ObjectiveTo investigate the correlation between serum Klotho levels and cognitive function in individuals with chronic Schizophrenia (SZ).MethodsA total of 108 patients diagnosed with chronic SZ and 83 age-matched healthy controls were recruited from four psychiatric specialist hospitals in Lianyungang from January to December 2024. Serum Klotho levels were measured using an enzyme-linked immunosorbent assay. Psychopathology and cognitive function were assessed using the Positive and Negative Syndrome Scale and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), respectively. Kendall’s tau-b correlation analyses were conducted to assess the associations between serum Klotho levels and cognitive function.ResultsCompared with healthy controls, patients with SZ had significantly lower serum Klotho levels (233.61 ± 50.35 pg/mL vs 347.11 ± 62.64 pg/mL, P < 0.001). They also showed significantly lower total scores in the overall cognitive performance and across the RBANS sub-domains (all P < 0.01). ROC curve analysis revealed that serum Klotho levels discriminated patients with schizophrenia from healthy controls with an AUC of 0.914 (95% CI: 0.876–0.951), with an optimal cutoff of 268.25 pg/mL (sensitivity 76.9%, specificity 89.2%). After Bonferroni correction, serum Klotho levels were positively correlated with immediate memory in patients (corrected P = 0.010). No significant associations between serum Klotho levels and cognitive measures were found in healthy controls.ConclusionPatients with chronic SZ have lower serum Klotho levels and show cognitive impairment, and Klotho levels are specifically associated with immediate memory in this population.

BACKGROUND Neuroinflammation is strongly implicated in the pathophysiology of schizophrenia. Key inflammatory markers including tumor necrosis factor-alpha (TNF-alpha), which modulates neuronal survival and synaptic transmission; interleukin (IL)-8, a neutrophil chemoattractant involved in synapse modulation; and IL-18, which regulates neuronal plasticity and cognitive processes, show distinct alterations in acute schizophrenia. Electroconvulsive therapy (ECT) demonstrates efficacy in acute schizophrenia, yet its effects on these specific inflammatory pathways remain unclear. AIM To investigate the effects of ECT on serum cytokine levels and their association with clinical symptoms in acute schizophrenia. METHODS Seventy-seven patients with acute schizophrenia (first-episode or relapsed after 4 weeks medication discontinuation, diagnosed per Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition) receiving antipsychotic treatment and 55 well-matched healthy controls were recruited. Groups were matched for age, sex, smoking status, and body mass index. Serum TNF-alpha, IL-8, and IL-18 were measured using Luminex technology. Clinical symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). Both PANSS and cytokines were remeasured after 8-10 ECT treatments at 48-hour intervals. RESULTS Compared to controls, patients exhibited significantly higher serum concentrations of TNF-alpha (t = 5.445, P < 0.001) and IL-8 (t = 9.612, P < 0.001) but lower IL-18 (t = -10.007, P < 0.001). ECT resulted in significant elevation of IL-8 and IL-18 levels (t = -3.188, P = 0.002; t = -4.682, P < 0.001, respectively), while TNF-alpha showed no significant change (t = -1.830, P = 0.071). Before ECT, the serum TNF-alpha concentration positively correlated with the PANSS general psychopathology score (r = 0.251, P = 0.028) and that of IL-8 negatively correlated with the PANSS negative symptom score (r = -0.250, P = 0.028). However, after ECT, the serum IL-8 concentration negatively correlated with the PANSS general psychopathology score (r = -0.320, P = 0.005). In ECT responders, the post-ECT serum IL-8 concentration positively correlated with a reduced PANSS positive symptom score (r = 0.414, P = 0.001). CONCLUSION ECT may mitigate the clinical symptoms of acute schizophrenia through modulation of inflammatory signaling.

Adolescent-onset schizophrenia (AOS) is characterized by severe cognitive impairment. Insulin-like growth factor binding protein-7 (IGFBP-7), a biomarker of vascular aging and neuroinflammation, and hepatocyte growth factor (HGF), involved in neurodevelopment, have been linked to cognitive decline, but their roles in AOS remain unexplored. This case–control study enrolled 91 first-episode drug-naïve AOS patients and 40 healthy controls. Clinical symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) and its five-factor model, and cognitive function was evaluated using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). AOS patients exhibited significantly lower serum IGFBP-7 levels compared to healthy controls (10.15 ± 3.62 vs. 11.75 ± 3.41 ng/mL, t = -2.377, P = 0.019), while HGF levels showed no significant difference (P > 0.05). IGFBP-7 levels were negatively correlated with PANSS cognitive factor scores (r = -0.308, P = 0.003) and positively correlated with RBANS total scores (r = 0.353, P = 0.001). IGFBP-7 was independently associated with RBANS total score (β = 0.284, P = 0.002) after controlling for confounding factors. Sex (β = 0.467, t = 5.325, P < 0.001) was identified as a confounder but did not moderate the IGFBP-7-cognition relationship (P > 0.05). Modified Poisson regression revealed that low IGFBP-7 levels independently predicted AOS risk (RR = 1.298, 95

