MicroRNAs expression changes associated with trauma-focused psychotherapy efficacy in treatment-resistant depression: An exploratory study
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.
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BibTeX
@article{buson2026micrornas,
title = {{MicroRNAs expression changes associated with trauma-focused psychotherapy efficacy in treatment-resistant depression: An exploratory study}},
author = {Lisa Buson and Rosana Carvalho Silva and Chiara Galbiati and Marco Bortolomasi and Monica Scaglia and Giulia Perusi and Maria Abate and Elisabetta Maffioletti and Massimo Gennarelli and Nicola Lorenzon and Mara Dierssen and Bernhard Baune and Alessandra Minelli and Alessandro Serretti and Mara Dierssen and Eduard Maron and Marie-Claude Potier and Massimo Gennarelli and Roos van Westrhenen and Alessio Squassina and Vincenzo Oliva and Georgios Schoretsanitis and Divja Mehta and Joost G.E. Janzing and Chiara Fabbri and Pietro Lio and Filip Rybakowski and Claudia Pisanu and Alessandra Minelli},
journal = {Neuroscience Applied},
year = {2026},
month = oct,
doi = {10.1016/j.nsa.2026.107020},
url = {https://hal.science/hal-05844242v1},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - MicroRNAs expression changes associated with trauma-focused psychotherapy efficacy in treatment-resistant depression: An exploratory study
AU - Lisa Buson
AU - Rosana Carvalho Silva
AU - Chiara Galbiati
AU - Marco Bortolomasi
AU - Monica Scaglia
AU - Giulia Perusi
AU - Maria Abate
AU - Elisabetta Maffioletti
AU - Massimo Gennarelli
AU - Nicola Lorenzon
AU - Mara Dierssen
AU - Bernhard Baune
AU - Alessandra Minelli
AU - Alessandro Serretti
AU - Mara Dierssen
AU - Eduard Maron
AU - Marie-Claude Potier
AU - Massimo Gennarelli
AU - Roos van Westrhenen
AU - Alessio Squassina
AU - Vincenzo Oliva
AU - Georgios Schoretsanitis
AU - Divja Mehta
AU - Joost G.E. Janzing
AU - Chiara Fabbri
AU - Pietro Lio
AU - Filip Rybakowski
AU - Claudia Pisanu
AU - Alessandra Minelli
PY - 2026
DA - 2026/10/29
JO - Neuroscience Applied
DO - 10.1016/j.nsa.2026.107020
UR - https://hal.science/hal-05844242v1
AB - 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.
SN - 2772-4085
ER -