FKBP5-associated miRNA signature as a putative biomarker for PTSD in recently traumatized individuals
The epigenetic regulation of microRNA (miRNA) expression related to the FK506-binding protein 5 (FKBP5) gene may contribute to the risk of stress-related disorders such as posttraumatic stress disorder (PTSD). Here, we identified candidate miRNAs derived from FKBP5 knockout mice as a potential diagn...
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| Veröffentlicht in: | Scientific reports 2020-02, Vol.10 (1), p.3353, Article 3353 |
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| creator | Kang, Hyo Jung Yoon, Sujung Lee, Suji Choi, Koeul Seol, Sihwan Park, Shinwon Namgung, Eun Kim, Tammy D. Chung, Yong-An Kim, Jungyoon Han, Jung-Soo Lyoo, In Kyoon |
| description | The epigenetic regulation of microRNA (miRNA) expression related to the FK506-binding protein 5 (FKBP5) gene may contribute to the risk of stress-related disorders such as posttraumatic stress disorder (PTSD). Here, we identified candidate miRNAs derived from FKBP5 knockout mice as a potential diagnostic biomarker of PTSD. Using a translational approach, candidate miRNAs found to alter in expression within the medial prefrontal cortex of FKBP5 knockout mice were selected. Each candidate miRNA was examined in the serum of 48 recently traumatized individuals with PTSD and 47 healthy individuals. Multimodal imaging was also conducted to identify the neural correlates for the expression of candidate exosomal miRNAs in response to trauma exposure. Differential miRNA expression was found according to PTSD diagnosis in two composite marker groups. The differential miRNA expression between the composite marker groups contributed to PTSD symptom severity, which may be explained by differential recruitment of prefrontolimbic activity in brain imaging. The present study reveals that a set of circulating exosomal miRNAs showing altered expression in FKBP5 knockout mice play a potential role as epigenetic markers of PTSD. The corroborative evidence from multiple levels including molecular, brain, and behavioral indicates that these epigenetic biomarkers may serve as complementary measures for the diagnosis and prognosis prediction of PTSD in recently traumatized individuals. |
| doi_str_mv | 10.1038/s41598-020-60334-6 |
| format | Article |
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Here, we identified candidate miRNAs derived from FKBP5 knockout mice as a potential diagnostic biomarker of PTSD. Using a translational approach, candidate miRNAs found to alter in expression within the medial prefrontal cortex of FKBP5 knockout mice were selected. Each candidate miRNA was examined in the serum of 48 recently traumatized individuals with PTSD and 47 healthy individuals. Multimodal imaging was also conducted to identify the neural correlates for the expression of candidate exosomal miRNAs in response to trauma exposure. Differential miRNA expression was found according to PTSD diagnosis in two composite marker groups. The differential miRNA expression between the composite marker groups contributed to PTSD symptom severity, which may be explained by differential recruitment of prefrontolimbic activity in brain imaging. The present study reveals that a set of circulating exosomal miRNAs showing altered expression in FKBP5 knockout mice play a potential role as epigenetic markers of PTSD. The corroborative evidence from multiple levels including molecular, brain, and behavioral indicates that these epigenetic biomarkers may serve as complementary measures for the diagnosis and prognosis prediction of PTSD in recently traumatized individuals.