Background Schizophrenia (SCZ) is a psychotic disorder with an unknown pathogenesis accompanied by varying degrees of cognitive deficits. Recent studies have shown that immune dysregulation plays an important role in developing symptoms and cognitive deficits in SCZ. This study aimed to determine the complete blood count (CBC), including white blood cells, neutrophils, monocytes, lymphocytes, platelets, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and monocyte-lymphocyte ratio (MLR), in patients with SCZ and explore their correlations with SCZ symptom dimensions and cognitive function. Methods Seventy-four patients with SCZ and 57 age- and sex-matched healthy controls with available demographic and clinical information were recruited for this study. Blood samples were collected, and symptom dimensions and cognitive function were evaluated using the Positive and Negative Syndrome Scale (PANSS) and MATRICS Consensus Cognitive Battery (MCCB) separately. Results Our results demonstrate that SCZ patients showed higher monocyte counts, PLR, MLR, and worse performance in the total MCCB than healthy controls. Neutrophil and lymphocyte counts and NLR were positively related to symptom severity and negatively related to depressive symptoms. White blood cell (WBC) count, monocyte count, and MLR were positively correlated with cognitive performance in patients with SCZ. Conclusion In summary, this study suggests that cognitive deficits and symptom severity in patients were associated with dysregulation of immunity. Moreover, we found that WBC could be used as a marker for symptom severity and cognitive deficits in SCZ and that neutrophils are more closely related to the former and monocytes to the latter. We hope that clinicians will pay more attention to dysregulated immunity in patients with SCZ in the future.

BACKGROUND:Many studies have explored the relationship between depression and metabolic syndrome (MetS), especially in older people. China has entered an aging society. However, there are still few studies on the elderly in Chinese communities.AIM:To investigate the incidence and risk factors of depression in MetS patients in mainland China and to construct a predictive model.METHODS:Data from four waves of the China Health and Retirement Longitudinal Study were selected, and middle-aged and elderly patients with MetS (n = 2533) were included based on the first wave. According to the center for epidemiological survey-depression scale (CESD), participants with MetS were divided into depression (n = 938) and non-depression groups (n = 1595), and factors related to depression were screened out. Subsequently, the 2-, 4-, and 7-year follow-up data were analyzed, and a prediction model for depression in MetS patients was constructed.RESULTS:The prevalence of depression in middle-aged and elderly patients with MetS was 37.02%. The prevalence of depression at the 2-, 4-, and 7-year follow-up was 29.55%, 34.53%, and 38.15%, respectively. The prediction model, constructed using baseline CESD and Physical Self-Maintenance Scale scores, average sleep duration, number of chronic diseases, age, and weight had a good predictive effect on the risk of depression in MetS patients at the 2-year follow-up (area under the curve = 0.775, 95% confidence interval: 0.750-0.800, P < 0.001), with a sensitivity of 68% and a specificity of 74%.CONCLUSION:The prevalence of depression in middle-aged and elderly patients with MetS has increased over time. The early identification of and intervention for depressive symptoms requires greater attention in MetS patients.

Importance: The global increase in urbanization has coincided with a rise in depression prevalence. However, the effect of urbanization on depression remains controversial, especially for the elderly. Objective: To clarify how urbanization impacts depression in the elderly from a network perspective. Design, setting, and participants: This sectional cohort study used data from China Health and Retirement Longitudinal Study (CHARLS). Main outcomes and measures: The occurrence of depressive symptoms in urban and rural elderly residents. Network metrics of depressive symptoms. Results: Of the 13,993 participants, lower incidence of depressive symptoms was observed in urban (26.3 %, 95 % CI, 24.7 %-27.8 %) than in rural (40.4 %, 95 % CI, 39.5 %-41.3 %, P < 0.0001) residents. However, higher incidence of depressive symptoms was observed in urban (26.3 %, 95 % CI, 25.2 %-28.4 %) than in rural (17.5 %, 95 % CI, 16.1 %-18.9 %, P < 0.0001) residents in a subset of 2898 pairs of participants after PSM. No difference in the network structure and metrics between urban and rural residents before (M = 0.071, p = 0.054, S = 0.037, p = 0.80) and after (M = 0.085, p = 0.133, S = 0.086, p = 0.47) PSM was detected. The networks structure revealed that negative affect was strongly connected to somatic symptoms and that the two anhedonic symptoms were also strongly connected. Conclusions: The current study indicated the homogeneity of the ultimate nature of depression between rural and urban residents from the network perspective, supporting the viewpoint that urbanization might not impose influence on depression. Further researches delving deeper into the complexity of the issue may provide new insights into our understanding of depression in an urban environment among the elderly.

