Associations between expression of indoleamine 2, 3-dioxygenase enzyme and inflammatory cytokines in patients with first-episode drug-naive Schizophrenia

AbstractThe indoleamine 2,3-dioxygenase (IDO) enzyme is the first rate-limiting enzyme of the tryptophan degradation pathway in which dysfunction of neuroactive metabolites has been implicated in the pathophysiology of schizophrenia. Inflammatory molecules such as pro-inflammatory cytokines could enhance the activity of IDO. There are few studies on the expression of IDO levels and its correlation with levels of inflammatory cytokines in first-episode drug-naive patients with schizophrenia. One hundred inpatients (female = 33, male = 67) with first-episode drug-naive schizophrenia entered a 6-week, double-blind, randomized, placebo-controlled clinical trial. All individuals were assigned celecoxib or placebo combined with risperidone. Serum levels of IDO and six inflammatory cytokines (IL-1β, IL-6, TNF-α IL-17, IL-4, and INF-γ) were measured. The Positive and Negative Syndrome Scale (PANSS) was used to assess the severity of psychotic symptoms. Compared to healthy subjects, patients had significantly elevated levels of IDO and six cytokines at baseline. Over the 6-week treatment period, the decrease in the levels of IDO and TNF-α and the improvement in the PANSS total score, positive scores, and negative scores in the celecoxib group were significantly greater than in the placebo group. There was a significantly positive correlation between IDO levels and the PANSS negative scores and between IDO levels and TNF-α and IFN-γ levels in the celecoxib group. These findings showed abnormal expression of IDO levels which correlated with negative symptoms and pro-inflammatory cytokine levels in patients with first-episode drug-naive schizophrenia, suggesting the important role of IDO in the pathological mechanism of schizophrenia. Registration number: ChiCTR2000041403.

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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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Early psychosis in young women

European Psychiatry ◽

10.1016/j.eurpsy.2016.01.789 ◽

2016 ◽

Vol 33 (S1) ◽

pp. S7-S7

Author(s):

A. Riecher-Rössler

Keyword(s):

Young Women ◽

Help Seeking ◽

Negative Symptoms ◽

Stress Reactivity ◽

Psychotic Symptoms ◽

First Episode ◽

Seeking Behavior ◽

Drug Naïve ◽

Competing Interest ◽

The University

IntroductionIt is well known that young women are at lower risk for schizophrenic psychoses than young men. However, little is known about the peculiarities of emerging psychosis in young women.ObjectivesTo describe characteristics of emerging psychosis in women.MethodsWithin the FePsy (Früherkennung von Psychosen = early detection of psychosis) study at the University of Basel Psychiatric Clinics we have examined consecutively all patients with a first episode of psychosis (FEP) or an at-risk mental state (ARMS) referred to us between 2000 and 2015.ResultsWomen did not significantly differ from men regarding psychopathology, neither in the ARMS nor in the FEP group. This was true for positive as well as negative symptoms and basic symptoms. Interestingly, women had a higher correlation of self-rating with observer-rating regarding psychotic symptoms. Duration of untreated psychosis was significantly lower in women than in men. Women seek help more quickly than men and their first contact is more often their partner.Regarding neurocognition women showed a slightly better performance in verbal tasks. They also had higher prolactin levels and larger pituitary volumes, even when drug-naive.Transition to psychosis occurred as often and as quickly in women as in men.ConclusionsThere are only few gender differences in patients with emerging psychosis, which resemble mainly those found in the general population, with women showing a better help-seeking behavior, being more partner-oriented, having a better verbal performance and potentially also a higher stress reactivity [1].Disclosure of interestThe author has not supplied his declaration of competing interest.

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Expression and functionality study of 9 Toll-like receptors in drug-naïve non-affective first episode psychosis individuals: a 3-month study

10.21203/rs.3.rs-17979/v1 ◽

2020 ◽

Author(s):

Maria Juncal-Ruiz ◽

Laura Riesco-Davila ◽

Mariluz Ramirez-Bonilla ◽

Victor Ortiz-Garcia de la Foz ◽

Javier Vazquez-Bourgon ◽

...

