Sex difference in the interrelationship between TNF-α and oxidative stress status in first-episode drug-naïve schizophrenia

Abstract Background Increasing evidence indicates that dysregulated TNF-α and oxidative stress (OxS) contribute to the pathophysiology of schizophrenia. Additionally, previous evidence has demonstrated sex differences in many aspects of schizophrenia including clinical characteristics, cytokines, and OxS markers. However, to the best of our knowledge, there is no study investigating sex differences in the association between TNF-α, the OxS system, and their interaction with clinical symptoms in schizophrenia patients, especially in first-episode drug-naïve (FEDN) patients. Methods A total of 119 FEDN schizophrenia patients and 135 healthy controls were recruited for this study. Serum TNF-α, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and malondialdehyde (MDA) were measured. The Positive and Negative Syndrome Scale (PANSS) was applied to evaluate psychotic symptoms. Two-way ANOVA, partial correlation analysis, and multivariate regression analysis were performed. Results A sex difference in MDA levels was demonstrated only in healthy controls (F = 7.06, pBonferroni = 0.045) and not seen in patients. Furthermore, only male patients had higher MDA levels than male controls (F = 8.19, pBonferroni = 0.03). Additionally, sex differences were observed in the association of TNF-α and MDA levels with psychotic symptoms (all pBonferroni < 0.05). The interaction of TNF-α and MDA was only associated with general psychopathology symptom in male patients (B = − 0.07, p = 0.02). Conclusion Our results demonstrate the sex difference in the relationship between TNF-α, MDA, and their interaction with psychopathological symptoms of patients with schizophrenia.

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Sex Difference in the Interrelationship Between TNF-α and Oxidative Stress Status in First-episode Drug-naïve Schizophrenia

10.21203/rs.3.rs-126760/v1 ◽

2020 ◽

Author(s):

Minghuan Zhu ◽

Zhenjing Liu ◽

Jaelin Rippe ◽

Mst. Sadia Sultana ◽

Kang Wu ◽

...

Keyword(s):

Oxidative Stress ◽

Sex Differences ◽

Sex Difference ◽

Psychotic Symptoms ◽

First Episode ◽

Healthy Controls ◽

Tnf Α ◽

Drug Naïve ◽

Male Patients ◽

And Oxidative Stress

Abstract BackgroundIncreasing evidence indicates that dysregulated TNF-α and oxidative stress (OxS) contribute to the pathophysiology of schizophrenia. Additionally, previous evidence has demonstrated sex differences in many aspects of schizophrenia including clinical characteristics, cytokines and OxS markers. However, to the best of our knowledge, there is no study investigating sex differences in the association between TNF-α, the OxS system, and their interaction with clinical symptoms in schizophrenia patients, especially in first-episode drug-naïve (FEDN) patients. MethodsA total of 119 FEDN schizophrenia patients and 135 healthy controls were recruited for this study. Serum TNF-α, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and malondialdehyde (MDA) were measured. The Positive and Negative Syndrome Scale (PANSS) was applied to evaluate psychotic symptoms. Two-way ANOVA, partial correlation analysis and multivariate regression analysis were performed. ResultsA sex difference in MDA levels was demonstrated only in healthy controls (F = 7.06, p Bonferroni = 0.045) and not seen in patients. Furthermore, only male patients had higher MDA levels than male controls (F = 8.19, p Bonferroni = 0.03). Additionally, sex differences were observed in the association of TNF-α and MDA levels with psychotic symptoms (all pBonferroni<0.05). The interaction of TNF-α and MDA was only associated with general psychopathology symptom in male patients (B = -0.07, p = 0.02). ConclusionOur results demonstrate the sex difference in the relationship between TNF-α, MDA, and their interaction with psychopathological symptoms of patients with schizophrenia.

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Insulin Resistance and Oxidative Stress: In Relation to Cognitive Function and Psychopathology in Drug-Naïve, First-Episode Drug-Free Schizophrenia

Frontiers in Psychiatry ◽

10.3389/fpsyt.2020.537280 ◽

2020 ◽

Vol 11 ◽

Author(s):

Qi Tao ◽

Yu Miao ◽

Huihui Li ◽

Xiuxia Yuan ◽

Xufeng Huang ◽

...

