Functional disconnection between subsystems of the default mode network in schizophrenia.

BACKGROUND: A dysfunctional default mode network (DMN) has been reported in patients with schizophrenia. However, the stability of the deficits has not been determined across different stages of the disorder. METHODS: We examined the functional connectivity of the DMN subsystems of 125 patients with first-episode schizophrenia (FES) or recurrent schizophrenia (RES), compared to that of 82 healthy controls. We tested the robustness of the findings in an independent cohort of 158 patients and 39 healthy controls. We performed resting-state functional connectivity analysis, and examined the strength of the connections within and between the three subsystems of the DMN (core, dorsal medial prefrontal cortex [dMPFC], and medial temporal lobe [MTL]). We also analyzed the connectivity correlations to symptoms and illness duration. RESULTS: We found reduced connectivity strength between the core and MTL subsystems in schizophrenia patients compared to controls, with no differences between the FES and RES patient groups; these findings were validated in the second sample. Schizophrenia patients also showed a significant reduction in connectivity within the MTL and between the dMPFC-MTL subsystems, similarly between FES and RES groups. The connectivity strength within the core subsystem was negatively correlated with clinical symptoms in schizophrenia. There was no significant correlation between the DMN subsystem connectivity and illness duration. CONCLUSIONS: DMN subsystem connectivity deficits are present in schizophrenia, and the homochronicity of their appearance indicates the trait-like nature of these alterations. The DMN deficit may be useful for early diagnosis, and MTL dysfunction may be a crucial mechanism underlying schizophrenia.

Childhood trauma and cognitive deficits in patients with schizophrenia: mediation by orbitofrontal cortex H-shaped sulci volume.

BACKGROUND: A line of evidence has shown that childhood trauma and patterns of H-shaped sulci in the orbitofrontal cortex (OFC) are associated with cognitive deficits in patients with schizophrenia. Studies have also suggested that childhood trauma is associated with OFC volumetrics. This study investigated the interrelationship between childhood trauma, OFC H-shaped sulci volume and cognitive function in patients with first-episode schizophrenia. We hypothesized that OFC H-shaped sulci volume would mediate the relationship between childhood trauma and cognitive function in patients with first-episode schizophrenia. METHODS: We recruited patients with first-episode schizophrenia (n = 63) and healthy controls (n = 48), and quantified OFC H-shaped sulci volumes with 3.0 T high-resolution MRI. We assessed cognitive function and childhood trauma experiences using the MATRICS Consensus Cognitive Battery (MCCB) and the Childhood Trauma Questionnaire (CTQ). RESULTS: Patients with first-episode schizophrenia had smaller left OFC H-shaped sulci volumes, more severe childhood trauma experiences and worse cognitive function than healthy controls. CTQ total score and emotional and physical neglect subscores were negatively correlated with left OFC H-shaped sulci volume. CTQ total score and emotional neglect and sexual abuse subscores were negatively correlated with cognitive function in patients with first-episode schizophrenia. Interestingly, the CTQ total score and physical neglect subscore were positively correlated with cognitive function in healthy controls. Left OFC H-shaped sulci volume played a mediating role in CTQ emotional neglect subscore, CTQ total score and MCCB composite score. LIMITATIONS: The small sample size and retrospective design need to be considered. CONCLUSION: Childhood trauma might contribute to cognitive deficits in patients with first-episode schizophrenia by affecting left OFC H-shaped sulci volume. This finding can help in the design of strategies to improve cognitive function in patients with first-episode schizophrenia.

The mediating effect of brain-derived neurotrophic factor levels on childhood trauma and psychiatric symptoms in patients with first-episode schizophrenia.

