Homocysteine levels in first-episode patients with psychiatric disorders.

A high homocysteine (Hcy) level is a risk factor for schizophrenia, depression, and bipolar disorder. However, the role of hyperhomocysteinemia as either an independent factor or an auxiliary contributor to specific psychiatric symptoms or disorders remains unclear. This study aimed to examine Hcy levels in first-episode inpatients with psychotic symptoms and various psychiatric diseases to elucidate the association between Hcy levels and psychiatric disorders. This study enrolled 191 patients (aged 18-40 years) with psychiatric disorders. Seventy-five patients were diagnosed with schizophrenia, 48 with acute and transient psychotic disorders, 36 with manic episodes with psychosis, 32 with major depressive episodes with psychosis, and 56 healthy controls. Serum Hcy levels were measured using the enzyme cycle method. A Hcy concentration level of > 15 µmol/L was defined as hyperhomocysteinemia. Hcy levels were significantly higher in first-episode patients with psychiatric disorders compared to healthy controls (5.99 ± 3.60 vs. 19.78 ± 16.61 vs. 15.50 ± 9.08 vs. 20.00 ± 11.33 vs. 16.22 ± 12.06, F = 12.778, P < 0.001). Hcy levels were significantly higher in males with schizophrenia, acute and transient psychotic disorder, and major depressive disorder but not in mania [schizophrenia, (t = -4.727, P < 0.001); acute and transient psychotic disorders, (t = -3.389, P = 0.001); major depressive episode with psychosis, (t = -3.796, P < 0.001); manic episodes with psychosis, (t = -1.684, P = 0.101)]. However, serum Hcy levels were not significantly different among the psychiatric disorder groups (F = 0.139, P = 0.968). Multivariate linear regression showed that males had an increased risk for homocysteinemia. (95% CI = 8.192-15.370, P < 0.001). These results suggest that first-episode patients with psychiatric disorders have higher Hcy levels than in the general population, and men are at greater risk for psychiatric disorders. In conclusion, elevated Hcy levels may contribute to the pathogenesis of first-episode patients with psychotic symptoms.

Overexpression of forebrain PTP1B leads to synaptic and cognitive impairments in obesity.

Obesity has reached pandemic proportions and is a risk factor for neurodegenerative diseases, including Alzheimer's disease. Chronic inflammation is common in obese patients, but the mechanism between inflammation and cognitive impairment in obesity remains unclear. Accumulative evidence shows that protein-tyrosine phosphatase 1B (PTP1B), a neuroinflammatory and negative synaptic regulator, is involved in the pathogenesis of neurodegenerative processes. We investigated the causal role of PTP1B in obesity-induced cognitive impairment and the beneficial effect of PTP1B inhibitors in counteracting impairments of cognition, neural morphology, and signaling. We showed that obese individuals had negative relationship between serum PTP1B levels and cognitive function. Furthermore, the PTP1B level in the forebrain increased in patients with neurodegenerative diseases and obese cognitive impairment mice with the expansion of white matter, neuroinflammation and brain atrophy. PTP1B globally or forebrain-specific knockout mice on an obesogenic high-fat diet showed enhanced cognition and improved synaptic ultrastructure and proteins in the forebrain. Specifically, deleting PTP1B in leptin receptor-expressing cells improved leptin synaptic signaling and increased BDNF expression in the forebrain of obese mice. Importantly, we found that various PTP1B allosteric inhibitors (e.g., MSI-1436, well-tolerated in Phase 1 and 1b clinical trials for obesity and type II diabetes) prevented these alterations, including improving cognition, neurite outgrowth, leptin synaptic signaling and BDNF in both obese cognitive impairment mice and a neural cell model of PTP1B overexpression. These findings suggest that increased forebrain PTP1B is associated with cognitive decline in obesity, whereas inhibition of PTP1B could be a promising strategy for preventing neurodegeneration induced by obesity.

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.

Vocal emotion perception in schizophrenia and its diagnostic significance.