Keyword(s):

Oxidative Stress ◽

Insulin Resistance ◽

Cognitive Function ◽

Serum Levels ◽

First Episode ◽

Healthy Controls ◽

Healthy Control ◽

Drug Naïve ◽

Drug Free ◽

And Oxidative Stress

Objective: The present study aimed to examine whether insulin resistance and oxidative stress are associated with cognitive impairment in first-episode drug-free schizophrenia (SZ) patients.Methods: Ninety first-episode SZ patients and 70 healthy controls were enrolled. Fasting insulin (FINS) and markers of oxidative stress [oxidized glutathione (GSSG), superoxide dismutase (SOD), nitric oxide (NO) and uric acid (UA) levels] were measured in serum before pharmacological treatment was initiated. Psychiatric symptoms and cognitive function were assessed with the Positive and Negative Syndrome Scale (PANSS) and MATRICS Consensus Cognitive Battery (MCCB), respectively. In addition, the homeostatic model assessment of insulin resistance (HOMA-IR) was also studied.Results: HOMA-IR and serum levels of GSSG and NO were significantly higher in SZ patients than in healthy controls (P < 0.001), while the serum levels of SOD were significantly lower than in healthy controls (P < 0.001). HOMA-IR, GSSG and NO levels were significantly correlated to the total cognitive function scores of the patient group (r = −0.345,−0.369,−0.444, respectively, P < 0.05). But these factors were not co-related to the cognitive functions in the healthy control group. And, levels of SOD, UA were not associated with the total cognitive function scores in both the patient and the healthy control groups. NO was positively correlated with general pathological and the total score in the PANSS, and was negatively correlated with six cognitive domains (r = −0.316 to −0.553, P < 0.05).Conclusions: The levels of insulin resistance and oxidative stress are elevated, and correlated with the severity of cognitive impairment in drug-naïve, first-episode SZ patients. Treatment approaches targeting on reducing insulin resistance and oxidative stress may improve cognitive function in SZ patients.

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Relationship between TNF-α levels and psychiatric symptoms in first-episode drug-naïve patients with schizophrenia before and after risperidone treatment and in chronic patients

BMC Psychiatry ◽

10.1186/s12888-021-03569-5 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Chen Lin ◽

Ke Chen ◽

Jianjin Yu ◽

Wei Feng ◽

Weihong Fu ◽

...

Keyword(s):

Negative Symptoms ◽

Psychiatric Symptoms ◽

Psychotic Symptoms ◽

First Episode ◽

Healthy Controls ◽

Chronic Patients ◽

Tnf Α ◽

Before And After ◽

Drug Naïve ◽

Factor Α

Abstract Background The influence of antipsychotic drugs on tumor necrosis factor-α (TNF-α) levels is unclear, and there is no consensus on the association between TNF-α and psychotic symptoms. This study aimed to investigate the differences in TNF-α levels and clinical correlations in first-episode drug-naïve (FEDN) patients with schizophrenia before and after treatment and in chronic patients. Methods A total of 103 (51 FEDN and 52 chronic) patients and 114 healthy controls were recruited. Demographic and clinical data, including TNF-α levels, were recorded. We used the Positive and Negative Syndrome Scale (PANSS) to measure the psychopathology of all patients. Results TNF-α levels before treatment were significantly higher in FEDN patients than in chronic patients and healthy controls. No significant sex differences were found in the TNF-α levels of patients with schizophrenia. The TNF-α levels before treatment were significantly positively related to changes in PANSS negative symptoms in FEDN patients. The TNF-α levels in chronic patients were significantly negatively correlated with the general psychopathology subscales and PANSS total scores. Conclusions Increased TNF-α levels in FEDN patients and their correlation with psychopathology indicate that inflammatory cytokines may play a crucial role in the etiopathogenesis of schizophrenia, and inflammation-directed therapy may, therefore, improve negative symptoms.

