Detailed Postmortem Profiling of Inflammatory Mediators Expression Revealed Post-inflammatory Alternation in the Superior Temporal Gyrus of Schizophrenia

Abstract

Recent studies have lent support to the possibility that inflammation is associated with the pathology of schizophrenia. In the study of measurement of inflammatory mediators, which are markers of inflammation, elevated inflammatory cytokine levels in the brain and blood have been reported in patients with schizophrenia. Several postmortem brain studies have also reported changes in the expression of inflammatory cytokines. However, it is not clear how these elevated inflammatory cytokines interact with other inflammatory mediators, and their association with the pathology of schizophrenia. We comprehensively investigated the expression of 30 inflammatory mediators in the superior temporal gyrus (STG) of 24 patients with schizophrenia and 26 controls using a multiplex method. Overall, inflammatory mediator expression in the STG was mostly unchanged. However, the expression of interleukin (IL)1-α and interferon-gamma-inducible protein (IP)-10 was decreased [IL-1α, median (IQR), 0.51 (0.37–0.70) vs. 0.87 (0.47–1.23), p = 0.01; IP-10, 13.99 (8.00–36.64) vs. 30.29 (10.23–134.73), p = 0.05], whereas that of IFN-α was increased [2.34 (1.84–4.48) vs. 1.94 (1.39–2.36), p = 0.04] in schizophrenia, although these alterations did not remain significant after multiple testing. Clustering based on inflammatory mediator expression pattern and analysis of upstream transcription factors using pathway analysis revealed that the suppression of IL-1α and IP-10 protein expression may be induced by regulation of a common upstream pathway. Neuroinflammation is important in understanding the biology of schizophrenia. While neuroimaging has been previously used, direct observation to determine the expression of inflammatory mediators is necessary. In this study, we identified protein changes, previously unreported, using comprehensive protein analysis in STG. These results provide insight into post-inflammatory alternation in chronic schizophrenia.

Consensus on potential biomarkers developed for use in clinical tests for schizophrenia

“…Inflammation is considered to play a crucial role in the pathogenesis of schizophrenia. A postmortem study revealed decreased interleukin (IL)-1α and interferon (IFN)-ɣ-inducible protein 10 expression as well as increased IFN-α expression in the superior temporal gyrus of patients with schizophrenia, 58 suggesting a direct association of inflammatory markers with the disease. Since then, a variety of inflammatory markers have been assessed in different types of biospecimens, including peripheral blood and cerebrospinal fluid (CSF).…”

Long non-coding RNA-associated competing endogenous RNA axes in the olfactory epithelium in schizophrenia: a bioinformatics analysis

“…Hence, the FOS family regulates the proliferation, transformation, differentiation, and apoptotic death of cells 65 . Based on upstream transcription factor analysis and high-throughput gene studies, FOSL1 implicates in SCZ through various mechanisms, such as influencing accessible chromatin regions and connecting to neuroinflammation signaling cascades 66 – 68 . SLC7A5 , also known as LAT1 , encodes a large amino acid transporter located in the blood–brain barrier.…”

Schizophrenia and Alarmins

“…However, an elevated level of IL-1α was found in patients with schizophrenia with metabolic syndrome even after 6 weeks of treatment with atypical antipsychotics [43]. The decreased expression of IL1-α and interferon-gamma-inducible protein (IP)-10 was found in patients with schizophrenia [44]. As mentioned, they conjectured that there was a suppressed common upstream pathway.…”