Different countries have differences in social and cultural context and health system, which may affect the clinical characteristics of psychiatric inpatients. This study was the first to compare cross-cultural differences in the clinical characteristics of psychiatric inpatients in three hospitals from Western China and America. Overall, 905 and 1318 patients from three hospitals, one in America and two in Western China, respectively, were included. We used a standardised protocol and data collection procedure to record inpatients’ sociodemographic and clinical characteristics. Significant differences were found between hospitals from the two countries. Positive symptoms were the main reason for admission in the Chinese hospitals, while reported suicide and self-injury symptoms more frequently led to hospital admission in America. Moreover, there were more inpatients with combined substance abuse in the American hospital (97.6% vs. 1.9%, P < 0.001). The length of stay (LOS) in America was generally shorter than in China (10.5 ± 11.9 vs. 20.7 ± 13.4, P < 0.001). The dosage of antipsychotic drugs used in the American hospital was higher than in China (275.1 ± 306.9 mg vs. 238.3 ± 212.5 mg, P = 0.002). Regression analysis showed that male sex, older age, retirees, being admitted because of physical symptoms, and using higher doses of antipsychotic drugs were significantly associated with longer hospitalisation in the American hospital (P < 0.05). Comparatively, patients who were divorced, experiencing suicidal ideation, admitted involuntarily, admitted because of physical, depression, or anxiety symptoms, and using higher doses of antipsychotic drugs had longer hospitalisation in Chinese hospitals (P < 0.05). Significant variations in clinical characteristics of inpatients were found between hospitals from Western China and America. The LOS in Chinese hospitals was significantly longer, but patients used higher doses of antipsychotic drugs in the American hospital. Admission due to physical symptoms and the use of higher dosage drugs were related to longer LOS in both countries.

Abstract Schizophrenia is a psychotic disorder with unknown pathogenesis, and accompanied by varying degrees of cognitive deficits. Recent studies have shown that dysregulated immune may play an important role in schizophrenia. The aim of this study was to determine the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and monocyte-lymphocyte ratio (MLR) in patients with schizophrenia, and explore their correlations with cognitive function. 74 patients with schizophrenia and 57 age- and gender-matched healthy controls were recruited in this study with demographic and clinical information. And blood samples were taken and cognitive function were evaluated by MCCB. All the MCCB tasks in this study were found with worse performance in patients with schizophrenia compared to healthy controls. Compare to healthy controls, patients with schizophrenia showed lower Hb levels, and higher monocytes, PLR, and MLR. Spearman correlation analysis showed Hb levels and PLR were positive and negative correlated with global cognitive function respectively. In summary, this study suggests that cognitive deficits in patients with schizophrenia is associated with dysregulated immunity and poor nutrition, which should be paid more attention in the future.

Amino acid abnormalities have been suggested to be a key pathophysiological mechanism in schizophrenia (SZ). Recently, gut microbes were found to be critically involved in mental and metabolic diseases. However, the relationship between serum amino acid levels and gut microbes in SZ is rarely studied. Here, we analyzed serum amino acid levels in 76 untreated SZ patients and 79 healthy controls (HC). Serum levels of 10 amino acids were significantly altered in patients with SZ. We further classified the cut-off values for serum arginine, leucine, glutamine, and methionine levels to distinguish SZ patients from controls. These classifiers were shown to be effective in another validation cohort (49 SZ and 48 HC). The correlation between serum amino acids and clinical symptoms and cognitive functions was also analyzed. Arginine, leucine, glutamine, and methionine levels were significantly correlated with clinical symptoms and cognitive impairments in SZ patients. By metagenome shotgun sequencing of fecal samples, we found that patients with SZ with a low level of serum amino acids have higher richness and evenness of the gut microbiota. At the genus level, the abundances of Mitsuokella and Oscillibacter are significantly abnormal. At the mOTU level, 15 mOTUs in the low-level SZ group were significantly different from the HC group. In addition, Mitsuokella multacida was correlated with glutamine and methionine, respectively. Our research revealed that alterations in serum amino acid levels are critically related to changes in gut microbiota composition in SZ patients. These findings may shed light on new strategies for the diagnosis and treatment of SZ.