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Interaction between TNF-α and oxidative stress status in first-episode drug-naïve schizophrenia

Psychoneuroendocrinology ◽

10.1016/j.psyneuen.2020.104595 ◽

2020 ◽

Vol 114 ◽

pp. 104595 ◽

Cited By ~ 6

Author(s):

Shiguang Zhu ◽

Lei Zhao ◽

Yong Fan ◽

Qinyu Lv ◽

Kang Wu ◽

...

Keyword(s):

Oxidative Stress ◽

First Episode ◽

Tnf Α ◽

Oxidative Stress Status ◽

Drug Naïve ◽

And Oxidative Stress

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Evolution of inflammatory dysregulation and oxidative stress in patients with first episode of mania

European Psychiatry ◽

10.1016/j.eurpsy.2016.01.1152 ◽

2016 ◽

Vol 33 (S1) ◽

pp. S331-S331

Author(s):

S. García ◽

P. López Peña ◽

I. Zorrilla ◽

A. García-Alocen ◽

M. Martínez-Cengotitabengoa ◽

...

Keyword(s):

Oxidative Stress ◽

Plasma Concentrations ◽

First Episode ◽

Healthy Controls ◽

Illness Onset ◽

Inflammatory Parameters ◽

Tnf Α ◽

Assessment Time ◽

Competing Interest ◽

And Oxidative Stress

IntroductionRecent studies have focused on the imbalance in inflammatory and antioxidant pathways as possible causes of the underlying neurodegenerative processes in bipolar disorder. Thus, the study of these pathways in first episodes of mania (FEM) can increase knowledge about this issue.AimTo compare plasma concentrations of pro-inflammatory (MCP-1, PGE2, TNFα) and oxidative parameters (TAS, NO2 and TBARS) between controls and FEM patients and to analyze the evolution of these parameters in patients from baseline to 6 months assessment time.MethodsThis study included 44 FEM patients and 79 healthy controls, aged 18 to 40. Blood samples were available for controls at baseline and for patients at baseline and 6 months after. TAS and TBARS were measured using non-EIA assay kits, N02 was measured with Griess method and PGE2, MCP-1 and TNFα with ELISA kits.ResultsAt baseline, TAS was significantly lower in patients than in controls and TBARS, MCP-1 and TNFα were significantly higher in patients. Among patients, TAS and MCP1 were lower at 6 months than at the illness onset and PGE2 and NO2 were significantly higher than at baseline.ConclusionPatients presented an increased oxidative damage and also a higher activation of pro-inflammatory pathways than healthy controls at baseline. After 6 months their level of oxidative stress continue increased. Pro-inflammatory parameters decreased overtime (MCP-1 and TNF α) but PGE2, increased surprisingly. This can be due to the fact that antipsychotics are not able to completely reverse baseline inflammation.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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Antipsychotic drugs increase Neuregulin1b1 serum levels in first-episode drug-naïve patients and chronic schizophrenia with suggestions for improving the treatment of psychotic symptoms

10.21203/rs.3.rs-929283/v1 ◽

2021 ◽

Author(s):

Haidong Yang ◽

Wen Pan ◽

Wenhuan Xiao ◽

Man Yang ◽

Jianchun Xu ◽

...

Keyword(s):

