Association of serum interleukin-6 with negative symptoms in stable early-onset schizophrenia

BACKGROUND Accumulating evidence suggests that the inflammatory cytokine interleukin-6(IL-6)contributes to the pathophysiology of psychiatric disorders.However,there was no study concerning the relationship between IL-6 concentrations and clinical features in the chronic phase of early-onset schizophrenia(EOS).AIM To investigate the relationship between serum IL-6 concentration and the clinical features of EOS.METHODS We measured serum IL-6 Levels from 74 patients with chronic schizophrenia,including 33 with age at onset<21 years(EOS group)and 41 with onset≥21 years in[adult-onset schizophrenia(AOS)group],and from 41 healthy controls.Symptom severities were evaluated using the Positive and Negative Syndrome Scale(PANSS).RESULTS Serum IL-6 concentrations were higher in both EOS and AOS groups than healthy controls(F=22.32,P<0.01),but did not differ significantly between EOS and AOS groups(P>0.05)after controlling for age,body mass index,and other covariates.Negative symptom scores were higher in the EOS group than the AOS group(F=6.199,P=0.015).Serum IL-6 concentrations in the EOS group were negatively correlated with both total PANSS-negative symptom score(r=-0.389,P=0.032)and avolition/asociality subscore(r=-0.387,P=0.026).CONCLUSION Patients with EOS may have more severe negative symptoms than those with adult-onset schizophrenia during the chronic phase of the illness.IL-6 signaling may regulate negative symptoms and its avolition/asociality subsymptoms among the early-onset chronic schizophrenic patients.

Interaction between catechol-O-methyltransferase Val/Met polymorphism and cognitive reserve for negative symptoms in schizophrenia

BACKGROUND Cognitive reserve(CR)and the catechol-O-methyltransferase(COMT)Val/Met polymorphism are reportedly linked to negative symptoms in schizophrenia.However,the regulatory effect of the COMT genotype on the relationship between CR and negative symptoms is still unexamined.AIM To investigate whether the relationship between CR and negative symptoms could be regulated by the COMT Val/Met polymorphism.METHODS In a cross-sectional study,54 clinically stable patients with schizophrenia underwent assessments for the COMT genotype,CR,and negative symptoms.CR was estimated using scores in the information and similarities subtests of a short form of the Chinese version of the Wechsler Adult Intelligence Scale.RESULTS COMT Met-carriers exhibited fewer negative symptoms than Val homozygotes.In the total sample,significant negative correlations were found between negative symptoms and information,similarities.Associations between information,similarities and negative symptoms were observed in Val homozygotes only,with information and similarities showing interaction effects with the COMT genotype in relation to negative symptoms(information,β=-0.282,95%CI:-0.552 to-0.011,P=0.042;similarities,β=-0.250,95%CI:-0.495 to-0.004,P=0.046).CONCLUSION This study provides initial evidence that the association between negative symptoms and CR is under the regulation of the COMT genotype in schizophrenia.

Developments in Biological Mechanisms and Treatments for Negative Symptoms and Cognitive Dysfunction of Schizophrenia

The causal mechanisms and treatment for the negative symptoms and cognitive dysfunction in schizophrenia are the main issues attracting the attention of psychiatrists over the last decade.The first part of this review summarizes the pathogenesis of schizophrenia,especially the negative symptoms and cognitive dysfunction from the perspectives of genetics and epigenetics.The second part describes the novel medications and several advanced physical therapies(e.g.,transcranial magnetic stimulation and transcranial direct current stimulation)for the negative symptoms and cognitive dysfunction that will optimize the therapeutic strategy for patients with schizophrenia in future.

Changes of Serum Insulin-like Growth Factor-2 Response to Negative Symptom Improvements in Schizophrenia Patients Treated with Atypical Antipsychotics

Accumulating evidence suggests that a disruption of early brain development,in which insulin-like growth factor-2(IGF-2)has a crucial role,may underlie the pathophysiology of schizophrenia.Our previous study has shown that decreased serum IGF-2 was correlated with the severity of psychopathology in patients with schizophrenia.Here we conducted a prospective observation trial to investigate the effects of atypical antipsychotics on serum IGF-2 level and its relationship with clinical improvements in schizophrenia patients.Thirty-one schizophrenia patients with acute exacerbation and 30 healthy individuals were recruited in this study.Psychiatric symptoms were assessed using the Positive and Negative Syndrome Scale(PANSS)and serum IGF-2 levels were determined using ELISA.We found that schizophrenia patients with acute exacerbation had lower serum IGF-2 levels than control individuals at baseline(P<0.05).After 2 months of atypical antipsychotic treatment,a significant improvement in each PANSS subscore and total score was observed in patients(all P<0.01),and the serum IGF-2 levels of patients were significantly increased compared with those at baseline(203.13±64.62 vs.426.99±124.26 ng/mL;t=−5.044,P<0.001).Correlation analysis revealed that the changes of serum IGF-2 levels in patients were significantly correlated with the improvements of negative symptoms(r=−0.522,P=0.006).Collectively,our findings demonstrated changes of serum IGF-2 response to improvements of negative symptoms in schizophrenia patients treated with atypical antipsychotics,suggesting that serum IGF-2 might be a treatment biomarker for schizophrenia.