Objective To investigate the relationships among inflammatory cytokines, niacin skin sensitivity, and clinical symptoms of male patients with chronic schizophrenia. Methods The cohort included 80 male inpatients with chronic schizophrenia (illness duration ≥5 years, clinically stable) and 40 demographically matched healthy controls. Serum levels of inflammatory cytokines (IL-1α, IL-6, TNF-α, IFN-γ) were measured using Luminex technology. The niacin skin flush response (NSFR) was assessed using filter paper saturated with aqueous methylnicotinate (0.01 mol/L, scored at 10 min). Clinical symptoms were evaluated using the Positive and Negative Syndrome Scale (PANSS). Results As compared to controls, the NSFR of patients was significantly attenuated (p < 0.001). While IL-1α levels were comparable, patients had significantly elevated serum levels of IL-6, TNF-α, and IFN-γ (p < 0.001, Bonferroni-corrected). In the patient group, serum IL-6 level was positively correlated with PANSS positive subscale score (r = 0.316, adjusted p = 0.016) and PANSS total score (r = 0.347, adjusted p = 0.008). Patients were stratified into high- and low-NSFR groups. Binary logistic regression identified IFN-γ as a significant independent correlate of a low NSFR (β = 0.116, p < 0.001, OR = 1.123), after controlling for demographic and clinical variables. Conclusion Male patients with chronic schizophrenia demonstrate concurrent peripheral inflammatory cytokine elevation and impaired niacin sensitivity. The association between elevated IFN-γ levels and a reduced NSFR suggests a link between inflammatory imbalance and this established endophenotype. These findings contribute to a clearer understanding of the role of immune dysregulation in the pathophysiology of chronic schizophrenia.

This study examined oxidative stress (OS) markers in acute relapse schizophrenia, assessed the impact of electroconvulsive therapy (ECT), and explored correlations with clinical improvement. 110 Han Chinese patients and 55 healthy controls were enrolled. All enrolled patients had multi-episode schizophrenia with a mean illness duration of 11.15 ± 9.11 years. Patients received 8–12 bilateral ECT sessions plus antipsychotics. Serum levels of GSH-Px, MnSOD, CuZnSOD, and CAT were measured before and after ECT. Symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). At baseline, schizophrenia patients showed significantly lower serum levels of GSH-Px, MnSOD, and CAT, while the MnSOD/CuZnSOD ratio was decreased, CuZnSOD levels showed a non‑significant trend as compared to healthy controls. GSH-Px levels were negatively correlated with the PANSS positive subscale scores (p = 0.007). Following ECT, all PANSS scores significantly decreased (all p < 0.001). Serum levels of GSH-Px, TSOD, CuZnSOD, and CAT increased significantly, while MnSOD levels and the MnSOD/CuZnSOD ratio significantly decreased (all p < 0.01). In responders, changes to OS markers were significant (all p < 0.01). Increases in GSH-Px levels were positively correlated to reductions in the PANSS total score (Bonferroni corrected p = 0.024) and general subscale scores (Bonferroni corrected p = 0.008). Multivariate logistic regression analysis identified the baseline GSH-Px level as an independent potential indicator of clinical improvement (p = 0.001). Acute relapse schizophrenia shows significant redox imbalance. ECT in combination with antipsychotics modulates antioxidant enzymes, and GSH-Px dynamics correlate with symptom improvement, suggesting its potential as a predictive and monitoring biomarker for ECT outcomes. Not applicable.