BACKGROUND: Cognitive and emotional impairment are among the core features of schizophrenia; assessment of vocal emotion recognition may facilitate the detection of schizophrenia. We explored the differences between cognitive and social aspects of emotion using vocal emotion recognition and detailed clinical characterization. METHODS: Clinical symptoms and social and cognitive functioning were assessed by trained clinical psychiatrists. A vocal emotion perception test, including an assessment of emotion recognition and emotional intensity, was conducted. One-hundred-six patients with schizophrenia (SCZ) and 230 healthy controls (HCs) were recruited. RESULTS: Considering emotion recognition, scores for all emotion categories were significantly lower in SCZ compared to HC. Considering emotional intensity, scores for anger, calmness, sadness, and surprise were significantly lower in the SCZs. Vocal recognition patterns showed a trend of unification and simplification in SCZs. A direct correlation was confirmed between vocal recognition impairment and cognition. In diagnostic tests, only the total score of vocal emotion recognition was a reliable index for the presence of schizophrenia. CONCLUSIONS: This study shows that patients with schizophrenia are characterized by impaired vocal emotion perception. Furthermore, explicit and implicit vocal emotion perception processing in individuals with schizophrenia are viewed as distinct entities. This study provides a voice recognition tool to facilitate and improve the diagnosis of schizophrenia.

Genome-wide DNA methylation analysis in schizophrenia with tardive dyskinesia: a preliminary study.

BACKGROUND: Tardive dyskinesia (TD) develops in 20-30% of schizophrenia patients and up to 50% in patients > 50 years old. DNA methylation may play an important role in the development of TD. OBJECTIVE: DNA methylation analyses in schizophrenia with TD. METHODS: We conducted a genome-wide DNA methylation analysis in schizophrenia with TD using methylated DNA immunoprecipitation coupled with next-generation sequencing (MeDIP-Seq) in a Chinese sample including five schizophrenia patients with TD and five without TD (NTD), and five healthy controls. The results were expressed as the log2FC, fold change of normalized tags between two groups within the differentially methylated region (DMR). For validation, the pyrosequencing was used to quantify DNA methylation levels of several methylated genes in an independent sample (n = 30). RESULTS: Through genome-wide MeDIP-Seq analysis, we identified 116 genes that were significantly differentially methylated in promotor regions in comparison of TD group with NTD group including 66 hypermethylated genes (top 4 genes are GABRR1, VANGL2, ZNF534, and ZNF746) and 50 hypomethylated genes (top 4 genes are DERL3, GSTA4, KNCN, and LRRK1). Part of these genes (such as DERL3, DLGAP2, GABRR1, KLRG2, LRRK1, VANGL2, and ZP3) were previously reported to be associated with methylation in schizophrenia. Gene Ontology enrichment and KEGG pathway analyses identified several pathways. So far, we have confirmed the methylation of 3 genes (ARMC6, WDR75, and ZP3) in schizophrenia with TD using pyrosequencing. CONCLUSIONS: This study identified number of methylated genes and pathways for TD and will provide potential biomarkers for TD and serve as a resource for replication in other populations.

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.

Relationship between the tryptophan-kynurenine pathway and painful physical symptoms in patients with major depressive disorder.

OBJECTIVES: To investigate the relationship between the tryptophan-kynurenine (TRP-KYN) pathway and painful physical symptoms (PPS) in major depressive disorder (MDD). METHODS: Eighty-four patients with MDD (40 patients with PPS and 44 without PPS) and forty-six healthy controls (HC) were recruited. The serum levels of tryptophan (TRP), kynurenine(KYN), kynurenic acid (KA), quinolinic acid (QA), 3-hydroxy-kynurenine (3-HK), serotonin (5-HT) were measured using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Depression, anxiety and pain were assessed using Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA) and Short-form McGill pain questionnaire (SFMPQ) respectively. RESULTS: Patients in the MDD group exhibited significantly lower KA and 5-HT levels than HC, whereas MDD patients with PPS showed higher KYN and QA levels, and a higher KYN/TRP ratio than those without. There was a positive correlation between the scores of SFMPQ and QA levels and a negative correlation between the scores of SFMPQ and TRP levels or KA/QA ratios in MDD patients with PPS group. Stepwise multiple regression analysis showed that the KYN/TRP ratios, the KA/QA ratios, and the HAMD scores were significant predictor factors for SFMPQ scores. CONCLUSIONS: These results demonstrated that the TRP-KYN pathway may play a role in the pathophysiology of pain in patients with major depressive disorder, suggesting that further studies of this pathway as a potential biomarker or therapeutic target are required.

