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Both the brain-derived neurotrophic factor (BDNF) valine (Val)/methionine (Met) polymorphism and mismatch negativity (MMN) amplitude are reportedly linked to working memory impairments in schizophrenia. However, there is evident scarcity of research aimed at exploring the relationships among the three factors. In this secondary analysis of a randomized, controlled, double-blind trial, we investigated these relationships. The trial assessed the efficacy of transcranial direct current stimulation for enhancing working memory in clinically stable schizophrenia patients, who were randomly divided into three groups: dorsolateral prefrontal cortex stimulation, posterior parietal cortex stimulation, and sham stimulation groups. Transcranial direct current stimulation was administered concurrently with a working memory task over five days. We assessed the BDNF genotype, MMN amplitude, working memory capacity, and interference control subdomains. These assessments were conducted at baseline with 54 patients and followed up post-intervention with 48 patients. Compared to BDNF Met-carriers, Val homozygotes exhibited fewer positive and general symptoms and increased working memory capacity at baseline. A correlation between MMN amplitude and working memory capacity was noted only in BDNF Val homozygotes. The correlations were significantly different in the two BDNF genotype groups. Furthermore, in the intervention group that showed significant improvement in MMN amplitude, BDNF Val homozygotes exhibited greater enhancement in working memory capacity than Met-carriers. This study provides in vivo evidence for the interaction between MMN and BDNF Val/Met polymorphism for working memory capacity. As MMN has been considered a biomarker of N-methyl-D-aspartate receptor (NMDAR) function, these data shed light on the complex interactions between BDNF and NMDAR in terms of working memory in schizophrenia.

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Working memory deficits are linked to irregularities in the dorsolateral prefrontal cortex (DLPFC) and the posterior parietal cortex (PPC) in schizophrenia, effective intervention strategies are lacking. We evaluated the differential efficacy and underlying neuromechanisms of targeting transcranial direct current stimulation (tDCS) at the DLPFC and the PPC with concurrent cognitive performance for working memory in schizophrenia. In a randomized and double-blind clinical trial, sixty clinically stable schizophrenic patients with below-average working memory were randomly assigned to active DLPFC, active PPC, and sham tDCS groups. Two sessions of tDCS during N-back task were delivered daily for five days. The primary outcome was changes in spatial span test scores from baseline to week 1. The secondary outcomes included changes in scores of color delay-estimation task, other cognitive tasks, and mismatch negativity (biomarker of N-methyl-d-aspartate receptor functioning). Compared with the active DLPFC group, the active PPC group demonstrated significantly greater improvement in spatial span test scores (p = 0.008, d = 0.94) and an augmentation in color delay-estimation task capacity at week 1; the latter sustained to week 2. Compared with the sham tDCS group, the active PPC group did not show a significant improvement in spatial span test scores at week 1 and 2; however, significant enhancement was observed in their color delay-estimation task capacity at week 2. Additionally, mismatch negativity amplitude was enhanced, and changes in theta band measures were positively correlated with working memory improvement in the active PPC group, while no such correlations were observed in the active DLPFC group or the sham tDCS group. Our results suggest that tDCS targeting the PPC relative to the DLPFC during concurrent cognitive performance may improve working memory in schizophrenia, meriting further investigation. The improvement in working memory appears to be linked to enhanced N-methyl-d-aspartate receptor functioning.

Asunto(s)

Memoria a Corto Plazo , Lóbulo Parietal , Corteza Prefrontal , Esquizofrenia , Estimulación Transcraneal de Corriente Directa , Humanos , Memoria a Corto Plazo/fisiología , Estimulación Transcraneal de Corriente Directa/métodos , Esquizofrenia/terapia , Esquizofrenia/fisiopatología , Masculino , Femenino , Adulto , Método Doble Ciego , Lóbulo Parietal/fisiopatología , Corteza Prefrontal/fisiopatología , Corteza Prefontal Dorsolateral/fisiología , Persona de Mediana Edad , Resultado del Tratamiento , Cognición/fisiología , Adulto Joven , Pruebas Neuropsicológicas

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INTRODUCTION: A previous meta-analysis indicated stable progress in cognitive functions in early psychosis, assessed through various tools. To avoid assessment-related heterogeneity, this study aims to examine the longitudinal cognitive function changes in early psychosis utilizing the MATRICS Consensus Cognitive Battery (MCCB). METHODS: Embase, PubMed, and Scopus were systematically searched from their inception to September 26th 2023. The inclusion criteria were longitudinal studies that presented follow-up MCCB data for individuals experiencing first-episode psychosis (FEP) and those with ultra-high risk for psychosis (UHR). RESULTS: Twelve studies with 791 participants (566 FEP patients and 225 healthy controls) were subjected to analysis. Suitable UHR studies were absent. Over time, both FEP patients and healthy controls showed significant improvements in MCCB total scores. Furthermore, FEP patients demonstrated improvements across all MCCB domains, while healthy controls only showed augmentations in specific domains such as speed of processing, attention, working memory, and reasoning and problem-solving. Visuospatial learning improvements were significantly greater in FEP patients compared to healthy controls. Subgroup analyses suggested that neither diagnostic type nor follow-up duration influenced the magnitude of cognitive improvement in FEP patients. CONCLUSION: The magnitude of cognitive improvement for MCCB domains was not significantly different between FEP and healthy controls other than visuospatial learning. This underscores visuospatial learning as a potentially sensitive cognitive marker for early pathologic state changes in psychotic disorders.

