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Abnormalities in subcortical brain structures may reflect higher suicide risk in mood disorders, but less is known about its associations for schizophrenia. This cross-sectional imaging study aimed to explore whether the history of suicide attempts was associated with subcortical changes among individuals with schizophrenia. We recruited 44 individuals with schizophrenia and a history of suicide attempts (SZ-SA) and 44 individuals with schizophrenia but without a history of suicide attempts (SZ-NSA) and 44 healthy controls. Linear regression showed that SZ-SA had smaller volumes of the hippocampus (Cohen's d = −0.72), the amygdala (Cohen's d = −0.69), and some nuclei of the amygdala (Cohen's d, −0.57 to −0.72) than SZ-NSA after adjusting for age, sex, illness phase, and intracranial volume. There was no difference in the volume of the subfields of the hippocampus. It suggests the history of suicide attempts is associated with subcortical volume alterations in schizophrenia. [ABSTRACT FROM AUTHOR]

Background: About 20–30% of patients with schizophrenia develop tardive dyskinesia (TD). Oxidative stress is one potential causes of TD. CYP2E1 is considered as an oxidative stress-related gene, however, no study has been reported on the DNA methylation levels of the CYP2E1 in schizophrenia or TD. Methods: A total of 35 schizophrenia patients with TD, 35 schizophrenia patients without TD (NTD), and 35 health controls (HCs) were collected in Beijing, China. DNA was extracted from peripheral blood samples. The promoter methylation levels of CYP2E1 were detected using pyrosequencing. The generalized linear model (GLM) was used to examine the methylation levels of three CpG sites among three diagnostic groups (TD vs. NTD vs. HC). Results: The average methylation levels were 8.8 ± 10.0, 14.5 ± 11.9 and 15.1 ± 11.3 in TD, NTD and HC groups, respectively. The F-test in GLM revealed overall differences in the average of methylation levels of three CpG sites among three diagnostic groups (p = 0.0227) and in the third CpG site (p = 0.0026). Furthermore, the TD group had lower average methylation levels than HC and NTD groups (p = 0.0115 and 0.0268, respectively). Specifically, TD group showed lower methylation levels in the third CpG site than HC and NTD groups (p = 0.0012 and 0.0072, respectively). Additionally, associations of the methylation levels with clinical features in the TD group were observed using Spearman correlation analysis. Conclusion: This study provides the first evidence of DNA methylation levels in the promoter of CYP2E1 gene associated with schizophrenia and TD. The abnormal DNA methylation might serve as a potential mechanism for TD. [ABSTRACT FROM AUTHOR]

Objective: The present study aimed to evaluate the efficacy and safety of aripiprazole once-monthly (AOM) compared to oral aripiprazole in treating acute schizophrenia. Methods: This randomized, double-blind, non-inferiority study recruited patients from 15 trial sites across China from May 2017 to April 2019. Patients with an acute psychotic episode received AOM at 400 mg or oral aripiprazole at 10–20 mg for 12 weeks. The primary and secondary efficacy endpoints were the difference in scores from baseline to week 10, as assessed on the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impressions—Severity (CGI-S) scores, respectively. Results: A total of 436 patients were randomized. Among them, 159/218 (72.9%) and 165/218 (75.7%) in the AOM and oral aripiprazole groups completed 10 weeks of treatment, respectively. The least-squares (LS) mean changes from baseline to endpoint (week 10) in PANSS were − 33.6 for the AOM group and − 34.8 in the oral aripiprazole group, respectively, with a difference of − 1.2 (95% CI: − 4.1, 1.7). The non-inferiority margin of AOM to oral aripiprazole was − 4.1, which was above the lower limit of the pre-defined margin. The altered CGI-S score was − 2.2 and − 2.3 in the AOM and oral aripiprazole groups, respectively. The incidence of treatment-emergent adverse events (TEAEs) was similar in both groups. The rate of discontinuation due to TEAEs was 2.3% and 3.2% in the AOM and oral aripiprazole groups, respectively. Conclusions: This study confirmed the efficacy and safety of AOM for the treatment of Chinese patients with acute schizophrenia. The non-inferiority of AOM to oral aripiprazole was established, with comparable efficacy and tolerability. These findings suggested that AOM could be used as a treatment option for patients experiencing an acute episode of schizophrenia. Trial registration: ClinicalTrials.gov identifier: NCT03172871. [ABSTRACT FROM AUTHOR]