BACKGROUND: Previous studies have implicated childhood trauma and abnormal brain-derived neurotrophic factor in the pathogenesis of schizophrenia. Here, we explored whether brain-derived neurotrophic factor levels mediated the relationship between childhood trauma and psychopathological symptoms in patients with first-episode schizophrenia. METHODS: Patients with first-episode schizophrenia (n = 192) and healthy controls (n = 136) were enrolled. Childhood traumatic experiences and psychopathology were assessed by Childhood Trauma Questionnaire and Positive and Negative Syndrome Scale, respectively. Enzyme-linked immunosorbent assay was used to quantify brain-derived neurotrophic factor levels. RESULTS: The patients with first-episode schizophrenia experienced more severe childhood trauma and had lower serum brain-derived neurotrophic factor levels than healthy controls. Emotional abuse and Childhood Trauma Questionnaire total score showed positive correlation with Positive and Negative Syndrome Scale positive, general psychopathological subscore and total score. Emotional neglect showed positive correlation with Positive and Negative Syndrome Scale positive subscore. Physical neglect was positively associated with Positive and Negative Syndrome Scale negative subscore. Emotional neglect and Childhood Trauma Questionnaire total score were negatively correlated with serum brain-derived neurotrophic factor levels. The serum brain-derived neurotrophic factor levels mediated the relationship between both Childhood Trauma Questionnaire total score and Positive and Negative Syndrome Scale total score and negative symptoms in the patients. The brain-derived neurotrophic factor levels also mediated the relationship between emotional neglect and Positive and Negative Syndrome Scale total score in the patients. CONCLUSION: Childhood trauma might contribute to the clinical symptoms of schizophrenia by affecting brain-derived neurotrophic factor levels. Perhaps we can prevent schizophrenia by reducing childhood traumatic experiences.

Effects of Dose, Age, Sex, Body Weight, and Smoking on Plasma Concentrations of Olanzapine and N-desmethyl Olanzapine in Inpatients With Schizophrenia.

PURPOSE: This study aimed to investigate the combined effects of dose, age, sex, body weight, and smoking on plasma concentrations of olanzapine (OLA) and N-desmethyl olanzapine (DMO) in Chinese inpatients with schizophrenia. METHODS: A retrospective study including 185 inpatients was conducted. The steady-state plasma concentrations of OLA (COLA) and DMO (CDMO) were measured using high-performance liquid chromatography-tandem mass spectrometry. The combined effects of dose, age, sex, body weight, and smoking on COLA and CDMO were evaluated. FINDINGS: Multiple linear regression analyses revealed that dose, age, body weight, and smoking had significant effects on COLA and CDMO in inpatients with schizophrenia treated with OLA. The dose was the most important determinant of COLA and CDMO and was positively correlated with both. Furthermore, smokers exhibited a significantly lower COLA and COLA + DMO, whereas higher body weight led to the reduction of COLA, CDMO, and COLA + DMO. Advanced age was associated with lower CDMO. IMPLICATIONS: These results suggest that dose, age, body weight, and smoking have a significant influence on the plasma concentration of OLA and its metabolite DMO. Clinicians should consider the combined effects when prescribing OLA to patients with schizophrenia.

Who will benefit from computerized cognitive remediation therapy? Evidence from a multisite randomized controlled study in schizophrenia.

BACKGROUND: Computerized cognitive remediation therapy (CCRT) is generally effective for the cognitive deficits of schizophrenia. However, there is much uncertainty about what factors mediate or moderate effectiveness and are therefore important to personalize treatment and boost its effects. METHOD: In total, 311 Chinese inpatients with Diagnostic and Statistical Manual of Mental Disorders-IV schizophrenia were randomized to receive CCRT or Active control for 12 weeks with four to five sessions per week. All participants were assessed at baseline, post-treatment and 3-month follow-up. The outcomes were cognition, clinical symptoms and functional outcomes. RESULTS: There was a significant benefit in the MATRICS Consensus Cognitive Battery (MCCB) total score for CCRT (F1,258 = 5.62; p = 0.02; effect size was 0.27, 95% confidence interval 0.04-0.49). There were no specific moderators of CCRT improvements. However, across both groups, Wisconsin Card Sort Test improvement mediated a positive effect on functional capacity and Digit Span benefit mediated decreases in positive symptoms. In exploratory analyses younger and older participants showed cognitive improvements but on different tests (younger on Symbol Coding Test, while older on the Spatial Span Test). Only the older age group showed MSCEIT benefits at post-treatment. In addition, cognition at baseline negatively correlated with cognitive improvement and those whose MCCB baseline total score was around 31 seem to derive the most benefit. CONCLUSIONS: CCRT can improve the cognitive function of patients with schizophrenia. Changes in cognitive outcomes also contributed to improvements in functional outcomes either directly or solely in the context of CCRT. Age and the basic cognitive level of the participants seem to affect the cognitive benefits from CCRT.

