Treatment-emergent and trajectory-based peripheral gene expression markers of antidepressant response

Laura M. Fiori; Massimiliano Orri; Zahia Aouabed; Jean François Théroux; Rixing Lin; Corina Nagy; Benicio N. Frey; Raymond W. Lam; Glenda M. MacQueen; Roumen Milev; Daniel J. Müller; Sagar V. Parikh; Susan Rotzinger; Rudolf Uher; Jane A. Foster; Sidney H. Kennedy; Gustavo Turecki

doi:10.1038/s41398-021-01564-8

Treatment-emergent and trajectory-based peripheral gene expression markers of antidepressant response

Laura M. Fiori, Massimiliano Orri, Zahia Aouabed, Jean François Théroux, Rixing Lin, Corina Nagy, Benicio N. Frey, Raymond W. Lam, Glenda M. MacQueen, Roumen Milev, Daniel J. Müller, Sagar V. Parikh, Susan Rotzinger, Rudolf Uher, Jane A. Foster, Sidney H. Kennedy, Gustavo Turecki

Medicine

Résultat de recherche: Article › examen par les pairs

5 Citations (Scopus)

Résumé

Identifying biomarkers of antidepressant response may advance personalized treatment of major depressive disorder (MDD). We aimed to identify longitudinal changes in gene expression associated with response to antidepressants in a sample of MDD patients treated with escitalopram. Patients (N = 153) from the CAN-BIND-1 cohort were treated for 8 weeks, and depressive symptoms were assessed using the Montgomery-Åsberg Depression Rating Scale at 0, 2, 4, 6, and 8 weeks. We identified three groups of patients according to response status: early responders (22.9%), later responders (32.0%), and nonresponders (45.1%). RNA sequencing was performed in blood obtained at weeks 0, 2, and 8. RNA expression was modeled using growth models, and differences in the longitudinal changes in expression according to response were investigated using multiple regression models. The expression of RNAs related to response was investigated in the brains of depressed individuals, as well as in neuronal cells in vitro. We identified four RNAs (CERCAM, DARS-AS1, FAM228B, HBEGF) whose change over time was independently associated with a response status. For all except HBEGF, responders showed higher expression over time, compared to nonresponders. While the change in all RNAs differentiated early responders from nonresponders, changes in DARS-AS1 and HBEGF also differentiated later responders from nonresponders. Additionally, HBEGF was downregulated in the brains of depressed individuals, and increased in response to escitalopram treatment in vitro. In conclusion, using longitudinal assessments of gene expression, we provide insights into biological processes involved in the intermediate stages of escitalopram response, highlighting several genes with potential utility as biomarkers of antidepressant response.

Langue d'origine	English
Numéro d'article	439
Journal	Translational Psychiatry
Volume	11
Numéro de publication	1
DOI	https://doi.org/10.1038/s41398-021-01564-8
Statut de publication	Published - déc. 2021

Note bibliographique

Funding Information:
BF: has received a research grant from Pfizer. RM: has received consulting and speaking honoraria from AbbVie, Allergan, Janssen, KYE, Lundbeck, Otsuka, and Sunovion, and research grants from CAN-BIND, CIHR, Janssen, Lallemand, Lundbeck, Nubiyota, OBI and OMHF. SK: has received research funding or honoraria from the following sources: Abbott, Alkermes, Allergan, BMS, Brain Canada, Canadian Institutes for Health Research (CIHR), Janssen, Lundbeck, Lundbeck Institute, Ontario Brain Institute, Ontario Research Fund (ORF), Otsuka, Pfizer, Servier, Sunovion and Xian-Janssen. The remaining authors report no biomedical financial interests or potential conflicts of interest.

Funding Information:
GT holds a Canada Research Chair (Tier 1) and is supported by grants from the Canadian Institute of Health Research (CIHR) (FDN148374, EGM141899, ENP161427), and by the Fonds de recherche du Québec -Santé (FRQS) through the Quebec Network on Suicide, Mood Disorders, and Related Disorders. CAN-BIND is an Integrated Discovery Program carried out in partnership with, and financial support from, the Ontario Brain Institute, an independent nonprofit corporation, funded partially by the Ontario government. The opinions, results, and conclusions are those of the authors and no endorsement by the Ontario Brain Institute is intended or should be inferred. Additional funding is provided by the Canadian Institutes of Health Research (CIHR), and H. Lundbeck A/S. All study medications were independently purchased at wholesale market values.

Publisher Copyright:
© 2021, The Author(s).