The pathophysiological mechanisms of childhood- and adolescent-onset schizophrenia (CAOS) remain incompletely understood, with cytokine abnormalities potentially playing an important role. This study aimed to investigate the relationships of altered serum interleukin (IL)-10 and IL-19 levels with the clinical symptoms and cognitive function of CAOS patients. The cross-sectional study included 97 CAOS patients and 40 healthy controls. Serum IL-10 and IL-19 levels were measured. Clinical symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS), and cognitive function was evaluated using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Compared to healthy controls, the CAOS patients had significantly lower serum IL-10 levels (p = 0.005) and higher IL-19 levels (p = 0.046). IL-10 was significantly negatively correlated with PANSS negative symptoms (r=-0.338, p = 0.001). The CAOS patients performed significantly worse than healthy controls across all RBANS cognitive domains (all p < 0.001), with significant correlations observed between the severity of clinical symptoms and cognitive impairment. In the healthy controls, IL-10 was significantly negatively correlated with language (r=-0.394, p = 0.012), whereas no such correlation was observed in the CAOS patients (p > 0.05). Low IL-10 levels were significantly associated with CAOS (B = 0.387, p = 0.002, RR = 1.472, 95

Schizophrenia, a severe mental disorder with complex pathophysiology, involves neurotrophic factors, which play crucial roles in neurodevelopment and neuroplasticity. This study investigated NGF-β and BDNF levels in chronic schizophrenia and their association with clinical symptoms, cognitive function, and 1,25(OH)₂D levels. In this cross-sectional study, 72 male patients with chronic schizophrenia and 70 matched healthy controls were enrolled. Psychopathological symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS), and cognitive function was evaluated using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The serum levels of NGF-β, BDNF, and 1,25(OH)₂D were measured. Serum levels of NGF-β (F = 35.239, P < 0.001) and BDNF (F = 12.669, P < 0.001) were significantly decreased in patients with chronic schizophrenia compared to healthy controls. NGF-β levels were negatively correlated with PANSS negative symptoms (beta = -0.205, t = -2.098, P = 0.040) and positively correlated with 1,25(OH)₂D levels (r = 0.324, P = 0.006). Decreased serum BDNF concentrations were negatively correlated with language deficits (beta = -0.301, t = -2.762, P = 0.007). Significant associations were observed between chronic schizophrenia and reduced levels of NGF-β (B = 1.040, P < 0.001, RR = 2.829, 95

The considerable clinical heterogeneity of schizophrenia poses significant challenges for elucidating its neurobiology. The concept of deficit schizophrenia (DS) is a valuable framework for addressing the heterogeneity of schizophrenia. Growing evidence suggests notable differences between deficit (DS) and nondeficit (NDS) schizophrenia, indicating that DS could represent a separate disease entity. We aimed to use FreeSurfer to identify specific changes in cortical thickness among NDS patients and healthy controls (HCs) in a Chinese sample. Furthermore, we examined the potential relationships between changes in cerebral cortical thickness and negative symptoms and attention deficits in DS patients. A total of 142 subjects (48 HCs, 50 NDSs, and 44 DSs) underwent MRI scans and completed the assessment of psychopathological severity and cognitive performance. Compared with HCs, DS and NDS patients presented common cortical thinning in the right insula, whereas cortical thinning in the left supramarginal cortex was more prominent in DS patients. We also found that thinning of the temporal and insular cortex was correlated with negative symptoms and impaired attention in DS patients. Cortical thinning in specific brain regions in DS patients was found to be correlated with specific clinical and cognitive symptoms.

Early-onset schizophrenia (EOS) patients are at greater risk of poor long-term outcomes compared to later-onset patients, so it is essential to identify unique pathomechanisms and prognostic biomarkers for this EOS patient group. Deficits in neurotrophic and oxidative stress resistance are implicated in EOS, so this study investigated associations of EOS risk with peripheral blood platelet-derived growth factor (PDGF) subtype concentrations and superoxide dismutase (SOD) isoenzyme activities. Serum PDGF subtype concentrations and plasma SOD isoenzyme activities were measured in 99 first-episode drug-naïve EOS patients (ages 12–18 years) and 40 matched healthy controls (HCs). Disease severity was assessed using the five-factor model of the Positive and Negative Syndrome Scale (positive, negative, cognitive, excitement/hostility, and anxiety/depression). Serum PDGF-AB and PDGF-BB concentrations, as well as plasma total (T)-SOD and Mn-SOD activities, were significantly lower in EOS patients than HCs (all, P < 0.001 except for T-SOD, where P = 0.003). Serum PDGF-AB concentration was positively correlated with plasma Mn-SOD activity (r = 0.267, P = 0.007), while serum PDGF-BB concentration was negatively correlated with cognitive symptom severity (r = −0.406, P < 0.001), and T-SOD activity was negatively correlated with excitement/hostility symptom severity (r = −0.354, P < 0.001). Multivariate analysis with dichotomized factors identified low PDGF-AB (RR = 1.788, 95

