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).

Automatic Thoughts, Self-Stigma, and Resilience Among Schizophrenia Patients with Metabolic Syndrome: A Cross-Sectional Study.

Purpose: The study aims to clarify the negative psychological state and resilience impairments of schizophrenia (SCZ) with metabolic syndrome (MetS) while evaluating their potential as risk factors. Patients and Methods: We recruited 143 individuals and divided them into three groups. Participants were evaluated using the Positive and Negative Syndrome Scale (PANSS), Hamilton Depression Rating Scale (HAMD)-24, Hamilton Anxiety Rating Scale (HAMA)-14, Automatic Thoughts Questionnaire (ATQ), Stigma of Mental Illness scale and Connor-Davidson Resilience Scale (CD-RISC). Serum biochemical parameters were measured by automatic biochemistry analyzer. Results: The score of ATQ was highest in the MetS group (F = 14.5, p < 0.001), and the total score of CD-RISC, subscale tenacity score and subscale strength score of CD-RISC were lowest in the MetS group (F = 8.54, p < 0.001; F = 5.79, p = 0.004; F = 10.9, p < 0.001). A stepwise regression analysis demonstrated that a negative correlation was observed among the ATQ with employment status, high-density lipoprotein (HDL-C), and CD-RISC (ß=-0.190, t=-2.297, p = 0.023; ß=-0.278, t=-3.437, p = 0.001; ß=-0.238, t=-2.904, p = 0.004). A positive correlation was observed among the ATQ with waist, TG, WBC, and stigma (ß=0.271, t = 3.340, p = 0.001; ß=0.283, t = 3.509, p = 0.001; ß=0.231, t = 2.815, p = 0.006; ß=0.251, t=-2.504, p = 0.014). The area under the receiver-operating characteristic curve analysis showed that among all independent predictors of ATQ, the TG, waist, HDL-C, CD-RISC, and stigma presented excellent specificity at 0.918, 0.852, 0.759, 0.633, and 0.605, respectively. Conclusion: Results suggested that the non-MetS and MetS groups had grievous sense of stigma, particularly, high degree of ATQ and resilience impairment was shown by the MetS group. The TG, waist, HDL-C of metabolic parameters, CD-RISC, and stigma presented excellent specificity to predict ATQ, and the waist showed excellent specificity to predict low resilience level.

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.

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.

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.

The Predictive Role of Aberrant Metabolic Parameters and Negative Automatic Thinking on the Cognitive Impairments Among Schizophrenia Patients with Metabolic Syndrome.

Purpose: The study aimed to clarify the cognitive impairments of schizophrenia with metabolic syndrome while evaluating their potential as risk factors. Patients and Methods: We recruited 153 participants and divided them into three groups according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria and the guideline standards for the prevention and treatment of dyslipidemia in Chinese adults in 2007 for metabolic syndrome, as follows: healthy control group (n = 47); nonmetabolic syndrome group (n = 58); and metabolic syndrome group (n = 48). Psychotic symptoms were evaluated using the Positive and Negative Syndrome Scale. Cognitive function and automatic thinking were estimated using the Montreal Cognitive Assessment Scale, Verbal Fluency Test, and Automatic Thoughts Questionnaire. Serum biochemical parameters were measured by automatic biochemistry analyzer. Results: One-way ANOVA analysis revealed that differential cognition impairments in schizophrenia patients compared to controls. Furthermore, results of multiple comparisons showed that more serious barriers in orientation, language fluency, and negative automatic thinking existed in the metabolic syndrome group than in the healthy and non-metabolic syndrome groups. Spearman correlation and stepwise linear regression analyses showed that psychopathological symptoms, high waist circumference, and high triglyceride were the predictive factors for negative automatic thoughts, orientation, and language fluency. Those results collectively revealed that high waist circumference, high triglyceride and negative automatic thinking had validity and effectiveness in predicting the cognitive function impairments of the metabolic syndrome group. Conclusion: The present findings strongly supported the notion that aberrant parameters of high waist circumference, high triglyceride and high negative automatic thoughts had validity and effectiveness predictive role for cognitive impairments in the schizophrenics with metabolic syndrome. The schizophrenia patients with metabolic syndrome should receive regular monitoring and adequate treatment for metabolic and psychological risk factors.

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.