Abnormalities in chemokine levels in schizophrenia and their clinical correlates

Abstract

Chemokines are promising biomarkers of immune activation and inflammation, but evidence for chemokine abnormalities in schizophrenia and their relationship to clinical factors remains inconclusive. We aimed to understand chemokine-related diagnostic differences and clinical correlates using a comprehensive panel and studying a large, well-characterized sample of adults with and without schizophrenia. We studied 134 outpatients with schizophrenia or schizoaffective disorder and 112 healthy comparison (HC) individuals, 26 to 65 years of age. Clinical measures were obtained, and plasma levels of 11 chemokines were assessed using multiplex immunoassay. Schizophrenia vs. HC differences were tested for each chemokine, adjusting for age, gender, body mass index, and current smoking status. We also examined whether age and gender relationships differed between diagnostic groups. Using logistic regression, we created a Chemokine Index (CI) and explored its clinical correlates. Levels of monocyte chemoattractant protein-1 (MCP-1/CCL2), macrophage inflammatory protein-1β (MIP-1β/CCL4), Eotaxin-1 (CCL11), thymus and activation-regulated chemokine (TARC/CCL17), and macrophage-derived chemokine (MDC/CCL22) were significantly higher in persons with schizophrenia than HCs. Group differences in TARC were reduced after adjusting for covariates. The CI, a linear combination of Eotaxin-1 and MDC levels, was positively associated with age, duration of schizophrenia, and severity of negative symptoms. Levels of chemokines with neuroimmune regulatory effects were higher in individuals with schizophrenia, particularly in older and chronic patients. Treatments aimed at normalizing chemokine levels might improve mental and physical health among schizophrenia patients as they age.

Systemic Biomarkers of Accelerated Aging in Schizophrenia: A Critical Review and Future Directions

“…Consistent with previous reviews and meta-analyses, 66,67 73% of these reports observed elevated levels of pro-inflammatory cytokines and chemokines in schizophrenia, including interleukin (IL)-6, 23,28,38,48 IL-1β, 38,57 tumor necrosis factor alpha (TNFα), 48 Eotaxin-1, 35,45 Eotaxin-2, 35 monocyte chemoattractant protein-1, macrophage inflammatory protein-1β, thymus-and activation-regulated chemokine, macrophage-derived chemokine, 45 and lower levels of the anti-inflammatory cytokine IL-2. 30 For TNF-α and IL-6, group differences were reduced and in some cases nonsignificant after controlling for potential confounds.…”

“…57 Of the 11 articles, 3 reported effect sizes ranging from small to medium in size, for elevated levels in schizophrenia. 28,45,48 Other studies found no differences for C-reactive protein (CRP) 40 or intercellular adhesion molecule-1 (ICAM-1) 63 ; however, a more inclusive review and meta-analysis of all studies of CRP (without the specific study inclusion criteria that we used) has shown consistent elevations in CRP in schizophrenia. 68 Age Relationships Thirty-six percent of articles reported differential relationships between inflammation and age in schizophrenia and HCs.…”

“…68 Age Relationships Thirty-six percent of articles reported differential relationships between inflammation and age in schizophrenia and HCs. Three observed correlations between older age and increased IL-6, 28 S100B, 37 and scores on a chemokine index, 45 which included MDC and Eotaxin-1, in schizophrenia but not in HCs. The strengths of correlation coefficients suggest medium effects; however, these investigations did not statistically compare the age-relationship between groups.…”

Leukocyte telomere length: Effects of schizophrenia, age, and gender

“…These factors may be increased in schizophrenia compared to HCs (Emiliani et al, 2014;Muller et al, 2015;Shivakumar et al, 2014). This could, in theory, result in shortened LTL, but there is only mixed evidence that these factors are differentially prevalent in men vs women with schizophrenia (Joseph et al, 2015;Kunz et al, 2011;Lee et al, 2016;Ramsey et al, 2013;Reyazuddin et al, 2014).…”

“…Although we previously published data on high sensitivity C-reactive protein (hs-CRP) (Joseph et al, 2015), F2-isoprostanes (Lee et al, 2016), as well as cytokines (tumor necrosis factor-a (TNF-a), interleukin-6 (IL-6), and interferon-g (IFN-g) (Lee et al, In Press) and chemokines (Hong et al, In Press) in earlier subsets of this sample, the current report represents our first examination of LTL and its associations with demographic, psychiatric, and medical factors. The analyses were restricted to all participants who had LTL data available.…”