{
  "abstract": "Background\n\nTreatment-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\n\nWe 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\n\nLongitudinal 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\n\nDespite 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.",
  "abstract_shown": true,
  "affiliations": [
    "Ahmanson-Lovelace Brain Mapping Center, Department of Neurology, Geffen School of Medicine at the University of California, Los Angeles, CA, USA. azavalia@g.ucla.edu.",
    "Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.",
    "Ahmanson-Lovelace Brain Mapping Center, Department of Neurology, Geffen School of Medicine at the University of California, Los Angeles, CA, USA.",
    "Jane 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."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Artemis Zavaliangos-Petropulu",
      "orcid": "0000-0003-1953-8663"
    },
    {
      "affs": [
        1
      ],
      "name": "Ginny Ghang"
    },
    {
      "affs": [
        1
      ],
      "name": "Toni Boltz"
    },
    {
      "affs": [
        2
      ],
      "name": "Paloma Pfeiffer"
    },
    {
      "affs": [
        1
      ],
      "name": "Lingyu Zhan"
    },
    {
      "affs": [
        2
      ],
      "name": "Brandon Taraku"
    },
    {
      "affs": [
        3
      ],
      "name": "Eliza Congdon",
      "orcid": "0000-0003-2921-0944"
    },
    {
      "affs": [
        3
      ],
      "name": "Randall T Espinoza",
      "orcid": "0000-0003-2895-4212"
    },
    {
      "affs": [
        2
      ],
      "name": "Katherine L Narr",
      "orcid": "0000-0002-9396-7936"
    },
    {
      "affs": [
        1,
        3
      ],
      "name": "Roel A Ophoff",
      "orcid": "0000-0002-8287-6457"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/18fb7j9pfsger.bib",
  "cited_by": 0,
  "doi": "10.1038/s41398-026-04196-y",
  "fulltext_url": "https://europepmc.org/articles/PMC13724684",
  "id": "18fb7j9pfsger",
  "issns": [
    "2158-3188"
  ],
  "landing_url": "https://europepmc.org/article/MED/42967909",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "2736|Treatment of Major Depression"
    ]
  ],
  "openalex": "W4412767227",
  "pdf_url": "https://europepmc.org/articles/PMC13724684?pdf=render",
  "pmcid": "PMC13724684",
  "pmid": "42967909",
  "published": "2026-08-05",
  "publisher": "Nature Publishing Group",
  "ris": "https://research.draconitic.com/paper/18fb7j9pfsger.ris",
  "sources": [
    {
      "first_seen": "2026-11-03T15:20:54Z",
      "native_id": "MED:42967909",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42967909"
    },
    {
      "first_seen": "2026-11-04T12:23:13Z",
      "native_id": "PMC13724684",
      "source": "pmc",
      "url": "https://doi.org/10.1038/s41398-026-04196-y"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2736|Treatment of Major Depression",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "Transcriptional profiling of antidepressant ketamine and electroconvulsive therapy treatment.",
  "title_text": "Transcriptional profiling of antidepressant ketamine and electroconvulsive therapy treatment.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-05T12:21:25Z",
  "url": "https://research.draconitic.com/paper/18fb7j9pfsger",
  "venue": "Translational psychiatry",
  "versions": []
}