Antipsychotic Drugs ◽

Chronic Schizophrenia ◽

Serum Levels ◽

Psychotic Symptoms ◽

First Episode ◽

Antipsychotic Treatment ◽

Therapeutic Effects ◽

Pathophysiological Mechanism ◽

Healthy Controls ◽

Drug Naïve

Abstract Background: Neuregulin1 (NRG1) plays a role in neuronal migration, regulation of synaptic plasticity, and neural survival, and has been considered to be among the candidate genes for schizophrenia. This study focused on the variations in serum NRG1b1 levels following antipsychotic treatment and the relationship between NRG1b1 level and improvements in psychotic symptoms in first-episode drug-naïve (FEDN) patients and chronic schizophrenia.Methods: A total of 100 patients with schizophrenia were recruited and compared with 79 matched healthy controls. All patients had been drug-naïve for at least four weeks. Serum NRG1b1 levels and positive and negative syndrome scale (PANSS) scores were measured at the baseline and after four weeks. Serum NRG1b1 levels were measured using sandwich enzyme-linked immunosorbent assays (ELISA).Results: Baseline NRG1b1 levels were significantly lower in the patients with schizophrenia compared with the healthy controls. NRG1b1 levels increased significantly following antipsychotic treatment. NRG1b1 levels gradually increased with declining PANSS scores and its three subscales during antipsychotic therapy. The levels of NRG1b1 increased significantly in responders after four weeks of treatment, although non-responders showed no such effect. Correlation analyses showed that the levels of NRG1b1 were negatively correlated with the duration of illness and positively correlated with improvement in symptoms.Conclusion: The levels of serum NRG1b1 and the therapeutic effects gradually increased following treatment, indicating that NRG1b1 may be an indicator of therapy, and that it may also be associated with the pathophysiological mechanism causing schizophrenia, although this possible pathway requires further investigation. Antipsychotic drugs increase Neuregulin1b1 serum levels in first-episode drug-naïve patients and chronic schizophrenia with suggestions for improving the treatment of psychotic symptoms

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Prolactin levels in drug-naïve first episode nonaffective psychosis patients compared with healthy controls. Sex differences

Psychiatry Research ◽

10.1016/j.psychres.2019.03.027 ◽

2019 ◽

Vol 276 ◽

pp. 218-222 ◽

Cited By ~ 3

Author(s):

N. Del Cacho ◽

A. Butjosa ◽

R. Vila-Badia ◽

D. Cuadras ◽

M. Kaplan ◽

...

Keyword(s):

Sex Differences ◽

First Episode ◽

Healthy Controls ◽

Drug Naïve

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Serum levels of oxidants and protein S100B were associated in the first-episode drug naïve patients with schizophrenia

Global Clinical and Translational Research ◽

10.36316/gcatr.01.0013 ◽

2019 ◽

pp. 84-92

Author(s):

Lei Liu ◽

Yanli Li ◽

Yun Bian ◽

Fude Yang ◽

Xianyun Li ◽

...

Keyword(s):

Oxidative Stress ◽

Acute Phase ◽

Serum Levels ◽

S100b Protein ◽

First Episode ◽

Healthy Controls ◽

Serum S100b ◽

Drug Naïve ◽

Protein S100b ◽

Drug Free

Background: Patients with schizophrenia have been noted with an elevation of serum S100B protein concentration, but the pathological process is not known. This study was to investigate the relationship between levels of S100B protein and oxidative stress. Methods: General information and blood sample were collected from the first-episode drug naïve or drug-free acute stage of patients who met the Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) criteria for schizophrenia and healthy controls. The serum levels of S100B, total oxidants (TOS) and malonaldehyde (MDA) were used to measure the level of oxidative stress in both patients, and healthy controls. General linear regression analysis was performed to examine the association of S100B protein with the levels of oxidative stress. Results: The levels of serum protein S100B were associated with the concentration of both TOS (Beta=15.77; p=0.0038) and MDA (Beta=7.90; p=0.0068) in the first-episode drug-naive patients (n=29).While both associations were no longer significant (p>0.05) in the drug-free acute phase patients (n=29); the levels of serum S100B was still consistently associated with TOS (Beta=12.42;p=0.0026) and MDA(Beta=4.11;p=0.0480) in the combined group of patients group(n=58). Simultaneous analysis of both oxidative markers, we still found that both TOS (Beta=12.88; p=0.0103) and MDA (Beta=6.46; p=0.0167) were associated with the serum level of protein S100B in the first-episode drug-naive patients, but not drug-free acute phase patients. Conclusion: Our results suggest that astrocyte activity, serum levels of oxidants, and their cross-talking might be involved in the pathogenesis of schizophrenia. This warrants a further study for understanding the underlying mechanism.

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Sex differences in association between cognitive impairment and clinical correlates in Chinese patients with first-episode drug-naïve schizophrenia

Annals of General Psychiatry ◽

10.1186/s12991-021-00347-1 ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Na Zhao ◽

Xiao Hong Wang ◽

Chuan Yi Kang ◽

Yue Zheng ◽

Li Ying Yang ◽

...