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.

Gut microbiome and daytime function in Chinese patients with major depressive disorder.

BACKGROUND: Major depressive disorder (MDD) is underscored by daytime dysfunction-associated features, including mood disturbances, impaired cognition, fatigue, and daytime sleepiness. Importantly, the gut-brain axis may represent a potential mechanistic link between MDD and daytime dysfunction. Therefore, this study aimed to explore the gut microbiome composition and daytime dysfunction in Chinese patients with MDD. METHODS: We enrolled 36 patients with MDD and 45 healthy controls (HCs) matched by age, sex, and body mass index (BMI). Daytime function including emotion, fatigue, and sleepiness were assessed using the Epworth Sleepiness Scale (ESS), Fatigue Severity Scale (FSS), Hamilton Anxiety Scale (HAMA), and Hamilton Depression Scale (HAMD). 16S rRNA sequencing was employed to characterize the gut microbiota in stool samples. RESULTS: The operational taxonomic units (OTUs) OTU255, OUT363 were positively correlated with HAMD and HAMA. OTU244, OTU542 and OTU221 were positively correlated with ESS, HAMD and HAMA. OTU725 and OTU80 were positively correlated with FSS, ESS, HAMD and HAMA, while OTU423 and OTU502 were negatively correlated with all above. Flavonifractor positively correlated with fatigue in patients with MDD and all individuals simultaneously. The correlation between gut microbiome and daytime function was different in MDD and HCs. CONCLUSIONS: We identified several OTUs associated with the severity of fatigue, depression, daytime sleepiness and anxiety in all individuals. Our results revealed the differences in microbiome found between patients with MDD and HCs. These findings provide insights into the potential microbiota changes that occur in MDD, and will enable the development of specific therapeutic strategies for targeting the various symptoms of depression.

High-Dose Betahistine Improves Cognitive Function in Patients With Schizophrenia: A Randomized Double-Blind Placebo-Controlled Trial.

Background: There is currently no effective treatment for cognitive impairment associated with schizophrenia (CIAS). Recent studies have shown that increased histamine levels in the brain may help to improve CIAS symptoms. Betahistine is an H1-receptor agonist and H3-receptor antagonist. This study evaluated the effect of high-dose betahistine on cognitive function as well as its safety in Chinese Han patients with schizophrenia. Methods: This randomized double-blind, placebo-controlled trial enrolled 89 patients with schizophrenia who were randomly administered betahistine (72 mg/d) or placebo for 12 weeks. At baseline and at 4, 8, and 12 weeks after commencing the intervention, we measured changes in cognitive function and clinical symptoms using the MATRICS Consensus Cognitive Battery (MCCB) and Positive and Negative Syndrome Scale (PANSS), respectively. Furthermore, we used the Treatment Emergent Symptom Scale (TESS) to assess the adverse effects of the patients' medications. Results: Compared to the placebo group, the betahistine group showed significant improvements in the MCCB composite score after 12 weeks of treatment (p = 0.003) as well as improvements in MCCB verbal learning (p = 0.02) and visual learning (p = 0.001) domain scores. However, there were no significant improvements in the PANSS total scores or subscores (p > 0.05). Generally, high-dose betahistine treatment was considered safe in patients with schizophrenia. Conclusions: Additional use of high-dose betahistine can effectively improve cognitive function but not psychiatric symptoms in patients with schizophrenia. Betahistine (72 mg/d) is well tolerated by Chinese Han patients with schizophrenia. Trial Registration: chictr.org.cn, identifier: ChiCTR1900021078. http://www.chictr.org.cn/edit.aspx?pid=35484&htm=4.

