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

Transl Psychiatry. 2013 Oct 29;3(10):e321. doi: 10.1038/tp.2013.94.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, CD / genetics
  • Antigens, CD / immunology
  • Antigens, Differentiation / genetics
  • Antigens, Differentiation / immunology
  • Antigens, Differentiation, Myelomonocytic / genetics
  • Antigens, Differentiation, Myelomonocytic / immunology
  • Apolipoprotein L1
  • Apolipoproteins / genetics
  • Apolipoproteins / immunology
  • Case-Control Studies
  • Female
  • Gene Expression Profiling
  • Hippocampus / immunology*
  • Hippocampus / metabolism
  • Humans
  • Inflammation / genetics
  • Insulin-Like Growth Factor Binding Protein 4 / genetics
  • Insulin-Like Growth Factor Binding Protein 4 / immunology
  • Lipoproteins, HDL / genetics
  • Lipoproteins, HDL / immunology
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / immunology
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis
  • RNA, Messenger / analysis*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / immunology
  • Receptor, Adenosine A2A / genetics
  • Receptor, Adenosine A2A / immunology
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / immunology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Schizophrenia / genetics
  • Schizophrenia / immunology*
  • Up-Regulation

Substances

  • APOL1 protein, human
  • Antigens, CD
  • Antigens, Differentiation
  • Antigens, Differentiation, Myelomonocytic
  • Apolipoprotein L1
  • Apolipoproteins
  • CD163 antigen
  • IFITM2 protein, human
  • IFITM3 protein, human
  • Insulin-Like Growth Factor Binding Protein 4
  • Lipoproteins, HDL
  • Membrane Proteins
  • RNA, Messenger
  • RNA-Binding Proteins
  • Receptor, Adenosine A2A
  • Receptors, Cell Surface
  • leu-13 antigen