Changes in neurotransmitter levels,brain structural characteristics,and their correlation with PANSS scores in patients with firstepisode schizophrenia

BACKGROUND In patients with schizophrenia,the brain structure and neurotransmitter levels change,which may be related to the occurrence and progression of this disease.AIM To explore the relationships between changes in neurotransmitters,brain structural characteristics,and the scores of the Positive and Negative Symptom Scale(PANSS)in patients with first-episode schizophrenia.METHODS The case group comprised 97 patients with schizophrenia,who were evaluated using the Canadian Neurological Scale and confirmed by laboratory tests at Ningbo Mental Hospital from January 2020 to July 2022.The control group comprised 100 healthy participants.For all participants,brain structural characteristics were explored by measuring brain dopamine(DA),glutamic acid(Glu),and gamma-aminobutyric acid(GABA)levels,with magnetic resonance imaging.The case group was divided into negative and positive symptom subgroups using PANSS scores for hierarchical analysis.Linear correlation analysis was used to analyze the correlations between neurotransmitters,brain structural character istics,and PANSS scores.RESULTS Patients in the case group had higher levels of DA and lower levels of Glu and GABA,greater vertical and horizontal distances between the corpus callosum and the inferior part of the fornix and larger ventricle area than patients in the control group(P<0.05).Patients with positive schizophrenia symptoms had significantly higher levels of DA,Glu,and GABA than those with negative symptoms(P<0.05).In patients with positive schizophrenia symptoms,PANSS score was significantly positively correlated with DA,vertical and horizontal distances between the corpus callosum and the infrafornix,and ventricular area,and was significantly negatively correlated with Glu and GABA(P<0.05).In patients with negative schizophrenia symptoms,PANSS score was significantly positively correlated with DA,vertical distance between the corpus callosum and the infrafornix,horizontal distance between the corpus callosum and the infrafornix,and ventricular area,and was significantly negatively correlated with Glu and GABA(P<0.05).CONCLUSION In patients with first-episode schizophrenia,DA levels increased,Glu and GABA levels decreased,the thickness of the corpus callosum increased,and these variables were correlated with PANSS scores.

DTNBP1 Gene Is Associated with Some Symptom Factors of Schizophrenia in Chinese Han Nationality

Objective To study the association of DTNBP1 gene with some symptom factors of schizophrenia.Methods A total of 285 unrelated schizophrenic individuals were recruited from December 2004 to January 2009 for genetic analysis,and their symptom factors were assessed based on the Positive and Negative Syndrome Scale(PANSS).The quantitative trait test was performed by the UNPHASED program(version 3.0.12) to investigate the association between scored positive and negative symptoms and the single nucleotide polymorphisms(SNPs) in DTNBP1 gene.Results The quantitative trait test showed allelic association of rs909706 with the excitement symptom of schizophrenia(P<0.05,adjusted by 10 000 permutations),while the genotype C/G of rs2619539 with a negative symptom,lack of spontaneity and flow of conversation(P<0.05,adjusted by 10 000 permutations).Conclusion DTNBP1 variations are possibly associated with some symptoms of schizophrenia,which could partly explain the relationship between the susceptibility gene DTNBP1 and that disease.

A meta-analysis of phlegm-resolving Chinese medicine combined with risperidone for treatment of schizophrenia

Objective:The efficacy and occurrence of adverse reactions of prescriptions containing phlegm-resolving Chinese medicine combined with risperidone in the treatment of schizophrenia were retrospectively studied by means of meta-analysis.Methods:A variety of different Chinese and English databases were searched from January 1,2000 to May 1,2020.Review Manager 5.3 software was used to evaluate the methodological quality of the included studies.The positive and negative symptom scale(PANSS)was used as the evaluation standard to analyze the total scores,positive scores,negative scores and general psychopathological scores,clinical efficacy and safety of prescriptions containing phlegmresolving Chinese medicine combined with risperidone of schizophrenia.The heterogeneity test and sensitivity analysis were also carried out by Review Manager 5.3,and the potential publication bias was analyzed by"funnel plot".Results:A total of 1515 patients were included in 15 studies.Compared with control group of risperidone alone,the total PANSS scale score,positive symptom score,negative symptom score and general psychopathological score of the treatment group of phlegm-resolving Chinese medicine combined with risperidone were all lower than those of the control group(P=0.01,MD=-6.35,95%CI[-11.29,-1.40]),(P=0.04,MD=-1.42,95%CI[-2.74,-0.09]),(P<0.01,MD=-2.16,95%CI[-3.41,-0.91]),and(P<0.01,MD=-3.80,95%CI[-6.37,-1.24]),the clinical efficacy of phlegm-resolving Chinese medicine combined with risperidone treatment group on schizophrenia was better than that of the control group[P<0.01,RR=1.09,95%CI(1.05-1.13)].The incidence of adverse reactions was reduced(P=0.02,RR=0.56,95%CI[0.34-0.93]).Conclusion:The combination of prescriptions containing phlegm-resolving Chinese medicine and risperidone can effectively improve the efficacy of patients with schizophrenia and reduce the occurrence of adverse drug reactions compared with risperidone alone.