Dysregulation of interleukin-8 is involved in the onset and relapse of schizophrenia: An independent validation and meta-analysis.

As a major mental health disorder, symptoms of schizophrenia (SCZ) include delusions, reduced motivation, hallucinations, reduced motivation and a variety of cognitive disabilities. Many of these symptoms are now known to be associated with abnormal regulation of the immune system. Low blood levels of cytokines and chemokines have been suggested to be one of the underlying causes of SCZ. However, their biological roles at different stages of SCZ remain unclear. Our objective was to investigate expression patterns of cytokines and chemokines at different stages of onset and relapse in SCZ patients and to conduct an analysis of their relationship to disease progression. We also aimed to identify immune features associated with different disease trajectories in patients with SCZ. Gene set enrichment analysis (GSEA) was used to interrogate the GSE27383 dataset and identify key genes associated with inflammation. These results led us to recruit 36 healthy controls, 40 patients with first-episode psychosis (FEP), and 39 patients with SCZ relapse. Meso Scale Discovery technology was used to independently validate serum levels of 35 cytokines and chemokines. This was followed by a meta-analysis to gain a more comprehensive understanding of the role of interleukin-8 (IL-8/CXCL8) in SCZ. Analysis of the GSE27383 database revealed 3596 genes with distinct expression patterns. A significant portion of these genes were identified as inflammation-related and showed remarkable enrichment in three key pathways: IL-17, cytokine-cytokine receptor, and AGE-RAGE signaling in diabetic complications. We observed co-expression of CXCL8 and IL-16 within these three pathways. In a subsequent analysis of independently validated samples, a notable discrepancy was detected in the inflammatory status between individuals experiencing FEP and those in relapse. In particular, expression of CXCL8 demonstrated superior predictive capability in FEP and relapsed patients. Notably, results of the meta-analysis confirmed that Chinese and European populations were consistent with the overall results (Z = 4.60, P < 0.001; Z = 3.70, P < 0.001). However, in the American subgroup, there was no significant difference in CXCL8 levels between patients with SCZ compared to healthy controls (Z = 1.09, P = 0.277). Our findings suggest that the inflammatory response in patients with SCZ differs across the different stages, with CXCL8 emerging as a potential predictive factor. Collectively, our data suggest that CXCL8 has the potential to serve as a significant immunological signature of SCZ subtypes. Trial registration: The clinical registration number for this trial is ChiCTR2100045240 (Registration Date: 2021/04/09).

Heatwave characteristics complicate the association between PM2.5 components and schizophrenia hospitalizations in a changing climate: Leveraging of the individual residential environment.

BACKGROUND: In the era characterized by global environmental and climatic changes, understanding the effects of PM2.5 components and heatwaves on schizophrenia (SCZ) is essential for implementing environmental interventions at the population level. However, research in this area remains limited, which highlights the need for further research and effort. We aim to assess the association between exposure to PM2.5 components and hospitalizations for SCZ under different heatwave characteristics. METHODS: We conducted a 16 municipalities-wide, individual exposure-based, time-stratified, case-crossover study from January 1, 2017, to December 31, 2020, encompassing 160736 hospitalizations in Anhui Province, China. Daily concentrations of PM2.5 components were obtained from the Tracking Air Pollution in China dataset. Conditional logistic regression models were used to investigate the association between PM2.5 components and hospitalizations. Additionally, restricted cubic spline models were used to identify protective thresholds of residential environment in response to environmental and climate change. RESULTS: Our findings indicate a positive correlation between PM2.5 and its components and hospitalizations. Significantly, a 1 µg/m3 increase in black carbon (BC) was associated with the highest risk, at 1.58% (95%CI: 0.95-2.25). Exposure to heatwaves synergistically enhanced the impact of PM2.5 components on hospitalization risks, and the interaction varied with the intensity and duration of heatwaves. Under the 99th percentile heatwave events, the impact of PM2.5 and its components on hospitalizations was most pronounced, which were PM2.5 (2-4d: 4.59%, 5.09%, and 5.09%), sulfate (2-4d: 21.73%, 23.23%, and 25.25%), nitrate (2-4d: 17.51%, 16.93%, and 20.31%), ammonium (2-4d: 27.49%, 31.03%, and 32.41%), organic matter (2-4d: 32.07%, 25.42%, and 24.48%), and BC (2-4d: 259.36%, 288.21%, and 152.52%), respectively. Encouragingly, a protective effect was observed when green and blue spaces comprised more than 17.6% of the residential environment. DISCUSSION: PM2.5 components and heatwave exposure were positively associated with an increased risk of hospitalizations, although green and blue spaces provided a mitigating effect.

Decline in Working Memory in Stable Schizophrenia May Be Related to Attentional Impairment: Mediating Effects of Negative Symptoms, a Cross-Sectional Study.

