Creation of a gene expression portrait of depression and its application for identifying potential treatments

Abstract Depression is a complex mental health disorder and the goal here was to identify a consistent underlying portrait of expression that ranks all genes from most to least dysregulated and indicates direction of change relative to controls. Using large-scale neural gene expression depression da...

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Autor principal:	Stephen C. Gammie
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a2fdc4557aca453492b4f0f30655f09f
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spelling	oai:doaj.org-article:a2fdc4557aca453492b4f0f30655f09f2021-12-02T14:03:46ZCreation of a gene expression portrait of depression and its application for identifying potential treatments10.1038/s41598-021-83348-02045-2322https://doaj.org/article/a2fdc4557aca453492b4f0f30655f09f2021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-83348-0https://doaj.org/toc/2045-2322Abstract Depression is a complex mental health disorder and the goal here was to identify a consistent underlying portrait of expression that ranks all genes from most to least dysregulated and indicates direction of change relative to controls. Using large-scale neural gene expression depression datasets, a combined portrait (for men and women) was created along with one for men and one for women only. The depressed brain was characterized by a “hypo” state, that included downregulation of activity-related genes, including EGR1, FOS, and ARC, and indications of a lower brain temperature and sleep-like state. MAP kinase and BDNF pathways were enriched with overlapping genes. Expression patterns suggested decreased signaling for GABA and for neuropeptides, CRH, SST, and CCK. GWAS depression genes were among depression portrait genes and common genes of interest included SPRY2 and PSEN2. The portraits were used with the drug repurposing approach of signature matching to identify treatments that could reverse depression gene expression patterns. Exercise was identified as the top treatment for depression for the combined and male portraits. Other non-traditional treatments that scored well were: curcumin, creatine, and albiflorin. Fluoxetine scored best among typical antidepressants. The creation of the portraits of depression provides new insights into the complex landscape of depression and a novel platform for evaluating and identifying potential new treatments.Stephen C. GammieNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-19 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Stephen C. Gammie Creation of a gene expression portrait of depression and its application for identifying potential treatments
description	Abstract Depression is a complex mental health disorder and the goal here was to identify a consistent underlying portrait of expression that ranks all genes from most to least dysregulated and indicates direction of change relative to controls. Using large-scale neural gene expression depression datasets, a combined portrait (for men and women) was created along with one for men and one for women only. The depressed brain was characterized by a “hypo” state, that included downregulation of activity-related genes, including EGR1, FOS, and ARC, and indications of a lower brain temperature and sleep-like state. MAP kinase and BDNF pathways were enriched with overlapping genes. Expression patterns suggested decreased signaling for GABA and for neuropeptides, CRH, SST, and CCK. GWAS depression genes were among depression portrait genes and common genes of interest included SPRY2 and PSEN2. The portraits were used with the drug repurposing approach of signature matching to identify treatments that could reverse depression gene expression patterns. Exercise was identified as the top treatment for depression for the combined and male portraits. Other non-traditional treatments that scored well were: curcumin, creatine, and albiflorin. Fluoxetine scored best among typical antidepressants. The creation of the portraits of depression provides new insights into the complex landscape of depression and a novel platform for evaluating and identifying potential new treatments.
format	article
author	Stephen C. Gammie
author_facet	Stephen C. Gammie
author_sort	Stephen C. Gammie
title	Creation of a gene expression portrait of depression and its application for identifying potential treatments
title_short	Creation of a gene expression portrait of depression and its application for identifying potential treatments
title_full	Creation of a gene expression portrait of depression and its application for identifying potential treatments
title_fullStr	Creation of a gene expression portrait of depression and its application for identifying potential treatments
title_full_unstemmed	Creation of a gene expression portrait of depression and its application for identifying potential treatments
title_sort	creation of a gene expression portrait of depression and its application for identifying potential treatments
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/a2fdc4557aca453492b4f0f30655f09f
work_keys_str_mv	AT stephencgammie creationofageneexpressionportraitofdepressionanditsapplicationforidentifyingpotentialtreatments
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Creation of a gene expression portrait of depression and its application for identifying potential treatments

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