{
  "abstract": "Early life stress (ELS) increases vulnerability to major depressive disorder (MDD) and treatment-resistant depression (TRD) through lasting neurobiological and epigenetic alterations. MicroRNAs (miRNAs), key post-transcriptional regulators of gene expression, are emerging as potential biomarkers linking environmental stressors and depression pathophysiology. This study employed a miRNomic approach to investigate plasma miRNA changes associated with trauma-focused psychotherapy in TRD patients with a history of ELS. Twenty-four patients received either trauma-focused cognitive behavioural therapy (TF-CBT) or eye movement desensitization and reprocessing (EMDR) over eight weeks, with depressive symptoms assessed by the Montgomery-Åsberg Depression Rating Scale (MADRS) at baseline (T0) and post-treatment (T8). Plasma levels of 188 miRNAs were quantified using qRT-PCR. Of these, 148 passed quality control and were included in the analysis. Twenty-two miRNAs were nominally significantly downregulated after psychotherapy, with miR-132-3p remaining significant after correction for multiple testing, and four (let-7f-5p, miR-195-5p, miR-29c-3p, miR-32-5p) showing trends toward significance. Pathway enrichment analyses identified 120 pathways involved in inflammation, neuroplasticity, and stress response, including Hippo, TGF-β, TNF, Wnt, PI3K-Akt, Neurotrophin, glutamatergic synapse, and dopaminergic signaling. Subgroup analyses identified nominal downregulation of miRNAs following EMDR (miR-132-3p and let-7f-5p) and TF-CBT (miR-32-5p and let-7f-5p), with none remaining significant after correction. Correlational analyses between miRNAs changes and treatment outcomes showed, in the whole sample, that miR-139-5p downregulation was nominally associated with greater improvements in overall depressive symptoms, as well as cognitive and neurovegetative symptom domains. Subgroup correlational analyses identified significant nominal associations between miR-125b-5p downregulation and improvements in overall depressive symptoms, mood, and neurovegetative domains following TF-CBT, and between miR-139-5p downregulation and overall depressive symptoms (trend significant) and neurovegetative symptom improvement following EMDR; however, none of these associations survived multiple-testing correction. These findings suggest that trauma-focused psychotherapies may induce peripheral miRNA modulation linked to clinical response, with miR-132-3p, miR-125b-5p, and miR-139-5p emerging as potential biomarkers of treatment response. The results support a role for miRNA-mediated neuroplastic and inflammatory mechanisms in the molecular underpinnings of psychotherapy efficacy in TRD patients exposed to ELS.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 29,
  "authors": [
    {
      "name": "Lisa Buson"
    },
    {
      "name": "Rosana Carvalho Silva"
    },
    {
      "name": "Chiara Galbiati"
    },
    {
      "name": "Marco Bortolomasi"
    },
    {
      "name": "Monica Scaglia"
    },
    {
      "name": "Giulia Perusi"
    },
    {
      "name": "Maria Abate"
    },
    {
      "name": "Elisabetta Maffioletti"
    },
    {
      "name": "Massimo Gennarelli"
    },
    {
      "name": "Nicola Lorenzon"
    },
    {
      "name": "Mara Dierssen"
    },
    {
      "name": "Bernhard Baune"
    },
    {
      "name": "Alessandra Minelli"
    },
    {
      "name": "Alessandro Serretti"
    },
    {
      "name": "Mara Dierssen"
    },
    {
      "name": "Eduard Maron"
    },
    {
      "name": "Marie-Claude Potier"
    },
    {
      "name": "Massimo Gennarelli"
    },
    {
      "name": "Roos van Westrhenen"
    },
    {
      "name": "Alessio Squassina"
    },
    {
      "name": "Vincenzo Oliva"
    },
    {
      "name": "Georgios Schoretsanitis"
    },
    {
      "name": "Divja Mehta"
    },
    {
      "name": "Joost G.E. Janzing"
    },
    {
      "name": "Chiara Fabbri"
    },
    {
      "name": "Pietro Lio"
    },
    {
      "name": "Filip Rybakowski"
    },
    {
      "name": "Claudia Pisanu"
    },
    {
      "name": "Alessandra Minelli"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/cdfj5d8dk524n.bib",
  "cited_by": 0,
  "doi": "10.1016/j.nsa.2026.107020",
  "fulltext_url": null,
  "id": "cdfj5d8dk524n",
  "issns": [
    "2772-4085"
  ],
  "landing_url": "https://hal.science/hal-05844242v1",
  "language": "en",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "hal",
      "0.sdv"
    ],
    [
      "openalex",
      "1306|MicroRNA in disease regulation"
    ]
  ],
  "openalex": "W7167821701",
  "pdf_url": "https://www.sciencedirect.com/science/article/pii/S2772408526001390/pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-29",
  "publisher": "European College of Neuropsychopharmacology",
  "ris": "https://research.draconitic.com/paper/cdfj5d8dk524n.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:03Z",
      "native_id": "hal-05844242",
      "source": "hal",
      "url": "https://hal.science/hal-05844242v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:1306|MicroRNA in disease regulation",
      "subfield": "oncology"
    }
  ],
  "title": "MicroRNAs expression changes associated with trauma-focused psychotherapy efficacy in treatment-resistant depression: An exploratory study",
  "title_text": "MicroRNAs expression changes associated with trauma-focused psychotherapy efficacy in treatment-resistant depression: An exploratory study",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T12:20:56Z",
  "url": "https://research.draconitic.com/paper/cdfj5d8dk524n",
  "venue": "Neuroscience Applied",
  "versions": []
}