Background: Schizophrenia (SCZ) is a severe mental illness, Cognitive deficits and negative symptoms (NS) are prevalent in individuals with SCZ and are crucial indicators of functional recovery. It is well known that cognitive symptoms and negative symptoms are interrelated and that negative symptoms can affect the ability to take cognitive tests. However, the specific relationship between attention, working memory (WM), and NS in stable SCZ remains unclear. This study aims to explore these associations and provide valuable insights for the subsequent treatment of SCZ. Methods: We conducted a comprehensive assessment of 145 patients with stable SCZ using the Chinese Brief Neurocognitive Suite of Tests (C-BCT) and the Positive and Negative Symptom Scale (PANSS). Results: Patients with abnormal cognition exhibited significantly higher PANSS total scores, cognitive symptom scores, and NS than those with normal cognition (P<0.05). Pearson's correlation analysis revealed significant positive correlations between digital breadth(DB) and continuous operation(CO) (r=0.389, P<0.001), as well as a significant negative correlation between DB and NS (r=-0.291, P<0.001). Moreover, CO showed a negative correlation with NS (r=-0.173, P<0.05). However, no significant correlations were found between the digital breadth-anterograde score and CO or NS (r=0.148, P>0.05; r=-0.068, P>0.05). Notably, NS were identified as a mediator in the relationship between attention and WM (effect size=0.024). Conclusion: Our findings highlight significant associations between WM, attention, and NS in individuals with stable SCZ. Moreover, attention not only directly impacts WM but also indirectly influences it through NS. Addressing cognitive deficits and NS in the treatment of SCZ may lead to improved overall outcomes for affected individuals.

Correlation analysis of mental health conditions and personality of patients with alcohol addiction.

BACKGROUND: Alcohol addiction, or alcohol dependence, refers to a psychological state of strong craving for alcohol caused by drinking when both the drinking times and alcohol consumption reach a certain level. Alcohol addiction can cause irreversible damage, leading to mental illness or mental disorders, negative changes in their original personality, and a tendency to safety incidents such as committing suicide or violent attacks on others. Significant attention needs to be given to the mental health of alcohol addicts, which could reflect their abnormal personality traits. However, only a few papers on this issue have been reported in China. AIM: To investigate the correlation between mental health and personality in patients with alcohol addiction. METHODS: In this single-center observational study, we selected 80 patients with alcohol addiction as the research subjects, according to the criteria of the K10 scale to evaluate the mental health of patients with alcohol addiction, and divided these patients into four groups based on the evaluation results: Good, average, relatively poor and bad. And then analyzed the correlation between mental health conditions and personality characteristics from these four groups of patients. RESULTS: The average score of the K10 scale (Kessler 10 Simple Psychological Status Assessment Scale) in 80 patients with alcohol addiction was 25.45 points, the median score was 25 points, the highest score was 50 points, and the lowest score was 11 points. Pearson's analysis showed that the K10 score was positively correlated with the scores of these two subscales, such as the P-subscale and the N-subscale (P < 0.05). In contrast, the K10 score had no significant correlation with the scores from the E-subscale and the L-subscale (P > 0.05). CONCLUSION: The mental health conditions of patients with alcohol addiction are positively correlated with their personality characteristics.

Intricate role of intestinal microbe and metabolite in schizophrenia.

BACKGROUND: The brain-gut axis has gained increasing attention due to its contribution to the etiology of various central nervous system disorders. This study aims to elucidate the hypothesis that schizophrenia is associated with disturbances in intestinal microflora and imbalance in intestinal metabolites. By exploring the intricate relationship between the gut and the brain, with the goal of offering fresh perspectives and valuable insights into the potential contribution of intestinal microbial and metabolites dysbiosis to the etiology of schizophrenia. METHODS: In this study, we used a 16S ribosomal RNA (16S rRNA) gene sequence-based approach and an untargeted liquid chromatography-mass spectrometry-based metabolic profiling approach to measure the gut microbiome and microbial metabolites from 44 healthy controls, 41 acute patients, and 39 remission patients, to evaluate whether microbial dysbiosis and microbial metabolite biomarkers were linked with the severity of schizophrenic symptoms. RESULTS: Here, we identified 20 dominant disturbances in the gut microbial composition of patients compared with healthy controls, with 3 orders, 4 families, 9 genera, and 4 species. Several unique bacterial taxa associated with schizophrenia severity. Compared with healthy controls, 145 unusual microflora metabolites were detected in the acute and remission groups, which were mainly involved in environmental information processing, metabolism, organismal systems, and human diseases in the Kyoto encyclopedia of genes and genomes pathway. The Sankey diagram showed that 4 abnormal intestinal and 4 anomalous intestinal microbial metabolites were associated with psychiatric clinical symptoms. CONCLUSIONS: These findings suggest a possible interactive influence of the gut microbiota and their metabolites on the pathophysiology of schizophrenia.