Objective: To determine whether suicidal ideation or suicide attempts are linked to poor neurocognitive function among individuals with first‐episode schizophrenia (FES). Method: We performed a cross‐sectional study on 159 Chinese inpatients (Mage = 27.1 years; 52.2% females) with minimal‐treated FES and collected their suicidal history through interviews and medical records. Neurocognitive performance, psychopathology, and depressive symptoms were assessed using the MATRICS Consensus Cognitive Battery, the Positive and Negative Syndrome Scale, and the Calgary Depression Scale for Schizophrenia, respectively. Results: Approximately 1/10 FES inpatients had any suicide attempts, and more than 1/4 reported lifetime suicidal ideation. Inpatients with a suicide attempt or suicidal ideation scored significantly worse in the overall seven neurocognitive domains compared with those without past suicidal ideation or a suicide attempt. Linear regression suggested that suicide attempts were mainly associated with lower scores in working memory and speed of processing, after adjusting for education levels. The associations remained robust after further controlling for psychopathological and depressive symptoms. Conclusion: First‐episode schizophrenia patients with suicide attempts had more severely impaired neurocognitive performances in specific domains. Fundamental neurocognitive dysfunctions should be assessed, detected, and treated after their suicide risk assessments. [ABSTRACT FROM AUTHOR]

Aim: The aim of the present study was to evaluate the efficacy and safety of lurasidone for the treatment of Chinese schizophrenic patients. Methods: Hospitalized schizophrenia patients aged 18–65 were randomized to 6 weeks of double‐blind, double‐dummy, flexible‐dose treatment with lurasidone (40 or 80 mg/day) or risperidone (2, 4 or 6 mg/day). Efficacy was evaluated using a non‐inferiority comparison of lurasidone relative to risperidone based on week 6 change in the Positive and Negative Syndrome Scale (PANSS) total score. Safety assessments included adverse events, clinical laboratory measures, and electrocardiograms. Results: Four hundred and forty‐four patients were screened to obtain an intent‐to‐treat sample of 384 patients, of whom 54 patients discontinued treatment prior to 6 weeks. Lurasidone met the criteria for non‐inferiority versus risperidone on the PANSS total score. Adjusted mean (SE) change at week 6 on the PANSS total score was −31.2 (1.0) and −34.9 (1.0) in the lurasidone and risperidone group, respectively. The mean difference score was 3.7, and the upper boundary of the 95%‐confidence interval (1.0–6.3) was less than the prespecified margin of 7.0. No clinically meaningful between‐treatment group differences were evident on secondary efficacy measures, including PANSS positive, PANSS negative, Clinical Global Impression scale – Severity, and Calgary Depression Scale for Schizophrenia scales. The incidence of adverse events was lower for lurasidone vs risperidone for extrapyramidal symptoms (17.0% vs 38.2%), akathisia (7.2% vs 13.6%), prolactin increase (3.1% vs 14.1%), and weight increase (0.5% vs 5.2%). Conclusion: Lurasidone was found to be non‐inferior to risperidone on the primary endpoint with minimal effects on weight, metabolic parameters, or prolactin levels. [ABSTRACT FROM AUTHOR]

Introduction: Prepulse inhibition (PPI) of the auditory startle reflex, as an operational measurement used to evaluate the function of brain sensorimotor gating, appears to be a sensitive potential endophenotype for schizophrenia.CHRNA4is highly expressed in the central nervous system and has been demonstrated to be significantly associated with schizophrenia by previous studies. The purpose of the current study was to evaluate the effect ofCHRNA4on PPI and acoustic startle parameters in schizophrenia. Methods: 77 patients with schizophrenia and 62 controls were administered the test PPI, and 3 single nucleotide polymorphisms (SNPs) (rs3746372, rs1044396, and rs3787140) ofCHRNA4were genotyped in these subjects. Results: Patients with schizophrenia showed significantly lower levels of PPI at the 120 ms prepulse intervals and longer peak latency than controls, and the GG genotype of rs3746372 and the TT genotype of rs1044396 were associated with decreased PPI levels in schizophrenia but not in controls. Conclusion: PPI may be influenced by the polymorphisms of theCHRNA4in schizophrenia and it may be a potential endophenotype of schizophrenia. An independent replication would greatly increase the value of this study. [ABSTRACT FROM AUTHOR]

Background Mounting evidences have demonstrated the association of altered immune factors with neurodevelopmental and pathological progression of schizophrenia. However, whether immune factors play any role in the pathogenesis of tardive dyskinesia (TD) has been underexplored. To our best knowledge, ours is among the piloting studies examining the association of TNF alpha with extrapyramidal symptoms of schizophrenic patients so far. ObjectiveThe aim of this study was to assess the clinical significance of serum TNF alpha level in chronic schizophrenia, especially its potential association with TD. Methods Serum TNF alpha level was measured in a sandwich enzyme-linked immunosorbent assay (ELISA) from 46 medicated chronic schizophrenia patients with TD, 43 chronic schizophrenia patients without TD, and 43 healthy control subjects. The symptoms of schizophrenia were assessed by the positive and negative syndrome scale (PANSS). Results Chronic patients both with TD and without TD had significantly lower serum level of TNF alpha than controls (TD=9.5±2.1pg/ml, non-TD=10.7±1.8pg/ml, control=37.8±3.4pg/ml, p<0.001). Compared to patients without TD, TD patients showed marginally significant reduction in the serum TNF alpha level (p=0.05). The reduced TNF alpha level was not significantly affected by daily dose or duration of antipsychotic drugs (p>0.05). Serum TNF alpha level was negatively correlated with the PANSS total score in the whole schizophrenia patients (p<0.01), but no significant association with TD severity was observed. Conclusions Our results suggested that at chronic stage, serum TNF activity is associated with psychopathology of schizophrenia patients, but whether it can be a biomarker for TD needs further clarification in the future. [ABSTRACT FROM AUTHOR]