BACKGROUND:Type 2 diabetes (T2D) is a disease caused by a combination of genetic and environmental exposures. In addition, there is limited epidemiological evidence on the interaction between metal exposure and genetic risk for T2D. Therefore, we analyzed the interaction effect of serum concentrations of multiple metals and genetic variants on T2D incidence in the general population. METHODS:A prospective cohort study with 14 years of follow-up was performed with 4507 participants without noncommunicable diseases at baseline. Twenty-one metals were measured using inductively coupled plasma-mass spectrometry (ICP-MS). T2D-associated single nucleotide polymorphisms (SNPs) identified by Genome-wide association study (GWAS) were also genotyped. The polygenic risk score (PRS) models based on 46 SNPs identified from East Asians was constructed. A Cox regression model was used to explore the associations of serum metals and their interaction effects with PRS on T2D. RESULTS:Of the 4507 participants, 350 were newly diagnosed with T2D during the 14-year follow-up. After adjusting for covariates, serum vanadium, chromium, manganese, molybdenum, barium and lead levels were significantly associated with decreased T2D risk, while zinc levels were correlated with elevated T2D risk (P < 0.05). Furthermore, zinc, molybdenum, barium and lead showed additive interaction with the PRS derived from 46 SNPs specific for east Asians on T2D. CONCLUSIONS:Significant interaction effects were observed for zinc、molybdenum、barium、lead exposure and PRS. Our findings suggest that people with a high genetic risk of diabetes should pay attention to maintaining appropriate levels of metal.

Background Dysregulation of neuroplasticity contributes to the pathogenesis of schizophrenia. Matrix metalloproteinases (MMPs) and endogenous tissue MMP inhibitors (TIMPs) are key regulators of extracellular matrix (ECM) remodeling essential for neuroplasticity, while insulin-like growth factor binding protein-1 (IGFBP-1) modulates ECM dynamics through integrin receptor signaling and MMP-mediated proteolysis. The current study investigated potential abnormalities in serum MMP-9, TIMP-1, and IGFBP-1 concentrations as biomarkers of ECM dysfunction among long-term hospitalized male schizophrenia patients and assessed associations with clinical characteristics. Methods Serum MMP-2, MMP-9, TIMP-1, and IGFBP-1 concentrations were compared between 80 male schizophrenia patients hospitalized for ≥5 years and 59 age-matched healthy male controls. Clinical symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) and cognitive functions using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Correlations between serum measurements and scores on the PANSS and RBANS were assessed while controlling for multiple covariates. Results Serum TIMP-1 concentration was significantly lower in the patient group ( Z =-2.547, P = 0.012). Conversely, patients exhibited significantly elevated serum MMP-9 ( Z =-2.067, P = 0.039), MMP-9/TIMP-1 ratio ( Z =-2.195, P = 0.028), and IGFBP-1 ( Z =-5.994, P < 0.001). Serum IGFBP-1 concentration negatively correlated with RBANS immediate memory subscore ( r =-0.240, P = 0.024), and elevated IGFBP-1 was identified as an independent risk factor for long-term hospitalization ( RR = 2.257, P < 0.001, 95%CI:1.571–3.243). Serum TIMP-1 concentration also positively correlated with illness duration ( r = 0.376, P = 0.001). Conclusions Long-term hospitalized male schizophrenia patients exhibit an ECM remodeling imbalance associated with memory impairment and predictive of chronic disease status. Therefore, molecules regulating ECM dynamics may be effective therapeutic targets for schizophrenia.