Relationship between serum vitamin D and thyroid hormone profiles in male patients with alcohol dependence.

BACKGROUND: Alcohol dependence (AD) results in several medical problems including vitamin D deficiency and thyroid dysfunction. However, the relationship between these two complications remains unclear. The aim of the present study was to explore the relationship between serum vitamin D and thyroid hormone profiles in male patients with AD. METHODS: A total of 117 male patients with AD were enrolled. Vitamin D deficiency was defined as serum concentrations of the main circulating vitamin D, 25-hydroxy vitamin D [25(OH)D], below 50 nmol/L. The AD patients were divided into two groups accordingly: 46 patients with normal vitamin D levels (normal group) and 71 patients with vitamin D deficiency (deficiency group). The levels of thyroid hormone profiles including total triiodothyronine 3 (TT3), total thyroxine 4 (TT4), thyroid stimulating hormone (TSH), free triiodothyronine (fT3), and free thyroxine (fT4) between the two groups were compared. Correlation between the serum levels of 25(OH)D and thyroid hormone profiles was evaluated using simple correlation (Pearson's correlation) and multivariable analysis using linear regression models. RESULTS: The prevalence of vitamin D deficiency in male patients with AD is 60.7% (71/117; 95% confidence interval: 51.6-69.1%). Moreover, the serum levels of TT3 (t = -2.682, p = 0.009), TT4 (t = -2.033, p = 0.044), fT3 (t = -2.986, p = 0.003), and fT4 (t = -2.558, p = 0.012) in deficiency group were significantly higher than those in normal group. Post hoc power analyses showed that the power for fT3 was sufficient (power > 0.80). Furthermore, univariate analysis showed that the serum vitamin D levels were negatively correlated with the TT3 (r = -0.189, p = 0.044), fT3 (r = -0.350, p < 0.001), and fT4 (r = -0.198, p = 0.033) levels, while multivariate analysis indicated that only fT3 was independently related to the serum levels of vitamin D in male patients with AD. CONCLUSIONS: These results suggested that the serum vitamin D levels may be associated with fT3 in male patients with AD.

Potential role between inflammatory cytokines and Tie-2 receptor levels and clinical symptoms in patients with first-episode schizophrenia.

BACKGROUND: Schizophrenia (SCZ) is associated with chronic low-grade inflammation, which may be involved in the underlying pathological mechanism of the disease and may influence patient prognosis. We evaluated the differences in serum cytokine and Tie-2 receptor levels between patients with first-episode SCZ and healthy controls and explored the correlation thereof with clinical symptoms. METHODS: Seventy-six participants were recruited for the present study, including 40 patients with first-episode SCZ and 36 healthy controls. Positive and Negative Syndrome Scale (PANSS) and Brief Psychiatric Rating Scale (BPRS) scores, demographic data, and blood samples were collected at baseline. A hypersensitive Meso Scale Discovery (MSD) electrochemiluminescence assay system was used to measure cytokine and Tie-2 receptor levels. Spearman's correlation and stepwise linear regression were used to analyze the data. RESULTS: Serum interleukin-1ß and -4 levels were significantly increased, and Tie-2 levels were significantly decreased, in first-episode SCZ patients as compared to healthy controls. IL-1ß levels were positively correlated with total BPRS scores, resistance subscores, and PANSS positive subscores. Furthermore, IL-1ß levels were negatively correlated with Tie-2 receptor expression levels. Stepwise linear regression analysis demonstrated that IL-1ß levels correlated positively with PANSS positive subscores and BPRS total scores. PANSS negative subscores, general psychopathology subscores, and PANSS total scores had positive effects on the Tie-2 receptor. Receiver operating characteristic (ROC) curve analysis showed that IL-1ß and Tie-2 were highly sensitive and specific for predicting first-episode SCZ symptoms and achieving an area under the ROC curve of 0.8361 and 0.6462, respectively. CONCLUSION: Our results showed that patients with first-episode SCZ have low-grade inflammation. IL-1ß and Tie-2 receptors may be important mediators between inflammation and vascular dysfunction in patients with SCZ and may underlie the increased cardiovascular disease in this population. TRIAL REGISTRATION: The clinical trial registration date was 06/11/2018, registration number was chiCTR1800019343.

Correlation between elevated serum interleukin-1ß, interleukin-16 levels and psychiatric symptoms in patients with schizophrenia at different stages.