Schizophrenia patients with tardive dyskinesia (TD) are associated with accelerated biological aging, immunological dysfunction, and premature morbidity and mortality. Older individuals are particularly vulnerable to TD development. As a characteristic of immunosenescence, alterations in the relative proportions of naïve or memory T cell subpopulations may be negatively or positively associated with brain structure abnormalities; however, whether these changes are correlated with TD remains unclear. In this study, we investigated correlations between distributions of T cell phenotypes and brain structure abnormalities (especially white matter) in schizophrenia patients with (TD) and without (NTD) TD (n = 50 and 58, respectively) relative to healthy controls (HC, n = 41). Immune markers, including naïve (CD45RA+), memory (CD45RO+), and apoptotic (CD95+) CD4+ and CD8+ T cells, were examined by flow cytometry, as were the intracellular levels of cytokines (interferon (IFN)-γ, interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α) in CD8 + CD45RA + CD95+ and CD8 + CD45RO + CD95+ T cells. MRI was employed to evaluate the fractional anisotropy (FA) of white matter tracts and subcortical volumes, following published routines. The percentage of CD8 + CD45RO + CD95+ T cells was higher in TD compared with NTD and HC groups and correlated with the choroid plexus volume in TD group. The intracellular level of IFN-γ in CD8 + CD45RO + CD95+ T cells, the FA of the fornix/stria terminalis, and the pallidum volume were correlated with orofacial TD, whereas the FAs of the inferior fronto-occipital fasciculus, cingulum, and superior longitudinal fasciculus were correlated with limb-truncal TD. These findings provide preliminary evidence that the association between immunosenescence-related T cell subpopulations and brain structure may underline the pathological process of TD. [ABSTRACT FROM AUTHOR]

In the context of the COVID-19, inflammation emerges as a prominent characteristic. C-reactive protein (CRP) serves as a commonly employed marker for the evaluation of inflammation. This study aimed to examine the correlation between CRP levels and antipsychotic drug concentrations in patients diagnosed with SCZ during the COVID-19 pandemic. A total of 186 SCZ patients were included in this study, which utilized electronic medical records. The collected data encompassed SCZ diagnoses based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria, respiratory symptoms, and treatments. Laboratory assessments involved the measurement of CRP levels and monitoring of blood drug concentrations. The most prevalent symptoms observed in the patient cohort were fever (59.14%), cough (52.15%), fatigue (45.7%), sore throat (46.24%), runny nose (28.49%), and stuffy nose (25.27%). The levels of CRP during the infection period were significantly higher compared to both the prophase and anaphase of infection (all p < 0.001). The serum levels of clozapine, olanzapine, aripiprazole, quetiapine, and risperidone were elevated during the infection period (all p < 0.001). During the anaphase of infection, patients exhibited higher serum levels of clozapine, olanzapine, and risperidone (all p < 0.001) compared to the infection period, but there was no significant change in serum levels of aripiprazole and quetiapine. Multiple regression analysis revealed a statistically significant positive correlation (P < 0.0001) between CRP and clozapine concentration. In light of the COVID-19 pandemic, it is crucial to adjust the dosage based on drug serum concentration to prevent intoxication or adverse drug reactions. [ABSTRACT FROM AUTHOR]

In schizophrenia, the age at illness onset may reflect genetic loading and predict prognosis. We aimed to compare the pre-treatment symptom profiles and clinical symptom responses to antipsychotic treatment of individuals with late-onset schizophrenia (LOS; onset age: 40–59 years) with individuals with early-onset schizophrenia (EOS; onset age < 18 years) or typical-onset schizophrenia (TOS; onset age: 18–39 years). We conducted an 8-week cohort study in inpatient departments of five mental health hospitals in five cities in China. We included 106 individuals with LOS, 80 with EOS, and 214 with TOS. Their onset of schizophrenia was within three years and the disorders were minimally treated. The Positive and Negative Syndrome Scale (PANSS) was used to evaluate clinical symptoms at baseline and after 8 weeks of antipsychotic treatment. Mixed effect models were used to compare symptom improvement within eight weeks. Antipsychotic therapy reduced all PANSS factor scores in all three groups. LOS had significantly better improvement in PANSS positive factor scores than EOS at week 8 after adjusting for sex, duration of illness, dose equivalents of antipsychotics at baseline, sites as fixed effects, and individuals as random effects. LOS was associated with reduced positive factor scores at week 8 when receiving 1 mg olanzapine dose equivalent per 1 kg body weight compared with EOS or TOS. In conclusion, LOS had better early improvement of positive symptoms than EOS and TOS. Thus, personalized treatment for schizophrenia should consider the age of onset. • Age of schizophrenia onset is not related to the pre-treatment severity of positive symptoms. • Late-onset schizophrenia is related to better improvement of positive symptoms at week 8 than the early-onset. • Patients with late-onset schizophrenia are more sensitive to antipsychotics. [ABSTRACT FROM AUTHOR]