Background: In China, an increasing number of people are aging; therefore, attention should be paid to age-related cognitive impairment. With the increasing attention given to geriatric depression in recent years, we focused our investigation on the relationship between depression in the elderly and cognitive decline in a large Chinese community study. Methods: We screened 4,771 subjects that met the inclusion criteria from the China Health and Retirement Longitudinal Study database. Depressive symptoms and cognitive performance were assessed using the 10-item Center for Epidemiological Studies Depression Scale (CESD-10) and Mini-Mental State Examination (MMSE), respectively. Results: We found that 4.46% of the elderly have depression and 35.19% have depressive symptoms. Lower education, higher CESD-10 score, increased age, and more negative marital status were associated with poor cognitive performance in the Chinese elderly. CESD-10 is negatively correlated with each MMSE item, including orientation, memory, attention and computation, and language. Limitations: It was difficult to draw conclusions about causation since there was no follow-up data, and high CESD-10 scores do not represent the population study finally diagnosed with depression. Finally, it is not clear whether the decline in cognitive function had an impact on participants' understanding of the problems in the CESD-10. Conclusions: This study preliminary prompted severe depressive symptoms associated with worse cognitive performance in a Chinese elderly community population.

To compare 22 oral drugs, cognitive behavior therapy (CBT), and their combination treatments for the acute treatment of adults with panic disorder in terms of remission rate and acceptability.Systematic review and network meta-analysisPubMed, Web of Science, Cochrane Central Register of Controlled Trials, and Embase databases from their inception up to May 26, 2019.Randomized controlled clinical trials (RCTs) of any oral drugs, CBT, CBT combined with any drug, or placebo in the acute treatment of adults with panic disorder diagnosed according to standard operationalized criteria. The primary outcomes were efficacy (remission rate) and acceptability (treatment discontinuations due to any cause).We identified 6585 reports that included 68 full-text RCTs involving 11101 patients. In terms of efficacy, 13 (68%) of 19 interventions were associated with higher remission rates than those of for placebo, with ORs ranging from 2.1 (95% credible interval [CrI] = 1.1 to 4.0) for sertraline to 13 (CrI = 4.5 to 44) for CBT combined with any drug. Regarding acceptability, alprazolam, imipramine, and etizolam were associated with lower dropout rates, with ORs ranging from 0.23 (CrI = 0.15 to 0.33) for alprazolam to 0.076 (CrI = 0.0021 to 0.77) for etizolam. Most of the differences between the other interventions were unclear. In head-to-head analyses, CBT combined with any drug was more effective than the other interventions, but it was no associated with an improvement in acceptability (OR = 0.12 to 0.219).CBT combined with any drug was more effective than the other interventions analyzed in this study. CBT alone did not differ significantly from other drugs alone. We found that most drugs are effective against panic disorder, but they exhibit different acceptability and tolerability profiles.Some randomized controlled trials indicated that combined therapy are more effective than drug alone or cognitive behavior therapy alone. Nevertheless, drug monotherapy, cognitive behavior therapy, and combination therapy had never been compared in a comprehensive network meta-analysis. With this evidence gap remaining, the availability of reliable evidence of the relative merits of multiple interventions is essential to ensuring that clinicians choose the best option for each individual patient.This network meta-analysis is the first to evaluate the relative merits of cognitive behavior therapy, cognitive behavior therapy combined with any drug, and 22 oral drugs in the field of panic disorder. The results showed a significant higher remission rates for cognitive behavior therapy combined with any drug than those of the other interventions. Cognitive behavior therapy alone was superior to placebo but did not differ significantly from other active drugs. Additionally, paroxetine, venlafaxine, fluoxetine, sertraline, and clonazepam are more recommendable than the other drugs based on their remission rates, scores on panic-symptoms scales, and acceptability.

