Cytokines in cerebrospinal fluid of patients with schizophrenia spectrum disorders: New data and an updated meta-analysis

Abstract

Few studies have been conducted examining cytokines in cerebrospinal fluid of patients compared to healthy volunteers. The goals of this study were: 1) to report original data detailing cytokine levels in the cerebrospinal fluid (CSF) of 10 patients with a schizophrenia spectrum disorder (SSD) diagnosis and 10 healthy controls and 2) to conduct a meta-analysis of the available data on cytokine levels in the CSF of patients with SSD compared to healthy controls, including our new data. Cytokine concentrations were measured using the Q-plex Human Cytokine Screen array in CSF of 10 patients with SSD and 10 healthy volunteers. For the meta-analysis, an electronic PubMed and Google Scholar search without restrictions was conducted for articles that reported on cytokine levels in CSF in patients with an SSD compared to healthy controls. Our original data revealed statistically significant increases in levels of interleukin-8 (IL-8) and interleukin-1 beta (IL-1β) in the CSF of patients with an SSD compared to healthy volunteers. Our meta-analysis showed statistically significant increases in interleukin-6 (IL-6) and IL-8 in patients compared to healthy volunteers. Effect sizes between treated and untreated patients for IL-6 were of similar magnitude. However, IL-6 levels were higher in early stage schizophrenia patients compared to chronic schizophrenia patients. Studies with larger sample sizes, comprehensive assessments and ideally in the context of a randomized controlled intervention to minimize the impact of confounding factors are needed to fully understand the role of cytokines and inflammatory markers in the pathophysiology and treatment of schizophrenia.

Anti‐TSNARE1 IgG plasma levels differ by sex in patients with schizophrenia in a Chinese population

“…Interleukin‐10 (IL‐10) levels were found to be correlated with improvement in symptoms ; meta‐analysis conducted by Gallego et al . demonstrated an increase in CSF levels of IL‐8, IL‐1β and IL‐6 in patients with schizophrenia, further substantiated by Romeo et al . who investigated these pro‐inflammatory cytokine levels in blood.…”

“…Both pro-and anti-inflammatory mediators show differences between individuals with firstepisode psychosis, individuals on antipsychotic medication and healthy controls [7,8]. Interleukin-10 (IL-10) levels were found to be correlated with improvement in symptoms [9]; meta-analysis conducted by Gallego et al [10] demonstrated an increase in CSF levels of IL-8, IL-1b and IL-6 in patients with schizophrenia, further substantiated by Romeo et al [11] who investigated these pro-inflammatory cytokine levels in blood.…”

Inflammation and Negative Symptoms of Schizophrenia: Implications for Reward Processing and Motivational Deficits

“…These markers are able to access the brain to activate local inflammatory markers via a number of different mechanisms including 1) movement through leaky parts of the BBB, 2) active uptake via transporter systems, 3) activation of endothelial and immune cells in cerebral vasculature and subsequent release of inflammatory markers in the brain, and 4) via peripheral afferents, such as the vagus nerve, that may relay cytokine signals to the brain (127)(128)(129). One piece of evidence that suggests similar changes in in fl ammator y marker concentrations are occurring centrally comes from studies measuring cerebrospinal fluid (CSF) which demonstrate similar patterns in inflammatory marker concentrations in patients with schizophrenia relative to healthy controls (130,131). Recent evidence in patients with major depressive disorder demonstrates that peripheral CRP and inflammatory cytokines are strongly correlated with CSF markers, which suggests that peripheral markers may reflect similar findings in the central nervous system (132).…”

Inflammatory markers are associated with psychomotor slowing in patients with schizophrenia compared to healthy controls

“…Indeed, immune system abnormalities are posited to be involved in the neurodevelopment of schizophrenia [18][19][20][21][22][23][24] . Immune dysfunction is seen in patients with schizophrenia as evidenced by meta-analyses, demonstrating alterations in various inflammatory markers, including inflammatory cytokines (both in peripheral blood and cerebrospinal fluid) [25][26][27][28] , acute phase reactants such as C-reactive protein (CRP) 29,30 , and chemokines 31 . Moreover, inflammatory markers, including tumor necrosis factor (TNF), are associated with the deficit syndrome, which, as noted above, has been linked to reduced psychomotor speed 32 .…”