Immune disturbance has been postulated to be one of the mechanisms underlying the pathogenesis of tardive dyskinesia (TD). Recently, the role of autoimmune abnormality in TD has been increasingly recognized. Autoantibodies against neuronal N-methyl-D-aspartate receptor (NMDAR) may be cross-reactive in the brain in neuropsychiatric disorders, and the choroid plexus (CP) is a crucial immune barrier in the central nervous system (CNS). We supposed that NMDAR antibodies might underlie the pathophysiological process of TD through the mediation of CP. Serum NMDAR antibody levels were assessed by enzyme-linked immunosorbent assay, CP and ventricle volumes were assessed by magnetic resonance imaging in schizophrenia patients with TD (n = 61), without TD (NTD, n = 61), and in healthy controls (n = 74). Psychopathology and TD severity were assessed by the Positive and Negative Syndrome Scale and Abnormal Involuntary Movement Scale (AIMS). NMDAR antibody levels were significantly higher, CP volumes were larger in the TD group than in the NTD group (p = 0.022; p = 0.019, respectively). In the TD group, higher NMDAR antibody level was correlated with larger CP volume (β = 0.406, p = 0.002). An elevated NMDAR antibody level and enlarged CP volume were correlated with orofacial AIMS score (β = 0.331 , p = 0.011; β = 0.459 , p = 3.34 × 10−4, respectively). In a mediation model, the effect of NMDAR antibody level on the orofacial AIMS score was mediated by the CP volume (indirect effect: β = 0.08, 95% confidence interval = 0.002–0.225; direct effect: β = 0.14, p = 0.154). Our findings highlight a potential NMDAR antibody-associated mechanism in orofacial TD, which may be mediated by increased CP volume. [ABSTRACT FROM AUTHOR]

Accumulating evidence indicates that a dysregulated kynurenine (KYN) pathway (KP) metabolism may play an important role in the pathogenesis of both schizophrenia and metabolic syndrome (MS). However, the underlying mechanisms remain poorly understood. Here, we aimed to evaluate the potential roles of KP in the pathogenesis of MS in schizophrenia. A total of 160 schizophrenia patients and 70 healthy controls were enrolled in this study. KP metabolites were quantified, and MS scores were calculated, for comparisons between patients and controls. Associations among the indices were explored in both groups. Multiple linear regression analyses were performed to investigate the effects of KP metabolites on MS factors. We observed a significantly higher MS score, lower levels of all KP metabolites, and higher nicotinamide adenine dinucleotide (NAD+)/quinolinic acid (QUNA) in patients than in controls (all p < 0.01). Partial correlation analyses revealed that, in the patient group, QUNA and QUNA/KYN correlated positively with MS score (r = 0.24 and 0.27, respectively, both p < 0.025), and NAD+/QUNA correlated negatively with MS score (r = −0.25, p = 0.002). Results of multiple regression analyses showed significant QUNA × group interactions in the model representing QUNA effects on MS score (β = 0.25) and a significant QUNA/KYN × group interaction in the model representing QUNA/KYN effects on MS score (β = 0.23) (both p < 0.001). Among all factors contributing to MS in schizophrenia, an interactive effect of schizophrenia itself and dysregulated KP plays a contributory role. Conceivably, modulation of the KP could theoretically lead to treating schizophrenia and MS simultaneously. • Kynurenine pathway (KP) metabolism is dysregulated in schizophrenia. • Schizophrenia itself and the dysregulated KP metabolism jointly contribute to the susceptibility to MS in this population. • Modulation of the KP could theoretically lead to treating schizophrenia and MS simultaneously. [ABSTRACT FROM AUTHOR]

Norepinephrine has both central and peripheral origins and is known to influence cognitive processes in attention, learning, and working memory, but the research regarding the impact of norepinephrine on cognition in schizophrenia remains sparse, and mainly focuses on centrally regulated noradrenergic effects. This study examined the relationship between cumulative overnight norepinephrine levels in the urine and working memory in patients with schizophrenia and healthy controls. Urinary catecholamines were collected overnight in patients with schizophrenia (n = 75) and healthy controls (n = 33). Working memory was assessed using the digit sequencing task. Patients showed significantly higher average levels of overnight norepinephrine (t(103.10) = −3.16, p = 0.002) and reduced working memory performance (t(90) = 3.87, p = 0.001) compared with healthy individuals. There was a significant negative correlation between norepinephrine and working memory in patients (r = −0.38, p = 0.005), but not in controls (r = 0.08, p = 0.67). After controlling for age, sex, antipsychotic medications, and serotonin-norepinephrine reuptake inhibitor-based antidepressants, the correlation remained significant (r = −0.41, p = 0.004). High peripheral overnight levels of urinary norepinephrine are associated with lower working memory performance in patients with schizophrenia. These results parallel previous studies suggesting that high levels of central norepinephrine may result in working memory impairments. As norepinephrine rapidly breaks down and usually does not pass through the blood-brain barrier, the potential effect of peripheral cumulative norepinephrine on working memory is intriguing, and needs to be further investigated. [ABSTRACT FROM AUTHOR]