Asunto(s)

Disfunción Cognitiva , Trastornos Psicóticos , Humanos , Trastornos Psicóticos/fisiopatología , Trastornos Psicóticos/diagnóstico , Disfunción Cognitiva/etiología , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/fisiopatología , Estudios Longitudinales , Pruebas Neuropsicológicas , Adulto

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The aim of this study is to compare ecologically-valid measure (the Cambridge Prospective Memory Test, CAMPROMPT) and laboratory measure (eye-tracking paradigm) in assessing prospective memory (PM) in individuals with schizophrenia spectrum disorders (SSDs). In addition, eye-tracking indices are used to examine the relationship between PM and other cognitive domains in SSDs patients. Initially, the study sample was formed by 32 SSDs patients and 32 healthy control subjects (HCs) who were matched in sociodemographic profile and the performance on CAMPROMPT. An eye-tracking paradigm was employed to examine the differences in PM accuracy and key cognitive processes (e.g., cue monitoring) between the two groups. Additional 31 patients were then recruited to investigate the relationship between PM cue monitoring, other cognitive functions, and the severity of clinical symptoms within the SSDs group. The monitoring of PM cue was reflected in total fixation time and total fixation counts for distractor words. Cognitive functions were assessed using the Chinese version of the MATRICS Consensus Cognitive Battery (MCCB). The Positive and Negative Syndrome Scale (PANSS) was applied to assess psychopathology. SSDs patients exhibited fewer total fixation counts for distractor words and lower PM accuracy compared to HCs, even though they were priori matched on CAMPROMPT. Correlation analysis within the SSDs group (63 cases) indicated a negative correlation between PM accuracy and PANSS total score, and a positive correlation with working memory and attention/vigilance. Regression analysis within the SSDs group revealed that higher visual learning and lower PANSS total scores independently predicted more total fixation counts on distractor words. Impairment in cue monitoring is a critical factor in the PM deficits in SSDs. The eye-tracking laboratory paradigm has advantages over the ecologically-valid measurement in identifying the failure of cue detection, making it a more sensitive tool for PM deficits in patients with SSDs.

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Objective: The aim of this study was to investigate the impact of early life adversity on cognitive function in patients with schizophrenia, with a focus on social cognition (SC). Methods: Two groups of patients with schizophrenia were recruited and matched on sociodemographic and clinical characteristics. One group consisted of 32 patients with a history of childhood trauma (SCZ-ct), and the other group consisted of 30 patients without a history of childhood trauma (SCZ-nct). In addition, 39 healthy controls without a history of childhood trauma (HC-nct) were also recruited. The intelligence of the three groups was assessed using the Wechsler Abbreviated Scale of Intelligence (WAIS-RC) short version. The cognitive function evaluation was conducted using the MATRICS Consensus Cognitive Battery (MCCB), and early life adversity was measured using the Childhood Trauma Questionnaire-Short Form (CTQ) and Bullying Scale for Adults (BSA). Results: Patients with schizophrenia endosed significantly higher scores on the CTQ (F=67.61, p<0.001) and BSA (F=9.84, p<0.001) compared to the HC-nct. Analysis of covariance (ANCOVA) and post-hoc analyses revealed that SCZ-ct (F=11.20, p<0.001) exhibited the most pronounced cognitive impairment among the three groups, as indicated in MCCB total scores and in the domain score of SC. CTQ exhibited a negative correlation with MCCB (r=-0.405, p< 0.001); SC was negatively correlated with physical abuse (PA) of CTQ (r=-0.271, p=0.030) and emotional abuse (EA) of BSA (r=-0.265, p=0.034) in the whole patient sample. Higher SC performance was significantly predicted by CT_total (Beta =-0.582, p<0.001, 95% CI -0.96-0.46), and years of education (Beta=0.260, p =0.014, 95% CI 0.20-1.75) in schizophrenia. Conclusions: Besides familial trauma, schizophrenia patients appear to have a higher likelihood of experiencing bullying in their early life. These experiences seem to contribute significantly to their severe impairments in SC.

