Whole-blood expression of inflammasome- and glucocorticoid-related mRNAs correctly separates treatment-resistant depressed patients from drug-free and responsive patients in the BIODEP study
The mRNA expression signatures associated with the ‘pro-inflammatory’ phenotype of depression, and the differential signatures associated with depression subtypes and the effects of antidepressants, are still unknown. We examined 130 depressed patients (58 treatment-resistant, 36 antidepressant-resp...
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| Veröffentlicht in: | Translational psychiatry 2020-07, Vol.10 (1), p.232-232, Article 232 |
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| creator | Cattaneo, Annamaria Ferrari, Clarissa Turner, Lorinda Mariani, Nicole Enache, Daniela Hastings, Caitlin Kose, Melisa Lombardo, Giulia McLaughlin, Anna P. Nettis, Maria A. Nikkheslat, Naghmeh Sforzini, Luca Worrell, Courtney Zajkowska, Zuzanna Cattane, Nadia Lopizzo, Nicola Mazzelli, Monica Pointon, Linda Cowen, Philip J. Cavanagh, Jonathan Harrison, Neil A. de Boer, Peter Jones, Declan Drevets, Wayne C. Mondelli, Valeria Bullmore, Edward T. Pariante, Carmine M. |
| description | The mRNA expression signatures associated with the ‘pro-inflammatory’ phenotype of depression, and the differential signatures associated with depression subtypes and the effects of antidepressants, are still unknown. We examined 130 depressed patients (58 treatment-resistant, 36 antidepressant-responsive and 36 currently untreated) and 40 healthy controls from the BIODEP study, and used whole-blood mRNA qPCR to measure the expression of 16 candidate mRNAs, some never measured before: interleukin (
IL)-1-beta
,
IL-6
,
TNF-alpha
, macrophage inhibiting factor (
MIF
), glucocorticoid receptor (
GR
),
SGK1
,
FKBP5
, the purinergic receptor
P2RX7
,
CCL2
,
CXCL12
, c-reactive protein (
CRP
), alpha-2-macroglobulin (
A2M
), acquaporin-4 (
AQP4
),
ISG15
,
STAT1
and
USP-18
. All genes but
AQP4
,
ISG15
and
USP-18
were differentially regulated. Treatment-resistant and drug-free depressed patients had both increased inflammasome activation (higher
P2RX7
and proinflammatory cytokines/chemokines mRNAs expression) and glucocorticoid resistance (lower
GR
and higher
FKBP5
mRNAs expression), while responsive patients had an intermediate phenotype with, additionally, lower
CXCL12
. Most interestingly, using binomial logistics models we found that a signature of six mRNAs (
P2RX7
,
IL-1-beta, IL-6
,
TNF-alpha, CXCL12
and
GR
) distinguished treatment-resistant from responsive patients, even after adjusting for other variables that were different between groups, such as a trait- and state-anxiety, history of childhood maltreatment and serum CRP. Future studies should replicate these findings in larger, longitudinal cohorts, and test whether this mRNA signature can identify patients that are more likely to respond to adjuvant strategies for treatment-resistant depression, including combinations with anti-inflammatory medications. |
| doi_str_mv | 10.1038/s41398-020-00874-7 |
| format | Article |
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IL)-1-beta
,
IL-6
,
TNF-alpha
, macrophage inhibiting factor (
MIF
), glucocorticoid receptor (
GR
),
SGK1
,
FKBP5
, the purinergic receptor
P2RX7
,
CCL2
,
CXCL12
, c-reactive protein (
CRP
), alpha-2-macroglobulin (
A2M
), acquaporin-4 (
AQP4
),
ISG15
,
STAT1
and
USP-18
. All genes but
AQP4
,
ISG15
and
USP-18
were differentially regulated. Treatment-resistant and drug-free depressed patients had both increased inflammasome activation (higher
P2RX7
and proinflammatory cytokines/chemokines mRNAs expression) and glucocorticoid resistance (lower
GR
and higher
FKBP5
mRNAs expression), while responsive patients had an intermediate phenotype with, additionally, lower
CXCL12
. Most interestingly, using binomial logistics models we found that a signature of six mRNAs (
P2RX7
,
IL-1-beta, IL-6
,
TNF-alpha, CXCL12
and
GR
