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

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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.

Original languageEnglish (US)
Article number439
JournalTranslational psychiatry
Volume11
Issue number1
DOIs
StatePublished - Dec 2021
Externally publishedYes

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Biological Psychiatry

Fingerprint

Dive into the research topics of 'Treatment-emergent and trajectory-based peripheral gene expression markers of antidepressant response'. Together they form a unique fingerprint.

Cite this