title: Gene expression profiling of the dorsolateral and medial orbitofrontal cortex in schizophrenia.
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, andTTTY15. 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.
authors.affiliation: Department of Neuroscience, Croatian Institute for Brain Research, University of Zagreb Medical School, Zagreb, Croatia; Department of Psychiatry and Psychotherapy, University of Tübingen, Tübingen, Germany.
authors.forename: Mihovil
authors.initials: M
authors.lastname: Mladinov
authors.affiliation: Department of Neuroscience, Croatian Institute for Brain Research, University of Zagreb Medical School, Zagreb, Croatia.
authors.forename: Goran
authors.initials: G
authors.lastname: Sedmak
authors.affiliation: Wolfson Centre for Inherited Neuromuscular Disease, RJAH Orthopaedic Hospital, Oswestry, SY10 7AG, UK and Institute for Science and Technology in Medicine, Keele University, Staffordshire, ST5 5BG, United Kingdom of Great Britain and Northern Ireland.
authors.forename: Heidi R
authors.initials: HR
authors.lastname: Fuller
authors.affiliation: Department of Neuroscience, Croatian Institute for Brain Research, University of Zagreb Medical School, Zagreb, Croatia.
authors.forename: Mirjana
authors.initials: M
authors.lastname: Babić Leko
authors.affiliation: Department of Forensic Medicine, University of Zagreb Medical School, Zagreb, Croatia.
authors.forename: Davor
authors.initials: D
authors.lastname: Mayer
authors.affiliation: Department of Neuroscience, Croatian Institute for Brain Research, University of Zagreb Medical School, Zagreb, Croatia.
authors.forename: Jason
authors.initials: J
authors.lastname: Kirincich
authors.affiliation: Department of Neuroscience, Croatian Institute for Brain Research, University of Zagreb Medical School, Zagreb, Croatia.
authors.forename: Andrija
authors.initials: A
authors.lastname: Štajduhar
authors.affiliation: Department of Neurology, University Clinical Hospital Zagreb, Zagreb, Croatia.
authors.forename: Fran
authors.initials: F
authors.lastname: Borovečki
authors.affiliation: Fishberg Department of Neuroscience, and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States of America.
authors.forename: Patrick R
authors.initials: PR
authors.lastname: Hof
authors.affiliation: Department of Neuroscience, Croatian Institute for Brain Research, University of Zagreb Medical School, Zagreb, Croatia.
authors.forename: Goran
authors.initials: G
authors.lastname: Šimić
keywords: Brain asymmetry; Dorsolateral prefrontal cortex; Gene expression; Orbitofrontal cortex; Schizophrenia; Transcriptomics