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Background: Cognitive deficits are core characteristics of schizophrenia, presenting before the emergence of psychotic symptoms. Individuals with a clinical high-risk for psychosis (CHR) and those with genetically high-risk of psychosis (GHR) also exhibit cognitive impairments. Nonetheless, it remains uncertain in which domains of cognitive impairments in these two groups were more similar to those of schizophrenia patients. Moreover, it is unclear which domains of impairment are caused by quality factors and which are more related to the state of disease. This research initiative aimed to extensively examine the distinct cognitive impairment profiles among the CHR, GHR, and first-episode schizophrenia (FES) cohorts. Methods: We compared the cognitive functions of the three groups and a healthy control group (HCs) using the MATRICS Consensus Cognitive Battery (MCCB). The participants for this study were recruited from the Beijing Anding Hospital of Capital Medical University. Our sample consisted of 56 patients with FES, 42 with CHR, 26 with GHR, and 62 HCs. The participants across all groups were matched in terms of gender, age, and level of education. Results: Individuals with FES, GHR, and CHR showed significant impairment across the majority of MCCB domains, with the exception of visual learning, in comparison to HCs. None of the MCCB domains demonstrated a discerning ability to accurately differentiate between individuals with CHR and those with GHR. In the speed of processing and attention/vigilance domains, individuals with GHR and CHR exhibited scores between those of FES and HCs, with all group differences reaching statistical significance. This pattern of results indicates an intermediate level of cognitive function in individuals with GHR and CHR. Conversely, the levels of impairment observed in working memory and verbal learning were relatively consistent across all three groups: FES, CHR, and GHR. Notably, individuals in the CHR group exhibited performance akin to that of the HCs in the reasoning/problem-solving domain, while showing significant differences from the FES group, with the CHR individuals demonstrating better performance. Additionally, individuals with GHR displayed performance in social cognition similar to that of the HCs, while also demonstrating significant distinctions from the FES group, with the GHR individuals demonstrating better performance. Conclusion: Significant cognitive deficits exist in individuals with CHR, GHR, and FES, and these deficits vary across domains. Processing speed and attention/vigilance could potentially serve as robust biomarkers for identifying individuals at a risk of psychosis. The impairment observed in reasoning/problem-solving abilities might signify a qualitative trait, whereas deficits in social recognition could indicate a state characteristic specific to schizophrenia.

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Background: Sensory gating deficits are a common feature of schizophrenia and may be indicative of higher-order psychopathological impairments. It has been proposed that incorporating subjective attention components into prepulse inhibition (PPI) measures may improve the accuracy of assessing these deficits. This study aimed to investigate the relationship between modified PPI and cognitive function, with a specific focus on subjective attention, to gain a better understanding of the underlying mechanisms of sensory processing deficits in schizophrenia. Methods: Fifty-four unmedicated first-episode schizophrenia (UMFE) patients and 53 healthy controls participated in this study. The modified Prepulse Inhibition paradigm, including Perceived Spatial Separation PPI (PSSPPI) and Perceived Spatial Colocation PPI (PSCPPI), was used to evaluate sensorimotor gating deficits. Cognitive function was assessed in all participants using the Chinese version of the MATRICS Consensus Cognitive Suite Test (MCCB). Results: UMFE patients had lower MCCB scores and deficient PSSPPI scores than healthy controls. PSSPPI was negatively correlated with total PANSS scores and positively correlated with the speed of processing, attention/ vigilance, and social cognition. Multiple linear regression analysis showed that the PSSPPI at 60 ms had a significant effect on attentional/ vigilance and social cognition, even after controlling for gender, age, years of education, and smoking. Conclusion: The study revealed notable impairments in sensory gating and cognitive function in UMFE patients, best reflected by the PSSPPI measure. Specifically, PSSPPI at 60 ms was significantly associated with both clinical symptoms and cognitive performance, suggesting that PSSPPI at 60 ms may capture psychopathological symptoms related to psychosis.

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The study aimed to investigate the cognitive processing of prospective memory (PM) in patients with schizophrenia spectrum disorders (SSDs) by using an eye-tracking paradigm. In addition, the facilitating effects of prosocial intention (the desire to help others) on PM in SSDs were also examined. In phase 1, 26 patients (group1) and 25 healthy controls (HCs) were compared in an eye-tracking PM paradigm in terms of the PM accuracy and eye-tracking indices. In phase 2, 21 more patients (group2) were recruited, and a prosocial intention was introduced in the eye-tracking PM paradigm. Their PM accuracy and eye-tracking indices were compared with those in group1. The PM cue monitoring was indicated by the total fixation counts and fixation time on distractor words. In phase 1, group1 showed lower PM accuracy, fewer fixation counts and less fixation time on distractor words than HCs. In phase 2, group2 (with prosocial intention) performed significantly better than group1 (with typical instruction) on both PM accuracy and fixation time on distractor words. In both groups of SSDs, the PM accuracy was significantly correlated with both the fixation counts and the fixation time of distractor words. After controlling for the cue monitoring indices, the difference in PM accuracy remained significant between group1 and HCs but disappeared between group1 and group2. The cue monitoring deficit contributes to the PM impairment in SSDs. The facilitating effect of prosocial intention disappears after the control of cue monitoring, also indicating its critical role in PM.