MicroRNA (miR)-181b-5p is considered to be involved in the pathogenesis of schizophrenia, and one of its regulatory target genes BCL-2 (B-cell lymphoma 2) is suggested to associate with cognition of schizophrenia. Cognitive deficit is a core trait of schizophrenia. However, it remains unclear whether miR-181b-5p affects cognition and its possible pathway in schizophrenia. We hypothesized that miR-181b-5p affects cognition by targeting BCL- 2 mRNA and downregulating BCL-2 protein expression in schizophrenia patients. In this study, first-episode patients with schizophrenia (FEPS, n = 123) and age- and gender-matched healthy controls (HCs, n = 50) were enrolled in Chinese populations. Expression levels of miR-181b-5p and BCL- 2 mRNA in peripheral whole blood were measured with quantitative real-time PCR (Q-PCR) and BCL-2 protein in plasma were measured with Enzyme Linked Immunosorbent Assay (ELISA). Psychopathology was assessed with the Positive and Negative Syndrome Scale (PANSS), cognitive function was evaluated using the MATRICS Consensus Cognitive Battery (MCCB). Peripheral blood miR-181b-5p expression level was significantly upregulated (p = 0.001) whereas BCL- 2 mRNA and BCL-2 protein levels were significantly downregulated (p = 0.002, p = 0.023 respectively) in the FEPS compared with those in the HCs. The miR-181b-5p level was negatively (p = 0.005), whereas the BCL- 2 mRNA level was positively (p < 0.001), correlated with working memory in FEPS. Mediating effect analysis showed that the effect of miR-181b-5p on working memory in the FEPS was exerted via targeting BCL- 2 mRNA. MiR-181b-5p in combination with BCL- 2 mRNA might be suggested as potential biomarker for schizophrenia in our discovery sample. In conclusion, overexpressed miR-181b-5p may affect cognitive function in patients with schizophrenia. • Overexpressed microRNA-181b-5p may affect working memory of schizophrenia patients. • This effect was mediated by BCL- 2 mRNA in first-episode patients with schizophrenia. • MicroRNA-181b-5p and BCL-2 mRNA have the potential to be a biomarker. [ABSTRACT FROM AUTHOR]

Neural cell adhesion molecule (NCAM) plays an important role in neurodevelopmental processes and regulates hippocampal plasticity. This study investigated the relationship between the serum NCAM concentrations and hippocampal volume and psychotic symptoms in first-episode drug naïve schizophrenia (FES) patients. Forty-four FES patients and forty-four healthy controls (HC) were recruited in this study. Serum concentrations of NCAM were measured by ELISA. Psychiatric symptoms were assessed by the positive and negative syndrome scale (PANSS). Brain structural images were obtained using a 3T MRI Scanner and obtained T1 images were processed in order to determine hippocampal grey matter volumes. Schizophrenia patients revealed significantly decreased serum NCAM concentrations (p = 0.017), which were positively correlated with the left (r = 0.523, p < 0.001) and right (r = 0.449, p = 0.041) hippocampal volumes, but negatively correlated with the PANSS positive symptom scores (r = −0.522 p = 0.001). However, no such correlations existed in the HC group. This is the first time to report that decreased serum NCAM concentrations were associated with hippocampal volumes and symptom severity in FES patients. Our data indicate that the low NCAM is possible neuropathology that is associated with the decreased hippocampus in FES patients. [ABSTRACT FROM AUTHOR]

