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

TitleTreatment-emergent and trajectory-based peripheral gene expression markers of antidepressant response.
Publication TypeJournal Article
Year of Publication2021
AuthorsFiori LM, Orri M, Aouabed Z, Théroux JFrançois, 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
JournalTransl Psychiatry
Volume11
Issue1
Pagination439
Date Published2021 08 21
ISSN2158-3188
KeywordsAntidepressive Agents, Biomarkers, Citalopram, Depressive Disorder, Major, Gene Expression, Humans, Psychiatric Status Rating Scales, Treatment Outcome
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-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.

DOI10.1038/s41398-021-01564-8
Alternate JournalTransl Psychiatry
PubMed ID34420030
PubMed Central IDPMC8380246
Grant ListFDN148374 / / CIHR / Canada
EGM141899 / / CIHR / Canada
ENP161427 / / CIHR / Canada