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.

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.

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.