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Background: Second-generation antipsychotics (SGAs) frequently cause metabolic syndrome (MetS), which raises the risk of heart disease, type 2 diabetes, morbid obesity, atherosclerosis, and hypertension. MetS also impairs cognitive function in patients with schizophrenia. However, the fundamental reasons of MetS caused by SGAs are not yet fully understood. Thus, we aimed to identify potential therapeutic targets for MetS induced by SGAs. Methods: The serum biochemical parameters and the RNA-sequencing of peripheral blood mononuclear cells were measured in three groups (healthy controls and patients with schizophrenia with and without MetS taking SGAs). The study of the weighted gene co-expression network was utilized to pinpoint modules that were significantly connected to clinical markers. Results: Statistical analysis showed significant differences in triglyceride and high-density lipoprotein among the three groups. The TNF signaling pathway, TGF-β signaling pathway, fatty acid metabolism, NF-kappa B signaling pathway, MAPK signaling pathway, and Toll-like receptor signaling pathway were the pathways that were primarily enriched in the two unique co-expression network modules that were found. Finally, five specific genes (TNF, CXCL8, IL1B, TIMP1, and ESR1) associated with metabolism and immunity pathways were identified. Conclusions: This study indicated that SGAs differentially induced MetS of patients with schizophrenia through metabolic and inflammation-related pathways. Therefore, the potential side effects of drugs on inflammatory processes need to be considered when using SGAs for the treatment of schizophrenia.

Abstract 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.

Abstract 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-1β and -4 levels were significantly increased, and Tie-2 levels were significantly decreased, in first-episode SCZ patients as compared to healthy controls. IL-1β levels were positively correlated with total BPRS scores, resistance subscores, and PANSS positive subscores. Furthermore, IL-1β levels were negatively correlated with Tie-2 receptor expression levels. Stepwise linear regression analysis demonstrated that IL-1β 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-1β 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-1β 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.

Abstract 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-1β, 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-1β (F = 2.37, P = 0.014) and IL-16 (F = 4.40, P

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

ObjectivesChildhood 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.MethodsNinety-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.ResultsChildhood 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 (β = 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 (β = 0.672, t = 5.949, P < 0.001; β = 0.909, t = 2.463, P < 0.001), Furthermore, emotional neglect presented positively related to the suicide risk and proneness to suicidal behavior (β = 0.618, t = 5.518, P < 0.001; β = 0.809, t = 5.356, P < 0.001).ConclusionRelapsed 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.

Abstract Objective To the best of our knowledge, studies have been rarely conducted to assess the correlation between cognitive deficit, self‐esteem, and alexithymia in the depressive symptoms of schizophrenia (SCZ). Therefore, this study aims to explore the risk factors associated with impairment of cognitive function, alexithymia, and self‐esteem among a representative sample of first‐episode schizophrenic patients. Method We recruited 107 first‐episode schizophrenic patients (48.6% male, 51.4% female, 36.94 ± 10.73 years) into the research group, according to the Diagnostic and Statistical Manual of Mental Disorders (5th edition). A total of 45 healthy people (51.1% male, 48.9% female, 32.47 ± 10.94 years) were enlisted in the healthy control group. Psychotic symptoms were evaluated using the Positive and Negative Syndrome Scale (PANSS). Cognitive functions were estimated using the Montreal Cognitive Assessment Scale (MoCA). The feelings of respect and self‐acceptance were tested using the Rosenberg Self‐Esteem Scale (RSES). Emotion of identifying and describing were measured by self‐report scale of Toronto Alexithymia Scale‐20 (TAS‐20). Results Overall cognitive impairment and alexithymia were found more serious in the patients of SCZ than the healthy group (p

BackgroundAlthough 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.MethodsIn 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.ResultsThe 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.ConclusionOur 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.

BackgroundCardiovascular 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.MethodsA 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).ResultsBlood 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.ConclusionOur 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.

