Transcriptional profiling of antidepressant ketamine and electroconvulsive therapy treatment.
4 affiliations
- 1Ahmanson-Lovelace Brain Mapping Center, Department of Neurology, Geffen School of Medicine at the University of California, Los Angeles, CA, USA. [email protected].
- 2Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
- 3Ahmanson-Lovelace Brain Mapping Center, Department of Neurology, Geffen School of Medicine at the University of California, Los Angeles, CA, USA.
- 4Jane and Terry Semel Institute for Neuroscience and Human Behavior, Department of Psychiatry and Biobehavioral Sciences, Geffen School of Medicine at the University of California, Los Angeles, CA, USA.
Abstract
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.
Related
- Comparable Acute Antidepressant-like Effects of Two Subanesthetic Ketamine Doses Are Associated with Divergent Region-Specific Molecular Responses After Adolescent Chronic Stress
- Ketamine Infusion Protocol for the Treatment of Complex Regional Pain Syndrome
- The Antidepressant Effects of the mGlu2/3 Receptor Antagonist TS-161 in Treatment-Resistant Depression
- Clinical Outcomes and Treatment Characteristics of Seizure Threshold-Titrated Electroconvulsive Therapy in Schizophrenia: A 3.5-Year Retrospective Naturalistic Course-Level Study
- Insomnia and anxiety exhibit distinct short-term associations following ketamine in treatment-resistant depression
BibTeX
@article{zavaliangospetropulu2026transcriptional,
title = {{Transcriptional profiling of antidepressant ketamine and electroconvulsive therapy treatment.}},
author = {Artemis Zavaliangos-Petropulu and Ginny Ghang and Toni Boltz and Paloma Pfeiffer and Lingyu Zhan and Brandon Taraku and Eliza Congdon and Randall T Espinoza and Katherine L Narr and Roel A Ophoff},
journal = {Translational psychiatry},
year = {2026},
month = aug,
doi = {10.1038/s41398-026-04196-y},
url = {https://europepmc.org/article/MED/42967909},
note = {CC BY},
}
RIS
TY - JOUR
TI - Transcriptional profiling of antidepressant ketamine and electroconvulsive therapy treatment.
AU - Artemis Zavaliangos-Petropulu
AU - Ginny Ghang
AU - Toni Boltz
AU - Paloma Pfeiffer
AU - Lingyu Zhan
AU - Brandon Taraku
AU - Eliza Congdon
AU - Randall T Espinoza
AU - Katherine L Narr
AU - Roel A Ophoff
PY - 2026
DA - 2026/08/05
JO - Translational psychiatry
DO - 10.1038/s41398-026-04196-y
UR - https://europepmc.org/article/MED/42967909
AB - 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.
SN - 2158-3188
ER -