CHRNA4 was associated with prepulse inhibition of schizophrenia in Chinese: a pilot study.

INTRODUCTION: Prepulse inhibition (PPI) of the auditory startle reflex, as an operational measurement used to evaluate the function of brain sensorimotor gating, appears to be a sensitive potential endophenotype for schizophrenia. CHRNA4 is highly expressed in the central nervous system and has been demonstrated to be significantly associated with schizophrenia by previous studies. The purpose of the current study was to evaluate the effect of CHRNA4 on PPI and acoustic startle parameters in schizophrenia. METHODS: 77 patients with schizophrenia and 62 controls were administered the test PPI, and 3 single nucleotide polymorphisms (SNPs) (rs3746372, rs1044396, and rs3787140) of CHRNA4 were genotyped in these subjects. RESULTS: Patients with schizophrenia showed significantly lower levels of PPI at the 120 ms prepulse intervals and longer peak latency than controls, and the GG genotype of rs3746372 and the TT genotype of rs1044396 were associated with decreased PPI levels in schizophrenia but not in controls. CONCLUSION: PPI may be influenced by the polymorphisms of the CHRNA4 in schizophrenia and it may be a potential endophenotype of schizophrenia. An independent replication would greatly increase the value of this study.

Case report: Time response of plasma clozapine concentrations on cessation of heavy smoking.

Smoking cessation in patients treated with clozapine might lead to elevated plasma concentrations and severe side effects. This case report investigated the trajectory of clozapine plasma concentrations over time after smoking cessation in a Chinese inpatient with schizophrenia. This case report delineates the temporal response of plasma clozapine concentrations and dose-corrected clozapine plasma concentrations in a 33-year-old inpatient with schizophrenia who had a substantial smoking history and ceased smoking abruptly during dose titration. This case report presents a sudden increase in plasma clozapine concentrations and dose-corrected plasma clozapine concentrations after smoking cessation, followed by a rapid decline in dose-corrected plasma clozapine concentrations during the initial 2 weeks and a return to pre-cessation levels approximately 1 month later. The findings suggest that clinicians and pharmacists should adjust clozapine dosage in accordance with changes in smoking status, taking into consideration the temporal effects. Post-smoking cessation adjustments to clozapine dosage should be coupled with therapeutic drug monitoring, especially for patients with heavy smoking habits. Moreover, the advice of the clinical pharmacist should be considered in complex cases to ensure safe use of clozapine.

Reliability and validity of a novel mobile-based automatic battery of cognitive tests in healthy young Chinese adults.

PURPOSE: To evaluate the reliability and validity of a newly developed computerized Automated Battery of Cognitive Tests in healthy individuals without cognitive impairments or psychiatric disorders. METHODS: From April 20 to July 1, 2023, 142 healthy individuals in Beijing and Tangshan, China were assessed using the Automated Battery of Cognitive Tests. After a 3-week interval, 36 participants were randomly selected for retesting. The assessment also included administration of the Repeatable Battery for the Assessment of Neuropsychological Status and the Automated Battery of Cognitive Tests to 59 participants. RESULTS: The Automated Battery of Cognitive Tests consists of 16 subtests. Internal consistency reliability was 0.75. The test-retest reliability for each factor ranged from 0.337 to 0.850 (p < 0.05). The criterion-related validity, as measured by correlation with the total Repeatable Battery for the Assessment of Neuropsychological Status score, was 0.748 (p < 0.001). The cumulative variance contribution rate is 70.109%. The results of the confirmatory factor analysis indicated a good model fit. CONCLUSIONS: The computerized Automated Battery of Cognitive Tests is a cognitive self-assessment tool with good reliability and validity. It can evaluate multiple aspects of cognitive performance in healthy individuals and is suitable for self-administration through remote access via Internet.

Behavioral evidence of impaired self-referential processing in patients with affective disorders and first-episode schizophrenia.