Increasing evidence indicates an interaction between dysbiosis of the microbiota and the pathogenesis of schizophrenia. However, limited information is available on the specific microbial communities associated with symptoms of schizophrenia. Therefore, this study aimed to investigate gut microbiota dysbiosis and its relationship with psychopathologies in schizophrenia. We recruited 126 participants and divided them into three groups according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria—acute group (patients with acute schizophrenia), remission group (patients with schizophrenia in remission), and control group (healthy controls). Psychotic symptoms were evaluated using the Positive and Negative Syndrome Scale. Microbiota compositions, diversity and community structure were evaluated using 16S rRNA sequencing. Pearson's correlation analysis was used to evaluate the association between bacterial taxa and psychotic symptoms. The beta-diversity of microbiota composition in the acute group was distinct from that in the remission and control groups (PC1 = 21.11% vs. PC2 = 12.86%, P = 0.021). Furthermore, Pearson's correlation analysis revealed that abundance of Haemophilus was positively correlated with negative psychiatric symptoms (r = 0.303, P = 0.021), while abundance of Coprococcus was negatively correlated with negative psychiatric symptoms (r = −0.285, P = 0.025). Moreover, abundance of Haemophilus was positively correlated with cognition (r = 0.428, P = 0.009), excitement (r = 0.266, P = 0.037), and depression (r = 0.295, P = 0.020). The study findings suggest that alterations in certain gut microbiota may interfere with psychological symptoms in schizophrenia. Our results provide evidence that may help in the development of therapeutic strategies using microbial-based targets. The data that support the findings of this study have been deposited in the NCBI (https://submit.ncbi.nlm.nih.gov/) with accession number SUB9453991.

Viral encephalitis is a common clinical condition. Its clinical manifestations are variable and include neurological symptoms and psychiatric abnormalities, which makes clinical diagnosis and treatment difficult. To date, there are only a few reported cases on mental symptoms of chronic viral encephalitis. We present a case of a 16-year-old male patient who was previously hospitalised and diagnosed with schizophrenia and treated with aripiprazole 15 mg/day but failed to respond. The patient was then given antiviral therapy and recovered after 2 weeks. Clinicians should be aware of the possbility that chronic mental disorders could be caused by viral encephalitis. In the future, diagnosis of chronic functional mental disorders should include viral encephalitis in the differential diagnosis.

Abstract Objective Epidemiological evidence indicated a relationship between vitamin D (VD) and depression with anxiety, but their therapeutic relationship has not been fully elucidated. This study aimed to examine whether VD supplementation would relieve symptoms in patients with depression and anxiety with low serum 25‐hydroxy VD [25(OH) D] levels. Method Participants with low 25(OH)D levels were randomized to control or daily VD group and were followed up for 6 months. Serum concentrations of 25(OH) D were measured using commercial kits. Psychological symptoms were evaluated with the Hamilton Depression Rating Scale‐17 (HAMD‐17), Revised Social Anhedonia Scale (RSAS), Revised Physical Anhedonia scale (RPAS), and Hamilton Anxiety Rating Scale‐14 (HAMA‐14). The trial was listed in the trial registration (http://www.medresman.org.cn/uc/index.aspx; NTR number: ChiCTR2000030130). Results In this clinical population, no significant difference in depression symptoms was detected between VD group and control group at both baseline and at the endpoint of our study. The HAMD‐17, RSAS, and RPAS scores did not change significantly between VD and control groups from baseline to endpoint (all p > .05). However, there was a significant difference in time effect of the total HAMA‐14 scores between the two groups (β [95% Cl] = −2.235 [−3.818, −0.653], p = .006). Conclusions Vitamin D supplementation could improve the anxiety symptoms but not depressive symptoms in depressive patients with low VD level after the 6‐month intervention.

Restless legs syndrome (RLS) is a common sleep-related movement disorder characterised by an uncomfortable urge to move the legs that occurs during periods of inactivity. Although there have been many case reports on antipsychotic-induced RLS, ziprasidone has never been reported as a cause of RLS. We present a case of a female patient with schizophrenia who presented with symptoms of RLS following the administration of high doses of ziprasidone added to quetiapine and valproate. The patient’s symptoms of RLS occurred following the administration and titration of ziprasidone to 160 mg, and were relieved upon reducing the dose to 120 mg/day. Other potential causative medications and differential diagnoses that could have caused similar symptoms were excluded. Clinicians should be aware of the potential for ziprasidone-induced RLS. Dopamine and serotonin interaction could be the mechanism underlying ziprasidone-induced RLS.