) distinguished treatment-resistant from responsive patients, even after adjusting for other variables that were different between groups, such as a trait- and state-anxiety, history of childhood maltreatment and serum CRP. Future studies should replicate these findings in larger, longitudinal cohorts, and test whether this mRNA signature can identify patients that are more likely to respond to adjuvant strategies for treatment-resistant depression, including combinations with anti-inflammatory medications.</description><identifier>ISSN: 2158-3188</identifier><identifier>EISSN: 2158-3188</identifier><identifier>DOI: 10.1038/s41398-020-00874-7</identifier><identifier>PMID: 32699209</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>692/53/2422 ; 692/699/476/1414 ; Antidepressive Agents ; Behavioral Sciences ; Biological Psychology ; Cytokines ; Glucocorticoids ; Humans ; Inflammasomes ; Medicine ; Medicine & Public Health ; Neurosciences ; Pharmacotherapy ; Psychiatry ; Receptors, Glucocorticoid - genetics ; RNA, Messenger</subject><ispartof>Translational psychiatry, 2020-07, Vol.10 (1), p.232-232, Article 232</ispartof><rights>The Author(s) 2020</rights><rights>The Author(s) 2020. 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-c596t-6a070169947e43e1bc7bf6ef35ac9959c32360da48e7c9da417f6f5e0842a6523</citedby><cites>FETCH-LOGICAL-c596t-6a070169947e43e1bc7bf6ef35ac9959c32360da48e7c9da417f6f5e0842a6523</cites><orcidid>0000-0002-5214-305X ; 0000-0003-2738-8589 ; 0000-0002-9132-5091</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7376244/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7376244/$$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/32699209$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cattaneo, Annamaria</creatorcontrib><creatorcontrib>Ferrari, Clarissa</creatorcontrib><creatorcontrib>Turner, Lorinda</creatorcontrib><creatorcontrib>Mariani, Nicole</creatorcontrib><creatorcontrib>Enache, Daniela</creatorcontrib><creatorcontrib>Hastings, Caitlin</creatorcontrib><creatorcontrib>Kose, Melisa</creatorcontrib><creatorcontrib>Lombardo, Giulia</creatorcontrib><creatorcontrib>McLaughlin, Anna P.</creatorcontrib><creatorcontrib>Nettis, Maria A.</creatorcontrib><creatorcontrib>Nikkheslat, Naghmeh</creatorcontrib><creatorcontrib>Sforzini, Luca</creatorcontrib><creatorcontrib>Worrell, Courtney</creatorcontrib><creatorcontrib>Zajkowska, Zuzanna</creatorcontrib><creatorcontrib>Cattane, Nadia</creatorcontrib><creatorcontrib>Lopizzo, Nicola</creatorcontrib><creatorcontrib>Mazzelli, Monica</creatorcontrib><creatorcontrib>Pointon, Linda</creatorcontrib><creatorcontrib>Cowen, Philip J.</creatorcontrib><creatorcontrib>Cavanagh, Jonathan</creatorcontrib><creatorcontrib>Harrison, Neil A.</creatorcontrib><creatorcontrib>de Boer, Peter</creatorcontrib><creatorcontrib>Jones, Declan</creatorcontrib><creatorcontrib>Drevets, Wayne C.</creatorcontrib><creatorcontrib>Mondelli, Valeria</creatorcontrib><creatorcontrib>Bullmore, Edward T.</creatorcontrib><creatorcontrib>Pariante, Carmine M.</creatorcontrib><creatorcontrib>Neuroimmunology of Mood Disorders and Alzheimer’s Disease (NIMA) Consortium</creatorcontrib><creatorcontrib>the Neuroimmunology of Mood Disorders and Alzheimer’s Disease (NIMA) Consortium</creatorcontrib><title>Whole-blood expression of inflammasome- and glucocorticoid-related mRNAs correctly separates treatment-resistant depressed patients from drug-free and responsive patients in the BIODEP study</title><title>Translational psychiatry</title><addtitle>Transl Psychiatry</addtitle><addtitle>Transl Psychiatry</addtitle><description>The mRNA expression signatures associated with the ‘pro-inflammatory’ phenotype of depression, and the differential signatures associated with depression subtypes and the effects of antidepressants, are still unknown. We examined 130 depressed patients (58 treatment-resistant, 36 antidepressant-responsive and 36 currently untreated) and 40 healthy controls from the BIODEP study, and used whole-blood mRNA qPCR to measure the expression of 16 candidate mRNAs, some never measured before: interleukin (
IL)-1-beta
,
IL-6
,
TNF-alpha
, macrophage inhibiting factor (
MIF
), glucocorticoid receptor (
GR
),
SGK1
,
FKBP5
, the purinergic receptor
P2RX7
,
CCL2
,
CXCL12
, c-reactive protein (
CRP
), alpha-2-macroglobulin (
A2M
), acquaporin-4 (
AQP4
),
ISG15
,
STAT1
and
USP-18
. All genes but
AQP4
,
ISG15
