Shared and unique transcriptional changes in the orbitofrontal cortex in psychiatric disorders and suicide

Psychiatric disorders like major depressive disorder (MDD), schizophrenia (SCZ), and bipolar disorder (BPD), represent a significant global public health concern. Sex differences in the prevalence and presentation of psychiatric disorders, and the association of a psychiatric diagnosis with increas...

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Main Authors: Sinead O'Donovan, Suleiman Ali, William Deng, Gurnoor Patti, Joshua Wang, Mahmoud Eladawi, Ali Imami
Format: Article
Language:English
Published: The University of Toledo 2024-01-01
Series:Translation
Subjects:
Online Access:http://openjournals.utoledo.edu/index.php/translation/article/view/822
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author Sinead O'Donovan
Suleiman Ali
William Deng
Gurnoor Patti
Joshua Wang
Mahmoud Eladawi
Ali Imami
author_facet Sinead O'Donovan
Suleiman Ali
William Deng
Gurnoor Patti
Joshua Wang
Mahmoud Eladawi
Ali Imami
author_sort Sinead O'Donovan
collection DOAJ
description Psychiatric disorders like major depressive disorder (MDD), schizophrenia (SCZ), and bipolar disorder (BPD), represent a significant global public health concern. Sex differences in the prevalence and presentation of psychiatric disorders, and the association of a psychiatric diagnosis with increased risk of suicide, are well-established. However, the neurobiology underlying these features of disease are not well understood. Dysfunction of the orbitofrontal cortex (OFC), a brain region responsible for decision-making and sensory processing, has been implicated in psychiatric disorders but remains understudied compared to other frontocortical brain regions.  In this study we investigated sexual dimorphism in psychiatric illnesses and suicide by analyzing publicly available OFC transcriptional profiles (RNAseq data obtained from the Stanley Neuropathology Consortium) from individuals with SCZ, BPD, MDD, and non-psychiatric controls (n=15/group).   Gene set enrichment analysis (GSEA) revealed significant differences in immune-related processes in male and female comparisons and in psychiatric disorders relative to controls. Analysis of top differentially expressed genes found changes in P2RY12 in males and females who died by suicide. Additionally, downregulation of protein folding processes was observed in female suicide subjects, suggesting an association between dysregulated protein metabolism and suicide. Our results further our understanding of the shared and unique molecular pathways underlying psychiatric disorders and suicide.  
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spelling doaj.art-c68d3b2c2ca34460860ce410df7e9ce82024-02-04T14:05:00ZengThe University of ToledoTranslation2469-67062024-01-01121Shared and unique transcriptional changes in the orbitofrontal cortex in psychiatric disorders and suicide Sinead O'Donovan0Suleiman AliWilliam DengGurnoor PattiJoshua WangMahmoud EladawiAli ImamiUniversity of Toledo Psychiatric disorders like major depressive disorder (MDD), schizophrenia (SCZ), and bipolar disorder (BPD), represent a significant global public health concern. Sex differences in the prevalence and presentation of psychiatric disorders, and the association of a psychiatric diagnosis with increased risk of suicide, are well-established. However, the neurobiology underlying these features of disease are not well understood. Dysfunction of the orbitofrontal cortex (OFC), a brain region responsible for decision-making and sensory processing, has been implicated in psychiatric disorders but remains understudied compared to other frontocortical brain regions.  In this study we investigated sexual dimorphism in psychiatric illnesses and suicide by analyzing publicly available OFC transcriptional profiles (RNAseq data obtained from the Stanley Neuropathology Consortium) from individuals with SCZ, BPD, MDD, and non-psychiatric controls (n=15/group).   Gene set enrichment analysis (GSEA) revealed significant differences in immune-related processes in male and female comparisons and in psychiatric disorders relative to controls. Analysis of top differentially expressed genes found changes in P2RY12 in males and females who died by suicide. Additionally, downregulation of protein folding processes was observed in female suicide subjects, suggesting an association between dysregulated protein metabolism and suicide. Our results further our understanding of the shared and unique molecular pathways underlying psychiatric disorders and suicide.   http://openjournals.utoledo.edu/index.php/translation/article/view/822immune responsepsychiatric disorderssuicideorbitofrontal cortex
spellingShingle Sinead O'Donovan
Suleiman Ali
William Deng
Gurnoor Patti
Joshua Wang
Mahmoud Eladawi
Ali Imami
Shared and unique transcriptional changes in the orbitofrontal cortex in psychiatric disorders and suicide
Translation
immune response
psychiatric disorders
suicide
orbitofrontal cortex
title Shared and unique transcriptional changes in the orbitofrontal cortex in psychiatric disorders and suicide
title_full Shared and unique transcriptional changes in the orbitofrontal cortex in psychiatric disorders and suicide
title_fullStr Shared and unique transcriptional changes in the orbitofrontal cortex in psychiatric disorders and suicide
title_full_unstemmed Shared and unique transcriptional changes in the orbitofrontal cortex in psychiatric disorders and suicide
title_short Shared and unique transcriptional changes in the orbitofrontal cortex in psychiatric disorders and suicide
title_sort shared and unique transcriptional changes in the orbitofrontal cortex in psychiatric disorders and suicide
topic immune response
psychiatric disorders
suicide
orbitofrontal cortex
url http://openjournals.utoledo.edu/index.php/translation/article/view/822
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