Function In Schizophrenia Patients Research Articles

The Gaze of Schizophrenia Patients Captured by Bottom-up Saliency

Schizophrenia (SCHZ) notably impacts various human perceptual modalities, including vision. Prior research has identified marked abnormalities in perceptual organization in SCHZ, predominantly attributed to deficits in bottom-up processing. Our study introduces a novel paradigm to differentiate the roles of top-down and bottom-up processes in visual perception in SCHZ. We analysed eye-tracking fixation ground truth maps from 28 SCHZ patients and 25 healthy controls (HC), comparing these with two mathematical models of visual saliency: one bottom-up, based on the physical attributes of images, and the other top-down, incorporating machine learning. While the bottom-up (GBVS) model revealed no significant overall differences between groups (beta = 0.01, p = 0.281, with a marginal increase in SCHZ patients), it did show enhanced performance by SCHZ patients with highly salient images. Conversely, the top-down (EML-Net) model indicated no general group difference (beta = −0.03, p = 0.206, lower in SCHZ patients) but highlighted significantly reduced performance in SCHZ patients for images depicting social interactions (beta = −0.06, p < 0.001). Over time, the disparity between the groups diminished for both models. The previously reported bottom-up bias in SCHZ patients was apparent only during the initial stages of visual exploration and corresponded with progressively shorter fixation durations in this group. Our research proposes an innovative approach to understanding early visual information processing in SCHZ patients, shedding light on the interplay between bottom-up perception and top-down cognition.

Deficits in Key Brain Network for Social Interaction in Individuals with Schizophrenia.

Individuals with schizophrenia (SZ) show impairment in social functioning. The reward network and the emotional salience network are considered to play important roles in social interaction. The current study investigated alterations in the resting-state (rs-) amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), regional homogeneity (ReHo) and functional connectivity (fc) in the reward network and the emotional salience network in SZ patients. MRI scans were collected from 60 subjects, including 30 SZ patients and 30 matched healthy controls. SZ symptoms were measured using the Positive and Negative Syndrome Scale (PANSS). We analyzed the ALFF, fALFF and ReHo in key brain regions in the reward network and emotional salience network as well as rs-fc among the bilateral amygdala, lateral orbitofrontal cortex (OFC), medial OFC and insula between groups. The SZ patients demonstrated increased ALFF in the right caudate and right putamen, increased fALFF and ReHo in the bilateral caudate, putamen and pallidum, along with decreased fALFF in the bilateral insula. Additionally, reduced rs-fc was found between the right lateral OFC and the left amygdala, which simultaneously belong to the reward network and the emotional salience network. These findings highlight the association between impaired social functioning in SZ patients and aberrant resting-state ALFF, fALFF, ReHo and fc. Future studies are needed to conduct network-based statistical analysis and task-state fMRI, reflecting live social interaction to advance our understanding of the mechanism of social interaction deficits in SZ.

Augmentation therapy with serotonin1A receptor partial agonists on neurocognitive function in schizophrenia: A systematic review and meta-analysis

BackgroundIn a previous meta-analysis, the use of serotonin1A(5-HT1A) receptor partial agonists of the azapirone class as an add-on therapy was associated with beneficial effects on positive symptoms and attention/processing speed in schizophrenia patients. This meta-analysis builds on that study by examining the effects of adjunctive treatment with 5-HT1A partial agonists in improving other domains of neurocognitive function in schizophrenia patients. MethodsA literature search was performed from 1987 to May 2023 to identify randomized controlled trials. The standardized mean difference (SMD) with 95 % confidence intervals (CI) was calculated when there were two or more studies. Four studies, involving 313 patients, met the inclusion criteria and were used in the analysis. Results5-HT1A partial agonists (buspirone or tandospirone) did not have a significant effect on verbal learning (SMD = 0.08, 95 % CI = −0.31 to 0.47) or working memory (SMD = 0.15, 95 % CI = −0.09 to 0.39). Regarding executive functions (Wisconsin Card Sorting Test), positive but non-significant results were seen with the category number (SMD = 0.26, 95 % CI = −0.81 to 1.32), while non-significant effects were noted for percent preservation errors (SMD = −0.10, 95 % CI = −0.53 to 0.33). ConclusionsThe absence of any significant benefits in the cognitive domains studied here may have been due to the variance in the concomitant medication (typical vs atypical antipsychotic drugs), the level of cognition at baseline, or other factors. Further studies with various types of 5-HT1A agonists are warranted to examine the potential cognitive efficacy of stimulating these receptors.