Keyword(s):

Sex Differences ◽

Cognitive Impairment ◽

Clinical Symptoms ◽

Verbal Learning ◽

Chinese Patients ◽

First Episode ◽

Hamilton Depression Scale ◽

Female Patients ◽

Drug Naïve ◽

Male Patients

Abstract Background Schizophrenia is a complex mental illness with significant sex differences. Cognitive impairment is common in patients with schizophrenia, even in remission. This study was designed to examine the sex differences in the relationship between cognitive impairment and clinical correlations with first-episode drug-naïve (FEDN) schizophrenia. Methods 93 FEDN patients (male/female = 45/48) and 160 controls (male/female = 74/86) were enrolled to compare the sex differences in cognitive functions measured by the MATRICS Consensus Cognitive Battery (MCCB). Positive and Negative Syndrome Scale (PANSS) and Hamilton Depression Scale (HAMD) were used to evaluate patients' clinical symptoms. We compared cognitive impairment with sociodemographic characteristics and measures of different genders, as well as group-by-sex interactions. Results Our results showed that male patients had significantly lower scores for symbol coding, digital sequence, and verbal learning than female patients, while the healthy controls showed similar sex differences. In female patients, multiple linear regression analysis confirmed that PANSS negative symptoms and general psychopathology scores, HAMD total score, and education level were independent contributors to MCCB total score. In male patients, only education was an independent contributor to MCCB total score. Conclusions These findings revealed significant sex differences in cognitive impairments and clinical symptoms in FEDN, which will be worthy of a follow-up study of schizophrenia in the future.

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Neurotrophins, cytokines, oxidative stress mediators and mood state in bipolar disorder: systematic review and meta-analyses

The British Journal of Psychiatry ◽

10.1192/bjp.2018.144 ◽

2018 ◽

Vol 213 (3) ◽

pp. 514-525 ◽

Cited By ~ 36

Author(s):

Tobias Rowland ◽

Benjamin I. Perry ◽

Rachel Upthegrove ◽

Nicholas Barnes ◽

Jayanta Chatterjee ◽

...

Keyword(s):

Oxidative Stress ◽

Systematic Review ◽

Bipolar Disorder ◽

Inflammatory Markers ◽

Healthy Controls ◽

Oxidative Stress Markers ◽

Stress Markers ◽

Tnf Α ◽

Meta Analyses ◽

And Oxidative Stress

BackgroundA reliable biomarker signature for bipolar disorder sensitive to illness phase would be of considerable clinical benefit. Among circulating blood-derived markers there has been a significant amount of research into inflammatory markers, neurotrophins and oxidative stress markers.AimsTo synthesise and interpret existing evidence of inflammatory markers, neurotrophins and oxidative stress markers in bipolar disorder focusing on the mood phase of illness.MethodFollowing PRISMA (Preferred Reporting Items for Systematic reviews and Meta-analyses) guidelines, a systematic review was conducted for studies investigating peripheral biomarkers in bipolar disorder compared with healthy controls. We searched Medline, Embase, PsycINFO, SciELO and Web of Science, and separated studies by bipolar mood phase (mania, depression and euthymia). Extracted data on each biomarker in separate mood phases were synthesised using random-effects model meta-analyses.ResultsIn total, 53 studies were included, comprising 2467 cases and 2360 controls. Fourteen biomarkers were identified from meta-analyses of three or more studies. No biomarker differentiated mood phase in bipolar disorder individually. Biomarker meta-analyses suggest a combination of high-sensitivity C-reactive protein/interleukin-6, brain derived neurotrophic factor/tumour necrosis factor (TNF)-α and soluble TNF-α receptor 1 can differentiate specific mood phase in bipolar disorder. Several other biomarkers of interest were identified.ConclusionsCombining biomarker results could differentiate individuals with bipolar disorder from healthy controls and indicate a specific mood-phase signature. Future research should seek to test these combinations of biomarkers in longitudinal studies.Declaration of interestNone.

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