Despite the critical role of self-disturbance in psychiatric diagnosis and treatment, its diverse behavioral manifestations remain poorly understood. This investigation aimed to elucidate unique patterns of self-referential processing in affective disorders and first-episode schizophrenia. A total of 156 participants (41 first-episode schizophrenia [SZ], 33 bipolar disorder [BD], 44 major depressive disorder [MDD], and 38 healthy controls [HC]) engaged in a self-referential effect (SRE) task, assessing trait adjectives for self-descriptiveness, applicability to mother, or others, followed by an unexpected recognition test. All groups displayed preferential self- and mother-referential processing with no significant differences in recognition scores. However, MDD patients showed significantly enhanced self-referential recognition scores and increased bias compared to HC, first-episode SZ, and BD. The present study provides empirical evidence for increased self-focus in MDD and demonstrates that first-episode SZ and BD patients maintain intact self-referential processing abilities. These findings refine our understanding of self-referential processing impairments across psychiatric conditions, suggesting that it could serve as a supplementary measure for assessing treatment response in first-episode SZ and potentially function as a discriminative diagnostic criterion between MDD and BD.

Effects of smoking cessation on plasma clozapine concentrations in male patients with schizophrenia during the COVID-19 pandemic.

Introduction: This study aimed to investigate the effect of smoking cessation on plasma clozapine (CLO) concentrations in long-term hospitalized Chinese male patients with schizophrenia treated with CLO during the COVID-19 pandemic. Methods: Therapeutic drug monitoring (TDM) data for CLO were collected at Beijing HuiLongGuan Hospital between December 1, 2019 (before smoking cessation) and January 31, 2020 (after smoking cessation) in this retrospective study. Fifty-three male smokers and inpatients with schizophrenia who were treated with CLO were included. Plasma concentrations of CLO were measured using high-performance liquid chromatography-tandem mass spectrometry. The fagerstrom test for nicotine dependence (FTND) was used to assess smoking behavior. Results: The plasma CLO concentrations and dose-corrected plasma CLO concentrations were significantly increased by 29.3 and 23.5%, respectively, after smoking cessation. Discussion: The results suggested that clinicians and pharmacists should adjust the CLO dose based on changes in smoking status in patients stabilized with CLO during the COVID-19 pandemic. Careful TDM for CLO should be performed prior to dose adjustment，to reduce the increased risk of smoking cessation induced side effects, especially for older patients receiving multiple medications.

Relationship Between Plasma Aripiprazole and Dehydroaripiprazole Concentrations and Prolactin Levels in Chinese Children and Adolescents.

Objective: To investigate the relationship between plasma aripiprazole (ARI) and its metabolite dehydroaripiprazole (DARI) concentrations and prolactin (PRL) levels in Chinese children and adolescents. Methods: This was a retrospective cross-sectional study and the data were collected at Beijing HuiLongGuan Hospital, a Beijing City owned psychiatric hospital, between January 1 and December 31, 2021. Fifty-two child and adolescent inpatients (17 males, 35 females) aged 13-18 years and received ARI regardless of diagnosis were included. The steady-state ARI and DARI plasma concentrations were measured using high-performance liquid chromatography-tandem mass spectrometry. The serum PRL levels were measured by chemiluminescence immunoassay. Results: The plasma concentrations of ARI, DARI, and the total of ARI and DARI were negatively correlated with serum PRL levels in female children and adolescents. Approximately 15% of child and adolescent inpatients treated with ARI exhibited subnormal PRL serum levels. Conclusions: The results suggest that in addition to regularly monitoring PRL levels, therapeutic drug monitoring for ARI and its main metabolite DARI can help to mitigate the adverse medical consequences associated with PRL reduction. Thus, clinicians should consider the ARI-induced reduction of PRL levels when prescribing ARI to child and adolescent patients, particularly among females.

Longitudinal Associations Between Serum Bilirubin Level and Carotid Atherosclerosis Plaque in a Health Screening Population.