Background Schizophrenia is a debilitating mental disorder linked to oxidative stress (OS) and inflammatory dysregulation. Emerging evidence suggests impaired niacin sensitivity in schizophrenia patients, potentially reflecting OS and inflammation. This study examined the relationships between OS markers and niacin sensitivity in male chronic schizophrenia patients to explore potential pathophysiological mechanisms and identify associated biomarkers. Methods The cohort of this cross-sectional study included 80 male chronic schizophrenia patients and 40 matched healthy controls. Blood samples were collected for analysis of nitric oxide (NO), total nitric oxide synthase (TNOS), inducible nitric oxide synthase (iNOS), constitutive nitric oxide synthase (cNOS), total antioxidant capacity (TAC), and vitamin E (VE). Skin niacin sensitivity was assessed via the erythema response to topical niacin. Clinical symptoms were evaluated using the Positive and Negative Syndrome Scale (PANSS). Statistical analyses (t-tests, analysis of variance, and logistic regression) were conducted to identify associations. Results TNOS, iNOS, cNOS,TAC, and VE levels were significantly lower in the patient group than the healthy control group (p < 0.001). Reduced skin erythema response in patients (p < 0.001) was correlated with lowerTAC activity and VE levels. Plasma NO levels were positively correlated with PANSS positive symptom scores (r = 0.370, p = 0.004).TAC was a significant protective predictor of an impaired niacin response (OR = 0.990, p = 0.001). Conclusion Chronic schizophrenia is associated with disrupted redox balance and reduced niacin sensitivity, suggesting an interplay between the oxidative and inflammatory pathways. A weakened niacin response, related to antioxidant deficits, may be linked to the severity of OS. These findings highlight the importance of further research into antioxidant pathways. Additional longitudinal studies are warranted to clarify the nature of these relationships and their clinical relevance.

Inflammatory responses may play a significant role in the pathophysiology of schizophrenia, but the relationship of inflammatory cytokines with clinical symptoms of acute patients remains incompletely understood. This study aimed to investigate serum levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-8, and IL-18 and the potential association with clinical symptoms of acute schizophrenia patients. The cohort of the cross-sectional study included 71 acute schizophrenia patients (medication-free ≥ 4 weeks) and 55 healthy controls. Clinical symptoms were assessed using the five-factor Positive and Negative Syndrome Scale (PANSS). Serum TNF-α, IL-8, and IL-18 levels were measured using Luminex liquid suspension chip assay technology. As compared to healthy controls, acute schizophrenia patients exhibited significantly higher serum levels of TNF-α and IL-8 (both, p < 0.001), while IL-18 levels were significantly lower (p < 0.001). After controlling for confounding factors, serum levels of TNF-α (β = 0.368, p = 0.003) and IL-8 (β = 0.414, p = 0.001) were positively correlated with the PANSS anxiety/depression factor. TNF-α was positively correlated with IL-8 (r = 0.334, p = 0.004) and IL-18 (r = 0.301, p = 0.011). Sex did not modulate the relationship between IL-8 and anxiety/depression symptoms (p = 0.572). Additionally, IL-18 was positively correlated with body mass index (r = 0.295, p = 0.019) and sex (r = 0.384, p = 0.001), while the excitement/hostility factor was positively correlated with age of disease onset (r = 0.293, p = 0.013). These findings support the involvement of inflammatory processes in the pathophysiology of acute schizophrenia, particularly the association of TNF-α and IL-8 with anxiety/depression symptoms. Not applicable.

BACKGROUND AND AIMS:We aimed to explore the association between coronavirus disease-19 (COVID-19) vaccination and long COVID according to the status of chronic multimobidity. METHODS:A total of 1913 participants were recruited in the cross-sectional study on the basis of the Survey of Health and Retirement in Europe. COVID-19 vaccination was defined as vaccination within the last 12 months. Chronic multimorbidity was defined as history of 2 + chronic disease. The study outcome was long COVID during the 12-month follow-up. Multivariable logistic models were performed to estimate the influence of chronic multimorbidity on the association of vaccination with long COVID. Net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were calculated. RESULTS:Chronic multimorbidity significantly modified the association of COVID-19 vaccination with long COVID (Pinteraction = 0.024). The rates of study outcome were significantly lower among vaccinated participants in the chronic multimorbidity subgroup, but not in the other subgroup. Multivariable odds ratios (95 % confidence intervals) of study outcome for unvaccination vs. vaccination were 1.494 (1.013-2.203) in those with multimorbidity and 0.915 (0.654-1.280) in those without multimorbidity, respectively. Adding COVID-19 vaccination to a model containing conventional risk factors significantly improved risk reclassification for study outcome among those with chronic multimobidity (continuous NRI was 25.39 % [P = 0.002] and IDI was 0.42 % [P = 0.075]) CONCLUSION: An inverse association of COVID-19 vaccination with long COVID was found among participants with chronic multimorbidity, but not among those without chronic multimorbidity. Chronic multimorbidity might expand the influence of unvaccination on developing long COVID among European aged ≥50 years.