ASJC Scopus Subject Areas

Psychiatry and Mental health
Cellular and Molecular Neuroscience
Biological Psychiatry

PubMed: MeSH publication types

Journal Article
Research Support, Non-U.S. Gov't

ODD de l’ONU

Cette action contribue à la réalisation des objectifs de développement durable suivants

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10.1038/s41398-021-01564-8

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Fiori, L. M., Orri, M., Aouabed, Z., Théroux, J. F., Lin, R., Nagy, C., Frey, B. N., Lam, R. W., MacQueen, G. M., Milev, R., Müller, D. J., Parikh, S. V., Rotzinger, S., Uher, R., Foster, J. A., Kennedy, S. H., & Turecki, G. (2021). Treatment-emergent and trajectory-based peripheral gene expression markers of antidepressant response. Translational Psychiatry, 11(1), Article 439. https://doi.org/10.1038/s41398-021-01564-8

Fiori, LM, Orri, M, Aouabed, Z, Théroux, JF, Lin, R, Nagy, C, Frey, BN, Lam, RW, MacQueen, GM, Milev, R, Müller, DJ, Parikh, SV, Rotzinger, S, Uher, R, Foster, JA, Kennedy, SH & Turecki, G 2021, 'Treatment-emergent and trajectory-based peripheral gene expression markers of antidepressant response', Translational Psychiatry, vol. 11, n° 1, 439. https://doi.org/10.1038/s41398-021-01564-8

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abstract = "Identifying biomarkers of antidepressant response may advance personalized treatment of major depressive disorder (MDD). We aimed to identify longitudinal changes in gene expression associated with response to antidepressants in a sample of MDD patients treated with escitalopram. Patients (N = 153) from the CAN-BIND-1 cohort were treated for 8 weeks, and depressive symptoms were assessed using the Montgomery-{\AA}sberg Depression Rating Scale at 0, 2, 4, 6, and 8 weeks. We identified three groups of patients according to response status: early responders (22.9%), later responders (32.0%), and nonresponders (45.1%). RNA sequencing was performed in blood obtained at weeks 0, 2, and 8. RNA expression was modeled using growth models, and differences in the longitudinal changes in expression according to response were investigated using multiple regression models. The expression of RNAs related to response was investigated in the brains of depressed individuals, as well as in neuronal cells in vitro. We identified four RNAs (CERCAM, DARS-AS1, FAM228B, HBEGF) whose change over time was independently associated with a response status. For all except HBEGF, responders showed higher expression over time, compared to nonresponders. While the change in all RNAs differentiated early responders from nonresponders, changes in DARS-AS1 and HBEGF also differentiated later responders from nonresponders. Additionally, HBEGF was downregulated in the brains of depressed individuals, and increased in response to escitalopram treatment in vitro. In conclusion, using longitudinal assessments of gene expression, we provide insights into biological processes involved in the intermediate stages of escitalopram response, highlighting several genes with potential utility as biomarkers of antidepressant response.",

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note = "Funding Information: BF: has received a research grant from Pfizer. RM: has received consulting and speaking honoraria from AbbVie, Allergan, Janssen, KYE, Lundbeck, Otsuka, and Sunovion, and research grants from CAN-BIND, CIHR, Janssen, Lallemand, Lundbeck, Nubiyota, OBI and OMHF. SK: has received research funding or honoraria from the following sources: Abbott, Alkermes, Allergan, BMS, Brain Canada, Canadian Institutes for Health Research (CIHR), Janssen, Lundbeck, Lundbeck Institute, Ontario Brain Institute, Ontario Research Fund (ORF), Otsuka, Pfizer, Servier, Sunovion and Xian-Janssen. The remaining authors report no biomedical financial interests or potential conflicts of interest. Funding Information: GT holds a Canada Research Chair (Tier 1) and is supported by grants from the Canadian Institute of Health Research (CIHR) (FDN148374, EGM141899, ENP161427), and by the Fonds de recherche du Qu{\'e}bec -Sant{\'e} (FRQS) through the Quebec Network on Suicide, Mood Disorders, and Related Disorders. CAN-BIND is an Integrated Discovery Program carried out in partnership with, and financial support from, the Ontario Brain Institute, an independent nonprofit corporation, funded partially by the Ontario government. The opinions, results, and conclusions are those of the authors and no endorsement by the Ontario Brain Institute is intended or should be inferred. Additional funding is provided by the Canadian Institutes of Health Research (CIHR), and H. Lundbeck A/S. All study medications were independently purchased at wholesale market values. Publisher Copyright: {\textcopyright} 2021, The Author(s).",

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doi = "10.1038/s41398-021-01564-8",

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AU - Fiori, Laura M.

AU - Orri, Massimiliano

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AU - Lin, Rixing

AU - Nagy, Corina

AU - Frey, Benicio N.

AU - Lam, Raymond W.

AU - MacQueen, Glenda M.

AU - Milev, Roumen

AU - Müller, Daniel J.

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AU - Rotzinger, Susan

AU - Uher, Rudolf

AU - Foster, Jane A.

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Treatment-emergent and trajectory-based peripheral gene expression markers of antidepressant response

Résumé

Note bibliographique

ASJC Scopus Subject Areas

PubMed: MeSH publication types

ODD de l’ONU

Accès au document

Autres fichiers et liens

Empreinte numérique

Citer