Smartphone video games improve cognitive function in patients with chronic schizophrenia: a randomized controlled trial.

This study aimed to examine the efficacy of video games in improving cognitive function in chronic patients with schizophrenia and to evaluate the biomarker of video games for cognitive function. The patients in the game group were requested to play single-player video games on their smartphones for 1h per day, five times a week for 6weeks. Those in the control group watched television for 1h per day, five times a week for 6weeks. Cognitive function was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and Stroop Color and Word Test (SCWT). Clinical symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS), Global Assessment of Functioning (GAF), General Self-Efficacy Scale (GSE), Problematic Mobile Gaming Questionnaire (PMGQ), and Patient Health Questionnaire-9 (PHQ-9). The game group demonstrated improved RBANS total score during the trial. There were no significant group effects among all SCWT scores. The game group demonstrated greater improvement on the PANSS Negative Scale, and global function (GAF score). The PMGQ scores were lower than the cutoff score at all time points in both groups. There were no significant group differences in the PHQ-9 and GSE scores. The serum BDNF levels were significantly higher in the game group following 6weeks of video game intervention. The BDNF serum levels of all participants were positively associated with the RBANS total scores. This preliminary study suggested that video games can improve cognitive function in schizophrenia patients. Serum BDNF levels may be a suitable biomarker for predicting an improvement in cognitive function in schizophrenia patients.Trial registration: This study was registered on March 11, 2021 (ChiCTR2100044113).Clinical trials: Smartphone video games improve cognitive function in patients with chronic schizophrenia; https://www.chictr.org.cn/hvshowproject.aspx?id=95623 ; ChiCTR2100044113.

The motivation and pleasure deficits but not expressivity affects social functioning through cognitive function in male patients with schizophrenia: A structural equation model.

This study aims to compare cognitive function and social functioning in male schizophrenia patients with deficit syndrome (DS) and non-DS, and to explore the associations among two different dimensions of negative symptoms (motivation and pleasure (MAP) and expressivity (EXP) deficits), cognitive function and social functioning base on a Structural Equation Model (SEM). The current study enrolled 161 male schizophrenia patients and 120 age- and education- matched healthy controls. The DS and non-DS group were categorized by the Chinese version of Schedule for the Deficit Syndrome (SDS). The psychotic and negative symptoms were evaluated by the Brief Psychiatric Rating Scale (BPRS) and the Brief Negative Symptoms Scale (BNSS). The Social functioning was measured by Scale of Social function in Psychosis Inpatients (SSPI). A battery of classical neurocognitive tests was used for assessing cognition including sustained vigilance/attention, cognitive flexibility, ideation fluency and visuospatial memory. Our study indicated that DS patients performed worser in cognitive function and social functioning than non-DS patients. The SEM model demonstrated that MAP significantly affected social functioning through direct influence and mediation of cognitive function. However, our results found that EXP had little influence on cognitive function and social function. Our findings provided evidence supporting that DS may represent as a subtype of schizophrenia, and the MAP factor play a pivotal role to influence the cognitive and social functioning in schizophrenia patients.

Evaluation of the Relationships between Irisin Levels and Cognitive Functions in Individuals with Schizophrenia.

