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

Abstract

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.

Cerebrospinal fluid markers of inflammation and infections in schizophrenia and affective disorders: a systematic review and meta-analysis

“…Concerning pro-inflammatory cytokines, IL-2 was detected in 95%, IL-5 in 40%, IFN-gamma in 14%, TNF-beta in 41%, and TNF-alpha in 50% of cases [7]. Other studies found no difference to neurological controls in levels of IL-2, IL-6, and TNF alpha [33] or decreased levels of IL-1beta, sIL-2r [33], and TNF-alpha [56] compared to neurological and surgical controls. Interferon was reported to be absent [31] or present in up to 59% of cases [57–60] but with no difference in the study comparing to psychiatric controls [60].…”

Systemic Inflammation in C57BL/6J Mice Receiving Dietary Aluminum Sulfate; Up-Regulation of the Pro-Inflammatory Cytokines IL-6 and TNFα, C-Reactive Protein (CRP) and miRNA-146a in Blood Serum

“…Similar to IL-6, TNFα is a relatively abundant circulating inflammatory mediator-biomarker whose levels are positively correlated to the physiological state of systemic inflammation [ 1 – 4 , 39 – 43 ]. Interestingly this pro-inflammatory cytokine may also play a role in neuroprotection and increases in the serum may be part of an inflammatory sensing-and-signaling system linked to physiological attempts at CNS and PNS cell repair and neutralization of SI [ 40 – 42 ]. Average published concentrations of TNFα reported are 4–11 pg/ml in human serum [ 40 – 42 ].…”

“…Interestingly this pro-inflammatory cytokine may also play a role in neuroprotection and increases in the serum may be part of an inflammatory sensing-and-signaling system linked to physiological attempts at CNS and PNS cell repair and neutralization of SI [ 40 – 42 ]. Average published concentrations of TNFα reported are 4–11 pg/ml in human serum [ 40 – 42 ]. Interestingly we observed that after 5 months of dietary aluminum sulfate exposure there was an increase in C57BL/6J mouse serum of TNFα, an increase that is significant and highly suggestive of the establishment of a systemic inflammation in the murine circulatory system [ 1 – 4 , 42 , 43 ].…”

“…Average published concentrations of TNFα reported are 4–11 pg/ml in human serum [ 40 – 42 ]. Interestingly we observed that after 5 months of dietary aluminum sulfate exposure there was an increase in C57BL/6J mouse serum of TNFα, an increase that is significant and highly suggestive of the establishment of a systemic inflammation in the murine circulatory system [ 1 – 4 , 42 , 43 ].…”

“…These focused increases: (i) were found to be progressive and aluminum-induced accumulation of inflammatory biomarkers in the blood serum was age-related over the period of 0–5 months; and (ii) this may be reflective of the degree of development of SI expression programs and ensuing neuropathology. Interestingly, similar elevations of many of these circulating cytokines and related biomarkers are known to increase with advancing age and in various inflammation-associated disease conditions that include SI, systemic bacterial infection, fever, autoimmune disease, type II diabetes, periodontal disease and AD [ 35 – 42 ]. Together these blood serum metrics may be useful, as a group, in SI diagnosis, prognosis and/or predictive of chronic inflammatory neurodegeneration and cell death in the CNS [ 47 ].…”