BACKGROUND: There is increasing evidence that immune dysfunction plays an important role in the pathogenesis of schizophrenia. Meso Scale Discovery (MSD) is bioanalytical method, which can detect serum inflammatory factors in patients. MSD has higher sensitivities, capturing a narrower range of proteins compared to other methods typically used in similar studies. The present study was aimed to explore the correlation between the levels of serum inflammatory factors and psychiatric symptoms in patients with schizophrenia at different stages and investigate a wide panel of inflammatory factors as independent factors for the pathogenesis of schizophrenia. METHODS: We recruited 116 participants, including patients with first-episode schizophrenia (FEG, n = 40), recurrence patients (REG, n = 40) with relapse-episode schizophrenia, and a control group (healthy people, HP, n = 36). Patients are diagnosed according to the DSM -V. The plasma levels of IFN-γ, IL-10, IL-1ß, IL-2, IL-6, TNF-α, CRP, VEGF, IL-15, and IL-16 were tested by the MSD technique. Patient-related data was collected, including sociodemographic data, positive and negative symptom scale (PANSS), and brief psychiatric rating scale (BPRS) and subscale scores. The independent sample T test, χ2 test, Analysis of covariance (ANCOVA), the least significant difference method (LSD), Spearman's correlation test, binary logistic regression analysis and ROC curve analysis were used in this study. RESULTS: There were significant differences in serum IL-1ß (F = 2.37, P = 0.014) and IL-16 (F = 4.40, P < 0.001) levels among the three groups. The level of serum IL-1ß in the first-episode group was significantly higher than in the recurrence group (F = 0.87, P = 0.021) and control group (F = 2.03, P = 0.013), but there was no significant difference between the recurrence group and control group (F = 1.65, P = 0.806). The serum IL-16 levels in the first-episode group (F = 1.18, P < 0.001) and the recurrence group (F = 0.83, P < 0.001) were significantly higher than in the control group, and there was no significant difference between the first-episode group and the recurrence group (F = 1.65, P = 0.61). Serum IL-1ß was negatively correlated with the general psychopathological score (GPS) of PANSS (R=-0.353, P = 0.026). In the recurrence group, serum IL-16 was positively correlated with the negative score (NEG) of the PANSS scale (R = 0.335, P = 0.035) and negatively correlated with the composite score (COM) (R=-0.329, P = 0.038). In the study, IL-16 levels were an independent variable of the onset of schizophrenia both in the first-episode (OR = 1.034, P = 0.002) and recurrence groups (OR = 1.049, P = 0.003). ROC curve analysis showed that the areas under IL-16(FEG) and IL-16(REG) curves were 0.883 (95%CI:0.794-0.942) and 0.887 (95%CI:0.801-0.950). CONCLUSIONS: Serum IL-1ß and IL-16 levels were different between patients with schizophrenia and healthy people. Serum IL-1ß levels in first-episode schizophrenia and serum IL-16 levels in relapsing schizophrenia were correlated with the parts of psychiatric symptoms. The IL-16 level may be an independent factor associating with the onset of schizophrenia.

Intermediary roles of prospective memory and retrospective memory in the comorbidity of depression and pain.

Background: Patients who suffer comorbidity of major depressive disorder (MDD) and chronic pain (CP) maintain a complex interplay between maladaptive prospective memory (PM) and retrospective memory (RM) with physical pain, and their complications are still unknown. Aims: We aimed to focus on the full cognitive performance and memory complaints in patients with MDD and CP, patients with depression without CP, and control subjects, considering the possible influence of depressed affect and chronic pain severity. Methods: According to the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders and the criteria given by the International Association of Pain, a total of 124 participants were included in this cross-sectional cohort study. Among them, 82 depressed inpatients and outpatients from Anhui Mental Health centre were divided into two groups: a comorbidity group(patients with MDD and CP) (n=40) and a depression group (patients with depression without CP) (n=42). Meanwhile, 42 healthy controls were screened from the hospital's physical examination centre from January 2019 to January 2022. The Hamilton Depression Rating Scale-24 (HAMD-24) and Beck Depression Inventory-II (BDI-II) were used to evaluate the severity of depression. The Pain Intensity Numerical Rating Scale (PI-NRS), Short-Form McGill Pain Questionnaire-2 Chinese version (SF-MPQ-2-CN), Montreal Cognitive Assessment-Basic Section (MoCA-BC), and Prospective and Retrospective Memory Questionnaire (PRMQ) were used to assess pain-related features and the global cognitive functioning of study participants. Results: The impairments in PM and RM differed remarkably among the three groups (F=7.221, p<0.001; F=7.408, p<0.001) and were severe in the comorbidity group. Spearman correlation analysis revealed the PM and RM were positively correlated with continuous pain and neuropathic pain (r=0.431, p<0.001; r=0.253, p=0.022 and r=0.415, p<0.001; r=0.247, p=0.025), respectively. Regression analysis indicated a significant positive relationship between affective descriptors and total BDI-II score (ß=0.594, t=6.600, p<0.001). Examining the mediator pathways revealed the indirect role of PM and RM in patients with comorbid MDD and CP. Conclusions: Patients with comorbid MDD and CP presented more PM and RM impairments than patients with MDD without CP. PM and RM are possibly mediating factors that affect the aetiology of comorbid MDD and CP. Trial registration number: chiCTR2000029917.