: Irisin is a myokine that is involved in neurogenesis, neuronal proliferation, and neuronal differentiation. Many research examine the relationship between irisin and schizophrenia. In this study, we aimed to evaluate the relationship between irisin levels and cognitive functions in individuals with schizophrenia. : Ninety-six individuals who were diagnosed with schizophrenia were included. The Brief Psychiatric Rating Scale (BPRS) was used to assess disease severity. To evaluate the cognitive functions of the patients, the trail-making test was evaluated with the A and B forms and the verbal memory processes scale. After a 12-hour night fast, samples of fasting blood were obtained from the participants. : There was no significant correlation between irisin, duration of disease, and BPRS total score. In the analysis performed, a positive correlation was found between the plasma irisin level and the error score of the trail-making test form B. Other than that, no correlation was found between irisin level and cognitive performance in schizophrenia patients. In addition, in subgroup analysis between genders, it was determined that the duration of the trail-making test B was longer in female schizophrenia patients. : In this study, there was a positive correlation between the trail-making test B-form error scores and the irisin levels. This relationship between impaired executive functions and irisin levels may suggest that the irisin level is increased as compensation for the impairment in executive functions. More research is needed to understand the role of irisin in cognitive impairment and schizophrenia.

Sex difference in association between tardive dyskinesia and cognitive deficits in patients with chronic schizophrenia.

Tardive dyskinesia (TD), a side effect due to long-term use of antipsychotic medication, is associated with cognitive impairment. Several studies have found sex differences in cognitive impairment in schizophrenia patients, while whether there are sex differences in cognitive performance in schizophrenia patients with TD has not been reported. A total of 496 schizophrenia inpatients and 362 healthy controls were recruited for this study. We used the Positive and Negative Syndrome Scale (PANSS) to assess patients' psychopathological symptoms and the Abnormal Involuntary Movement Scale (AIMS) to assess the severity of TD. Cognitive function was measured in 313 of these inpatients and 310 of healthy controls using the Repeatable Battery for Assessment of Neuropsychological Status (RBANS). Patients with schizophrenia performed worse in all cognitive domains than healthy controls(all p<0.001). Compared to patients without TD, patients with TD had higher PANSS total, PANSS negative symptom subscale and AIMS scores (all p<0.001), while RBANS total, visuospatial/constructional and attention subscale scores were significantly lower (all p<0.05). In addition, the visuospatial/constructional and attention indices remained significantly lower in male patients with TD than those without TD (both p<0.05), but these results were not observed in female patients. Moreover, visuospatial/constructional and attention indices were negatively correlated with total AIMS scores only in male patients (both p<0.05). Our results suggest that there may be sex differences in cognitive impairment in schizophrenia patients with comorbid TD, indicating that female gender may have a protective effect on cognitive impairment in schizophrenia patients caused by TD.

Study investigating executive function in schizophrenia patients and their unaffected siblings.

Schizophrenia (SCZ) is characterized by widespread cognitive impairments, such as executive functions. Most of the available research indicate that executive impairment has a certain genetic predisposition. Shared neuropathological characteristics of patients with SCZ and their siblings may reveal intermediate behavioral phenotypes that can be used to further characterize the illness. Our study involved 32 SCZ patients, 32 unaffected siblings (US), and 33 persons as healthy controls (HCS). These three groups underwent a computerized version of the Wisconsin Card Sorting Test (WCST), and a battery of cognitive neuropsychological assessments. These tests also evaluate executive function and several cognitive domains. The performed study on SCZ patients and their unaffected siblings showed an inferior WCST performance to the HCS subjects, further indicating that unaffected siblings have a functional impairment, and they also performed poorly on the neuropsychological assessment compared with the HCS. This result supports the claim that the development of functional impairment is not limited to SCZ patients and unaffected siblings may also have a certain level of abnormal brain function. Consequently. neurological abnormalities lead to the abnormal functioning in siblings and patients, suggesting that genetics plays a considerable role in such results.

Resting-State EEG Connectivity at High-Frequency Bands and Attentional Performance Dysfunction in Stabilized Schizophrenia Patients.

Background and Objectives: Attentional dysfunction has long been viewed as one of the fundamental underlying cognitive deficits in schizophrenia. There is an urgent need to understand its neural underpinning and develop effective treatments. In the process of attention, neural oscillation has a central role in filtering information and allocating resources to either stimulus-driven or goal-relevant objects. Here, we asked if resting-state EEG connectivity correlated with attentional performance in schizophrenia patients. Materials and Methods: Resting-state EEG recordings were obtained from 72 stabilized patients with schizophrenia. Lagged phase synchronization (LPS) was used to measure whole-brain source-based functional connectivity between 84 intra-cortical current sources determined by eLORETA (exact low-resolution brain electromagnetic tomography) for five frequencies. The Conners' Continuous Performance Test-II (CPT-II) was administered for evaluating attentional performance. Linear regression with a non-parametric permutation randomization procedure was used to examine the correlations between the whole-brain functional connectivity and the CPT-II measures. Results: Greater beta-band right hemispheric fusiform gyrus (FG)-lingual gyrus (LG) functional connectivity predicted higher CPT-II variability scores (r = 0.44, p < 0.05, corrected), accounting for 19.5% of variance in the CPT-II VAR score. Greater gamma-band right hemispheric functional connectivity between the cuneus (Cu) and transverse temporal gyrus (TTG) and between Cu and the superior temporal gyrus (STG) predicted higher CPT-II hit reaction time (HRT) scores (both r = 0.50, p < 0.05, corrected), accounting for 24.6% and 25.1% of variance in the CPT-II HRT score, respectively. Greater gamma-band right hemispheric Cu-TTG functional connectivity predicted higher CPT-II HRT standard error (HRTSE) scores (r = 0.54, p < 0.05, corrected), accounting for 28.7% of variance in the CPT-II HRTSE score. Conclusions: Our study indicated that increased right hemispheric resting-state EEG functional connectivity at high frequencies was correlated with poorer focused attention in schizophrenia patients. If replicated, novel approaches to modulate these networks may yield selective, potent interventions for improving attention deficits in schizophrenia.

Differences in olfactory dysfunction and its relationship with cognitive function in schizophrenia patients with and without auditory verbal hallucinations.

Olfactory discrimination dysfunction has been observed in patients with schizophrenia (SCZ), but its relationship with cognitive function has not been clarified. The purpose of this study was to examine the differences in olfactory identification function in SCZ patients with and without auditory verbal hallucinations (AVHs) and its relationship with cognitive function. Olfactory identification function was measured in 80 SCZ patients with AVHs, 57 SCZ patients without AVHs, and 87 healthy controls (HC). Clinical symptom scores and neuropsychological measures were also administered to all corresponding subjects. Compared to HC, SCZ patients showed significant deficits in olfactory identification and cognitive function, but there were no differences in olfactory identification dysfunction and cognitive dysfunction between the two subgroups. In the non-AVHs subgroup only, poorer Olfactory Stick Identification Test for Japanese (OSIT-J) scores were significantly and positively correlated with total and delayed recall (Bonferroni correction, p < 0.002). Stepwise regression analysis revealed that factors affecting olfactory identification impairment differed in the two SCZ patient subgroups. In conclusion, this study highlights the commonality of olfactory identification dysfunction in SCZ patients and the importance of olfactory assessment of different subtypes of SCZ patients.

Association of serum homocysteine levels with intestinal flora and cognitive function in schizophrenia

Some studies have indicated that elevated homocysteine (Hcy) levels and intestinal flora may be involved in schizophrenia (SZ) cognition pathophysiology. This study was the first to investigate the association among Hcy, intestinal flora and schizophrenia cognition. Here, 140 individuals were divided into two groups: SZ patients (N = 68) and healthy controls (HCs, N = 72). Participant data on serum Hcy levels, intestinal flora and cognitive function evaluation using the MATRICS Consensus Cognitive Battery (MCCB) were collected. Clinical symptoms of patients were evaluated using the Positive and Negative Syndrome Scale. Serum Hcy levels and the incidence of hyperhomocysteinaemia were considerably increased in SZ patients compared with HCs. Hcy levels were significantly negatively associated with verbal learning index scores (r = −0.425, p < 0.001) but positively associated with Eubacterium (r = 0.32, p = 0.007), Lactobacillus (r = 0.32, p = 0.008), Corynebacterium (r = 0.26, p = 0.035), Mogibacterium (r = 0.31, p = 0.01), and Bulleidia (r = 0.31, p = 0.01) in SZ patients. Our findings suggest that serum Hcy levels are associated with cognitive function and intestinal flora in SZ patients. However, the mechanism of the interaction between Hcy and intestinal flora and its effects on cognitive function in SZ patients requires further investigation.