Abstract Objective It has been identified that the smoking rate is higher in schizophrenic patients than general population. This study aimed to explore the association between schizophrenia and tobacco use, and provide rational recommendations for clinical care of schizophrenia. Methods We recruited 244 patients with schizophrenia and 225 healthy controls. Of schizophrenia patients, 54 patients were untreated with any antipsychotics over the previous 6 months or first‐episode and drug‐naïve. These patients (nonmedication subgroup) were followed up for 8 weeks. The associations between tobacco use and susceptibility to schizophrenia and psychotic symptoms were analyzed. Results Although there was no significant difference between schizophrenia patients and healthy controls in the entire sample, stratification analysis showed the rate of smoking was higher in male patients versus healthy controls and that male smokers exhibited higher odds ratios for schizophrenia than nonsmokers. Next, when we repeated analyses in first‐episode patients and healthy controls, significant differences were not observed, indicating tobacco use is an outcome rather than a cause of schizophrenia. Furthermore, among nonmedication subgroup, smokers presented with more severe psychotic symptoms at baseline, and better improvement after medication than nonsmokers, suggesting patients with worse symptoms tend to smoke to relieve symptoms. Conclusion This study supports the self‐medication hypothesis. Nonetheless, considering the serious health hazard associated with tobacco use, we should encourage patients to stop smoking. Further investigations are warranted to determine the tobacco constituents that are beneficial or harmful to schizophrenia.

Background Depressive symptoms are often seen in schizophrenia. The overlap in presentation makes it difficult to distinguish depressive symptoms from the negative symptoms of schizophrenia. The adipokine leptin was found to be altered in both depression and schizophrenia. There are few studies focusing on the prediction of leptin in diagnosis and evaluation of depressive symptoms in schizophrenia.ObjectiveAims To assess the plasma leptin level in patients with schizophrenia and its relationships with depressive symptoms.Methods Cross-sectional studies were applied to (1) compare the levels of plasma leptin between schizophrenia (n=74) and healthy controls (n=50); and (2) investigate the relationship between plasma leptin levels and depressive subscores.Results (1) Plasma leptin levels were significantly higher in patients with schizophrenia than in healthy controls. (2) Correlation analysis revealed a significant negative association between leptin levels and the depressed factor scores on the Positive and Negative Syndrome Scale (PANSS). (3) Stepwise multiple regression analyses identified leptin as an influencing factor for depressed factor score on PANSS.Conclusion Leptin may serve as a predictor for the depressive symptoms of chronic schizophrenia.

Major depressive disorder (MDD) and chronic pain are two complex disorders that often coexist. The underlying basis for this comorbidity is unknown. In the current investigation, microglia and the brain-derived neurotrophic factor (BDNF)-cAMP response element-binding protein (CREB) pathway were investigated. A comorbidity model, with characteristics of both MDD and chronic pain, was developed by the administration of dextran sodium sulfate (DSS) and the induction of chronic unpredictable psychological stress (CUS). Mechanical threshold sensory testing and the visceromotor response (VMR) were employed to measure mechanical allodynia and visceral hypersensitivity, respectively. RT-qPCR and western blotting were used to assess mRNA and protein levels of ionized calcium-binding adaptor molecule 1 (Iba-1), nuclear factor-kappa B (NF-κB), nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBa), BDNF, and CREB. In comorbid animals, mechanical allodynia and visceral hypersensitivities were significant with increased mRNA and protein levels for NF-κB-p65 and IκBa. Furthermore, the comorbid animals had deceased mRNA and protein levels for Iba-1, BDNF, and CREB as well as a reduced number and density of microglia in the medial prefrontal cortex (mPFC). These results together suggest that DSS and CUS can induce the comorbidities of chronic pain and depression-like behavior. The pathology of this comorbidity involves loss of microglia within the mPFC with subsequent activation of NF-κB-p65 and down-regulation of BDNF/p-CREB signaling.