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Background: <p>Treatment-resistant depression (TRD) affects 30–50% of patients with major depressive disorder (MDD). Electroconvulsive therapy (ECT) and sub-anesthetic ketamine treatment can relieve TRD, yet their antidepressant mechanisms remain unclear. We hypothesized that peripheral blood gene expression might offer a non-invasive proxy of potential treatment-response biomarkers.</p> Methods: <p>We conducted a transcriptome analysis on peripheral blood samples from individuals with TRD undergoing ECT (N = 37) or serial ketamine infusions (N = 60), and non-depressed controls (N = 35). Samples were collected at baseline and at multiple follow-up time points. Differential gene expression (DGE) at the single gene and network level identified transcriptional changes and co-regulated gene modules associated with diagnosis, treatment, and response/remission status using Weighted Gene Co-Expression Network Analysis (WGCNA), correcting for multiple comparisons.</p> Results: <p>Longitudinal transcriptional changes were not detected for either treatment for individual genes or networks (FDR corrected or |logFC| &gt;0.05). When comparing remitters and non-remitters at baseline in the ketamine group, we observed evidence of enrichment for immune-related functions overall with one gene significantly differentially expressed (i.e., IGKV1-9) (p = 2.5E-05, logFC = −0.51). In the ECT sample, when considering gene networks, we observed significant interaction effects between time and diagnosis. At least six co-regulated gene modules yielded significant differences at baseline between ECT patients and controls.</p> Conclusion: <p>Despite the robust clinical improvements associated with ECT and ketamine, peripheral blood RNA-seq revealed only limited longitudinal gene expression changes. However, pre-treatment differences in gene expression profiles suggest some potential predictive value. Larger samples may be warranted to detect possible peripheral molecular signatures of rapid-acting antidepressant response.</p>

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Transcriptional profiling of antidepressant ketamine and electroconvulsive therapy treatment

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年8月5日

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  • Artemis Zavaliangos-Petropulu,
  • Ginny Ghang,
  • Toni Boltz,
  • Paloma Pfeiffer,
  • Lingyu Zhan,
  • Brandon Taraku,
  • Eliza Congdon,
  • Randall T. Espinoza,
  • Katherine L. Narr,
  • Roel A. Ophoff

摘要

Background:

Treatment-resistant depression (TRD) affects 30–50% of patients with major depressive disorder (MDD). Electroconvulsive therapy (ECT) and sub-anesthetic ketamine treatment can relieve TRD, yet their antidepressant mechanisms remain unclear. We hypothesized that peripheral blood gene expression might offer a non-invasive proxy of potential treatment-response biomarkers.

Methods:

We conducted a transcriptome analysis on peripheral blood samples from individuals with TRD undergoing ECT (N = 37) or serial ketamine infusions (N = 60), and non-depressed controls (N = 35). Samples were collected at baseline and at multiple follow-up time points. Differential gene expression (DGE) at the single gene and network level identified transcriptional changes and co-regulated gene modules associated with diagnosis, treatment, and response/remission status using Weighted Gene Co-Expression Network Analysis (WGCNA), correcting for multiple comparisons.

Results:

Longitudinal transcriptional changes were not detected for either treatment for individual genes or networks (FDR corrected or |logFC| >0.05). When comparing remitters and non-remitters at baseline in the ketamine group, we observed evidence of enrichment for immune-related functions overall with one gene significantly differentially expressed (i.e., IGKV1-9) (p = 2.5E-05, logFC = −0.51). In the ECT sample, when considering gene networks, we observed significant interaction effects between time and diagnosis. At least six co-regulated gene modules yielded significant differences at baseline between ECT patients and controls.

Conclusion:

Despite the robust clinical improvements associated with ECT and ketamine, peripheral blood RNA-seq revealed only limited longitudinal gene expression changes. However, pre-treatment differences in gene expression profiles suggest some potential predictive value. Larger samples may be warranted to detect possible peripheral molecular signatures of rapid-acting antidepressant response.