This study aimed to determine the relationship between bilirubin levels and carotid atherosclerosis (CAS) in the health screening population. After propensity score matching, this retrospective cohort study included 4360 subjects who underwent health examinations regularly in Hebei General Hospital between January 2010 and December 2019 and had no carotid plaque at baseline. After an average follow-up of 26.76 months, the main endpoint Cox regression analysis of carotid plaques was performed. After adjusting the confounding factors, Cox regression analysis showed that when serum total bilirubin (TBIL) and unconjugated bilirubin (UCB) increased by 1 standard deviation (SD), the risk of carotid plaque decreased by 7.30% (95% confidence interval (CI): 2.80-11.60%) and 15.70% (95% CI: 11.40-19.80%), respectively. When conjugated bilirubin (CB) increased by 1 SD, the risk of carotid plaques increased by 24.3% (95% CI: 19.7-29.0%). TBIL and UCB levels were negatively associated with CAS, and CB levels were positively associated with CAS.

Behavioral and electrophysiological analyses of self-referential neural processing in major depressive disorder.

Cognitive theories suggest that patients with major depressive disorder (MDD) constantly negatively evaluate their self-referential information. Unlike Westerners with an independent self, self-representation is strongly influenced by cultural differences; the Chinese self may include others (interdependent self). This study uses a self-referential effect task combined with event-related potentials (ERP), and 34 patients with MDD and 54 healthy controls (HC) were asked to judge whether an adjective was suitable for describing the self, mother, or a public person, followed by an unexpected recognition task. They were required to judge whether a word was presented during the encoding phase. The results reveal that during the encoding phase, for both self- and mother-referential adjectives, patients with MDD endorsed fewer positive adjectives and more negative adjectives than the HCs. During the recognition phase, both groups showed a typical task effect (self = mother > other), while patients recognized more self-referential adjectives than the HCs. ERP data reveal that patients with MDD show larger P2 amplitudes during the encoding stage than healthy individuals. During the recognition phase, negative adjectives evoked larger P2 amplitudes in patients than in HCs under the self-referential condition. These findings shed important light on the information processes that may contribute to our understanding of depression and may offer implications for clinical interventions.

Correlation Between Aggressive Behavior and Impulsive and Aggressive Personality Traits in Stable Patients with Schizophrenia.

Purpose: To explore the correlation between aggressive behavior and impulsive and aggressive personality traits in inpatients with schizophrenia. Methods: In total, 367 inpatients with schizophrenia were divided into two groups: the aggressive group and the non-aggressive group. We assessed inpatients' psychotic symptoms as well as their aggressive and impulsive personality traits using the Positive and Negative Symptom Scale, the Barratt Impulsiveness Scale, and the Buss-Perry Aggression Questionnaire. Results: Compared with the scores of inpatients in the non-aggressive group, the total Buss-Perry Aggression Questionnaire, subscale, and Barratt Impulsiveness Scale behavioral factor scores in those in the aggressive group were higher (p < 0.05). The results of logistic regression analysis suggested that a high Positive and Negative Symptom Scale positive factor score (odds ratio = 1.07) and a high Buss-Perry Aggression Questionnaire physical aggression score (odds ratio = 1.02) were risk factors for aggressive behavior. Conclusion: Hospitalized patients with schizophrenia with more severe positive symptoms and aggressive traits may be more prone to aggressive behavior.

Association between video gaming time and cognitive functions: A cross-sectional study of Chinese children and adolescents.

This study sought to explore relationships between video gaming time and cognitive functioning in children and adolescents to provide a scientific reference for a reasonable time range of game use. A total of 649 participants aged 6-18 years were recruited through an online survey using convenience sampling. We used a combination of multiple linear regression models, smoothing splines, piecewise linear regression models, and log-likelihood ratio tests to comprehensively analyze the linear and nonlinear relationships between video gaming time and cognitive functions. Neurocognitive functioning was assessed using the digit symbol test, spatial span back test, Stroop task, and Wisconsin card sorting test. Facial and voice emotion recognition tests were used to evaluate social cognitive functioning. Video gaming time had a saturation effect on improving correct answers to the digit symbol test, which means that performance did not increase with increasing video gaming time when the video gaming duration reached 20 h/week (adjusted ß = -0.58; 95% CI: -1.22, 0.05). Furthermore, both the relationship between video gaming time and the Wisconsin Card Sorting Test and the facial emotion recognition score showed a threshold effect. The completed categories of the Wisconsin Card Sorting Test began to decline after 17 h/week of playtime, and a decline in facial emotion recognition occurred after playing video games for over 20 h/week. These results suggest that children and adolescents should restrict their video gaming time to within a certain range, which could help reduce the negative effects of video games and retain their positive effects.