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

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

Prediction of violence in male schizophrenia using sMRI, based on machine learning algorithms.

BACKGROUND: Violent behavior in patients with schizophrenia (SCZ) is a major social problem. The early identification of SCZ patients with violence can facilitate implementation of targeted intervention. METHODS: A total of 57 male SCZ patients were recruited into this study. The general linear model was utilized to compare differences in structural magnetic resonance imaging (sMRI) including gray matter volume, cortical surface area, and cortical thickness between 30 SCZ patients who had exhibited violence and 27 SCZ patients without a history of violence. Based on machine learning algorithms, the different sMRI features between groups were integrated into the models for prediction of violence in SCZ patients. RESULTS: After controlling for the whole brain volume and age, the general linear model showed significant reductions in right bankssts thickness, inferior parietal thickness as well as left frontal pole volume in the patients with SCZ and violence relative to those without violence. Among seven machine learning algorithms, Support Vector Machine (SVM) have better performance in differentiating patients with violence from those without violence, with its balanced accuracy and area under curve (AUC) reaching 0.8231 and 0.841, respectively. CONCLUSIONS: Patients with SCZ who had a history of violence displayed reduced cortical thickness and volume in several brain regions. Based on machine learning algorithms, structural MRI features are useful to improve predictive ability of SCZ patients at particular risk of violence.

Childhood maltreatment increases the suicidal risk in Chinese schizophrenia patients.

Objectives: Childhood trauma might be a modifiable risk factor among adults with serious mental illness. However, the correlation of child trauma and suicide is unclear, which were cited most frequently as the biggest challenge to schizophrenia (SCZ) patients in China. We aim to study relationships between child trauma and suicide in SCZ patients of different disease stages. Methods: Ninety-one participants were included and divided into two groups, namely, first-episode group (n = 46), relapsed group (n = 45). The Positive and Negative Syndrome Scale was used to evaluate the severity of psychotic symptoms. The Beck's Suicide Intent Scale and The Nurses' Global Assessment of Suicide Risk were conducted by patient self-report to assess suicide symptom. The childhood trauma questionnaire was used to estimate severity of traumatic stress experienced during childhood. Results: Childhood trauma and different dimensions of suicide were significantly higher in the relapsed group than first-episode group (P < 0.01, respectively). BMI has a significant positive relationship with recent psychosocial stress (ß = 0.473, t = 3.521, P < 0.001) in first-episode group. As in relapsed group, BMI has a positive effect between severe mental illness and suicide ideation (ß = 0.672, t = 5.949, P < 0.001; ß = 0.909, t = 2.463, P < 0.001), Furthermore, emotional neglect presented positively related to the suicide risk and proneness to suicidal behavior (ß = 0.618, t = 5.518, P < 0.001; ß = 0.809, t = 5.356, P < 0.001). Conclusion: Relapsed group of patients had significantly more severe childhood trauma, recent psychosocial stress, suicidal risk and proneness to suicidal behavior. BMI and emotional neglect are unique predictors for different dimensions of suicide.

Long-term maintenance of synaptic plasticity by Fullerenol Ameliorates lead-induced-impaired learning and memory in vivo.

Fullerenol, a functional and water-soluble fullerene derivative, plays an important role in antioxidant, antitumor and antivirus, implying its enormous potential in biomedical applications. However, the in vivo performance of fullerenol remains largely unclear. We aimed to investigate the effect of fullerenol (i.p., 5 mg/kg) on the impaired hippocampus in a rat model of lead exposure. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) is a kind of newly developed soft-ionization mass spectrometry technology. In the present study, an innovative strategy for biological distribution analysis using MALDI-TOF-MS confirmed that fullerenol could across the blood-brain barrier and accumulate in the brain. Results from behavioral tests showed that a low dose of fullerenol could improve the impaired learning and memory induced by lead. Furthermore, electrophysiology examinations indicated that this potential repair effect of fullerenol was mainly due to the long-term changes in hippocampal synaptic plasticity, with enhancement lasting for more than 2-3 h. In addition, morphological observations and biochemistry analyses manifested that the long-term change in synaptic efficacy was accompanied by some structural alteration in synaptic connection. Our study demonstrates the therapeutic feature of fullerenol will be beneficial to the discovery and development as a new drug and lays a solid foundation for further biomedical applications of nanomedicines.