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-020-60334-6</identifier><identifier>PMID: 32098997</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/378 ; 631/553 ; 692/53/2421 ; 692/53/2422 ; Adult ; Animals ; Biomarkers ; Biomarkers - metabolism ; Diagnosis ; Disease Models, Animal ; Epigenesis, Genetic - genetics ; Epigenetics ; Female ; Gene Expression Regulation - drug effects ; Genetic Predisposition to Disease ; Genotype ; Humanities and Social Sciences ; Humans ; Male ; Mice ; Mice, Knockout ; MicroRNAs ; MicroRNAs - genetics ; miRNA ; multidisciplinary ; Neuroimaging ; Polymorphism, Single Nucleotide - genetics ; Post traumatic stress disorder ; Prefrontal cortex ; Prefrontal Cortex - diagnostic imaging ; Prefrontal Cortex - physiopathology ; Science ; Science (multidisciplinary) ; Stress Disorders, Post-Traumatic - genetics ; Stress Disorders, Post-Traumatic - physiopathology ; Tacrolimus ; Tacrolimus - pharmacology ; Tacrolimus Binding Proteins - genetics ; Tacrolimus-binding protein ; Trauma</subject><ispartof>Scientific reports, 2020-02, Vol.10 (1), p.3353, Article 3353</ispartof><rights>The Author(s) 2020</rights><rights>This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c507t-1c0a6195754fc0dd5ec2009dcbdcd9dba9af9062bff6f68ffedacc81521772573</citedby><cites>FETCH-LOGICAL-c507t-1c0a6195754fc0dd5ec2009dcbdcd9dba9af9062bff6f68ffedacc81521772573</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7042218/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7042218/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,41096,42165,51551,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32098997$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kang, Hyo Jung</creatorcontrib><creatorcontrib>Yoon, Sujung</creatorcontrib><creatorcontrib>Lee, Suji</creatorcontrib><creatorcontrib>Choi, Koeul</creatorcontrib><creatorcontrib>Seol, Sihwan</creatorcontrib><creatorcontrib>Park, Shinwon</creatorcontrib><creatorcontrib>Namgung, Eun</creatorcontrib><creatorcontrib>Kim, Tammy D.</creatorcontrib><creatorcontrib>Chung, Yong-An</creatorcontrib><creatorcontrib>Kim, Jungyoon</creatorcontrib><creatorcontrib>Han, Jung-Soo</creatorcontrib><creatorcontrib>Lyoo, In Kyoon</creatorcontrib><title>FKBP5-associated miRNA signature as a putative biomarker for PTSD in recently traumatized individuals</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>The epigenetic regulation of microRNA (miRNA) expression related to the FK506-binding protein 5 (FKBP5) gene may contribute to the risk of stress-related disorders such as posttraumatic stress disorder (PTSD). Here, we identified candidate miRNAs derived from FKBP5 knockout mice as a potential diagnostic biomarker of PTSD. Using a translational approach, candidate miRNAs found to alter in expression within the medial prefrontal cortex of FKBP5 knockout mice were selected. Each candidate miRNA was examined in the serum of 48 recently traumatized individuals with PTSD and 47 healthy individuals. Multimodal imaging was also conducted to identify the neural correlates for the expression of candidate exosomal miRNAs in response to trauma exposure. Differential miRNA expression was found according to PTSD diagnosis in two composite marker groups. The differential miRNA expression between the composite marker groups contributed to PTSD symptom severity, which may be explained by differential recruitment of prefrontolimbic activity in brain imaging. The present study reveals that a set of circulating exosomal miRNAs showing altered expression in FKBP5 knockout mice play a potential role as epigenetic markers of PTSD. The corroborative evidence from multiple levels including molecular, brain, and behavioral indicates that these epigenetic biomarkers may serve as complementary measures for the diagnosis and prognosis prediction of PTSD in recently traumatized individuals.</description><subject>631/378</subject><subject>631/553</subject><subject>692/53/2421</subject><subject>692/53/2422</subject><subject>Adult</subject><subject>Animals</subject><subject>Biomarkers</subject><subject>Biomarkers - metabolism</subject><subject>Diagnosis</subject><subject>Disease Models, Animal</subject><subject>Epigenesis, Genetic - genetics</subject><subject>Epigenetics</subject><subject>Female</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Genetic Predisposition to Disease</subject><subject>Genotype</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>MicroRNAs</subject><subject>MicroRNAs - 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pharmacology</topic><topic>Tacrolimus Binding Proteins - genetics</topic><topic>Tacrolimus-binding protein</topic><topic>Trauma</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kang, Hyo Jung</creatorcontrib><creatorcontrib>Yoon, Sujung</creatorcontrib><creatorcontrib>Lee, Suji</creatorcontrib><creatorcontrib>Choi, Koeul</creatorcontrib><creatorcontrib>Seol, Sihwan</creatorcontrib><creatorcontrib>Park, Shinwon</creatorcontrib><creatorcontrib>Namgung, Eun</creatorcontrib><creatorcontrib>Kim, Tammy D.