Cholinergic receptor nicotinic beta 3 subunit polymorphisms and smoking in male Chinese patients with schizophrenia.

OBJECTIVE: The aim of this study was to examine if cholinergic receptor nicotinic beta 3 subunit (CHRNB3) was a common genetic basis for both nicotine dependence and schizophrenia. METHODS: Two CHRNB3 promoter single nucleotide polymorphisms (SNPs) were genotyped in 773 patients with schizophrenia and 302 healthy volunteers. Associations between smoking, schizophrenia, smoking+schizophrenia and CHRNB3 were analyzed. The mRNA expression of CHRNB3 in human brains was examined, and the expression correlations between CHRNB3 and dopaminergic and GABAergic receptor genes were evaluated. RESULTS: The association between CHRNB3 and smoking was significant in the total sample, less significant in the smoking with schizophrenia, and suggestive in the smoking without schizophrenia. CHRNB3 had significant mRNA expression that was correlated with dopaminergic or GABAergic receptor expression in human brains. The two CHRNB3 SNPs had significant cis-acting regulatory effects on CHRNB3 mRNA expression. CONCLUSIONS: Risk for smoking behavior was associated with CHRNB3. CHRNB3 mRNA is abundant in human brain and could play important role in the pathogenesis of smoking behavior.

Gut Microbiome Composition Associated With Major Depressive Disorder and Sleep Quality.

The microbiota-gut-brain axis plays a critical role in the pathogenesis of major depressive disorder (MDD) and related subclinical symptoms. However, studies on the gut microbiota in MDD are inconsistent, and data on MDD's effects on sleep are lacking. This study aimed to analyze the gut microbiota composition and sleep quality of patients with MDD. We performed 16S rRNA sequencing of stool samples from 36 patients with MDD and 45 healthy controls (HC). Sleep quality was assessed using the Pittsburgh Sleep Quality Index, depressive severity with the Hamilton Depression Scale, and insomnia severity using the Insomnia Severity Index. Forty-eight microbiota targets showed significant differences between MDD and HC. In MDD, six microbiota targets were associated with the severity of depression, 11 with sleep quality, and 3 with sleep severity. At the genus level, Dorea was simultaneously related to depression and sleep quality, while Intestinibacter was more closely related to sleep problems. Coprococcus and Intestinibacter were associated with sleep quality independent of the severity of depression. In conclusion, the present findings enable a better understanding of the relationship between gut microbiota and MDD-related symptoms. Gut microbiota alterations may become potential biomarkers and/or treatment targets for sleep quality in MDD.

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.

Subcortical Brain Volumes Relate to Neurocognition in First-Episode Schizophrenia, Bipolar Disorder, Major Depression Disorder, and Healthy Controls.

OBJECTIVE: To explore differences and similarities in relationships between subcortical structure volumes and neurocognition among the four subject groups, including first-episode schizophrenia (FES), bipolar disorder (BD), major depression disorder (MDD), and healthy controls (HCs). METHODS: We presented findings from subcortical volumes and neurocognitive analyses of 244 subjects (109 patients with FES; 63 patients with BD, 30 patients with MDD, and 42 HCs). Using the FreeSurfer software, volumes of 16 selected subcortical structures were automatically segmented and analyzed for relationships with results from seven neurocognitive tests from the MATRICS (Measurement and Treatment Research to Improve Cognition in Schizophrenia) Cognitive Consensus Battery (MCCB). RESULTS: Larger left lateral ventricle volumes in FES and BD, reduced bilateral hippocampus and amygdala volumes in FES, and lower bilateral amygdala volumes in BD and MDD were presented compared with HCs, and both FES and BD had a lower bilateral amygdala volume than MDD; there were seven cognitive dimension, five cognitive dimension, and two cognitive dimension impairments in FES, BD, and MDD, respectively; significant relationships were found between subcortical volumes and neurocognition in FES and BD but not in MDD and HCs; besides age and years of education, some subcortical volumes can predict neurocognitive performances variance. CONCLUSION: The different degrees of subcortical volume lessening may contribute to the differences in cognitive impairment among the three psychiatric disorders.