Sensory gating deficits and childhood trauma in the onset of first-episode schizophrenia.

BACKGROUND: Studies have shown sensory gating deficits and severe childhood trauma in patients with schizophrenia; however, their relationship with this condition remains unclear. Here, we hypothesized that sensory gating deficits mediate the effects of childhood trauma on schizophrenia onset. METHODS: We recruited 79 patients with first-episode schizophrenia (PFES) and 76 health controls (HC). The auditory conditioning (S1) and testing (S2) stimulus paradigm was used to detect P50 sensory gating. The Childhood Trauma Questionnaire (CTQ) was used to assess childhood trauma experiences. RESULTS: Compared with HC, the PFES group had more severe childhood trauma experiences together with sensory gating deficits. In a partial correlation analysis, sexual abuse was negatively correlated with the P50 S2 latency, physical neglect was negatively correlated with the S1 latency, while emotional neglect was positively correlated with the S2/S1 ratio and negatively correlated with the S1-S2 difference in the PFES group. However, there was no correlation between the CTQ total and each sub-scores and P50 indicators in the HC. The S1-S2 difference was the mediator between emotional neglect and the onset of schizophrenia. CONCLUSION: Childhood trauma might be associated with schizophrenia by influencing sensory gating deficits. Early intervention targeting childhood trauma might reduce the incidence of sensory gating deficits and thus schizophrenia.

Integrated Analysis of Competitive Endogenous RNA Networks in Acute Ischemic Stroke.

Background: Acute ischemic stroke (AIS) is a severe neurological disease with complex pathophysiology, resulting in the disability and death. The goal of this study is to explore the underlying molecular mechanisms of AIS and search for new potential biomarkers and therapeutic targets. Methods: Integrative analysis of mRNA and miRNA profiles downloaded from Gene Expression Omnibus (GEO) was performed. We explored differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMirs) after AIS. Target mRNAs of DEMirs and target miRNAs of DEGs were predicted with target prediction tools, and the intersections between DEGs and target genes were determined. Subsequently, Gene Ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses, Gene set enrichment analysis (GSEA), Gene set variation analysis (GSVA), competitive endogenous RNA (ceRNA) (lncRNA-miRNA-mRNA) network, protein-protein interaction (PPI) network, and gene transcription factors (TFs) network analyses were performed to identify hub genes and associated pathways. Furthermore, we obtained AIS samples with evaluation of immune cell infiltration and used CIBERSORT to determine the relationship between the expression of hub genes and infiltrating immune cells. Finally, we used the Genomics of Drug Sensitivity in Cancer (GDSC) database to predict the effect of the identified targets on drug sensitivity. Result: We identified 293 DEGs and 26 DEMirs associated with AIS. DEGs were found to be mainly enriched in inflammation and immune-related signaling pathways through enrichment analysis. The ceRNA network included nine lncRNAs, 13 miRNAs, and 21 mRNAs. We used the criterion AUC >0.8, to screen a 3-gene signature (FBL, RPS3, and RPS15) and the aberrantly expressed miRNAs (hsa-miR-125a-5p, hsa-miR-125b-5p, hsa-miR-148b-3p, and hsa-miR-143-3p) in AIS, which were verified by a method of quantitative PCR (qPCR) in HT22 cells. T cells CD8, B cells naïve, and activated NK cells had statistical increased in number compared with the acute cerebral infarction group. By predicting the IC50 of the patient to the drug, AZD0530, Z.LLNle.CHO and NSC-87877 with significant differences between the groups were screened out. AIS demonstrated heterogeneity in immune infiltrates that correlated with the occurrence and development of diseases. Conclusion: These findings may contribute to a better understanding of the molecular mechanisms of AIS and provide the basis for the development of novel treatment targets in AIS.

Alterations in innate immune defense distinguish first-episode schizophrenia patients from healthy controls.

