side effects. This intervention may be particularly useful when considering treatment with antipsychotics with one major metabolic pathway, and therefore more susceptible to be affected by functional variants of CYP enzymes.

Cognitive Reserve Assessment Scale in Health (CRASH): Its Validity and Reliability.

(1) Background: The cognitive reserve (CR) concept has not been precisely defined in severe mental disorders and has been estimated using heterogeneous methods. This study aims to investigate and develop the psychometric properties of the Cognitive Reserve Assessment Scale in Health (CRASH), an instrument designed to measure CR in people with severe mental illness; (2) Methods: 100 patients with severe mental illness (non-affective psychoses and affective disorders) and 66 healthy controls were included. The internal consistency and convergent validity of CRASH were assessed. Spearman's correlations coefficients were also performed to examine the relationship between CRASH and neuropsychological tests, psychosocial functioning, and clinical course; (3) Results: The internal consistency was high (Cronbach's alpha coefficient = 0.903). The CRASH global score had a large positive correlation with the Cognitive reserve questionnaire total score (r = 0.838, p < 0.001), demonstrating good convergent validity. The correlation coefficients between the CRASH total scores and clinical, functional, and neuropsychological performance were different between groups. In order to provide clinical interpretation, severity classification based on diagnosis (non-affective psychotic disorders, affective disorders, and healthy controls) have been created; (4) Conclusions: CRASH is the first CR measure developed specifically for patients with severe mental illness, facilitating reliable and valid measurement of this construct. The scale may aid in the stratification of patients and the implementation of personalized interventions.

Neuroimaging Studies of Cognitive Function in Schizophrenia.

Persons suffering from schizophrenia present cognitive impairments that have a major functional impact on their lives. Particularly, executive functions and episodic memory are consistently found to be impaired. Neuroimaging allows the investigation of affected areas of the brain associated with these impairments and, moreover, the detection of brain functioning improvements after cognitive remediation interventions. For instance, executive function impairments have been associated with prefrontal cortex volume and thickness; cognitive control impairments are correlated with an increased activation in the anterior cingulate cortex, and episodic memory impairments are linked to hippocampal reduction. Some findings suggest the presence of brain compensatory mechanisms in schizophrenia, e.g. recruiting broader cortical areas to perform identical tasks. Similarly, neuroimaging studies of cognitive remediation in schizophrenia focus differentially on structural, functional and connectivity changes. Cognitive remediation improvements have been reported in two main areas: the prefrontal and thalamic regions. It has been suggested that those changes imply a functional reorganisation of neural networks, and cognitive remediation interventions might have a neuroprotective effect. Future studies should use multimodal neuroimaging procedures and more complex theoretical models to identify, confirm and clarify these and newer outcomes. This chapter highlights neuroimaging findings in anatomical and functional brain correlates of schizophrenia, as well as its application and potential use for identifying brain changes after cognitive remediation.

BDNF as a marker of response to cognitive remediation in patients with schizophrenia: A randomized and controlled trial.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) is considered to be a putative biomarker for cognitive recovery in schizophrenia. However, current evidence is still scarce for pharmacological treatments, and the use of BDNF as a biomarker has only been tested once with cognitive remediation treatment (CRT). METHODS: A randomized and controlled trial (NCT02341131) with 70 schizophrenia outpatients and 15 healthy volunteers was conducted. The participants with schizophrenia were randomly assigned to either CRT or the control group. All the participants were assessed in terms of cognition, quality of life, and their serum BDNF levels at both baseline and after the intervention. Additionally, comparisons of the effects of the different genotypes of the Val66Met polymorphism at the BDNF gene on the outcome variables were also performed. RESULTS: The patients in the CRT group presented with improvements in both cognition and quality of life. However, no significant changes were detected in the serum levels of BDNF. Interestingly, we found a significant positive interaction effect between the serum BDNF levels and the different BDNF genotypes. The Val/Val group showed significantly higher serum levels after the CRT treatment. However, the interaction among the serum BDNF levels, the BDNF genotypes and the treatment condition was not statistically significant. CONCLUSIONS: The replication of the previous finding of increased serum BDNF levels after cognitive remediation in clinically stable individuals with schizophrenia was not achieved. However, our data indicated that genetic variability may be mediating serum BDNF activity in the context of CRT.

Do FSH/LH ratio and gonadal hormone levels predict clinical improvement in postmenopausal schizophrenia women?

