Gene expression profiling by mRNA sequencing reveals increased expression of immune/inflammation-related genes in the hippocampus of individuals with schizophrenia

Abstract

Whole-genome expression profiling in postmortem brain tissue has recently provided insight into the pathophysiology of schizophrenia. Previous microarray and RNA-Seq studies identified several biological processes including synaptic function, mitochondrial function and immune/inflammation response as altered in the cortex of subjects with schizophrenia. Now using RNA-Seq data from the hippocampus, we have identified 144 differentially expressed genes in schizophrenia cases as compared with unaffected controls. Immune/inflammation response was the main biological process over-represented in these genes. The upregulation of several of these genes, IFITM1, IFITM2, IFITM3, APOL1 (Apolipoprotein L1), ADORA2A (adenosine receptor 2A), IGFBP4 and CD163 were validated in the schizophrenia subjects using data from the SNCID database and with quantitative RT-PCR. We identified a co-expression module associated with schizophrenia that includes the majority of differentially expressed genes related to immune/inflammation response as well as with the density of parvalbumin-containing neurons in the hippocampus. The results indicate that abnormal immune/inflammation response in the hippocampus may underlie the pathophysiology of schizophrenia and may be associated with abnormalities in the parvalbumin-containing neurons that lead to the cognitive deficits of the disease.

CX3CR1 is dysregulated in blood and brain from schizophrenia patients

“…methods). This was further supported by results from recent next generation sequencing investigations (Fillman et al, 2013;Hwang et al, 2013), that were not included in this report.…”

Clinical studies of neuroinflammatory mechanisms in schizophrenia

“…Others argue that expression of inflammatory genes may be brain region specific or have a temporal relationship to a specific brain insult. One microarray and RNA sequence study shows abnormal immune/inflammatory responses limited to the hippocampus (Hwang et al, 2013). Another study looking at mRNA expression of inflammatory genes in a cohort of schizophrenia subjects showed a difference in psychotic patients older 40 years of age compared to those under 40 (Tang et al, 2012).…”

Integrated Post-GWAS Analysis Sheds New Light on the Disease Mechanisms of Schizophrenia

“…3. The differential expression gene set are based on previous studies (GLATT et al 2005;MAYCOX et al 2009;PEREZ-SANTIAGO et al 2012;FILLMAN et al 2013;GARDINER et al 2013;HWANG et al 2013;SAINZ et al 2013;SANDERS et al 2013;SELLMANN et al 2014). Figure 5) and the expression values of a training gene across the same combinations of brain regions and time stages.…”