Blood Transcriptional Response in TRD Treated With ECT: Study From Israel

Out on PubMed, from researchers in Israel, is this paper:

Blood transcriptional response to treatment-resistant depression during electroconvulsive therapy.

Israel-Elgali I, Hertzberg L, Shapira G, Segev A, Krieger I, Nitzan U, Bloch Y, Pillar N, Mayer O, Weizman A, Gurwitz D, Shomron N.J Psychiatr Res. 2021 Jun 22;141:92-103. doi: 10.1016/j.jpsychires.2021.06.039. Online ahead of print.PMID: 34182381

The abstract is copied below:

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.

Keywords: Electroconvulsive therapy; FKBP5; ITGA2B; Major depressive disorder; Treatment-resistant depression.

The pdf is here.

And from the text:

The aim of the current study was to explore and compare the effects of conservative antidepressant drug treatment alone, i.e., treatment as usual (TAU), or in combination with ECT or ketamine, on gene and miRNA expression in peripheral blood mononuclear cells (PBMC) of individuals with TRD. Our findings show that ECT alters expression levels of the genes FKBP5 and ITGA2B, as well as miR-24–3p expression in PBMC of individuals with TRD. Furthermore, we identified ITGA2B as a direct target of miR-24–3p. Importantly, we show that ECT affects gene expression differently than antidepressants or ketamine. This suggests a difference in the working mechanism, which awaits further validation by additional studies.

In  conclusion, we  detected specific gene and miRNA changes in PBMC (peripheral blood mononuclear cells) following treatments for TRD. This supports associations of these treatments with neuronal and psychological indices. Our study is limited by the small sample size in all the treatment groups, and particularly in analyses stratified by response to treatment. Nevertheless, we observed differences in  mechanisms of  treatments. Further studies and larger patient cohorts are required to clarify our findings on differential FKBP5, ITGA2B, and miR-24–3p expression during ECT in the context of TRD. 

Here is yet another small genetic biomarker study. It is of interest in that it shows a differential effect of ECT, compared to ketamine and antidepressant medications.

Replication will be needed to to determine if there is a true ECT biomarker here and if it correlates with response.

Students of psychiatric genetics will want to read this article in full, ~35 minutes. For the rest of us, the findings described in the abstract should suffice.