Do Leptin Play a Role in Metabolism-Related Psychopathological Symptoms?

Objectives: Leptin is a crucial regulator of energy balance and is associated with obesity. In recent years, it has also been recognized as involved in the psychopathological mechanism. Our study aimed to elucidate the relationships between serum leptin levels, body mass index (BMI), and psychopathology symptoms in patients with schizophrenia. Methods: A cross-sectional assessment of 324 inpatients with schizophrenia was conducted. Schizophrenia symptoms were measured using the Positive and Negative Syndrome Scale (PANSS) and the Brief Psychiatric Rating Scale (BPRS). Serum leptin levels were assessed by the Enzyme-Linked Immunosorbent Assay (ELISA). Results: Significant differences in sex, BMI, and negative symptom subscale (PANSS-N) scores were found between the groups with high and low leptin levels in the study. Leptin levels were positively correlated with BMI (B = 2.322, t = 9.557, P < 0.001) and negatively correlated with PANSS-N scores (B = -0.303, t = -2.784, P = 0.006). Conclusions: Our results suggest that the increase in leptin levels is responsible for antipsychotic-induced weight gain and improved psychopathological symptoms.

Sex Differences in the Association of HOMA-IR Index and BDNF in Han Chinese Patients With Chronic Schizophrenia.

Background: Previous research has indicated that there are significant sex differences in serum BDNF levels and metabolic indicators in patients with schizophrenia. Studies have found that BDNF is involved in blood sugar regulation. Homeostasis model assessment of insulin resistance (HOMA-IR) is currently a sensitive indicator for measuring insulin resistance. Our study aims to explore the sex differences in the relationship between serum BDNF levels and HOMA-IR in patients with chronic schizophrenia (CS). Methods: A total of 332 patients with CS were enrolled in this study. General information of all participants was collected. Haematological indicators were collected, and the Positive and Negative Syndrome Scale (PANSS) was used to evaluate psychiatric symptoms. Sex differences in serum BDNF levels, HOMA-IR index and other metabolic indexes were investigated. Then, linear regression analysis was used to analyse the relationship between the HOMA-IR index and BDNF levels in male and female patients. Results: The HOMA-IR index of female patients was significantly higher than that of males, but there was no significant difference in serum BDNF levels between male patients and female patients. There was a positive correlation between BDNF level and HOMA-IR index, and this relationship only existed in female patients. Conclusion: The results show that there are significant sex differences in HOMA-IR in patients with CS. In addition, only in female patients was there a positive correlation between the HOMA-IR index and BDNF level, which suggests that sex factors should be taken into account in evaluating the relationship between BDNF and blood glucose in patients with CS.

Patterns of antipsychotic prescriptions in patients with schizophrenia in China: A national survey.

INTRODUCTION: To investigate the patterns and correlates of antipsychotic prescriptions among recently discharged inpatients with schizophrenia in China. METHODS: The study included discharged patients from 41 tertiary psychiatric hospitals in 29 provinces between March 19-30, 2019. A total of 1032 inpatients with schizophrenia were included. Socio-demographic and clinical data were retrieved from medical records upon discharge. RESULTS: Patients received a total of 13 unique antipsychotic medications, which included 9 s-generation antipsychotics (SGAs) and 4 first-generation antipsychotics (FGAs). The utilization rates of SGAs and FGAs were 98.8 % and 6.1 % respectively. The three most commonly antipsychotic medications were risperidone (35.1 %), olanzapine (31.3 %), and clozapine (24.6 %). The mean chlorpromazine equivalent dose was 452.12 ± 230.74 mg/day. The utilization rate of mood stabilizers was 18.9 %, 8.8 % for antidepressants, 20.3 % for sleep improvers, and 9.9 % for anticholinergics. More than two fifths patients (43.1 %) received two or more antipsychotic medications. Predictors of antipsychotic polypharmacy included younger age, residing in Central or West China, a longer duration of illness, a history of prior hospitalizations, and having agitated behavior during the hospitalization. CONCLUSION: Antipsychotic polypharmacy in China is common on inpatients settings. The proportion of antipsychotic polypharmacy in China is higher than in many other countries, despite limited data to support the efficacy of many combinations. Clozapine remains one of most commonly prescribed antipsychotics in China, either as a monotherapy or combination therapy.

Do proinflammatory cytokines play a role in clozapine-associated glycometabolism disorders?

RATIONALE AND OBJECTIVE: Clozapine (CLZ) is the most effective drug for treatment-resistant schizophrenia but is associated with many side effects, including glycometabolism disorders. Immunological mechanisms may be involved in the development of clozapine side effects. Research relating the immunomodulatory effects of clozapine and its early markers to clinically relevant adverse events is needed to reduce the harmful side effects of clozapine. This study aimed to investigate the role of proinflammatory cytokines in clozapine-associated glycometabolism disorders. METHODS: We measured the effect of a range of doses of clozapine on glycometabolism-related parameters and proinflammatory cytokines levels in mice peripheral blood. We also examined the differences between these indicators in the peripheral blood of clozapine-treated schizophrenia patients and healthy controls. Furthermore, we detected proinflammatory cytokines expression in mice pancreatic tissue. RESULTS: Following clozapine administration, glucagon significantly decreased in mouse serum, and proinflammatory cytokine IL-ß levels markedly increased. Clozapine reliably increased proinflammatory cytokines (IL-1ß, IL-6, and TNF-α) expression in murine pancreatic tissue. Compared with healthy controls, clozapine-treated patients' BMI, blood glucose, and proinflammatory cytokines (IL-1ß, IL-6, and TNF-α) increased significantly. In clozapine-treated patients, a higher clozapine daily dosage was associated with higher levels of the proinflammatory cytokines IL-1ß and IL-6, and a significant positive correlation was observed between blood glucose levels and the proinflammatory cytokines IL-6 and TNF-α. CONCLUSION: Findings from animal experiments and clinical trials have shown clear evidence that clozapine has a regulatory effect on immune-related proinflammatory cytokines and influences glycometabolism indicators.