Potential Role of Pain Catastrophic Thinking in Comorbidity Patients of Depression and Chronic Pain.

Background: Although comorbidity of major depressive disorder (MDD) and chronic pain (CP) has been well-studied, their association with pain catastrophizing is largely elusive. This study aimed to investigate the potential effects of pain catastrophizing in patients with a comorbidity. Methods: In total, 140 participants were included in this study and divided into three groups according to the Diagnostic and Statistical Manual of Mental Disorders and the International Association for the study of pain (i.e., the comorbidity group: patients with depression with chronic pain, n = 45; depression group: patients with depression without chronic pain, n = 47; and healthy controls: n = 48). The Hamilton Depression Rating Scale (HAMD)-24 and Hamilton Anxiety Rating Scale (HAMA)-14 were used by professional psychiatrists to evaluate the severity of depression and anxiety. Beck Depression Inventory-II (BDI-II) and Beck Anxiety Inventory (BAI) were conducted by patients' self-report to assess the symptom severity. The pain intensity numerical rating scale (PI-NRS) was used to assess the pain intensity. Pain Catastrophizing Scale (PCS) and Pain Anxiety Symptoms Scale (PASS) were used to estimate pain-related negative thinking. Results: The results showed that PASS and PCS scores were significantly different among the three groups. Particularly, the scores in the comorbidity group were the highest. The Pearson correlation analysis revealed a positive correlation between PCS (including the patients' helplessness, magnification, rumination, and total scores) and the severity of depression symptoms, anxiety symptoms, and pain intensity (P < 0.05). A stepwise regression analysis further demonstrated that the total PCS score, high monthly income level, and BDI score had positive impacts on PASS (P < 0.05). We also found that the total BDI score, disease course ≥1 year, and pain intensity had positive effects on PCS (P < 0.05), whereas years of education (≤ 12 years) had a negative effect on PCS (P = 0.012). In all, we have clearly demonstrated that PCS and PASS could serve as potentially predictive factors in patients suffering from comorbidity of MDD and CP. Conclusion: Our results suggested that the pain-related catastrophic thinking and anxiety were more severe in the comorbidity group than in MDD-only group and healthy group. Pain-related catastrophizing thoughts and anxiety may have potentially effects on the comorbidity of depression and chronic pain.

Effects of Modified Electroconvulsive Therapy on Serum Cortisol, Nesfatin-1, and Pro-inflammatory Cytokine Levels in Elderly Patients With Treatment-Resistant Depression.

Aim: Modified electroconvulsive therapy (MECT) is an effective strategy for treatment-resistant depression (TRD); however, the mechanism underlying effects of MECT remains unclear. Accumulating evidence suggests that TRD is closely associated with dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis, anorexigenic peptides, and pro-inflammatory cytokines. However, MECT effects on the HPA axis, anorexigenic peptides, and pro-inflammatory cytokines in elderly patients with TRD remain unclear. In this study, we investigated whether the HPA axis (cortisol), anorexigenic peptides (nesfatin-1), and pro-inflammatory cytokines (C-reactive protein, tumor necrosis factor-α, and interleukin-6, and interleukin-1ß) are involved in the mechanism underlying MECT effects in elderly patients with TRD. Methods: Elderly patients with TRD were enrolled in this study between December 2019 and October 2021; all patients underwent MECT after physical examination. Serum cortisol, nesfatin-1, and pro-inflammatory cytokine levels were measured before and after the first, third, and sixth MECT sessions. The Hamilton Depression Rating Scale-24 (HAMD-24) and the Mini-Mental State Examination (MMSE) were used to evaluate depression and cognitive impairment, respectively. We compared pre- and post-MECT serum cortisol, nesfatin-1, and pro-inflammatory cytokine levels to confirm the short-term effects of MECT on these serum indices. We compared these serum indices across three time points (before the first, third, and sixth MECT sessions) to determine the long-term effects of MECT on serum cortisol, nesfatin-1, and pro-inflammatory cytokine levels. Results: We observed no statistically significant changes in the pre- and post-MECT serum cortisol, nesfatin-1, or pro-inflammatory cytokine levels. No significant changes in serum cortisol, nesfatin-1, and pro-inflammatory cytokine levels were observed across the aforementioned time points. Moreover, there were no statistically significant sex-based differences in the aforementioned serum indices. Furthermore, the serum cortisol level was negatively correlated with the serum IL-6 level before and after the first MECT session in patients with high cortisol levels (> the 50th percentile value of all samples). Additionally, the post-MECT HAMD-24 and MMSE scores were significantly lower. Conclusions: MECT reduced depressive symptoms despite an adverse effect on cognition and had no significant effect on the serum cortisol, nesfatin-1, and pro-inflammatory cytokine levels in elderly patients with TRD.

