Mladinov, M, Sedmak, G, Fuller, HR ORCID: https://orcid.org/0000-0001-8868-896X, Babić Leko, M, Mayer, D, Kirincich, J, Štajduhar, A, Borovečki, F, Hof, PR and Šimić, G (2016) Gene expression profiling of the dorsolateral and medial orbitofrontal cortex in schizophrenia. Translational Neuroscience, 7 (1).

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Abstract

Schizophrenia is a complex polygenic disorder of unknown etiology. Over 3,000 candidate genes associated with schizophrenia have been reported, most of which being mentioned only once. Alterations in cognitive processing - working memory, metacognition and mentalization - represent a core feature of schizophrenia, which indicates the involvement of the prefrontal cortex in the pathophysiology of this disorder. Hence we compared the gene expression in postmortem tissue from the left and right dorsolateral prefrontal cortex (DLPFC, Brodmann's area 46), and the medial part of the orbitofrontal cortex (MOFC, Brodmann's area 11/12), in six patients with schizophrenia and six control brains. Although in the past decade several studies performed transcriptome profiling in schizophrenia, this is the first study to investigate both hemispheres, providing new knowledge about possible brain asymmetry at the level of gene expression and its relation to schizophrenia. We found that in the left hemisphere, twelve genes from the DLPFC and eight genes from the MOFC were differentially expressed in patients with schizophrenia compared to controls. In the right hemisphere there was only one gene differentially expressed in the MOFC. We reproduce the involvement of previously reported genes TARDBP and HNRNPC in the pathogenesis of schizophrenia, and report seven novel genes: SART1, KAT7, C1D, NPM1, EVI2A, XGY2, and TTTY15. As the differentially expressed genes only partially overlap with previous studies that analyzed other brain regions, our findings indicate the importance of considering prefrontal cortical regions, especially those in the left hemisphere, for obtaining disease-relevant insights.

Item Type: Article
Additional Information: This work is made available online in accordance with publishers policies
Uncontrolled Keywords: brain asymmetry; dorsolateral prefrontal cortex; gene expression; orbitofrontal cortex; schizophrenia; transcriptomics
Subjects: R Medicine > R Medicine (General)
Divisions: Faculty of Medicine and Health Sciences > Institute for Science and Technology in Medicine
Depositing User: Symplectic
Date Deposited: 10 Nov 2016 10:44
Last Modified: 04 Apr 2019 09:46
URI: https://eprints.keele.ac.uk/id/eprint/2450

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