The Role of Two Factors of Negative Symptoms and Cognition on Social Functioning in Male Patients with Schizophrenia: A Mediator Model

This study aims to compare the cognitive function and social functioning in male patients with deficit syndrome (DS) and non-DS, and to explore whether cognitive function serves as a mediator in the relationship between the two factors of negative symptoms (motivation and pleasure (MAP) and expressivity (EXP) deficits, and social functioning in schizophrenia patients. One hundred and fifty-six male patients with schizophrenia and 109 age- and education-matched normal controls were enrolled in the current study. The Chinese version of a Schedule for Deficit Syndrome (SDS) was used for DS and non-DS categorization. The Brief Psychiatric Rating Scale (BPRS) and the Brief Negative Symptoms Scale (BNSS) were used to assess psychotic and negative symptoms in patients. The Social-Adaptive Functioning Evaluation (SAFE) was adopted to evaluate patients' social functioning, and a battery of classical neurocognitive tests was used to assess cognition, including sustained vigilance/attention, cognitive flexibility, ideation fluency, and visuospatial memory. We found that male patients with DS performed worse in all four cognitive domains and social functioning compared to non-DS patients. Both total negative symptoms and its two factors were significantly associated with all four domains of cognition and social functioning in male patients. Interestingly, our results indicate that only cognitive flexibility mediates the relationship between negative symptoms and social functioning in schizophrenia patients, but there were no differences between EXP and MAP negative factors in this model. Our findings suggest that DS patients may represent a unique clinical subgroup of schizophrenia, and the integrated interventions targeting both negative symptoms and cognition, especially cognitive flexibility, may optimally improve functional outcomes in schizophrenia patients.

Associations of polycyclic aromatic hydrocarbons, water-soluble ions and metals in PM2.5 with liver function: Evidence from schizophrenia cohort

BackgroundFine particulate matter (PM2.5) was reported to impact liver function, but the roles of specific PM2.5 chemical components remained to be explored. Besides, severe liver dysfunction in schizophrenia patients deserves attention. ObjectiveTo investigate the associations of short-term PM2.5 components with liver function in schizophrenia patients. MethodsA repeated-measures study based on schizophrenia cohort including 1023 visits (n = 446) was conducted during 2017–2020. Liver function was reflected by 10 indicators including liver enzymes, proteins and bilirubin et al. Monitoring data of PM2.5 and its components, including 16 polycyclic aromatic hydrocarbons (PAHs), 4 water-soluble ions and 10 metals were collected. Linear mixed effect and Bayesian kernel machine regression (BKMR) models were used to evaluate the single and combined effects of PM2.5 components (0–3 day) on liver function in schizophrenia patients. ResultsSeveral PAHs were significantly associated with liver enzymes, while water-soluble ions and metal components had almost no association. Specifically, with per interquartile range (IQR) increased in Fluoranthene, levels of alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate transaminase (AST) and gamma-glutamyl transpeptidase (GGT) increased by 2.06 %, 5.07 %, 4.94 % and 5.56 %, respectively. An IQR increases in Benzo[a]pyrene was significantly associated with 6.62 %, 3.67 % and 7.83 % increase in ALT, AST and GGT. Almost all PAHs, sulfate, nitrate, ammonium, Sb, Al, As, Pb, Mn and Tl were positively associated with albumin (ALB). Phenanthrene was associated with increased levels of direct bilirubin (DBIL) and total bilirubin (TBIL). The combined effects of significant PM2.5 components on ALP, GGT, ALB, globulin (GLOB), ratio of albumin to globulin (A/G), TBIL and total bile acid (TBA) were found by BKMR, respectively. ConclusionsFindings highlight the short-term combined effects of PM2.5 components, especially PAHs, on liver function in schizophrenia patients, which contribute to the management of PM2.5 sources including combustion activities and traffic emissions as well as improving schizophrenia comorbidities.

The effect of cognitive behavioral therapy for insomnia on neuropsychological performance in schizophrenia patients with insomnia: A randomized controlled trial

Background: Cognitive behavioral therapy for insomnia (CBT-I) is considered the gold standard for insomnia, but its relative role in improving cognition has not been addressed. Hence, we aimed to study the effect of CBT-I on sleep quality, psychopathology, and neuropsychological performance in schizophrenia. Methods: Randomly allocated 40 right-handed schizophrenia patients with insomnia were delivered four sessions of weekly CBT-I. Pre-postassessments with Pittsburgh Sleep Quality Index (PSQI), AIIMS Comprehensive Neuropsychological Battery (AIIMS NCB), Positive and Negative Syndrome Scale, Multidimensional Fatigue Inventory, Warwick-Edinburg Mental Well-being Scale (WEMWBS), and Global Assessment Functioning (GAF) were done. Results: CBT-I had significant effects on PSQI, AIIMS NCB total and memory scores, WEMWBS, and GAF compared to the control group. Conclusion: In a subset of schizophrenia patients with insomnia, sleep-based interventions improve sleep quality and neuropsychological performance.

Gut mycobiota dysbiosis in drug-naïve, first-episode schizophrenia

Bacterial dysbiosis has been demonstrated in patients with schizophrenia (SCH). The aim of the present study was to investigate alterations in mycobiota composition and fungi-bacteria correlation network in drug-naïve, first episode SCH. We recruited 205 SCH patients and 125 healthy controls (HCs), whose gut bacterial and fungal compositions were characterized by 16S and 18S ribosomal RNA gene amplicon sequencing, respectively. Fungal-bacterial relative correlation network analysis was performed using the Spearman's test and distance correlation. We also computed relative networks connectedness, which represents the ratio of significant interactions (edges) and taxa (nodes) in the network. SCH patients showed lower fungal α-diversity compared with that of HCs. Furthermore, we identified 29 differential fungal markers at multiple taxonomies between SCH patients and HCs. SCH patients also showed a significantly lower fungi-to-bacteria α-diversity ratio compared with that of HCs (p = 1.81 × 10−8). In risk prediction models, we observed that combining bacterial and fungal markers achieved higher accuracy than that of bacterial markers alone (AUC = 0.847 vs AUC = 0.739; p = 0.043). Fungal-bacterial correlation network was denser in HCs than in SCH patients and was characterized by a high number of neighbors (p < 0.05). In addition, an increased abundance of Purpureocillium was associated with more severe psychiatric symptoms and poorer cognitive function in SCH patients (p < 0.05). Our study demonstrated a disrupted and weakened fungi-bacteria network in SCH patients, which might be associated with their clinical manifestations. Future research on fungal-bacterial correlation network is warranted to advance our understanding about the role of mycobiota in the etiology of SCH and to explore novel intervention approaches.

Influence of cardiovascular risk factors on the cognitive functions of schizophrenia patients

Cardiovascular risk factors (CVRF) are quite often observed in the group of patients with schizophrenia, contributing to a deterioration in their standard of living. In addition, CVRF can cause death of such patients. However, the influence of these factors on many spheres of schizophrenia patients, in particular cognitive functions, remain understudied. The objective of the research was to study the effect of CVRF (hypertension (HT), cardiac disorders (ischemic heart disease), intracardiac conduction disturbance), diabetes mellitus (DM), and myocardial infarction (MI) on cognitive functions of schizophrenia patients. The study involved 102 patients diagnosed with paranoid schizophrenia who were hospitalized in psychiatric departments № 1 and № 5 of the State Institution «Lugansk Republican Clinical Psychoneurological Hospital», Lugansk People»s Republic. All study participants were divided into two study groups: 1st — the control group (n = 52), 2nd — the group of patients with CVFR (n = 50). The mean age of the patients was 47.7±5.6 years; there were 40 males (39.2 %) and 62 females (60.8 %). Clinical, psychopathological, catamnestic, psychometric, and statistical research methods were used. As a result of the study, it was found that the patients with CVFR had poorer cognitive test scores for almost all of the presented parameters. Regression analysis in relation to the effect of CVFR on the general state of cognitive functions showed that all these factors considerably affected the cognitive status, with HT being the most statistically significant. CVFR can have a negative impact on the state of cognitive functions in schizophrenia patients.