Innate immune components involved in host defense have been implicated in schizophrenia (SCZ). However, studies exploring their clinical utility in SCZ diagnosis are limited. The main purpose of this study was to evaluate whether circulating endotoxin, high mobility group box 1 protein (HMGB1) and complement component 4 (C4) could act as peripheral biomarkers to distinguish first-episode schizophrenia (FES, n = 42) patients from healthy controls (HCs, n = 35) in associations with psychopathological symptoms and cognitive dysfunctions. Also, their changes after 8-week antipsychotic treatment were investigated. The Positive and Negative Syndrome Scale (PANSS), Psychotic Symptom Rating Scale (PSYRATS), and MATRICS Consensus Cognitive Battery (MCCB) were administered. Receiver operating characteristic (ROC) curves were conducted to evaluate the diagnostic effectiveness of the three biological indicators. Compared to HCs, levels of endotoxin, HMGB1, and C4 were remarkably increased in FES patients after controlling for age, gender, body mass index (BMI) and education years, and the combination of the three biomarkers demonstrated desirable diagnostic performance (AUC = 0.933). Moreover, the endotoxin level was positively correlated with the severity of auditory hallucinations. After 8 weeks of treatment, HMGB1 was decreased significantly in patients but still higher than that in HCs, whereas endotoxin and C4 did not change statistically. The baseline levels of endotoxin, HMGB1, and C4, as well as their changes were not associated with changes in any PANSS subscale score and total score. Our preliminary results suggest that a composite peripheral biomarker of endotoxin, HMGB1, and C4 may have accessory diagnostic value to distinguish SCZ patients from HCs. Additionally, endotoxin might be implicated in the pathogenesis of auditory hallucinations.

Structural brain imaging abnormalities correlate with positive symptom in schizophrenia.

Accumulating evidence indicates neuroanatomical mechanisms underlying positive symptoms in schizophrenia; however, the exact structural determinants of positive symptoms remain unclear. This study aimed to investigate associations between positive symptoms and structural brain changes, including alterations in grey matter (GM) volume and cortical thickness, in patients with first-episode schizophrenia (FES). This study included 44 patients with FES and 48 healthy controls (HCs). Clinical symptoms of patients were evaluated and individual-level GM volume and cortical thickness were assessed. Patients with FES showed reduced GM volume in the right superior temporal gyrus (STG) and increased cortical thickness in the left inferior segment of the circular sulcus of the insula (S_circular_insula_inf) compared with HCs. Increased thickness of the left S_circular_insula_inf correlated positively with positive symptoms in patients with FES. Exploratory correlation analysis found that increased thickness of the left S_circular_insula_inf correlated positively with conceptual disorganization and excitement symptoms, and the right STG GM volume correlated negatively with hallucinations. This study suggests that GM abnormalities in the STG and altered cortical thickness of the S_circular_insula_inf, which were detected at the early stage of schizophrenia, may underlie positive symptoms in patients with FES.

Relationship Between Plasma Olanzapine and N-Desmethyl-Olanzapine Concentration and Metabolic Parameters in Patients With Schizophrenia.

Objectives: The aim of the present study was to investigate a potential relationship between metabolic parameters and steady-state plasma concentrations of olanzapine (OLA) and its metabolite, 4-N'-desmethyl-olanzapine (DMO) in patients with schizophrenia taking therapeutic doses. Methods: A total of 352 inpatients, diagnosed with schizophrenia according to the DSM-V criteria and treated with OLA, were investigated. The plasma concentrations of OLA and DMO were measured by high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS). Fasting blood samples were measured for insulin, glucose, total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), C-reactive protein (CRP) and homocysteine, and differences in these parameters were investigated in relation to plasma concentrations of OLA and DMO. Results: Lower plasma DMO concentrations were associated with higher glucose and TG levels and homeostasis model assessment of insulin resistance (HOMA-IR), while higher plasma OLA concentrations were associated with higher CRP and homocysteine levels in the OLA-treated patients with schizophrenia. Conclusion: These results demonstrate that OLA and its metabolite DMO may have different effects on OLA-induced metabolic abnormalities. DMO might have a counteracting effects on glucose-insulin homeostasis and lipid metabolic abnormalities, which suggests that regular measure of various metabolic parameters and drug monitoring on both OLA and DMO are recommended in OLA-treated patients with schizophrenia.