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 Neuroimmunology of Mood Disorders and Alzheimer’s Disease (NIMA) Consortium

doi:10.1038/s41398-020-00874-7

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 Neuroimmunology of Mood Disorders and Alzheimer’s Disease (NIMA) Consortium

Research output: Contribution to journal › Article › peer-review

81 Citations (Scopus)

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.

Original language	English
Article number	232
Journal	Translational psychiatry
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41398-020-00874-7
Publication status	Published - 1 Dec 2020

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the Neuroimmunology of Mood Disorders and Alzheimer’s Disease (NIMA) Consortium (2020). 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. Translational psychiatry, 10(1), Article 232. https://doi.org/10.1038/s41398-020-00874-7

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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",

abstract = "The mRNA expression signatures associated with the {\textquoteleft}pro-inflammatory{\textquoteright} 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.",

author = "{the Neuroimmunology of Mood Disorders and Alzheimer{\textquoteright}s Disease (NIMA) Consortium} and Annamaria Cattaneo and Clarissa Ferrari and Lorinda Turner and Nicole Mariani and Daniela Enache and Caitlin Hastings and Melisa Kose and Giulia Lombardo and McLaughlin, {Anna P.} and Nettis, {Maria A.} and Naghmeh Nikkheslat and Luca Sforzini and Courtney Worrell and Zuzanna Zajkowska and Nadia Cattane and Nicola Lopizzo and Monica Mazzelli and Linda Pointon and Cowen, {Philip J.} and Jonathan Cavanagh and Harrison, {Neil A.} and {de Boer}, Peter and Declan Jones and Drevets, {Wayne C.} and Valeria Mondelli and Bullmore, {Edward T.} and Pariante, {Carmine M.}",

year = "2020",

month = dec,

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doi = "10.1038/s41398-020-00874-7",

language = "English",

volume = "10",

journal = "Translational psychiatry",

issn = "2158-3188",

publisher = "Nature Publishing Group",

number = "1",

}

the Neuroimmunology of Mood Disorders and Alzheimer’s Disease (NIMA) Consortium 2020, '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', Translational psychiatry, vol. 10, no. 1, 232. https://doi.org/10.1038/s41398-020-00874-7

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 Neuroimmunology of Mood Disorders and Alzheimer’s Disease (NIMA) Consortium.
In: Translational psychiatry, Vol. 10, No. 1, 232, 01.12.2020.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - 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

AU - the Neuroimmunology of Mood Disorders and Alzheimer’s Disease (NIMA) Consortium

AU - Cattaneo, Annamaria

AU - Ferrari, Clarissa

AU - Turner, Lorinda

AU - Mariani, Nicole

AU - Enache, Daniela

AU - Hastings, Caitlin

AU - Kose, Melisa

AU - Lombardo, Giulia

AU - McLaughlin, Anna P.

AU - Nettis, Maria A.

AU - Nikkheslat, Naghmeh

AU - Sforzini, Luca

AU - Worrell, Courtney

AU - Zajkowska, Zuzanna

AU - Cattane, Nadia

AU - Lopizzo, Nicola

AU - Mazzelli, Monica

AU - Pointon, Linda

AU - Cowen, Philip J.

AU - Cavanagh, Jonathan

AU - Harrison, Neil A.

AU - de Boer, Peter

AU - Jones, Declan

AU - Drevets, Wayne C.

AU - Mondelli, Valeria

AU - Bullmore, Edward T.

AU - Pariante, Carmine M.

PY - 2020/12/1

Y1 - 2020/12/1

N2 - 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.

AB - 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.

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U2 - 10.1038/s41398-020-00874-7

DO - 10.1038/s41398-020-00874-7

M3 - Article

C2 - 32699209

AN - SCOPUS:85088368060

SN - 2158-3188

VL - 10

JO - Translational psychiatry

JF - Translational psychiatry

IS - 1

M1 - 232

ER -

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

Abstract

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