Decreased serum NCAM is positively correlated with hippocampal volumes and negatively correlated with positive symptoms in first-episode schizophrenia patients.

BACKGROUND: Neural cell adhesion molecule (NCAM) plays an important role in neurodevelopmental processes and regulates hippocampal plasticity. This study investigated the relationship between the serum NCAM concentrations and hippocampal volume and psychotic symptoms in first-episode drug naïve schizophrenia (FES) patients. METHODS: Forty-four FES patients and forty-four healthy controls (HC) were recruited in this study. Serum concentrations of NCAM were measured by ELISA. Psychiatric symptoms were assessed by the positive and negative syndrome scale (PANSS). Brain structural images were obtained using a 3T MRI Scanner and obtained T1 images were processed in order to determine hippocampal grey matter volumes. RESULTS: Schizophrenia patients revealed significantly decreased serum NCAM concentrations (p = 0.017), which were positively correlated with the left (r = 0.523, p < 0.001) and right (r = 0.449, p = 0.041) hippocampal volumes, but negatively correlated with the PANSS positive symptom scores (r = -0.522 p = 0.001). However, no such correlations existed in the HC group. CONCLUSIONS: This is the first time to report that decreased serum NCAM concentrations were associated with hippocampal volumes and symptom severity in FES patients. Our data indicate that the low NCAM is possible neuropathology that is associated with the decreased hippocampus in FES patients.

Suicidal ideation, suicide attempts, and neurocognitive dysfunctions among patients with first-episode schizophrenia.

OBJECTIVE: To determine whether suicidal ideation or suicide attempts are linked to poor neurocognitive function among individuals with first-episode schizophrenia (FES). METHOD: We performed a cross-sectional study on 159 Chinese inpatients (Mage  = 27.1 years; 52.2% females) with minimal-treated FES and collected their suicidal history through interviews and medical records. Neurocognitive performance, psychopathology, and depressive symptoms were assessed using the MATRICS Consensus Cognitive Battery, the Positive and Negative Syndrome Scale, and the Calgary Depression Scale for Schizophrenia, respectively. RESULTS: Approximately 1/10 FES inpatients had any suicide attempts, and more than 1/4 reported lifetime suicidal ideation. Inpatients with a suicide attempt or suicidal ideation scored significantly worse in the overall seven neurocognitive domains compared with those without past suicidal ideation or a suicide attempt. Linear regression suggested that suicide attempts were mainly associated with lower scores in working memory and speed of processing, after adjusting for education levels. The associations remained robust after further controlling for psychopathological and depressive symptoms. CONCLUSION: First-episode schizophrenia patients with suicide attempts had more severely impaired neurocognitive performances in specific domains. Fundamental neurocognitive dysfunctions should be assessed, detected, and treated after their suicide risk assessments.

Resting-state functional connectivity of neural circuits associated with primary and secondary rewards in patients with bipolar disorder.

OBJECTIVE: We used resting-state functional connectivity (rsFC) to evaluate the integrity of the neural circuits associated with primary and secondary rewards in bipolar disorder (BD) with different mood phases. METHODS: Sixty patients with BD [21 patients with depressive episode of BD (BDD) and 41 patients with maniac episode of BD (BDM)] and 42 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging. rsFC was assessed using region of interest-wise analyses. RESULTS: Attenuation of rsFC at the orbitofrontal cortex (OFC) and the left ventral striatum (LVS) was observed in the secondary reward circuit of patients with BD compared to that of HCs. Among BDD, BDM and HCs, the rsFC between OFC and LVS in BDM was intermediate, while the rsFC between OFC and right ventral striatum/right amygdala in BDM was the highest; the corresponding rsFC values in BDD were the lowest. Furthermore, a positive correlation was found between rsFC and Young Mania Rating Scale scores in BDM. CONCLUSIONS: This study suggests that there may be an abnormal rsFC between OFC and LVS in the second reward of patients with BD and the discrepant patterns of rsFC may exist between different mood states in patients with BD.

