Selective increases in the cytokine, TNFα, in the prefrontal cortex                 of PCP-treated rats and human schizophrenic subjects: influence of antipsychotic drugs

Paterson, Gavin; Ohashi, Yoshiaki; Reynolds, Gavin P.; Pratt, Judith A.; Morris, Brian J.

doi:10.1177/0269881106062025

Cited by 34 publications

(19 citation statements)

References 35 publications

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“…Viviani et al [61] reported that IL-1 ␤ enhances NMDA-receptor-mediated calcium receptors, resulting in neurotoxicity. Paterson et al [62] demonstrated that antipsychotics inhibit TNF-␣ mRNA expression in the prefrontal cortex of phencyclidine-treated rats, suggesting that antipsychotics may affect the cytokine network by modulating the NMDA receptor. Again, our results showing that only monocytic proinflammatory cytokines significantly decreased after antipsychotic treatment support those results.…”

Section: Discussionmentioning

confidence: 99%

Monocytic, Th1 and Th2 Cytokine Alterations in the Pathophysiology of Schizophrenia

Na¹,

Kim²

2007

Neuropsychobiology

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A growing body of evidence suggests that changes in the serum levels and cellular production of various cytokines are associated with the immunological abnormalities of schizophrenia. Several studies have examined alterations in T helper type 1 (Th1) and T helper type 2 (Th2) cytokines in schizophrenia. We explored monocytic, Th1 and Th2 cytokines in 43 schizophrenia patients and 50 normal controls. The mitogen-induced production of tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), IL-4, γ-interferon (IFN-γ) and IL-2 was measured with enzyme-linked immunosorbent assays before and after antipsychotic treatment. IL-6 and TNF-α production by schizophrenic patients was significantly higher than by normal controls, while IL-2, IL-4 and IFN-γ production was significantly lower in schizophrenic patients. After 6 weeks of antipsychotic treatment, IL-6 and TNF-α production was significantly decreased, while IL-4, IFN-γ and IL-2 productions were not significantly changed. Our results suggest that increased monocytic cytokines and decreased Th1 and Th2 cytokines may be associated with the immunopathogenesis of acute psychotic schizophrenia, and that antipsychotics may play an important role in immune response by decreasing elevated monocytic cytokines.

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Section: Discussionmentioning

confidence: 99%

Monocytic, Th1 and Th2 Cytokine Alterations in the Pathophysiology of Schizophrenia

Na¹,

Kim²

2007

Neuropsychobiology

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“…Nevertheless, associations between polymorphisms in the TNF-α gene and schizophrenia have not been clearly demonstrated 8,16,17. Many studies have measured the serum levels of TNF-α; however, the results from studies taking this approach have also not been consistent 18–20. Studies measuring the level of TNF-α in the CSF are relatively rare, and these levels are commonly below the threshold of detection.…”

Section: Introductionmentioning

confidence: 99%

The reduction of CSF tumor necrosis factor alpha levels in schizophrenia: no correlations with psychopathology and coincident metabolic characteristics

Zhu¹,

Wang²,

Liu³

2016

NDT

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AimThe aim of this study was to assess whether tumor necrosis factor alpha (TNF-α) levels are correlated with the behavioral syndrome of schizophrenia and/or metabolic abnormalities.MethodsSixty patients with first-onset schizophrenia were recruited. The concentrations of TNF-α in the cerebrospinal fluid (CSF) were determined in 22 schizophrenia patients and ten patients with nonsuppurative appendicitis using a radioimmunoassay. Physiological characteristics such as fasting blood glucose, fasting insulin, triglycerides, corrected QT interval, waist circumference, and body mass index were measured prior to CSF collection. Subjects were screened for insulin resistance using the homeostasis model assessment. The extent of positive and negative behavioral symptoms was scored using the Positive and Negative Syndrome Scale.ResultsThe CSF TNF-α levels in schizophrenic patients were significantly lower than those in the control group. The age of disease onset was positively correlated with the CSF TNF-α level using Pearson correlation analysis (r=0.37, P<0.05). There were no significant differences in CSF TNF-α levels in terms of age, duration of schizophrenia, or systolic and diastolic blood pressure. Furthermore, the CSF TNF-α levels were not significantly correlated with fasting blood glucose, fasting insulin, insulin resistance index, triglycerides, corrected QT interval, waist circumference, or body mass index. No significant correlation was found between CSF TNF-α levels and the Positive and Negative Syndrome Scale total scores or other factors scores. There were also no significant differences in CSF TNF-α levels between patients with schizophrenia types I and II.ConclusionCSF TNF-α levels are decreased in schizophrenia, although this reduction does not correlate with the psychopathology or coincident metabolic characteristics of this disease.