</creatorcontrib><creatorcontrib>Chung, Yong-An</creatorcontrib><creatorcontrib>Kim, Jungyoon</creatorcontrib><creatorcontrib>Han, Jung-Soo</creatorcontrib><creatorcontrib>Lyoo, In Kyoon</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kang, Hyo Jung</au><au>Yoon, Sujung</au><au>Lee, Suji</au><au>Choi, Koeul</au><au>Seol, Sihwan</au><au>Park, Shinwon</au><au>Namgung, Eun</au><au>Kim, Tammy D.</au><au>Chung, Yong-An</au><au>Kim, Jungyoon</au><au>Han, Jung-Soo</au><au>Lyoo, In Kyoon</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>FKBP5-associated miRNA signature as a putative biomarker for PTSD in recently traumatized individuals</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2020-02-25</date><risdate>2020</risdate><volume>10</volume><issue>1</issue><spage>3353</spage><pages>3353-</pages><artnum>3353</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>The epigenetic regulation of microRNA (miRNA) expression related to the FK506-binding protein 5 (FKBP5) gene may contribute to the risk of stress-related disorders such as posttraumatic stress disorder (PTSD). Here, we identified candidate miRNAs derived from FKBP5 knockout mice as a potential diagnostic biomarker of PTSD. Using a translational approach, candidate miRNAs found to alter in expression within the medial prefrontal cortex of FKBP5 knockout mice were selected. Each candidate miRNA was examined in the serum of 48 recently traumatized individuals with PTSD and 47 healthy individuals. Multimodal imaging was also conducted to identify the neural correlates for the expression of candidate exosomal miRNAs in response to trauma exposure. Differential miRNA expression was found according to PTSD diagnosis in two composite marker groups. The differential miRNA expression between the composite marker groups contributed to PTSD symptom severity, which may be explained by differential recruitment of prefrontolimbic activity in brain imaging. The present study reveals that a set of circulating exosomal miRNAs showing altered expression in FKBP5 knockout mice play a potential role as epigenetic markers of PTSD. The corroborative evidence from multiple levels including molecular, brain, and behavioral indicates that these epigenetic biomarkers may serve as complementary measures for the diagnosis and prognosis prediction of PTSD in recently traumatized individuals.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>32098997</pmid><doi>10.1038/s41598-020-60334-6</doi><oa>free_for_read</oa></addata></record> |
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| subjects | 631/378 631/553 692/53/2421 692/53/2422 Adult Animals Biomarkers Biomarkers - metabolism Diagnosis Disease Models, Animal Epigenesis, Genetic - genetics Epigenetics Female Gene Expression Regulation - drug effects Genetic Predisposition to Disease Genotype Humanities and Social Sciences Humans Male Mice Mice, Knockout MicroRNAs MicroRNAs - genetics miRNA multidisciplinary Neuroimaging Polymorphism, Single Nucleotide - genetics Post traumatic stress disorder Prefrontal cortex Prefrontal Cortex - diagnostic imaging Prefrontal Cortex - physiopathology Science Science (multidisciplinary) Stress Disorders, Post-Traumatic - genetics Stress Disorders, Post-Traumatic - physiopathology Tacrolimus Tacrolimus - pharmacology Tacrolimus Binding Proteins - genetics Tacrolimus-binding protein Trauma |
| title | FKBP5-associated miRNA signature as a putative biomarker for PTSD in recently traumatized individuals |
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