• FEP with schizophrenia had higher serum anti-NMDAR Ab level and poorer cognitive performance than controls. • Patient's serum Ab levels were positively and inversely correlated with psychiatric symptoms and cognition, respectively. • Autoimmunity against NMDAR may be a major factor in schizophrenia. Accumulating evidence has shown that N-methyl-D-aspartate (NMDA) glutamate receptors (NMDAR) are implicated in the pathophysiology of neurological and psychiatric disorders, and that patients with NMDAR antibody encephalitis develop psychopathological symptoms. Therefore, we hypothesized that NMDAR antibodies play a key role in the etiology of schizophrenia. In this study, we enrolled 110 first-episode patients with schizophrenia (FEP) and 50 healthy controls (HC). Cognitive function and psychopathology were assessed using the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) and Positive and Negative Syndrome Scale (PANSS), respectively. NMDAR antibody levels were measured using enzyme-linked immunosorbent assay. Our results showed that FEP with schizophrenia exhibited cognitive deficits in all domains of the MCCB and had elevated levels of serum anti-NMDAR antibody compared with the healthy controls (9.2 ± 3.5 vs. 7.3 ± 2.9 ng/ml, t = 3.10, p = 0.002). Furthermore, serum antibody levels were positively correlated with PANSS positive, negative and total score, and inversely correlated with performances of verbal learning and memory, working memory, speed of processing and MCCB total score in the patient group. These results indicate that elevated levels of NMDAR antibody may play a role in the pathogenesis of schizophrenia, leading to NMDAR dysfunction, thereby inducing symptoms of psychosis and cognitive impairment. Therefore, NMDAR antibodies may serve as a biomarker and provide a new avenue for treatment of schizophrenia. [ABSTRACT FROM AUTHOR]

• Regional Homogeneity of the whole brain among TDs were investigated. • TD was associated with higher regional homogeneity of Left Inferior Semilunar Lobule, a part of the neocerebellum critical to movement and cognitive control. • Higher regional homogeneity was negatively correlated with dyskinesia severity assessed by the Abnormal Involuntary Movement Scale. Neuronal degeneration and apoptosis may play an important role in the pathogenesis of tardive dyskinesia (TD). Previous studies suggested brain structural and functional abnormalities in patients with TD. We investigated changes in cerebral regional homogeneity (ReHo) in patients with TD using resting-state functional magnetic resonance imaging (rs-fMRI). Imaging data were collected from schizophrenia patients with TD (TD group, n=58) and without TD (non-TD group, n=66) and healthy controls (HC group, n=67), processed with SPM, and evaluated at a corrected threshold. Psychopathology and severity of TD were assessed with the Positive and Negative Syndrome Scale (PANSS) and Abnormal Involuntary Movement Scale (AIMS), respectively. Results: TD vs. non-TD group showed significantly higher ReHo in the Left Inferior Semilunar Lobule and Right Fusiform Gyrus and lower ReHo in Left Supramarginal Gyrus, Right Inferior Tempotal Gyrus, and Left Medial Frontal Gyrus. The ReHo value in the Left Inferior Semilunar Lobule was negatively correlated with AIMS upper limbs scores. Conclusions: The findings suggest altered regional neural connectivities in association with TD and may inform research of the etiology and monitor the course of TD in patients with schizophrenia and potentially other psychotic disorders. [ABSTRACT FROM AUTHOR]

S100B, a biomarker of glial dysfunction and blood-brain barrier (BBB) disruption, has been proposed to be involved in the pathophysiology of schizophrenia. In the present study, we aimed at exploring the association of serum S100B levels with cognitive deficits using MATRICS Consensus Cognitive Battery (MCCB) in schizophrenia, by excluding the impact of antipsychotics. Sixty-two unmedicated patients with schizophrenia during their acute phases were divided into a drug-naïve group (n=34) and a drug-free group (n=28). S100B serum concentrations were measured and MCCB was administered to all of the patients. Forty healthy controls donated their blood samples for S100B assessment. The results indicated that serum S100B was significantly elevated in the drug-naive/free acute-stage schizophrenic patients when compared to the healthy controls. In the drug-free group, the serum S100B level was an independent contributor to the global cognitive dysfunctions, particularly for the speed of processing, attention/vigilance, visual learning and reasoning/problem solving subscores. Nevertheless, no significant associations between S100B and MCCB composite score or any cognitive domain subscore were observed in the drug-naïve group. These findings support the hypothesis that glial dysfunction and associated marker protein S100B may contribute to the pathophysiologic development of neurocognitive deficits in the relapsed individuals with schizophrenia. [ABSTRACT FROM AUTHOR]

Individual-level cognitive remediation therapy (CRT) has been shown to be effective for cognitive improvement and social function amelioration. Here, we aimed to test the efficacy of group-based CRT in Chinese subjects with schizophrenia. One-hundred and four inpatients were randomly assigned to either 40 sessions of small-group CRT therapy or therapeutic contact-matched Musical and Dancing Therapy (MDT). Cognitive and social functioning, as well as clinical symptoms, were evaluated over the course of treatment. Specifically, cognitive function was evaluated using a battery of cognitive measurements, clinical symptoms were evaluated using the Positive and Negative Syndrome Scale, and social function was evaluated using the Nurse's Observation Scale for Inpatient Evaluation-30. All patients were evaluated pre- and post-treatment. Forty-four individuals in the CRT group and 46 in the MDT group completed all of the planned treatments and analyses. Cognitive functions, especially cognitive flexibility and memory, showed significant improvement in the CRT group over the course of the study. The MDT group also showed improvement in several cognitive flexibility assessments, but the degree of improvement was significantly greater in the CRT group. Several social-function factors exhibited a significant improvement in the CRT group, but not in the MDT group. Cognitive function improvement correlated positively with social function without predicting social function change. We conclude that group-based CRT is an effective and promising therapy. [ABSTRACT FROM AUTHOR]

