Decreased serum TNF-alpha levels in chronic schizophrenia patients on long-term antipsychotics: correlation with psychopathology and cognition

Lv, Meng; Tan, Yun Long; Shao, Yan; Tian, Li; Chen, Da Chun; Tan, Shu Ping; Wang, Zhi Ren; Yang, Fu De; Yoon, Jin Ho; Zunta-Soares, Giovana; Soares, Jair C.; Zhang, Xiang Yang

doi:10.1007/s00213-014-3650-y

Cited by 59 publications

(51 citation statements)

References 57 publications

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“…The roles of TNF-α in controlling neuronal excitability and metabolisms of glutamate, dopamine, and serotonin neurotransmitters make it an outstanding candidate for etiology and pathophysiology of schizophrenia (Tian et al, 2014). Alterations in serum TNF-α level in chronic schizophrenia patients have been reported previously, but with inconsistent results, being no different (Pedrini et al, 2012; Kunz et al, 2011), elevated (Lin et al, 1998; Naudin et al, 1997; Beumer et al, 2012; García-Miss et al, 2010; Luo et al, 2014) or reduced (Francesconi et al, 2011; Lv et al, 2014; Potvin et al, 2008), as compared with healthy control subjects. Nonetheless, these evidences implicate the role of TNF-α and TNF-α-related signaling pathways in the pathophysiology of schizophrenia.…”

Section: Discussionmentioning

confidence: 79%

“…In the present study, we found that serum TNF-α level was significantly lower in chronic ketamine users (p < 0.05) and serum TNF-α level showed a significant negative association with PANSS total score and negative subscore (p < 0.01). Recent studies have shown that decreased serum TNF-α level in chronic schizophrenia patients was significantly negatively correlated with PANSS total score and positive subscore (Lv et al, 2014; Potvin et al, 2008), suggesting patients with lowered TNF-α levels would be more likely to have severer psychopathological symptoms. The negative correlation TNF-α level with the severity of psychopathological symptoms may seem contradictory to what proinflammatory cytokines are generally recognized as worsening factors for the pathology of psychiatric disorders at the first glance.…”

Section: Discussionmentioning

confidence: 99%

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Relationship of serum levels of TNF-α, IL-6 and IL-18 and schizophrenia-like symptoms in chronic ketamine abusers

Fan

Luo

Zhang

et al. 2015

Schizophrenia Research

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Objective Exposing to NMDAR receptor antagonists, such as ketamine, produces schizophrenia-like symptoms in humans and deteriorates symptoms in schizophrenia patients. Meanwhile, schizophrenia is associated with alterations of cytokines in the immune system. This study aims to examine the serum TNF-α, IL-6 and IL-18 levels in chronic human ketamine users as compared to healthy subjects. The correlations between the serum cytokines levels with the demographic, ketamine use characteristics and psychiatric symptoms were also assessed. Methods 155 subjects who fulfilled the criteria of ketamine dependence and 80 healthy control subjects were recruited. Serum TNF-α, IL-6 and IL-18 levels were measured using an enzyme-linked immunosorbent assay (ELISA). The psychiatric symptoms of the ketamine abusers were assessed using the Positive and Negative Syndrome Scale (PANSS). Results Serum IL-6 and IL-18 levels were significantly higher, while serum TNF-α level was significantly lower among ketamine users than among healthy controls (p < 0.05). Serum TNF-α levels showed a significant negative association with PANSS total score (r = −0.210, p < 0.01) and negative subscore (r = −0.300, p < 0.01). No significant association was found between PANSS score and serum levels of IL-6 and IL-18. Conclusions Serum levels of TNF-α, IL-6 and IL-18 were altered in chronic ketamine abusers which may play a role in schizophrenia-like symptoms in chronic ketamine abusers.

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Section: Discussionmentioning

confidence: 79%

Section: Discussionmentioning

confidence: 99%

Relationship of serum levels of TNF-α, IL-6 and IL-18 and schizophrenia-like symptoms in chronic ketamine abusers

Fan

Luo

Zhang

et al. 2015

Schizophrenia Research

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“…Firstly, it should be noted that our sample size was limited; however, it is one of the largest studies analyzing serum cytokine levels with respect to cognitive functioning in schizophrenia 50,54,55,76. Secondly, all our patients were medicated, while the association of TGF-β level with cognitive functioning in unmedicated first-episode schizophrenia patients would be much more reliable.…”

Section: Discussionmentioning

confidence: 99%

Sex differences in TGFB-β signaling with respect to age of onset and cognitive functioning in schizophrenia