Background Polypharmacy increases the risk of potential drug-drug interactions (pDDIs). This retrospective analysis was conducted to detect pDDIs and adverse drug reactions (ADRs) among older adults with psychiatric disorder, and identify pDDIs with clinical significance. Methods A retrospective analysis was carried out based on the medical records of older adults with psychiatric disorders. Data on demographic characteristics, substance abuse, medical history, and medications were extracted. The Lexi-Interact online database was used to detect pDDIs. The minimal clinically important difference (MCID) was set as the change in the Treatment Emergent Symptom Scale (TESS) score between admission and discharge. The median and interquartile ranges were used for continuous variables, and frequencies were calculated for dichotomous variables. Poisson regression was implemented to determine the factors influencing the number of ADR types. The influencing factors of each ADR and the clinical significance of the severity of the ADR were analysed using binary logistic regression. P < 0.05 was considered statistically significant. Results A total of 308 older adults were enrolled, 171 (55.52%) of whom had at least 1 pDDI. Thirty-six types of pDDIs that should be avoided were found, and the most frequent pDDI was the coadministration of lorazepam and olanzapine (55.5%). A total of 26 ADRs induced by pDDIs were identified, and the most common ADR was constipation (26.05%). There was a 9.4 and 10.3% increase in the number of ADR types for each extra medical diagnosis and for each extra drug, respectively. There was a 120% increase in the number of ADR types for older adults hospitalized for 18-28 days compared with those hospitalized for 3-17 days. There was an 11.1% decrease in the number of ADR types for each extra readmission. The length of hospitalization was a risk factor for abnormal liver function (P < 0.05). The use of a large number of drugs was a risk factor for gastric distress (P < 0.05) and dizziness and fainting (P < 0.05). None of the four pDDIs, including coadministrations of olanzapine and lorazepam, quetiapine and potassium chloride, quetiapine and escitalopram, and olanzapine and clonazepam, showed clinical significance of ADR severity (P > 0.05). Conclusions pDDIs are prevalent in older adults, and the rate is increasing. However, many pDDIs may have no clinical significance in terms of ADR severity. Further research on assessing pDDIs, and possible measures to prevent serious ADRs induced by DDIs is needed to reduce the clinical significance of pDDIs.

BACKGROUND:Several previous cross-sectional studies suggested that body roundness index (BRI) may be associated with cardiovascular disease (CVD). However, the association should be further validated. Our study aimed to assess the association of the BRI trajectories with CVD among middle-aged and older Chinese people in a longitudinal cohort. METHODS AND RESULTS:A total of 9935 participants from the CHARLS (China Health and Retirement Longitudinal Study) with repeated BRI measurements from 2011 to 2016 were included. The BRI trajectories were identified by group-based trajectory modeling. The primary outcome was incident CVD (stroke or cardiac events), which occurred in 2017 to 2020. Cox proportional hazards regression models were used to examine the association of BRI trajectories with CVD risk. Participants were divided into 3 BRI trajectories, named the low-stable BRI trajectory, moderate-stable BRI trajectory and high-stable BRI trajectory, accounting for 49.81%, 42.35%, and 7.84% of the study population, respectively. Compared with participants in the low-stable BRI trajectory group, those in the moderate-stable and high-stable BRI trajectory groups had an increased risk of CVD, with multivariable adjusted hazard ratios of 1.22 (95% CI, 1.09-1.37) and 1.55 (95% CI, 1.26-1.90), respectively. Furthermore, simultaneously adding the BRI trajectory to the conventional risk model improved CVD risk reclassification (all P<0.05). CONCLUSIONS:A higher BRI trajectory was associated with an increased risk of CVD. The BRI can be included as a predictive factor for CVD incidence.

Background Accumulating evidence has indicated that oxidative stress (OS) and matrix metalloproteinase-9 (MMP-9) may contribute to the mechanism of schizophrenia. In the present study, we aimed to evaluate the associations of OS parameters and MMP-9 levels with psychopathological symptoms in male chronic schizophrenia patients. Methods This study was an observational, cross-sectional, retrospective case-control study. Plasma hydrogen peroxide (H 2 O 2 ), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), serum matrix metalloproteinase-9 (MMP-9), and tissue inhibitors of metalloproteinases-1 (TIMP-1) levels were assayed in 80 male patients with chronic schizophrenia and 80 matched healthy controls. Schizophrenia symptoms were assessed by the Positive and Negative Syndrome Scale (PANSS). Multivariate regression was used to analyze relationships between OS parameters and MMP-9, and clinical symptoms. Results Our results demonstrated that levels of antioxidant enzymes, SOD, GSH-Px, H 2 O 2 , and MDA were significantly decreased, whereas CAT and MMP-9 levels were increased in patients with schizophrenia, when compared with healthy controls (all P < 0.05). In schizophrenia patients, correlation analyses showed that H 2 O 2 levels were significantly and positively correlated with PANSS positive scores, CAT and MDA levels were significant negatively correlated with PANSS negative scores and PANSS total scores, and MDA levels were significantly positively correlated with MMP-9 levels (all P < 0.05). However, we did not find that MMP-9 played an interaction role between OS parameters and PANSS total scores and subscales scores (all P > 0.05). Conclusions Our results showed that alterations of plasma OS parameters in male patients with chronic schizophrenia were associated with psychopathology and MMP-9, suggesting that OS and neuroinflammation may play important role in the mechanism of schizophrenia.