Prevalence and clinical demography of hyperhomocysteinemia in Han Chinese patients with schizophrenia.

Previous studies have shown that high homocysteine worsens the occurrence, symptoms, and prognosis of patients with schizophrenia. The purpose of this study was to evaluate the prevalence, clinical correlation, and demographic characteristics of hyperhomocysteinemia in Han Chinese schizophrenia patients. In this study, we enrolled 330 schizophrenia patients and 190 healthy controls. Positive and Negative Syndrome Scale (PANSS) was used to evaluate the psychiatric symptoms of patients with schizophrenia. The plasma homocysteine level was measured by the enzyme cycle method and the concentration of homocysteine > 15 µmol/L was defined as hyperhomocysteinemia. The prevalence of hyperhomocysteinemia in Han Chinese schizophrenia patients and healthy controls was 55.05% and 26.98%, respectively. Schizophrenia patients with hyperhomocysteinemia had more male proportion, older age, higher smoking rate, lower HDL level, higher PANSS total score, and higher negative factor than those patients without hyperhomocysteinemia. Binary logical regression result showed that gender and age were the independent risk factors of hyperhomocysteinemia. Han Chinese patients with schizophrenia had high prevalence hyperhomocysteinemia than healthy controls, and elderly male patients have a higher risk of hyperhomocysteinemia. This study was registered in the China Clinical Trial Registration Center (chiCTR 1800017044).

Schizophrenia patients with a metabolically abnormal obese phenotype have milder negative symptoms.

BACKGROUND: Schizophrenia patients with a metabolically abnormal obese (MAO) phenotype have been shown poor cardiovascular outcomes, but the characteristics of their current psychiatric symptoms have not been characterized. This study mainly explored the psychiatric symptoms of schizophrenia patients with the MAO phenotype. METHODS: A total of 329 patients with schizophrenia and 175 sex- and age-matched people without schizophrenia from Anhui Province in China were enrolled. The Positive and Negative Syndrome Scale (PANSS) was used to evaluate the mental symptoms of the schizophrenia patients. The MAO phenotype was defined as meeting 1-4 metabolic syndrome criteria (excluding waist circumference) and having a body mass index (BMI) ≥ 28 kg/m2. And, metabolically healthy normal-weight (MHNW) phenotype was defined as meeting 0 criteria for metabolic syndrome and 18.5 ≤ BMI < 24 kg/m2. RESULTS: Overall, 15.8% of the schizophrenia patients and 9.1% of the control group were consistent with the MAO phenotype, and the prevalence of MAO in the schizophrenia group was higher than that in the control group. Among the patients with schizophrenia, the MAO group had lower negative factor, cognitive factor and total PANSS scores than the MHNW group. However, when confounding factors were controlled, only the negative factor remained lower significantly. CONCLUSION: We found that schizophrenia patients with the MAO phenotype had reduced negative symptoms, which may indicate an internal mechanism linking metabolic disorders and negative symptoms. TRIAL REGISTRATION: This study was registered in the China Clinical Trial Registration Center (No. chiCTR 1,800,017,044 ).

A higher body mass index in Chinese inpatients with chronic schizophrenia is associated with elevated plasma orexin-A levels and fewer negative symptoms.

Objective: Orexin-A is involved in numerous physiological functions, such as feeding behavior and energy balance. Yet, the associations among the orexin system, weight changes and the clinical symptoms of schizophrenia patients remain uncertain, especially in inpatients with chronic schizophrenia (CS). The purpose of this study was to investigate the relationship between the orexin-A levels, body mass index (BMI) and clinical symptoms of CS inpatients.Methods: Altogether, 324 inpatients were enrolled in our study. The clinical symptoms of all inpatients were measured using a 30-item Positive and Negative Syndrome Scale (PANSS), and then we calculated the BMI of each subject and tested the orexin-A levels by ELISA methods.Results: The orexin-A levels of the CS inpatients in the obesity group (1.24 ± 1.45 ng/ml, n = 52) were significantly higher than those in the non-overweight group (0.85 ± 1.18 ng/ml, n = 176) and the overweight group (0.97 ± 1.15 ng/ml, n = 96). Spearman's correlation analysis showed that higher BMIs were associated with higher plasma orexin-A levels and fewer negative symptoms. Furthermore, the multiple regression analysis indicated that the orexin-A level could be a contributor to BMI (F = 30.21, p < 0.001). However, there was no correlation between plasma orexin-A concentrations and clinical symptoms in our research.Conclusion: A higher plasma orexin-A level may be a factor influencing the BMI of inpatients with CS, and fewer negative symptoms seem to be correlated with higher BMI, but the causality among BMI, orexin-A and clinical symptoms of schizophrenia requires further clinical research.