Baseline global brain structural and functional alterations at the time of symptom onset can predict subsequent cognitive deterioration in drug-naïve first-episode schizophrenia patients: Evidence from a follow-up study.

Alterations in the global brain gray matter volume (gGMV) and global functional connectivity density (gFCD) play a pivotal role in the cognitive impairment and further deterioration in schizophrenia. This study aimed to assess the correlation between alterations in the gGMV and gFCD at baseline (ΔgGMV and ΔgFCD), and the subsequent alterations of cognitive function in schizophrenia patients after 2-year antipsychotic treatment. Global-brain magnetic resonance imaging scans were acquired from 877 drug-naïve, first-episode schizophrenia patients at baseline and after two years of antipsychotic treatment with adequate dosage and duration, and 200 healthy controls. According to ΔgGMV at baseline, schizophrenia patients were divided into mild, moderate, and severe alteration groups. The MATRICS consensus cognitive battery and Global Deficit Score (GDS) were used to assess cognitive impairment. We found that ΔgGMV and ΔgFCD at baseline were significantly correlated with the severity of the cognitive deterioration (ΔGDS). The correlation coefficient indicated a significant positive correlation between baseline ΔgFCD and subsequent cognitive deterioration, with a relatively stronger relation in the mild alteration group (r = 0.31). In addition, there was a significant positive correlation between baseline ΔgGMV and subsequent cognitive deterioration, with a stronger relation in the moderate and severe alteration groups (r = 0.303; r = 0.302, respectively). Our results showed that ΔgGMV and ΔgFCD are correlated with the severity of cognitive deterioration after completion of a 2-year antipsychotic treatment in schizophrenia patients. These findings suggest that baseline alterations in gGMV and gFCD hold potential for predicting subsequent cognitive decline in schizophrenia.

Galectin-3 mediated risk of inflammation in stable schizophrenia, with only possible secondary consequences for cognition.

BACKGROUNDEvidence suggests that cytokines cause immune disturbances, shape immunological sequelae later in life, and modulate the risk of schizophrenia (SC). Galectin-3 (Gal-3), a multifaceted molecule of the glycan family, is involved in the formation of the immunological synapse and modulates the signalling pathway and effector functions of T lymphocytes, which are major producers of cytokines. We have previously reported elevated serum Gal-3 levels in stable SC patients. However, Gal-3 as a link between cognitive functioning and inflammation has not yet been investigated in SC.AIMTo investigate the relationship between serum Gal-3 levels and cognitive performance, serum cytokines, and white blood cell count in three-month stably treated SC patients.METHODSTwenty-seven patients with SC in remission and 18 healthy volunteers participated in this case-control and correlational study. Clinical assessment was performed using the Positive and Negative Syndrome Scale and the Montreal-Cognitive Assessment. The results of previously measured serum levels of Gal-3, interleukin (IL)-33, soluble suppression of tumorigenicity 2 (sST2), tumor necrosis factor-alpha (TNF-α), IL-6 and IL-17 were used for further statistical analyses, and IL-4, IL-23, IL-1β and transforming growth factor-beta (TGF-β) were now additionally measured with a sensitive enzyme-linked immunosorbent assay. The number of leukocytes in the blood and the percentage of neutrophils, lymphocytes, and monocytes were determined with a standardized routine measurement procedure (Sysmex Technology). Statistical analyses were performed using SPSS 20.0 software.RESULTSWe found no correlation between serum Gal-3 levels and cognitive functioning in SC patients. A positive correlation was found between the levels of Gal-3 and TNF-α (r = 0.476; P = 0.012), Gal-3 and IL-23 (r = 0.417; P = 0.031), and Gal-3 and sST2 (r = 0.402; P = 0.038). The binary logistic model, which included all nine cytokines measured in this patient sample, indicated the particular role of Gal-3 and TGF-β in the duration of SC. In the stabilization phase of SC, we observed a moderate and negative correlation between serum Gal-3 levels and leukocytes (r = -0.449; P < 0.019). Additional linear regression analysis showed a positive correlation between Gal-3 expression and risperidone dose (F: 4.467; P < 0.045; r2 = 0.396).CONCLUSIONThe combined activity of Gal-3 and proinflammatory cytokines, TGF-β downregulation and lower counts of leukocytes influence the SC duration. Gal-3 likely manifests indirect immunometabolic regulation of cognition in SC.

Brain Stimulation and Group Therapy to Improve Gesture and Social Skills in Schizophrenia-The Study Protocol of a Randomized, Sham-Controlled, Three-Arm, Double-Blind Trial.

An important component of nonverbal communication is gesture performance, which is strongly impaired in 2/3 of patients with schizophrenia. Gesture deficits in schizophrenia are linked to poor social functioning and reduced quality of life. Therefore, interventions that can help alleviate these deficits in schizophrenia are crucial. Here, we describe an ongoing randomized, double-blind 3-arm, sham-controlled trial that combines two interventions to reduce gesture deficits in schizophrenia patients. The combined interventions are continuous theta burst stimulation (cTBS) and social cognitive remediation therapy (SCRT). We will randomize 72 patients with schizophrenia spectrum disorders in three different groups of 24 patients. The first group will receive real cTBS and real SCRT, the second group will receive sham cTBS and real SCRT, and finally the third group will receive sham SCRT. Here, the sham treatments are, as per definition, inactive interventions that mimic as closely as possible the real treatments (similar to placebo). In addition, 24 age- and gender-matched controls with no interventions will be added for comparison. Measures of nonverbal communication, social cognition, and multimodal brain imaging will be applied at baseline and after intervention. The main research aim of this project will be to test whether the combination of cTBS and SCRT improves gesture performance and social functioning in schizophrenia patients more than standalone cTBS, SCRT or sham psychotherapy. We hypothesize that the patient group receiving the combined interventions will be superior in improving gesture performance.Clinical Trial Registration[www.ClinicalTrials.gov], identifier [NCT04106427].

Correlation of Orexin-A and brain-derived neurotrophic factor levels in metabolic syndrome and cognitive impairment in schizophrenia treated with clozapine

Orexin-A and brain-derived neurotrophic factor (BDNF) are implicated in regulating metabolic syndrome (MetS) and cognitive impairment of schizophrenia. However, the associations among them remains unclear. Here, we aimed to investigate the relationship between Orexin-A levels, BDNF, MetS, clinical symptom profile, and cognitive function in schizophrenia patients following long-term clozapine treatment. We measured Orexin-A and BDNF levels in 140 schizophrenia patients with and without MetS. We assessed clinical symptoms on the Positive and Negative Syndrome Scale and cognitive function by the assessment of Neuropsychological Status (RBANS), and examined their associations with Orexin-A. Patients with MetS had significantly lower Orexin-A levels and higher coding test, attention span and delayed retention in RBANS (P < 0.05). Correlation analysis showed that Orexin-A was associated with BDNF, TG, HDLC, PANSS active social avoidance and emotional withdrawal significantly. Besides, Orexin-A significantly interacted with BDNF for metabolic and cognitive profiles including waist circumference, delayed retention and list recognition. Logistic regression analysis showed that Orexin-A level (odds ratio [OR] = 0.380, 95% confidence interval [CI]: 0.151–0.952, P = 0.039) and total illness duration (OR = 0.932, 95% CI: 0.875–0.991, P = 0.025) were predictive variables of MetS. However, there was no significant relationship between Orexin-A and cognitive function after adjustment for age, sex and educational levels. Totally, a lower plasma Orexin-A level seems to be related to metabolic parameters more than cognitive profiles. The interaction of Orexin-A with BDNF may be partly responsible for worse MetS and better cognition of elderly schizophrenia, but the causal relationship needs further clarification.