Immune dysregulation has been identified as a contributing factor in the pathophysiology of schizophrenia. This study aimed to investigate variations in specific immune regulators and their correlation with psychopathology and cognitive functions in male patients with chronic schizophrenia. Employing a cross-sectional design, this study included 72 male patients with chronic schizophrenia. The Positive and Negative Syndrome Scale (PANSS) and the Repeatable Battery for the Assessment of Neuropsychological Status were utilized to assess psychopathology and cognitive functions, respectively. Serum levels of interleukin (IL)-4, IL-10, IL-12p40, IL-13, and monocyte chemoattractant protein-1 (MCP-1) were measured. There were significantly increased levels of IL-4, IL-13, and MCP-1, alongside decreased levels of IL-10 in patients compared to controls (all P < 0.05). IL-4 levels showed a significant negative association with PANSS positive symptoms (beta=-0.222, P = 0.042). After controlling for antipsychotic medication, BMI, and smoking, this correlation was no longer significant (r=-0.232, P = 0.055). Additionally, positive correlations of IL-4 (beta = 0.297, P = 0.008), IL-13 (beta = 0.371, P = 0.001), and MCP-1 (beta = 0.280, P = 0.013) with language scores were observed. Increased levels of IL-4 (P = 0.044, OR = 1.994), IL-13 (P = 0.019, OR = 2.245), as well as IL-4 and MCP-1 interactions (P = 0.043, OR = 2.000) were positively associated with the risk of chronic schizophrenia, while lower levels of IL-10 (P = 0.003, OR = 0.2.867) were also linked to an increased risk. The identified associations between specific immune markers and the clinical and cognitive features of chronic schizophrenia in males underscored the potential immune-mediated mechanisms underlying schizophrenia.