Distinct basolateral amygdala excitatory inputs mediate the somatosensory and aversive-affective components of pain.

Pain is a multidimensional perception that includes unpleasant somatosensory and affective experiences; however, the underlying neural circuits that mediate different components of pain remain elusive. Although hyperactivity of basolateral amygdala glutamatergic (BLAGlu) neurons is required for the somatosensory and emotional processing of pain, the precise excitatory inputs to BLAGlu neurons and their roles in mediating different aspects of pain are unclear. Here, we identified two discrete glutamatergic neuronal circuits in male mice: a projection from the insular cortex glutamatergic (ICGlu) to BLAGlu neurons, which modulates both the somatosensory and affective components of pain, and a projection from the mediodorsal thalamic nucleus (MDGlu) to BLAGlu neurons, which modulates only the aversive-affective component of pain. Using whole-cell recording and fiber photometry, we found that neurons within the IC→BLA and MD→BLA pathways were activated in mice upon inflammatory pain induced by injection of complete Freund's adjuvant (CFA) into their paws. Optical inhibition of the ICGlu→BLA pathway increased the nociceptive threshold and induced behavioral place preference in CFA mice. In contrast, optical inhibition of the MDGlu→BLA pathway did not affect the nociceptive threshold but still induced place preference in CFA mice. In normal mice, optical activation of the ICGlu→BLA pathway decreased the nociceptive threshold and induced place aversion, while optical activation of the MDGlu→BLA pathway only evoked aversion. Taken together, our results demonstrate that discrete ICGlu→BLA and MDGlu→BLA pathways are involved in modulating different components of pain, provide insights into its circuit basis, and better our understanding of pain perception.

The Prediction and Influential Factors of Violence in Male Schizophrenia Patients With Machine Learning Algorithms.

Background: Early to identify male schizophrenia patients with violence is important for the performance of targeted measures and closer monitoring, but it is difficult to use conventional risk factors. This study is aimed to employ machine learning (ML) algorithms combined with routine data to predict violent behavior among male schizophrenia patients. Moreover, the identified best model might be utilized to calculate the probability of an individual committing violence. Method: We enrolled a total of 397 male schizophrenia patients and randomly stratified them into the training set and the testing set, in a 7:3 ratio. We used eight ML algorithms to develop the predictive models. The main variables as input features selected by the least absolute shrinkage and selection operator (LASSO) and logistic regression (LR) were integrated into prediction models for violence among male schizophrenia patients. In the training set, 10 × 10-fold cross-validation was conducted to adjust the parameters. In the testing set, we evaluated and compared the predictive performance of eight ML algorithms in terms of area under the curve (AUC) for the receiver operating characteristic curve. Result: Our results showed the prevalence of violence among male schizophrenia patients was 36.8%. The LASSO and LR identified main risk factors for violent behavior in patients with schizophrenia integrated into the predictive models, including lower education level [0.556 (0.378-0.816)], having cigarette smoking [2.121 (1.191-3.779)], higher positive syndrome [1.016 (1.002-1.031)] and higher social disability screening schedule (SDSS) [1.081 (1.026-1.139)]. The Neural Net (nnet) with an AUC of 0.6673 (0.5599-0.7748) had better prediction ability than that of other algorithms. Conclusion: ML algorithms are useful in early identifying male schizophrenia patients with violence and helping clinicians take preventive measures.

The impact of cold spells on schizophrenia admissions and the synergistic effect with the air quality index.

OBJECTIVES: Under current global climate conditions, there are insufficient studies on the health influences of cold spells, especially on mental health. This study aimed to examine the effect of cold spells on schizophrenia admissions and to analyze the potential interaction effect with the air quality index (AQI). METHODS: Daily data on schizophrenia admissions and climatic variables in Hefei were collected from 2013 to 2019. Based on 20 definitions, the impacts of cold spells were quantified separately to find the most appropriate definition for the region, and meta-regression was used to explore the different effect sizes of the different days in a cold spell event. In addition, the potential interaction effect was tested by introducing a categorical variable, CSH, reflecting the cold spell and AQI level. RESULTS: The cold spell defined by temperature below the 6th centile while lasting for at least three days produced the optimum model fit performance. In general, the risk of schizophrenia admissions increased on cold spell days. The largest single-day effect occurred on the 12th day with RR = 1.081 (95% CI: 1.044, 1.118). In a single cold spell event, the effect of the 3rd and subsequent days of a cold spell (RR = 1.082, 95% CI: 1.036, 1.130) was higher than that on the 2nd day (RR = 1.054, 95% CI: 1.024, 1.085). Similarly, the effect of the 2nd day was also higher than that of the 1st day (RR = 1.027, 95% CI: 1.012, 1.042). We found a synergistic effect between cold spells and high AQI in the male group, and the relative excess risk due to interaction (RERI) was 0.018 (95% CI: 0.005-0.030). CONCLUSIONS: This study suggested that the impacts of cold spells should be considered based on the definition of the most appropriate for the region when formulating targeted measures of schizophrenia. The discovery of the synergistic effect was referred to help the selection of the timing of precautions for susceptible people.

