Blood transcriptional response to treatment-resistant depression during electroconvulsive therapy

Ifat Israel-Elgali, Libi Hertzberg, Guy Shapira, Aviv Segev, Israel Krieger, Uri Nitzan, Yuval Bloch, Nir Pillar, Ori Mayer, Abraham Weizman, David Gurwitz*, Noam Shomron*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Selective serotonin reuptake inhibitors (SSRIs) are currently the first-line antidepressant drug treatment for major depressive disorder (MDD). Treatment-resistant depression (TRD), defined as failure to achieve remission despite adequate treatment, affects ~30% of persons with MDD. The current recommended treatment for TRD is electroconvulsive therapy (ECT), while ketamine is an experimentally suggested treatment. This study aimed to elucidate the transcriptional differences in peripheral blood mononuclear cells (PBMC) between individuals with TRD and a control group without a psychiatric illness; and between patients with TRD, treated with either standard antidepressant drugs alone, or in combination with ECT or ketamine. Additionally, PBMC transcriptomics were compared between treatment responders, following completion of their treatment protocols. Total RNA was extracted from PBMC of the TRD group at two time points, and RNA and miRNA expression were profiled. Multiple mRNAs and miRNAs were found to be modified, with two protein coding genes, FKBP5 and ITGA2B, which are up- and downregulated, respectively; and several miRNAs have shown changes following successful ECT treatment. Further analysis demonstrated the direct functional regulation of ITGA2B by miR-24–3p. Our findings suggest that PBMC expression levels of FKBP5, ITGA2B, and miR-24–3p should be further explored as tentative ECT response biomarkers.

Original languageEnglish
Pages (from-to)92-103
Number of pages12
JournalJournal of Psychiatric Research
Volume141
DOIs
StatePublished - Sep 2021

Funding

FundersFunder number
Aufzien Family Center for the Prevention and Treatment of Parkinson's Disease
CBRN
Israeli Ministry of Science and Technology , Israeli–Russia
Israeli Ministry of Science and Technology, Israeli–Russia
Koret-UC Berkeley-Tel Aviv University
Office of Assistant Minister of Defense for Chemical, Biological, Radiological and Nuclear
UCSF-Tel Aviv University
Achelis Foundation
Foundation Fighting Blindness
Yonsei University
Israel Science Foundation1852/16
Tel Aviv University
Queensland Brain Institute
Horizon 2020
Ministry of Defense

    Keywords

    • Electroconvulsive therapy
    • FKBP5
    • ITGA2B
    • Major depressive disorder
    • Treatment-resistant depression

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