Frydecka¹,

Misiak²,

Pawlak³

et al. 2015

NDT

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There are studies showing that gene polymorphisms within the transforming growth factor-β (TGF-β) signaling constitute schizophrenia risk variants. However, the association between TGFB1 gene polymorphisms (+869T/C and +915G/C), TGF-β level with schizophrenia course, and its symptomatology together with cognitive functioning has not been investigated so far. We included 151 patients with schizophrenia and 279 healthy controls. Cognitive functioning was assessed using Rey Auditory Verbal Learning Test, Trail Making Test (TMT)-A and TMT-B, Verbal Fluency task, Stroop test, as well as selected subtests from the Wechsler Adults Intelligence Scale – Revised, Polish adaptation (WAIS-R-Pl): Digit Symbol Coding, Digit Span Forward and Backward, and Similarities. Additionally, serum TGF-β levels were measured in 88 schizophrenia patients and 88 healthy controls. Serum TGF-β level was significantly higher among patients with schizophrenia in comparison with healthy controls; however, the studied polymorphisms were not associated with TGF-β level in schizophrenia patients. Subjects carrying the +869T allele performed significantly worse in comparison with +869CC homozygotes on Stroop task, Verbal Fluency task and Digit Symbol Coding task. There was a significant difference in age of psychosis onset in female schizophrenia patients with respect to the TGFB1 +869T/C polymorphism. Additionally, adjustment for possible confounders revealed that there was a significant difference in cognitive performance on Digit Symbol Coding task with respect to the TGFB1 +869T/C polymorphism among female schizophrenia patients. Our results suggest that TGF-β signaling might be a valid link contributing to observed differences in age of onset and the level of cognitive decline between male and female schizophrenia patients.

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“…There is a trend towards TNF-α increase in SZ. One study showed lower levels of TNF-α in SZ subjects than in controls, demonstrating that we need to better understand the biological mechanisms in SZ to produce stronger evidence [40]. Therefore, chronic SZ patients on antipsychotics might show no cytokine differences when compared to HC or their respective SB [41].…”

Section: Discussionmentioning

confidence: 99%

The Relationship between Cytokines and Verbal Memory in Individuals with Schizophrenia and Their Unaffected Siblings

Rebouças

Rabelo‐da‐Ponte

Massuda

et al. 2018

Neuroimmunomodulation

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Background: Verbal memory impairment may be considered an endophenotype in schizophrenia (SZ), also affecting the siblings of SZ subjects. Furthermore, the immune-inflammatory system response has an important modulatory effect on brain processes, especially on memory circuits. Objective: Investigating the relationship between TNF-α and IL-6 and memory performance in patients with SZ, their unaffected siblings (SB) and healthy controls (HC). Methods: 35 subjects with SZ, 36 SB, and 47 HC underwent a neurocognitive assessment for verbal memory by means of the revised Hopkins Verbal Learning Test (HVLT-R) in addition to serum cytokines analyses. Results: SZ patients performed worse in HVLT-R than SB and HC, but SB and HC were not different. Regarding the biomarker levels, we found significant results of TNF-α for both groups. However, we did not find differences between groups after multiple-comparisons analysis. There were no significant correlations between episodic verbal memory, TNF-α, and IL-6. Conclusion: The results are compatible with the hypothesis that deficits in verbal memory of individuals with SZ could be secondary to inadequate functioning of cognitive processing areas, such as proactive cognitive control.

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Decreased serum TNF-alpha levels in chronic schizophrenia patients on long-term antipsychotics: correlation with psychopathology and cognition

Abstract: The significant relations observed in the current study between TNFα and the PANSS and its subscales suggest that immune disturbance may be involved in the psychopathology and cognitive deficits of schizophrenia.

Cited by 59 publications

References 57 publications

Relationship of serum levels of TNF-α, IL-6 and IL-18 and schizophrenia-like symptoms in chronic ketamine abusers

Relationship of serum levels of TNF-α, IL-6 and IL-18 and schizophrenia-like symptoms in chronic ketamine abusers

Sex differences in TGFB-β signaling with respect to age of onset and cognitive functioning in schizophrenia

The Relationship between Cytokines and Verbal Memory in Individuals with Schizophrenia and Their Unaffected Siblings

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Decreased serum TNF-alpha levels in chronic schizophrenia patients on long-term antipsychotics: correlation with psychopathology and cognition

Abstract: The significant relations observed in the current study between TNFα and the PANSS and its subscales suggest that immune disturbance may be involved in the psychopathology and cognitive deficits of schizophrenia.

Cited by 59 publications

References 57 publications

Relationship of serum levels of TNF-α, IL-6 and IL-18 and schizophrenia-like symptoms in chronic ketamine abusers

Relationship of serum levels of TNF-α, IL-6 and IL-18 and schizophrenia-like symptoms in chronic ketamine abusers

Sex differences in TGFB-&beta; signaling with respect to age of onset and cognitive functioning in schizophrenia

The Relationship between Cytokines and Verbal Memory in Individuals with Schizophrenia and Their Unaffected Siblings

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Sex differences in TGFB-β signaling with respect to age of onset and cognitive functioning in schizophrenia