Inflammation-related genes up-regulated in schizophrenia brains.
BACKGROUND
Multiple studies have shown that brain gene expression is disturbed in subjects suffering from schizophrenia. However, disentangling disease effects from alterations caused by medication is a challenging task. The main goal of this study is to find transcriptional alterations in schizophrenia that are independent of neuroleptic treatment.


METHODS
We compared the transcriptional profiles in brain autopsy samples from 55 control individuals with that from 55 schizophrenic subjects, subdivided according to the type of antipsychotic medication received.


RESULTS
Using global and high-resolution mRNA quantification techniques, we show that genes involved in immune response (GO:0006955) are up regulated in all groups of patients, including those not treated at the time of death. In particular, IFITM2, IFITM3, SERPINA3, and GBP1 showed increased mRNA levels in schizophrenia (p-values from qPCR < or = 0.01). These four genes were co-expressed in both schizophrenic subjects and controls. In-vitro experiments suggest that these genes are expressed in both oligodendrocyte and endothelial cells, where transcription is inducible by the inflammatory cytokines TNF-alpha, IFN-alpha and IFN-gamma.


CONCLUSIONS
Although the modified genes are not classical indicators of chronic or acute inflammation, our results indicate alterations of inflammation-related pathways in schizophrenia. In addition, the observation in oligodendrocyte cells suggests that alterations in inflammatory-related genes may have consequences for myelination. Our findings encourage future research to explore whether anti-inflammatory agents can be used in combination with traditional antipsychotics for a more efficient treatment of schizophrenia.
Saetre
Peter
P
Department of Development and Genetics, Uppsala University, Sweden. peter.saetre@ebc.uu.se
Emilsson
Lina
L
Axelsson
Elin
E
Kreuger
Johan
J
Lindholm
Eva
E
Jazin
Elena
E
D014150:Antipsychotic Agents / Q000627:therapeutic use; D001921:Brain / Q000473:pathology; D002478:Cells, Cultured; D005625:Frontal Lobe / Q000473:pathology; D019204:GTP-Binding Proteins / Q000235:genetics; D015870:Gene Expression / Q000235:genetics*; D006801:Humans; D006824:Hybridization, Genetic; D007249:Inflammation / Q000235:genetics* / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics; D040081:Protein Array Analysis / Q000379:methods; D012333:RNA, Messenger / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012559:Schizophrenia / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D015843:Serpins / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics*