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MRI-guided dmPFC-rTMS as a Treatment for Treatment-resistant Major Depressive Disorder
Published on: August 11, 2015
MicroRNAs expression changes associated with trauma-focused psychotherapy efficacy in treatment-resistant depression:
Lisa Buson1, Rosana Carvalho Silva2, Chiara Galbiati3
1IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Genetic Unit, Brescia, Italy.
Neuroscience Applied
|July 28, 2026
Summary
Trauma-focused psychotherapy in treatment-resistant depression (TRD) patients with early life stress (ELS) history modulated plasma microRNAs (miRNAs). Specific miRNAs like miR-132-3p, miR-125b-5p, and miR-139-5p may indicate treatment response and underlying neuroplastic mechanisms.
Area of Science:
- Neuroscience
- Genetics
- Psychiatry
Background:
- Early life stress (ELS) is a significant risk factor for major depressive disorder (MDD) and treatment-resistant depression (TRD).
- MicroRNAs (miRNAs) are crucial gene regulators implicated in stress response and depression pathophysiology, acting as potential biomarkers.
- Lasting neurobiological and epigenetic changes from ELS contribute to depression vulnerability.
Purpose of the Study:
- To investigate plasma miRNA expression changes in TRD patients with ELS history following trauma-focused psychotherapy.
- To identify potential miRNA biomarkers associated with treatment response in this patient population.
- To explore the role of miRNA-mediated pathways in the efficacy of psychotherapy for TRD.
Main Methods:
- A miRNomic approach was used, quantifying plasma miRNA levels in 24 TRD patients before and after 8 weeks of trauma-focused cognitive behavioural therapy (TF-CBT) or eye movement desensitization and reprocessing (EMDR).
- Depressive symptoms were assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS).
- Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was employed for miRNA quantification, followed by statistical analyses, including pathway enrichment and correlational analyses.
Main Results:
- Psychotherapy led to nominal downregulation of 22 miRNAs, with miR-132-3p significantly downregulated after multiple testing correction.
- Pathway analysis revealed involvement of inflammation, neuroplasticity, and stress response pathways (e.g., Hippo, Wnt, PI3K-Akt).
- Correlational analyses suggested miR-139-5p, miR-125b-5p, and miR-132-3p may serve as potential biomarkers for treatment response, although not all reached statistical significance after correction.
Conclusions:
- Trauma-focused psychotherapies may induce peripheral miRNA modulations correlated with clinical improvements in TRD patients with ELS.
- Specific miRNAs, including miR-132-3p, miR-125b-5p, and miR-139-5p, show potential as biomarkers for psychotherapy efficacy.
- These findings support the involvement of miRNA-mediated neuroplastic and inflammatory mechanisms in the molecular basis of psychotherapy for ELS-exposed TRD patients.