and
USP-18
were differentially regulated. Treatment-resistant and drug-free depressed patients had both increased inflammasome activation (higher
P2RX7
and proinflammatory cytokines/chemokines mRNAs expression) and glucocorticoid resistance (lower
GR
and higher
FKBP5
mRNAs expression), while responsive patients had an intermediate phenotype with, additionally, lower
CXCL12
. Most interestingly, using binomial logistics models we found that a signature of six mRNAs (
P2RX7
,
IL-1-beta, IL-6
,
TNF-alpha, CXCL12
and
GR
) distinguished treatment-resistant from responsive patients, even after adjusting for other variables that were different between groups, such as a trait- and state-anxiety, history of childhood maltreatment and serum CRP. Future studies should replicate these findings in larger, longitudinal cohorts, and test whether this mRNA signature can identify patients that are more likely to respond to adjuvant strategies for treatment-resistant depression, including combinations with anti-inflammatory medications.</description><subject>692/53/2422</subject><subject>692/699/476/1414</subject><subject>Antidepressive Agents</subject><subject>Behavioral Sciences</subject><subject>Biological Psychology</subject><subject>Cytokines</subject><subject>Glucocorticoids</subject><subject>Humans</subject><subject>Inflammasomes</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Neurosciences</subject><subject>Pharmacotherapy</subject><subject>Psychiatry</subject><subject>Receptors, Glucocorticoid - genetics</subject><subject>RNA, 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Group</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-5214-305X</orcidid><orcidid>https://orcid.org/0000-0003-2738-8589</orcidid><orcidid>https://orcid.org/0000-0002-9132-5091</orcidid></search><sort><creationdate>20200723</creationdate><title>Whole-blood expression of inflammasome- and glucocorticoid-related mRNAs correctly separates treatment-resistant depressed patients from drug-free and responsive patients in the BIODEP study</title><author>Cattaneo, Annamaria ; Ferrari, Clarissa ; Turner, Lorinda ; Mariani, Nicole ; Enache, Daniela ; Hastings, Caitlin ; Kose, Melisa ; Lombardo, Giulia ; McLaughlin, Anna P. ; Nettis, Maria A. ; Nikkheslat, Naghmeh ; Sforzini, Luca ; Worrell, Courtney ; Zajkowska, Zuzanna ; Cattane, Nadia ; Lopizzo, Nicola ; Mazzelli, Monica ; Pointon, Linda ; Cowen, Philip J. ; Cavanagh, Jonathan ; Harrison, Neil A. ; de Boer, Peter ; Jones, Declan ; Drevets, Wayne C. ; Mondelli, Valeria ; Bullmore, Edward T. ; Pariante, Carmine M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c596t-6a070169947e43e1bc7bf6ef35ac9959c32360da48e7c9da417f6f5e0842a6523</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>692/53/2422</topic><topic>692/699/476/1414</topic><topic>Antidepressive Agents</topic><topic>Behavioral 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(NIMA) Consortium</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>Medical Database (Alumni Edition)</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 Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community 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Lorinda</au><au>Mariani, Nicole</au><au>Enache, Daniela</au><au>Hastings, Caitlin</au><au>Kose, Melisa</au><au>Lombardo, Giulia</au><au>McLaughlin, Anna P.</au><au>Nettis, Maria A.</au><au>Nikkheslat, Naghmeh</au><au>Sforzini, Luca</au><au>Worrell, Courtney</au><au>Zajkowska, Zuzanna</au><au>Cattane, Nadia</au><au>Lopizzo, Nicola</au><au>Mazzelli, Monica</au><au>Pointon, Linda</au><au>Cowen, Philip J.</au><au>Cavanagh, Jonathan</au><au>Harrison, Neil A.</au><au>de Boer, Peter</au><au>Jones, Declan</au><au>Drevets, Wayne C.</au><au>Mondelli, Valeria</au><au>Bullmore, Edward T.</au><au>Pariante, Carmine M.