ABSTRACTObjectiveGut microbiota dysbiosis and aberrant gut-brain functional modules including short-chain fatty acid (SCFA) production and long-lasting immune activation (IA) are presented in schizophrenia. Given the key roles of gut microbiota and SCFA in shaping immunity, we propose that dysbiosis-induced SCFA upregulation could contribute to IA and behavioral symptoms in schizophrenia.DesignGut microbiota, SCFA, and IA biomarkers were compared between schizophrenic patients and healthy controls. The roles of SCFA in schizophrenia-related IA were analyzed in cultured peripheral blood mononuclear cells (PBMCs) and a mouse model of schizophrenia. The effects of SCFAs on schizophrenia-related phenotypes were analyzed in both human and mouse.ResultsBoth microbial-derived SCFA and SCFA-producing bacteria were elevated in the guts of schizophrenic patients, and this increased SCFA production in gut was associated with IA in schizophrenia. The microbiome signature underpinning schizophrenia-related IA includes increased diversity and increased SCFA-producing bacteria and inflammation-associated bacteria. The impact of SCFAs on immune responses of cultured PBMC depend on the diagnosis and IA status of donors. Small-molecule serum filtrates from immune-activated schizophrenic patients increased the inflammatory response of PBMCs from healthy volunteers, which can be enhanced and attenuated by SCFAs supplementation and inhibition of SCFA signaling, respectively. Chronically elevated SCFAs in adolescence induced neuroinflammation and schizophrenia-like behaviors in adult mice. Moreover, chronically elevated SCFAs in adult mice prenatally exposed to IA potentiated their expression of schizophrenia-like behaviors.Conclusionmicrobiota-derived SCFAs are important mediators of dysregulated gut-brain axis and participant in pathogenesis via enhance IA in schizophrenia.SummarySignificance of this studyWhat is already known about this subject?➢ Schizophrenia pathogenesis goes beyond the brain since increasing peripheral abnormalities are revealed including gut microbiota dysbiosis, GI dysfunction, and systemic immune activation (IA).➢Systemic IA/inflammation contributes to the neuroinflammation and brain impairment underlying schizophrenia, and adjunctive immunotherapy can improve psychotic symptoms.➢Short-chain fatty acids (SCFA) mediate the microbiota-gut-brain communication and modulate several pathways involved in schizophrenia, including pathways of immunity and neurotransmitters.What are the new findings?➢Patients with schizophrenia displayed increased rates of IA and increased SCFA production compared with healthy controls, and increased SCFA is associated with IA in patients.➢A unique microbiota signature including enriched SCFA-producing bacterial species can distinguish patients with IA from other patients and controls.➢Small molecules in the serum of immune-activated patients with schizophrenia enhance LPS-induced immune response of cultured peripheral blood mononuclear cell (PBMCs), which is partially mediated by SCFA signaling.➢SCFA intake upregulates both peripheral and brain inflammation and potentiates the expression of schizophrenia-like behaviors in mice prenatally exposed to IA.How might it impact on clinical practice in the foreseeable future?➢Interference of SCFA signaling or targeted destruction of SCFA-producing bacteria may provide a new approach for the prevention and treatment of schizophrenia.➢Immune activation status of patients should be an important condition considered when selecting immunotherapy for future precision psychiatric therapy.