Keyword(s):

Healthy Volunteers ◽

Inflammatory Cytokines ◽

Mononuclear Cells ◽

Immune Cell ◽

First Episode ◽

Toll Like Receptors ◽

Tnf Α ◽

Drug Naïve ◽

Lower Expression ◽

Pro Inflammatory Cytokines

Abstract Background: Toll-like receptors (TLRs) are a pivotal component of the innate immune system, which are expressed by various subsets of immune cell types, included central nervous system. There are few publications that have studied TLR expression and/or functionality in psychosis, of which most of them have been based on chronic schizophrenia individuals.Objectives: To compare the expression and functionality of 9TLRs in three peripheral blood mononuclear cells (PBMCs) (monocytes, B cells and T cells) within a sample of 33 drug-naïve FEP individuals and 26 healthy volunteers, at baseline and after 3-month of antipsychotic treatment.Methods: The expression of TLR1-9 was assessed by ﬂow cytometry. For the assessment of the TLR functionality (measured as intracellular production of IL-1β, IL-6 and TNF-α following TLR stimulation), cells collected in sodium heparin tubes were polyclonally stimulated for 18h with different agonists for human TLR1–9.Results: Patients showed a lower expression of TLR5 and TLR8 on the three PBMCs at baseline and after 3-month of treatment regarding healthy volunteers (all ps <0.01). We also found less production of some intracellular pro-inflammatory cytokines (especially TNF-α) after TLR stimulation in patients at both baseline and following the medication (all ps <0.01). We have not found differences in the intra-subject analyses after 3-month of treatment.Conclusions: Drug-naive patients with schizophrenia spectrum disorders show lower expression of specific TLR receptors as well as lower intracellular concentrations of some pro-inflammatory cytokines after TLR stimulation. These findings may be a consequence of an excessive cell stimulation via exogenous ligands (such as pathogens) and/or endogenous ligands (such as autoimmunity) in such a way that PBMCs could be exhausted to be activated in the in vitro analyses.

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Safety and Efficacy of the Combination of BCc1 and Hep-S Nanochelating-Based Medicines in Hospitalized COVID-19 Adult Patients: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

10.21203/rs.3.rs-962691/v1 ◽

2021 ◽

Author(s):

Maryam Hafizi ◽

Somayeh Kalanaky ◽

Saideh Fakharzadeh ◽

Atefeh Fakharian ◽

Somayeh Lookzadeh ◽

...

Keyword(s):

Treatment Group ◽

Inflammatory Cytokines ◽

Clinical Symptoms ◽

Secondary Outcome ◽

Controlled Study ◽

Controlled Clinical Trial ◽

Double Blind ◽

Double Blind Placebo ◽

Reduce Mortality Rate ◽

Tnf Α

Abstract Background: The mortality and morbidity of COVID‐19 disease as well as the lack of a proper medication has forced researchers and clinicians to employ urgent efficient technologies to overcome this current pandemic. In the severe forms of COVID-19, the patients develop a cytokine storm syndrome (CSS) where pro-inflammatory cytokines such as IL-6 and TNF-α play a key role in the development of this serious process. The efficiency of nanomedicines - as efficient immunomodulators - that are synthesized based on nanochelating technology have been proved in the previous studies. In the present study, the therapeutic effect of the combination of BCc1 and Hep-S nanomedicines on hospitalized COVID-19 patients was evaluated.Method: Laboratory-confirmed moderate COVID-19 patients at Masih Daneshvari Hospital were enrolled to participate in a randomized, double-blind, placebo-controlled study in two separate groups: combination of BCc1 and Hep-S (N=62) (treatment) or placebo (N=60) (placebo). The primary outcome of the study was evaluating the safety of the nanomedicines combination and its effect on the number of deceased patients, while the secondary outcome was decrease in inflammatory cytokines.Results: The evaluation of blood biochemical indices as well as clinical symptoms showed that adding the combination of BCc1 and Hep-S nanomedicines to the standard protocol of the treatment caused no adverse effects. The results analysis revealed that 28-day consumption of the nanomedicines led to a significant decrease in the mean level of IL-6 cytokine of the patients in the treatment group (p < 0.05). In addition, the patients in the treatment group had lower TNF-α levels compared to those in the control (p > 0.05) and they also showed less need for oxygen therapy. Finally, the number of the deceased patients in the treatment group was 30% lower than that of the control (p > 0.05).Conclusion: The combination of BCc1 and Hep-S, as safe nanomedicines, inhibits IL-6 as a highly important and well-known cytokine in COVID-19 pathophysiology, and presents a promising view for immunomodulation that can manage CSS and reduce mortality rate in COVID19 patients.Trial registration IRCTID, IRCT20170731035423N2. Registered 12 Jun 2020, http://www.irct.ir/ IRCT20170731035423N2.

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

Journal of Neuroinflammation ◽

10.1186/s12974-021-02261-5 ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Minghuan Zhu ◽

Zhenjing Liu ◽

Yanhong Guo ◽

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 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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Metformin Addition Attenuates Olanzapine-Induced Weight Gain in Drug-Naive First-Episode Schizophrenia Patients: A Double-Blind, Placebo-Controlled Study

American Journal of Psychiatry ◽

10.1176/appi.ajp.2007.07010079 ◽

2008 ◽

Vol 165 (3) ◽

pp. 352-358 ◽

Cited By ~ 127

Author(s):

Ren-Rong Wu ◽

Jing-Ping Zhao ◽

Xiao-Feng Guo ◽

Yi-Qun He ◽

Mao-Sheng Fang ◽

...

Keyword(s):

Weight Gain ◽

Controlled Study ◽

First Episode ◽

Double Blind ◽

Double Blind Placebo ◽

Drug Naïve ◽

First Episode Schizophrenia

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The effect of the environment on symptom dimensions in the first episode of psychosis: a multilevel study

Psychological Medicine ◽

10.1017/s0033291713003188 ◽

2014 ◽

Vol 44 (11) ◽

pp. 2419-2430 ◽

Cited By ~ 17

Author(s):

F. J. Oher ◽

A. Demjaha ◽

D. Jackson ◽

C. Morgan ◽

P. Dazzan ◽

...

Keyword(s):

Depressive Symptoms ◽

Population Density ◽

Negative Symptoms ◽

Psychotic Disorders ◽

Urban Environments ◽

Psychotic Symptoms ◽

First Episode ◽

Multilevel Regression ◽

Symptom Dimensions ◽

Reality Distortion

BackgroundThe extent to which different symptom dimensions vary according to epidemiological factors associated with categorical definitions of first-episode psychosis (FEP) is unknown. We hypothesized that positive psychotic symptoms, including paranoid delusions and depressive symptoms, would be more prominent in more urban environments.MethodWe collected clinical and epidemiological data on 469 people with FEP (ICD-10 F10–F33) in two centres of the Aetiology and Ethnicity in Schizophrenia and Other Psychoses (AESOP) study: Southeast London and Nottinghamshire. We used multilevel regression models to examine neighbourhood-level and between-centre differences in five symptom dimensions (reality distortion, negative symptoms, manic symptoms, depressive symptoms and disorganization) underpinning Schedules for Clinical Assessment in Neuropsychiatry (SCAN) Item Group Checklist (IGC) symptoms. Delusions of persecution and reference, along with other individual IGC symptoms, were inspected for area-level variation.ResultsReality distortion [estimated effect size (EES) 0.15, 95% confidence interval (CI) 0.06–0.24] and depressive symptoms (EES 0.21, 95% CI 0.07–0.34) were elevated in people with FEP living in more urban Southeast London but disorganized symptomatology was lower (EES –0.06, 95% CI –0.10 to –0.02), after controlling for confounders. Delusions of persecution were not associated with increased neighbourhood population density [adjusted odds ratio (aOR) 1.01, 95% CI 0.83–1.23], although an effect was observed for delusions of reference (aOR 1.41, 95% CI 1.12–1.77). Hallucinatory symptoms showed consistent elevation in more densely populated neighbourhoods (aOR 1.32, 95% CI 1.09–1.61).ConclusionsIn people experiencing FEP, elevated levels of reality distortion and depressive symptoms were observed in more urban, densely populated neighbourhoods. No clear association was observed for paranoid delusions; hallucinations were consistently associated with increased population density. These results suggest that urban environments may affect the syndromal presentation of psychotic disorders.

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