</au><aucorp>Neuroimmunology of Mood Disorders and Alzheimer’s Disease (NIMA) Consortium</aucorp><aucorp>the Neuroimmunology of Mood Disorders and Alzheimer’s Disease (NIMA) Consortium</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Whole-blood expression of inflammasome- and glucocorticoid-related mRNAs correctly separates treatment-resistant depressed patients from drug-free and responsive patients in the BIODEP study</atitle><jtitle>Translational psychiatry</jtitle><stitle>Transl Psychiatry</stitle><addtitle>Transl Psychiatry</addtitle><date>2020-07-23</date><risdate>2020</risdate><volume>10</volume><issue>1</issue><spage>232</spage><epage>232</epage><pages>232-232</pages><artnum>232</artnum><issn>2158-3188</issn><eissn>2158-3188</eissn><abstract>The mRNA expression signatures associated with the ‘pro-inflammatory’ phenotype of depression, and the differential signatures associated with depression subtypes and the effects of antidepressants, are still unknown. We examined 130 depressed patients (58 treatment-resistant, 36 antidepressant-responsive and 36 currently untreated) and 40 healthy controls from the BIODEP study, and used whole-blood mRNA qPCR to measure the expression of 16 candidate mRNAs, some never measured before: interleukin (
IL)-1-beta
,
IL-6
,
TNF-alpha
, macrophage inhibiting factor (
MIF
), glucocorticoid receptor (
GR
),
SGK1
,
FKBP5
, the purinergic receptor
P2RX7
,
CCL2
,
CXCL12
, c-reactive protein (
CRP
), alpha-2-macroglobulin (
A2M
), acquaporin-4 (
AQP4
),
ISG15
,
STAT1
and
USP-18
. All genes but
AQP4
,
ISG15
and
USP-18
were differentially regulated. Treatment-resistant and drug-free depressed patients had both increased inflammasome activation (higher
P2RX7
and proinflammatory cytokines/chemokines mRNAs expression) and glucocorticoid resistance (lower
GR
and higher
FKBP5
mRNAs expression), while responsive patients had an intermediate phenotype with, additionally, lower
CXCL12
. Most interestingly, using binomial logistics models we found that a signature of six mRNAs (
P2RX7
,
IL-1-beta, IL-6
,
TNF-alpha, CXCL12
and
GR
) distinguished treatment-resistant from responsive patients, even after adjusting for other variables that were different between groups, such as a trait- and state-anxiety, history of childhood maltreatment and serum CRP. Future studies should replicate these findings in larger, longitudinal cohorts, and test whether this mRNA signature can identify patients that are more likely to respond to adjuvant strategies for treatment-resistant depression, including combinations with anti-inflammatory medications.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>32699209</pmid><doi>10.1038/s41398-020-00874-7</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0002-5214-305X</orcidid><orcidid>https://orcid.org/0000-0003-2738-8589</orcidid><orcidid>https://orcid.org/0000-0002-9132-5091</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2158-3188 |
| ispartof | Translational psychiatry, 2020-07, Vol.10 (1), p.232-232, Article 232 |
| issn | 2158-3188 2158-3188 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7376244 |
| source | MEDLINE; Nature Free; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Springer Nature OA Free Journals |
| subjects | 692/53/2422 692/699/476/1414 Antidepressive Agents Behavioral Sciences Biological Psychology Cytokines Glucocorticoids Humans Inflammasomes Medicine Medicine & Public Health Neurosciences Pharmacotherapy Psychiatry Receptors, Glucocorticoid - genetics RNA, Messenger |
| title | Whole-blood expression of inflammasome- and glucocorticoid-related mRNAs correctly separates treatment-resistant depressed patients from drug-free and responsive patients in the BIODEP study |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-08T17%3A26%3A06IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Whole-blood%20expression%20of%20inflammasome-%20and%20glucocorticoid-related%20mRNAs%20correctly%20separates%20treatment-resistant%20depressed%20patients%20from%20drug-free%20and%20responsive%20patients%20in%20the%20BIODEP%20study&rft.jtitle=Translational%20psychiatry&rft.au=Cattaneo,%20Annamaria&rft.aucorp=Neuroimmunology%20of%20Mood%20Disorders%20and%20Alzheimer%E2%80%99s%20Disease%20(NIMA)%20Consortium&rft.date=2020-07-23&rft.volume=10&rft.issue=1&rft.spage=232&rft.epage=232&rft.pages=232-232&rft.artnum=232&rft.issn=2158-3188&rft.eissn=2158-3188&rft_id=info:doi/10.1038/s41398-020-00874-7&rft_dat=%3Cproquest_pubme%3E2426013865%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2426013865&rft_id=info:pmid/32699209&rfr_iscdi=true |