OBJECTIVE:The risk of coronary heart disease (CHD) in patients with major depressive disorder (MDD) is higher than that in the general population. However, the mechanisms underlying the increased CHD risk in patients with MDD remain unclear. Inflammation plays an important role in the pathogenesis of MDD and CHD. Therefore, we explored the relationship between inflammatory biomarkers and CHD risk in patients with MDD.METHODS:We included 454 patients with acute MDD and 458 controls that matched the sample in age and gender. A readily available complete blood count was used to reflect inflammation, and the risk of CHD was assessed using the Framingham risk score.RESULTS:The results showed that patients with MDD showed low-grade inflammation with an elevated platelet (p<0.001) and monocyte count (p<0.001), high platelet/lymphocyte (p=0.003) and monocyte/lymphocyte ratios (p<0.001), and a raised systemic immune-inflammation index (p=0.002). In addition, monocyte count was the only factor significantly associated with CHD risk in patients with MDD (B=7.521, 95% CI: 3.409-11.633, t=3.594, p<0.001).CONCLUSION:Collectively, the results of this study support the hypothesis that MDD is systemic inflammation, and suggest that monocyte count predicts the risk of CHD in patients with MDD.

Objective: To evaluate the effects of different surgical dressings in reducing surgical site infection (SSI) and identify the optimal dressings. Methods: Randomized controlled trials investigating the application of surgical dressings were retrieved from electronic databases, including MEDLINE, EMBASE, and the Cochrane Library. The odds ratios (ORs) of the SSI rate were compared by direct meta-analysis, and the surface under the cumulative ranking (SUCRA) curve values were calculated based on the Bayesian theorem. A node-splitting model was applied to analyse the consistency of the comprehensive comparison results. Results: Twenty-two studies containing 5487 participants were pooled for the comprehensive comparison. Among all the studies included, 9 types of surgical dressings were identified for comparison. The results of the direct meta-analysis revealed that novel dressings significantly reduced the overall SSI rate with an OR of 1.026 (95% CI: 1.013-1.040, p < 0.001), which was determined to have low heterogeneity (I-2 = 32.1%). Specifically, 3 types of dressings presented significant effects in reducing SSI, namely, mupirocin-containing (OR = 1.076, 95% CI: 1.014-1.142, p = 0.015), dialkylcarbamoyl-chloride-containing (OR = 1.047, 95% CI: 1.012-1.083, p = 0.008) and vitamin E (VE)-silicone-containing (OR = 1.129, 95% CI: 1.016-1.255, p = 0.025) dressings. Network meta-analysis demonstrated that the VE-silicone dressing (SUCRA = 0.37) was the optimal dressing, followed by the mupirocin dressing, with a SUCRA of 0.31. Conclusion: The present network meta-analysis identified the superiority of VE-silicone and mupimcin dressings in preventing SSI. The evidence-based results provide suggestions and directions for future investigations on surgical dressings. More large-scale trials with rigorous designs are warranted to clarify the clinical value of novel dressings in surgical incision management.

Previous findings on the dysfunction of hypothalamic-pituitary-adrenal (HPA) axis in generalized anxiety disorder (GAD) are controversial, and the molecular mechanisms underlying such dysfunction remain unclear. We analyzed the methylation status of the NR3C1 1F promoter and the expression of glucocorticoid receptor-α isoform (GRα) in peripheral blood mononuclear cells (PMBCs), the basal cortisol level in serum, and a functional neuroendocrine marker for GR sensitivity in the PMBCs in 64 patients with current GAD and 85 healthy controls. We found that patients with GAD had significantly elevated levels of morning basal serum cortisol (P < 0.0001) and diminished GR sensitivity in the PBMCs (P < 0.0001) compared with healthy controls. The overall methylation levels across NR3C1 1F promoter (P < 0.0001) and percent methylation at each of the 5 CpG sites including CpG12, 21, 30, 31, and 32 (P < 0.001) significantly increased. Accordingly, the mRNA levels of GRα significantly decreased (P < 0.0001) in the PBMCs in patients with GAD compared with healthy controls, with the effects specific in patients without childhood traumatic experience. Moreover, both serum basal cortisol levels and GR sensitivity in the PBMCs were negatively correlated with the overall methylation levels of the NR3C1 1F promoter (P < 0.0001) and positively correlated with GRα mRNA levels (P = 0.007) in the PBMCs. In sum, our study revealed the increased activity of the HPA axis and diminished peripheral glucocorticoid responsiveness of GR underlying episodes of GAD. Furthermore, such dysfunction of the HPA axis is associated with both increased DNA methylation of NR3C1 1F promoter and decreased GRα expression.