Serum Cortisol, Nesfatin-1, and IL-1ß: Potential Diagnostic Biomarkers in Elderly Patients with Treatment-Resistant Depression.

Aim: Treatment-resistant depression (TRD) affects approximately 30% of patients with major depressive disorder (MDD), especially elderly patients. As individuals with TRD are at an increased risk of committing suicide and pose a higher risk of relapse, early diagnostic biomarkers of TRD and a better understanding of the resistance mechanism are highly needed. This study aimed to determine whether serum cortisol, nesfatin-1, and pro-inflammatory cytokines can be used as biomarkers for the diagnosis of elderly patients with TRD. Methods: Thirty elderly patients with TRD were selected as the TRD group. Thirty elderly patients with MDD who were effectively treated with conventional antidepressants were selected as the non-TRD group. The baseline levels of serum cortisol, nesfatin-1, and pro-inflammatory cytokines were measured and compared, and their diagnostic values were evaluated using the receiver operating characteristic (ROC) curve method for discriminating patients with TRD from those without TRD. Results: Serum cortisol, C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) levels were significantly higher in the non-TRD and TRD groups than in the control group. Moreover, serum cortisol, CRP, TNF-α, and IL-6 levels in the TRD group were significantly lower than those in the non-TRD group. Furthermore, serum nesfatin-1 levels in the non-TRD group were significantly lower than those in the control and TRD groups, while the serum IL-1ß levels in the non-TRD group were significantly higher than those in the control and TRD groups. Additionally, an ROC analysis revealed an area under the curve (AUC) of 0.929 for the combination of nesfatin-1 and IL-1ß and an AUC of 0.956 for the combination of cortisol, nesfatin-1, and IL-1ß in discriminating elderly patients with TRD from those without non-TRD. Conclusion: Serum cortisol, nesfatin-1, and IL-1ß may be potential diagnostic biomarkers for discriminating elderly patients with TRD from those without TRD.

Network Association of Biochemical and Inflammatory Abnormalities With Psychiatric Symptoms in First-Episode Schizophrenia Patients.

Background: Cardiovascular disease (CVD) risk factors such as dyslipidemia and systemic aberrant inflammatory processes may occur in patients with psychotic disorders, which may cause increased mortality. The interplay between immune and metabolic markers and its contribution to the clinical symptoms of schizophrenia (SCZ) remain unclear. This study aimed to examine the association of a series of inflammatory factors, plasma biochemical indicators, and SCZ clinical symptomatology with the severity of SCZ symptoms. Methods: A total of 115 participants, including 79 first-episode drug-naïve patients with SCZ and 36 healthy controls, were enrolled in this study. Semi-structured interviews were used to collect sociodemographic data, family history of SCZ, and medical and psychiatric history. The Brief Psychiatric Rating Scale (BPRS) and the Positive and Negative Syndrome Scale (PANSS) were administered by a clinical psychiatrist to evaluate the symptom severity of patients with SCZ. Plasma inflammatory cytokines were measured by a fully automated electrochemiluminescent immunoassay (Meso Scale Discovery). Results: Blood routine, biochemical, and inflammation cytokine test results showed that the levels of white blood cell count, neutrophil count, natrium, CRP, IL-8, IL-6, IL-13, and IL-16 significantly increased in the case group than in the healthy controls (p < 0.05), whereas levels of red blood cell count, hemoglobin concentration, mean corpuscular hemoglobin concentration, total protein, albumin, total bile acid, high-density lipoprotein (HDL), apolipoprotein A1, blood urea nitrogen, kalium and IL-15 were lower than in the healthy controls (p < 0.05). Correlation network analysis results shown that the natrium, HDL and red blood cell count were the top 3 factors closely to with BPRS and PANSS related clinical symptoms among of correlation network (degree = 4). ROC curve analysis explored the IL-16, IL-8, IL-13, IL-15, natrium, and HDL had highly sensitivity and specificity to the predictive validity and effectiveness for SCZ symptoms. Conclusion: Our study revealed a complex interactive network correlation among the cardiovascular risk factors, biological immunity profiles, and psychotic symptoms in first-episode patients. Abnormal inflammatory factors and CVD risk factors had high sensitivity and specificity for predicting SCZ symptoms. Generally, our study provided novel information on the immune-related mechanisms involved in early CVD risk in patients with psychotic disorders.