Article

Inflammation-related genes up-regulated in schizophrenia brains

Department of Development and Genetics, Uppsala University, Sweden.
BMC Psychiatry (Impact Factor: 2.21). 09/2007; 7(1):46. DOI: 10.1186/1471-244X-7-46
Source: PubMed

ABSTRACT

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.
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.
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.
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.

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    • "The primary evidence that supports the existence of this spectrum is as follows: a) Genetic studies, including the Genome-Wide Association Study (GWAS) with large population samples, that have described genetic variations of the major histocompatibility complex and of genes expressed in tissue with important roles in immune or inflammatory responses (Schizophrenia Working Group of the Psychiatric Genomics, 2014; Shi et al., 2009; Stefansson et al., 2009). There is also evidence of the upregulation of genes linked to inflammation in brain tissue (Drexhage et al., 2010; Saetre et al., 2007). b) Ecological studies that demonstrate an increased presentation of autoimmune illnesses and serious infections in this population (Benros et al., 2011; Torrey et al., 2012). "
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    • "While the basic pharmacology of the AAPs is known as it relates to serotonin and dopamine neurotransmission, the secondary pharmacology has yet to be determined. Within the schizophrenia literature it has been suggested that pharmacologically AAPs may alter lipid metabolism or cause perturbations within the inflammatory cascade, both of which may be mechanisms for this altered relationship between N-3 FA and arteriole endothelial-dependent vasodilatation within this group (Lauressergues et al., 2010; Saetre et al., 2007). Unfortunately, given the assessments included in our current research, we are unable to further elucidate any mechanisms behind the AAP's effect, so for now, we will be unable to answer this question. "

    Full-text · Article · Nov 2015
    • "The primary evidence that supports the existence of this spectrum is as follows: a) Genetic studies, including the Genome-Wide Association Study (GWAS) with large population samples, that have described genetic variations of the major histocompatibility complex and of genes expressed in tissue with important roles in immune or inflammatory responses (Schizophrenia Working Group of the Psychiatric Genomics, 2014; Shi et al., 2009; Stefansson et al., 2009). There is also evidence of the upregulation of genes linked to inflammation in brain tissue (Drexhage et al., 2010; Saetre et al., 2007). b) Ecological studies that demonstrate an increased presentation of autoimmune illnesses and serious infections in this population (Benros et al., 2011; Torrey et al., 2012). "
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