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“…The gene expression level of pro-inflammatory cytokines in preclinical models of schizophrenia and human subjects have been shown to be increased in the prefrontal cortex region of the brain 16 . Several transcriptomic studies have shown that inflammation-related genes which are increased in schizophrenia brains are also associated with oligodendrocyte and endothelial cells.…”

Section: Brain Studiesmentioning

confidence: 99%

Explorando o componente inflamatório da esquizofrenia

Rahmoune

Harris

Guest³

et al. 2012

Arch. Clin. Psychiatry (São Paulo)

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Schizophrenia is a heterogeneous disease characterised by an array of clinical manifestations. A large number of studies over the last 20 years have pointed towards immune system abnormalities in patients suffering from this condition. In addition, the psychosis and cognitive dysfunction associated with schizophrenia have been shown to be linked with autoimmune diseases. Here, we review the evidence, which suggests that a pro-inflammatory status of the immune system induces psychopathologic symptoms and may be involved in the pathophysiology of this major mental illness. We also propose that future preclinical and clinical studies should take such pre-defined causes and the dynamic status of the inflammatory component into account. Patient stratification and personalised medicine strategies based on targeting the inflammatory component of the disease could help in alleviation of symptoms and slowing disease progression. Ultimately, this could also lead to novel concepts in schizophrenia target/molecular identification and drug discovery strategies. H, et al. / Rev Psiq Clín. 2013;40(1):28-34 Keywords: Schizophrenia, inflammation, immune system, biomarkers. Rahmoune ResumoA esquizofrenia é uma doença heterogênea caracterizada por um conjunto de manifestações clínicas. Um grande número de estudos ao longo dos últimos 20 anos apontou para anormalidades no sistema imune em pacientes que sofrem dessa condição. Em adição, tem sido mostrado que a psicose e a disfunção cognitiva associadas com a esquizofrenia estão ligadas a doenças autoimunes. Aqui, revisamos a evidência que sugere que um status pró-inflamatório do sistema imune induz sintomas psicopatológicos e pode estar envolvido na fisiopatologia dessa principal doença mental. Também propomos que futuros estudos pré-clínicos e clínicos deveriam levar em conta tais causas predefinidas e o status do componente inflamatório. Estratificação de pacientes e estratégias de medicina personalizadas baseadas no direcionamento ao componente inflamatório da doença poderiam ajudar na redução de sintomas e da progressão da doença. Por fim, isso poderia levar a novos conceitos na identificação de alvos moleculares em esquizofrenia e estratégias de descoberta de drogas. H, et al. / Rev Psiq Clín. 2013;40(1):28-34 Palavras-chave: Esquizofrenia, inflamação, sistema imune, biomarcadores. Rahmoune

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Selective increases in the cytokine, TNFα, in the prefrontal cortex of PCP-treated rats and human schizophrenic subjects: influence of antipsychotic drugs

Cited by 34 publications

References 35 publications

Monocytic, Th1 and Th2 Cytokine Alterations in the Pathophysiology of Schizophrenia

Monocytic, Th1 and Th2 Cytokine Alterations in the Pathophysiology of Schizophrenia

The reduction of CSF tumor necrosis factor alpha levels in schizophrenia: no correlations with psychopathology and coincident metabolic characteristics

Explorando o componente inflamatório da esquizofrenia

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