Menopause is a process characterized by a decline in estrogen levels and is therefore a period of biological vulnerability for psychotic relapse in women with schizophrenia. Our goal was to correlate not only gonadal hormone levels but also follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels with improvement in specific clinical symptoms. Thirty-seven acutely ill postmenopausal schizophrenia women with a newly initiated, clinically determined change in antipsychotic medication participated in a 12-week prospective observational outcome study. Scales used were the PANSS scale for psychotic symptoms, the PSP for functioning, and CGI for global clinical impression. Circulating FSH, LH, estradiol, progesterone, and testosterone serum levels were determined by chemiluminescent immunoassay. Partial correlational analyses were performed along with a Bonferroni significance correction (p < 0.0007). After adjustment for confounding factors, the FSH/LH ratio correlated positively with mean changes in PANSS positive scores, and there was a correlation with worsening of CGI total and cognitive scores. Testosterone was also positively associated with improvement in PANSS positive scores. However, after correction for multiple testing, the initial correlations were no longer statistically significant. In summary, while the hormone assays we did in this small sample did not prove to be significantly linked to clinical improvement in any of the schizophrenia symptom domains, we recommend further investigation of pituitary, adrenal, and gonadal hormone ratios as potential markers of clinical improvement in this population.

Computer-assisted cognitive remediation therapy in schizophrenia: Durability of the effects and cost-utility analysis.

The durability of computer-assisted cognitive remediation (CACR) therapy over time and the cost-effectiveness of treatment remains unclear. The aim of the current study is to investigate the effectiveness of CACR and to examine the use and cost of acute psychiatric admissions before and after of CACR. Sixty-seven participants were initially recruited. For the follow-up study a total of 33 participants were enrolled, 20 to the CACR condition group and 13 to the active control condition group. All participants were assessed at baseline, post-therapy and 12 months post-therapy on neuropsychology, QoL and self-esteem measurements. The use and cost of acute psychiatric admissions were collected retrospectively at four assessment points: baseline, 12 months post-therapy, 24 months post-therapy, and 36 months post-therapy. The results indicated that treatment effectiveness persisted in the CACR group one year post-therapy on neuropsychological and well-being outcomes. The CACR group showed a clear decrease in the use of acute psychiatric admissions at 12, 24 and 36 months post-therapy, which lowered the global costs the acute psychiatric admissions at 12, 24 and 36 months post-therapy. The CACR is durable over at least a 12-month period, and CACR may be helping to reduce health care costs for schizophrenia patients.

Neuroimaging studies of cognitive remediation in schizophrenia: A systematic and critical review.

AIM: To examine the effects of cognitive remediation therapies on brain functioning through neuroimaging procedures in patients with schizophrenia. METHODS: A systematic, computerised literature search was conducted in the PubMed/Medline and PsychInfo databases. The search was performed through February 2016 without any restrictions on language or publication date. The search was performed using the following search terms: [("cogniti*" and "remediation" or "training" or "enhancement") and ("fMRI" or "MRI" or "PET" or "SPECT") and (schizophrenia or schiz*)]. The search was accompanied by a manual online search and a review of the references from each of the papers selected, and those papers fulfilling our inclusion criteria were also included. RESULTS: A total of 101 studies were found, but only 18 of them fulfilled the inclusion criteria. These studies indicated that cognitive remediation improves brain activation in neuroimaging studies. The most commonly reported changes were those that involved the prefrontal and thalamic regions. Those findings are in agreement with the hypofrontality hypothesis, which proposes that frontal hypoactivation is the underlying mechanism of cognitive impairments in schizophrenia. Nonetheless, great heterogeneity among the studies was found. They presented different hypotheses, different results and different findings. The results of more recent studies interpreted cognitive recovery within broader frameworks, namely, as amelioration of the efficiency of different networks. Furthermore, advances in neuroimaging methodologies, such as the use of whole-brain analysis, tractography, graph analysis, and other sophisticated methodologies of data processing, might be conditioning the interpretation of results and generating new theoretical frameworks. Additionally, structural changes were described in both the grey and white matter, suggesting a neuroprotective effect of cognitive remediation. Cognitive, functional and structural improvements tended to be positively correlated. CONCLUSION: Neuroimaging studies of cognitive remediation in patients with schizophrenia suggest a positive effect on brain functioning in terms of the functional reorganisation of neural networks.