Journal Article Cohort Profile: The Taihu Biobank of Tumour Biomarkers (TBTB) study in Wuxi, China Get access Lu Wang, Lu Wang Department of Chronic Non-Communicable Disease Control, Affiliated Wuxi Center for Disease Control and Prevention of Nanjing Medical University, Wuxi Center for Disease Control and Prevention, Wuxi, China Search for other works by this author on: Oxford Academic PubMed Google Scholar Jia Liu, Jia Liu Department of Chronic Non-Communicable Disease Control, Affiliated Wuxi Center for Disease Control and Prevention of Nanjing Medical University, Wuxi Center for Disease Control and Prevention, Wuxi, ChinaDepartment of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China Search for other works by this author on: Oxford Academic PubMed Google Scholar Meng Zhu, Meng Zhu Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, ChinaJiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing, China Search for other works by this author on: Oxford Academic PubMed Google Scholar Qian Shen, Qian Shen Department of Chronic Non-Communicable Disease Control, Affiliated Wuxi Center for Disease Control and Prevention of Nanjing Medical University, Wuxi Center for Disease Control and Prevention, Wuxi, China Search for other works by this author on: Oxford Academic PubMed Google Scholar Yongchao Liu, Yongchao Liu Department of Chronic Non-Communicable Disease Control, Affiliated Wuxi Center for Disease Control and Prevention of Nanjing Medical University, Wuxi Center for Disease Control and Prevention, Wuxi, China Search for other works by this author on: Oxford Academic PubMed Google Scholar Hai Chen, Hai Chen Department of Chronic Non-Communicable Disease Control, Affiliated Wuxi Center for Disease Control and Prevention of Nanjing Medical University, Wuxi Center for Disease Control and Prevention, Wuxi, China Search for other works by this author on: Oxford Academic PubMed Google Scholar Yunqiu Dong, Yunqiu Dong Department of Chronic Non-Communicable Disease Control, Affiliated Wuxi Center for Disease Control and Prevention of Nanjing Medical University, Wuxi Center for Disease Control and Prevention, Wuxi, China Search for other works by this author on: Oxford Academic PubMed Google Scholar Man Yang, Man Yang Department of Chronic Non-Communicable Disease Control, Affiliated Wuxi Center for Disease Control and Prevention of Nanjing Medical University, Wuxi Center for Disease Control and Prevention, Wuxi, China Search for other works by this author on: Oxford Academic PubMed Google Scholar Caiwang Yan, Caiwang Yan Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, ChinaJiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing, China Search for other works by this author on: Oxford Academic PubMed Google Scholar Zhijie Yang, Zhijie Yang Department of Chronic Non-Communicable Disease Control, Affiliated Wuxi Center for Disease Control and Prevention of Nanjing Medical University, Wuxi Center for Disease Control and Prevention, Wuxi, China Search for other works by this author on: Oxford Academic PubMed Google Scholar ... Show more Yaqi Liu, Yaqi Liu Department of Chronic Non-Communicable Disease Control, Affiliated Wuxi Center for Disease Control and Prevention of Nanjing Medical University, Wuxi Center for Disease Control and Prevention, Wuxi, China Search for other works by this author on: Oxford Academic PubMed Google Scholar Hongxia Ma, Hongxia Ma Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, ChinaJiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing, China https://orcid.org/0000-0002-2462-9693 Search for other works by this author on: Oxford Academic PubMed Google Scholar Zhibin Hu, Zhibin Hu Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, ChinaJiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing, China https://orcid.org/0000-0002-8277-5234 Search for other works by this author on: Oxford Academic PubMed Google Scholar Hongbing Shen, Hongbing Shen Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, ChinaJiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing, China https://orcid.org/0000-0002-2581-5906 Search for other works by this author on: Oxford Academic PubMed Google Scholar Yun Qian, Yun Qian Department of Chronic Non-Communicable Disease Control, Affiliated Wuxi Center for Disease Control and Prevention of Nanjing Medical University, Wuxi Center for Disease Control and Prevention, Wuxi, China https://orcid.org/0000-0002-7921-6407 Search for other works by this author on: Oxford Academic PubMed Google Scholar Guangfu Jin Guangfu Jin Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, ChinaJiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing, China Corresponding author. Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166, China. E-mail: guangfujin@njmu.edu.cn Search for other works by this author on: Oxford Academic PubMed Google Scholar International Journal of Epidemiology, Volume 53, Issue 1, February 2024, dyad173, https://doi.org/10.1093/ije/dyad173 Published: 18 December 2023 Article history Received: 25 March 2023 Editorial decision: 30 October 2023 Accepted: 01 December 2023 Published: 18 December 2023

Accumulating evidence suggests that imbalanced oxidative stress (OS) may contribute to the mechanism of schizophrenia. The aim of the present study was to evaluate the associations of OS parameters with psychopathological symptoms in male chronically medicated schizophrenia (CMS) and treatment-resistant schizophrenia (TRS) patients. Levels of hydrogen peroxide (H2O2), hydroxyl radical (·OH), peroxidase (POD), α-tocopherol (α-toc), total antioxidant capacity (TAC), matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of metalloproteinases-1 (TIMP-1) were assayed in males with CMS and TRS, and matched healthy controls. Schizophrenia symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). The results demonstrated significant differences in the variables H2O2 (F = 5.068, p = 0.008), ·OH (F = 31.856, p < 0.001), POD (F = 14.043, p < 0.001), α-toc (F = 3.711, p = 0.027), TAC (F = 24.098, p < 0.001), and MMP-9 (F = 3.219, p = 0.043) between TRS and CMS patients and healthy controls. For TRS patients, H2O2 levels were correlated to the PANSS positive subscale (r = 0.386, p = 0.032) and smoking (r = −0,412, p = 0.021), while TAC was significantly negatively correlated to the PANSS total score (r = −0.578, p = 0.001) and POD and TAC levels were positively correlated to body mass index (r = 0.412 and 0.357, p = 0.021 and 0.049, respectively). For patients with CMS, ·OH levels and TAC were positively correlated to the PANSS general subscale (r = 0.308, p = 0.031) and negatively correlated to the PANSS total score (r = −0.543, p < 0.001). Furthermore, H2O2, α-toc, and ·OH may be protective factors against TRS, and POD was a risk factor. Patients with CMS and TRS exhibit an imbalance in OS, thus warranting future investigations.