• Investigation of insula subregion-based functional networks in patients with first episode schizophrenia (FES). • FES patients exhibit abnormal functional connectivity of insula subregions. • Altered anterior insula-anterior middle cingulate cortex connectivity correlated with emotional regulation deficiency in FES patients. Dysfunctional insula is crucial in the development of social cognition deficits, especially emotional dysregulation in patients with schizophrenia. However, function networks of insula sub-regions in schizophrenia are rarely investigated. In this study, functional connectivity between insula sub-regions and whole-brain voxels and its relationship with social cognition ability were investigated in patients with first-episode schizophrenia (FES). This study included 47 patients with FES and 47 healthy controls (HCs). Resting-state functional connectivity (rsFC) was assessed using a seed-based approach, and social cognition was measured by the "managing emotions" branch of the Mayer–Salovey–Caruso Emotional Intelligence Test. Differences in rsFC of insula sub-regions between the two groups were examined. Patients with FES showed increased rsFC between the left anterior insula (AI) and the right inferior frontal gyrus or the right anterior middle cingulate cortex (aMCC) and between the right middle insula and the right aMCC. Moreover, the increased AI-aMCC connectivity correlated negatively with the "managing emotion" scores in patients. This study highlights the altered functional connectivity of insula sub-regions and its correlation with emotional dysregulation in patients with FES. Our findings provide some insights into underlying neuropathological mechanisms associated with emotional regulation deficiency in patients with schizophrenia. [ABSTRACT FROM AUTHOR]

• Patients with schizophrenia had higher HCY levels than healthy controls. • HCY levels were correlated with cognitive function in the patients. • Healthy controls had higher cortical thickness than the patients. • Cortical thickness had moderating effects on cognitive deficits in patients. The mechanism by which high homocysteine (HCY) may aggravate cognitive impairment in patients with schizophrenia is not well understood. We aimed to test the hypothesis that hyperhomocysteinaemia may exacerbate cognitive deficits by mediating the decrease in cortical thickness in patients with schizophrenia. One hundred and sixty-seven first-episode patients with schizophrenia (FEPS) and 120 healthy controls (HCs) were included. Psychopathology and cognitive function were assessed using the Positive and Negative Symptom Scale and Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB), respectively. Brain cortical thickness was measured by 3.0 T high-resolution magnetic resonance imaging. Serum HCY levels were tested using a sandwich enzyme-linked immunosorbent assay. Our findings showed that HCY levels in the FEPS were significantly higher than those in the HCs (P < 0.001). The MCCB total and subtest scores in the patients were significantly lower than those in the HCs (P < 0.001). The HCs had significantly higher cortical thickness than the patients (P < 0.001). Serum HCY levels were negatively correlated with Working Memory, Attention/Vigilance, and MCCB total scores in the FEPS (P < 0.05). Brain cortical thickness had positive moderating effects on cognitive impairment in FEPS with high HCY after controlling for sex, age, and education (P < 0.05). In HCs with high HCY, brain cortical thickness had no mediating or moderating effects on cognitive impairment. Compared with HCs, FEPS had thinner grey matter thickness, furthermore, the grey matter thickness might play a crucial role in relationship between high HCY and cognitive deficits. [ABSTRACT FROM AUTHOR]

Abstract: Controversial results concerning insulin resistance and lipid metabolism have been reported in antipsychotic-naive first-episode psychosis (AN-FEP) patients with schizophrenia of different countries. We aimed at determining whether schizophrenia-related psychopathology was associated with insulin resistance and/or dyslipidaemia in Chinese patients with AN-FEP schizophrenia. A cross-sectional study was performed in Chinese patients newly diagnosed with schizophrenia (n = 49, antipsychotic-naïve or antipsychotic medications< 2 weeks) and healthy volunteers (n = 30). The serum levels of insulin and triglyceride levels as well as homeostasis model of assessment-insulin resistance (HOMA-IR) index were significantly increased in AN-FEP patients, when compared with healthy volunteers. The gender difference had a significant impact on the insulin resistance and dyslipidaemia in these AN-FEP subjects. Multiple linear regression analysis demonstrated that the severity of positive symptoms of schizophrenia was negatively related to insulin resistance. No difference of serum glucose level, total cholesterol content, body mass index (BMI) and smoking status was detected between patients with schizophrenia and healthy controls. In conclusion, Chinese AN-FEP patients were more prone to insulin resistance and dyslipidaemia as compared to the healthy population, which is negatively correlated to positive symptoms. The results may contribute to the understanding of the relationship between the glucose/lipidaemia metabolic dysfunction and the psychopathology in patients with schizophrenia. [Copyright &y& Elsevier]