Plasma total antioxidant status and cognitive impairments in first-episode drug-naïve patients with schizophrenia.

Accumulating evidence suggest that excessive reactive oxygen species-induced oxidative damage may underlie neurodegeneration and cognitive impairment in several disorders including schizophrenia. In this study we examined the association of oxidative stress with cognitive deficits in first-episode drug-naïve (FEDN) patients with schizophrenia. We recruited 54 FEDN patients and 50 age- and sex-matched healthy controls and examined the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus cognitive Battery (MCCB) and plasma total antioxidant status (TAS). Psychopathological symptoms were assessed using the Positive and Negative Syndrome Scale. The results showed that plasma TAS levels were significantly lower in the patients than those in the healthy subjects (94.7 ± 25.0 U/ml vs 156.6 ± 46.7 U/ml, p < 0.0001). The patients scored lower than healthy controls on the MCCB total score, speed of processing, attention/vigilance and managing emotion test index and STROOP test. For the patients, TAS was associated with some domains of cognitive deficits in schizophrenia, such as speed of processing, attention/vigilance and emotion managing. Our results suggested that oxidative stress may be involved in the pathophysiology of schizophrenia at the early of stage and its cognitive impairment.

Elevated serum anti-NMDA receptor antibody levels in first-episode patients with schizophrenia.

Accumulating evidence has shown that N-methyl-D-aspartate (NMDA) glutamate receptors (NMDAR) are implicated in the pathophysiology of neurological and psychiatric disorders, and that patients with NMDAR antibody encephalitis develop psychopathological symptoms. Therefore, we hypothesized that NMDAR antibodies play a key role in the etiology of schizophrenia. In this study, we enrolled 110 first-episode patients with schizophrenia (FEP) and 50 healthy controls (HC). Cognitive function and psychopathology were assessed using the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) and Positive and Negative Syndrome Scale (PANSS), respectively. NMDAR antibody levels were measured using enzyme-linked immunosorbent assay. Our results showed that FEP with schizophrenia exhibited cognitive deficits in all domains of the MCCB and had elevated levels of serum anti-NMDAR antibody compared with the healthy controls (9.2 ±â€¯3.5 vs. 7.3 ±â€¯2.9 ng/ml, t = 3.10, p = 0.002). Furthermore, serum antibody levels were positively correlated with PANSS positive, negative and total score, and inversely correlated with performances of verbal learning and memory, working memory, speed of processing and MCCB total score in the patient group. These results indicate that elevated levels of NMDAR antibody may play a role in the pathogenesis of schizophrenia, leading to NMDAR dysfunction, thereby inducing symptoms of psychosis and cognitive impairment. Therefore, NMDAR antibodies may serve as a biomarker and provide a new avenue for treatment of schizophrenia.

Obesity, altered oxidative stress, and clinical correlates in chronic schizophrenia patients.

Antipsychotic pharmacotherapy is strongly obesogenic and is associated with increased oxidative stress in patients with schizophrenia. However, whether these changes reflect psychopathology, antipsychotic efficacy, or some other factor is not known. Our study aims to investigate the degree of oxidative stress in different BMI categories and to identify clinical symptomatology that may be paired with increased oxidative stress in a schizophrenia population. To this end, we performed a cross-sectional study and recruited 89 long-term inpatients with schizophrenia and collected the following variables: plasma malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), routine biochemical analysis, and psychopathology through the Positive and Negative Syndrome Scale (PANSS). The results indicate that the levels of the lipid peroxidation product, MDA, were significantly higher in the high BMI group than the low (normal) BMI group. As expected, high BMI was associated with an atherogenic lipid profile; however, it was also associated with fewer psychopathological symptoms. Multiple regression analysis found that MDA levels, the PANSS general psychopathology subscore, and triglyceride levels (all p < 0.05) were independent contributors to the BMI in patients. These results suggested that oxidative stress may play an important role in antipsychotic-induced weight gain. Further investigations using the longitudinal design in first-episode schizophrenia patients are needed to explore the beneficial effect of antioxidants on the abnormal lipid metabolism mediated by antipsychotic treatment.