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ORIGINAL RESEARCH article
Front. Psychiatry
Sec. Mood Disorders
Volume 16 - 2025 | doi: 10.3389/fpsyt.2025.1584673
Impact of repetitive Transcranial Magnetic Stimulation on clinical and cognitive outcomes, and brain-derived neurotrophic factor (BDNF) levels in treatment-resistant depression
Provisionally accepted
Enrico Ginelli 1 Lucia Sanna 1 Pasquale Paribello 1 Ulker Isayeva 1 Giorgio Corona 2
Clement C Zai 3 Daniela Manca 1 Maria Novella Iaselli 1
ROBERTO COLLU 4 Federica Pinna 1
Maria Scherma 4
Mirko Manchia 1* Paola Fadda 4
Bernardo Carpiniello 1- 1 Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Nova Scotia, Italy
- 2 Studio Corona, Cagliari, Sardinia, Italy
- 3 University of Toronto, Toronto, Ontario, Canada
- 4 Department of Biomedical Sciences, University of Cagliari, Cagliari, Nova Scotia, Italy
Treatment-resistant depression (TRD) affects approximately 30% of patients with major depressive disorder (MDD), for whom effective treatment options are limited. Repetitive transcranial magnetic stimulation (rTMS) has shown efficacy in alleviating depressive symptoms in TRD. However, it remains unclear if these improvements are driven or mediated by changes in cognitive function or biological markers, such as brain-derived neurotrophic factor (BDNF). This study examines the effects of rTMS on depressive symptoms, cognition, and BDNF levels, as well as the potential moderating role of lifetime suicidal attempts (LSA) on cognition and the predictive value of baseline BDNF for clinical outcomes. Twenty-five TRD patients were included, with 13 in the rTMS treatment group (receiving 20 sessions of rTMS over four weeks) and 12 as control group. Depression severity, cognitive function (Mini-Mental State Examination, Verbal Fluency, Digit Span), and serum BDNF levels were measured pre-and post-treatment. Mixed-effects linear regression models assessed clinical and biological associations. rTMS significantly reduced HAM-D (p < 0.001) and CGI (p < 0.001) scores compared to controls. Cognitive performance improved significantly in MMSE (p = 0.049) and Digit Span (p = 0.04), with no significant changes in BDNF levels (p = 0.39). LSA did not moderate cognitive outcomes, and baseline BDNF did not predict clinical improvement (p = 0.68). rTMS reduced depressive symptoms in TRD patients, with modest cognitive benefits. Baseline BDNF did not predict outcomes, though the lack of significant change suggests complex neuroplastic responses. Future studies should include larger samples and refined biomarker assessments.
Keywords: rTMS, Depression, treatment-resistance, BDNF, Suicidality, neuroplasticity
Received: 27 Feb 2025; Accepted: 20 Mar 2025.
Copyright: © 2025 Ginelli, Sanna, Paribello, Isayeva, Corona, Zai, Manca, Iaselli, COLLU, Pinna, Scherma, Manchia, Fadda and Carpiniello. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Mirko Manchia, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, B3H 2E2, Nova Scotia, Italy
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