Transcription profiling of brain samples from human control and schizophrenia patients who were treated with either typical, atypical or no antipsychotic medication

ABSTRACT: Multiple studies have shown that brain gene expression is disturbed in subjects suffering from schizophrenia. However, disentangling disease effects from alterations caused by neuroleptics is a challenging task.
To address the issues of disease heterogeneity and the effect of antipsychotic medication, we use a large collection of 110 brain autopsy samples, subdivided according to the type of antipsychotic medication received. We use global and high-resolution mRNA quantification techniques to analyse gene expression in brain tissues. We also analyse transcription in-vitro, in cell lines before and after treatment with cytokines.
Results. We show that inflammation-related genes are up regulated in all groups of patients, including those not treated at the time of death. In particular, four co-expressed genes that are inducible by inflammatory cytokines showed increased mRNA levels, namely IFITM2, IFITM3, SERPINA3, and GBP1 (p-values from qPCR ? 0.01). We also show that these genes are expressed in oligodendrocyte and endothelial cell lines, and transcription is inducible by inflammatory cytokines in both cell lines. Our results give molecular support to the inflammatory theory of schizophrenia and suggest that inflammatory cytokines may stimulate transcription in endothelial brain cells during schizophrenia progression. Unexpectedly, inflammation-related genes may also have a role in myelin producing cells, since they are also inducible by cytokines in oligodendrocyte cell lines. 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.

INSTRUMENT(S): GenePix Personal 4100A [Axon Instruments]

ORGANISM(S): Homo sapiens

DISEASE(S): reference

SUBMITTER: Johan Kreuger 

PROVIDER: E-MEXP-857 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress