Gene expression profiling of the dorsolateral and medial orbitofrontal cortex in schizophrenia

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...

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Autores principales:	Mladinov Mihovil, Sedmak Goran, Fuller Heidi R., Babić Leko Mirjana, Mayer Davor, Kirincich Jason, Štajduhar Andrija, Borovečki Fran, Hof Patrick R., Šimić Goran
Formato:	article
Lenguaje:	EN
Publicado:	De Gruyter 2016
Materias:	brain asymmetry dorsolateral prefrontal cortex gene expression orbitofrontal cortex schizophrenia transcriptomics Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Acceso en línea:	https://doaj.org/article/5229b6f198e74d4aa29c67d18956c28a
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spelling	oai:doaj.org-article:5229b6f198e74d4aa29c67d18956c28a2021-12-05T14:11:04ZGene expression profiling of the dorsolateral and medial orbitofrontal cortex in schizophrenia2081-693610.1515/tnsci-2016-0021https://doaj.org/article/5229b6f198e74d4aa29c67d18956c28a2016-01-01T00:00:00Zhttps://doi.org/10.1515/tnsci-2016-0021https://doaj.org/toc/2081-6936Schizophrenia 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.Mladinov MihovilSedmak GoranFuller Heidi R.Babić Leko MirjanaMayer DavorKirincich JasonŠtajduhar AndrijaBorovečki FranHof Patrick R.Šimić GoranDe Gruyterarticlebrain asymmetrydorsolateral prefrontal cortexgene expressionorbitofrontal cortexschizophreniatranscriptomicsNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENTranslational Neuroscience, Vol 7, Iss 1, Pp 139-150 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	brain asymmetry dorsolateral prefrontal cortex gene expression orbitofrontal cortex schizophrenia transcriptomics Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	brain asymmetry dorsolateral prefrontal cortex gene expression orbitofrontal cortex schizophrenia transcriptomics Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Mladinov Mihovil Sedmak Goran Fuller Heidi R. Babić Leko Mirjana Mayer Davor Kirincich Jason Štajduhar Andrija Borovečki Fran Hof Patrick R. Šimić Goran Gene expression profiling of the dorsolateral and medial orbitofrontal cortex in schizophrenia
description	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.
format	article
author	Mladinov Mihovil Sedmak Goran Fuller Heidi R. Babić Leko Mirjana Mayer Davor Kirincich Jason Štajduhar Andrija Borovečki Fran Hof Patrick R. Šimić Goran
author_facet	Mladinov Mihovil Sedmak Goran Fuller Heidi R. Babić Leko Mirjana Mayer Davor Kirincich Jason Štajduhar Andrija Borovečki Fran Hof Patrick R. Šimić Goran
author_sort	Mladinov Mihovil
title	Gene expression profiling of the dorsolateral and medial orbitofrontal cortex in schizophrenia
title_short	Gene expression profiling of the dorsolateral and medial orbitofrontal cortex in schizophrenia
title_full	Gene expression profiling of the dorsolateral and medial orbitofrontal cortex in schizophrenia
title_fullStr	Gene expression profiling of the dorsolateral and medial orbitofrontal cortex in schizophrenia
title_full_unstemmed	Gene expression profiling of the dorsolateral and medial orbitofrontal cortex in schizophrenia
title_sort	gene expression profiling of the dorsolateral and medial orbitofrontal cortex in schizophrenia
publisher	De Gruyter
publishDate	2016
url	https://doaj.org/article/5229b6f198e74d4aa29c67d18956c28a
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Gene expression profiling of the dorsolateral and medial orbitofrontal cortex in schizophrenia

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