• Both TD and NTD patients showed higher TLR4 signal pathway activity at baseline but weaker responses to lipopolysaccharide (LPS), as compared to healthy controls. These trends were less pronounced in TD patients than in NTD patients. • In TD patients, TLR4 levels were negatively or positively correlated with MCCB at baseline or after LPS stimulation, respectively. Mounting evidence suggests that the innate immune system is disrupted in schizophrenia patients with tardive dyskinesia (TD); however, the role of the toll-like receptor 4 (TLR4) signaling pathway remains unclear. In this study, we quantified the expression of the monocytic TLR4 signaling pathway using flow cytometry, before and after lipopolysaccharide (LPS) stimulation, in chronic schizophrenia patients with (n = 61) and without TD (NTD, n = 61) and healthy controls (HCs, n = 74). Psychopathological symptoms, the severity of TD, and cognitive function were assessed using the Positive and Negative Syndrome Scale (PANSS), Abnormal Involuntary Movement Scale (AIMS), and MATRICS Consensus Cognitive Battery (MCCB), respectively. 1) Both TD and NTD patients showed higher TLR4 signaling pathway activity at baseline than that in HCs, but their responses to LPS were weaker than those in HCs; 2) the alteration of the TLR4 signaling pathway was less severe in TD patients than in NTD patients; 3) TLR4 levels and MCCB scores were negatively correlated at baseline but positively correlated after LPS stimulation in TD patients; 4) there was no correlation between the TLR4 signals and PANSS or AIMS scores. Our findings suggested the TLR4 signaling pathway disturbance might be related to cognitive deficits in schizophrenia patients with TD. [ABSTRACT FROM AUTHOR]

• Functional connectivity of motor basal ganglia circuit among TDs were investigated. • Regions of interest were pre-defined subcortical and cortical motor circuit areas. • TD was associated with reduced connectivity of the motor circuit with right postcentral and inferior frontal cortices. • Reduced connectivity was this was negatively correlated with dyskinesia severity assessed by the Abnormal Involuntary Movement Scale. Animal and neuroimaging studies suggest that the volume of the motor-circuit region decreases in tardive dyskinesia (TD). This study examined the differences in functional connectivity within the motor circuit of patients with schizophrenia with and without TD to further clarify how the dysfunction is related to the pathogenesis of TD. Functional magnetic resonance images were taken of 56 schizophrenic patients with TD (TD group), 64 without TD (non-TD group), and 68 healthy controls (HC group). The motor-circuit area was selected as the seed region for a whole brain resting-state functional connectivity (rsFC) analysis. Psychopathological symptoms and TD severity were assessed with the Positive and Negative Syndrome Scale (PANSS) and Abnormal Involuntary Movement Scale (AIMS), respectively. Group differences and correlations among 18 brain regions of interest (e.g., the global strength of connectivity between two regions) were analyzed. The analysis of variance results were as follows: The three groups exhibited rsFC losses in the left primary motor cortex, bilateral parietal cortices, right postcentral gyrus, right putamen, right superior parietal lobule, right supplementary motor area and bilateral thalami (false discovery rate, p < 0.05). The TD group showed a significant rsFC loss between the right postcentral gyrus and the inferior frontal gyrus of the left triangular part when compared with the non-TD group (AlphaSim, p < 0.001), which was negatively correlated with the AIMS total score (r =-0.259, p = 0.03). These findings may suggest dysfunction of the postcentral and inferior frontal gyri of the triangular part in patients with schizophrenia and TD. [ABSTRACT FROM AUTHOR]

• CCRT improved social functioning and general cognitive function in community-dwelling patients with schizophrenia. • These improvements of social functioning and general cognitive function persisted for 6 months after treatment. • CCRT also led to improvements in functioning and symptom severity by modulating cognitive functioning. Computerized cognitive remediation therapy (CCRT) has been found to generally improve cognition among patients with schizophrenia, but its effect on functioning has not been extensively studied. This study addressed this gap in the literature by investigating the effect of CCRT and its long-term efficacy among community-dwelling patients with schizophrenia. 157 Chinese patients with schizophrenia were recruited from communities and randomized to CCRT (n = 78) or treatment as usual (TAU; n = 79) groups for 12 weeks with 4–5 sessions per week. Neurocognition, functioning, and symptoms of participants were assessed at baseline, after treatment, and at the 6 month follow-up. The CCRT group showed significantly greater improvements than the TAU group regarding the MATRICS Consensus Cognitive Battery (MCCB) total score and social cognition score. Significant cognitive benefits for functioning were observed (Personal and Social Performance scale, PSP). Moreover, improvement of the MCCB total score mediated a positive effect on functional capacity (UCSD Performance-based Skills Assessment, UPSA), and mediated decreases in negative symptoms across both groups. CCRT improved social functioning and general cognitive functioning among community-dwelling patients with schizophrenia. These improvements persisted for 6 months after treatment. CCRT also led to improvements in functioning and symptom severity by modulating cognitive functioning. [ABSTRACT FROM AUTHOR]