Impact of repetitive transcranial magnetic stimulation on clinical and cognitive outcomes, and brain-derived neurotrophic factor levels in treatment-resistant depression

IntroductionTreatment-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...

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Main Authors: Enrico Ginelli, Lucia Sanna, Pasquale Paribello, Ulker Isayeva, Giorgio Corona, Clement C. Zai, Daniela Manca, Maria Novella Iaselli, Roberto Collu, Federica Pinna, Maria Scherma, Mirko Manchia, Paola Fadda, Bernardo Carpiniello
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-04-01
Series:Frontiers in Psychiatry
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Online Access:https://www.frontiersin.org/articles/10.3389/fpsyt.2025.1584673/full
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author Enrico Ginelli
Lucia Sanna
Pasquale Paribello
Pasquale Paribello
Ulker Isayeva
Ulker Isayeva
Giorgio Corona
Clement C. Zai
Clement C. Zai
Daniela Manca
Maria Novella Iaselli
Roberto Collu
Federica Pinna
Federica Pinna
Maria Scherma
Maria Scherma
Mirko Manchia
Mirko Manchia
Mirko Manchia
Paola Fadda
Paola Fadda
Bernardo Carpiniello
Bernardo Carpiniello
author_facet Enrico Ginelli
Lucia Sanna
Pasquale Paribello
Pasquale Paribello
Ulker Isayeva
Ulker Isayeva
Giorgio Corona
Clement C. Zai
Clement C. Zai
Daniela Manca
Maria Novella Iaselli
Roberto Collu
Federica Pinna
Federica Pinna
Maria Scherma
Maria Scherma
Mirko Manchia
Mirko Manchia
Mirko Manchia
Paola Fadda
Paola Fadda
Bernardo Carpiniello
Bernardo Carpiniello
author_sort Enrico Ginelli
collection DOAJ
description IntroductionTreatment-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).MethodsThis 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.ResultsrTMS 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).DiscussionrTMS 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.
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spelling doaj-art-d0efffef4dad47da9395e5591f6bdf262025-08-20T02:25:59ZengFrontiers Media S.A.Frontiers in Psychiatry1664-06402025-04-011610.3389/fpsyt.2025.15846731584673Impact of repetitive transcranial magnetic stimulation on clinical and cognitive outcomes, and brain-derived neurotrophic factor levels in treatment-resistant depressionEnrico Ginelli0Lucia Sanna1Pasquale Paribello2Pasquale Paribello3Ulker Isayeva4Ulker Isayeva5Giorgio Corona6Clement C. Zai7Clement C. Zai8Daniela Manca9Maria Novella Iaselli10Roberto Collu11Federica Pinna12Federica Pinna13Maria Scherma14Maria Scherma15Mirko Manchia16Mirko Manchia17Mirko Manchia18Paola Fadda19Paola Fadda20Bernardo Carpiniello21Bernardo Carpiniello22Section of Psychiatry, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, ItalySection of Psychiatry, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, ItalySection of Psychiatry, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, ItalyUnit of Clinical Psychiatry, University Hospital Agency of Cagliari, Cagliari, ItalySection of Psychiatry, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, ItalyUnit of Clinical Psychiatry, University Hospital Agency of Cagliari, Cagliari, ItalyCenter for Transcranial Magnetic Stimulation, Cagliari, ItalyTanenbaum Centre for Pharmacogenetics, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, CanadaDepartment of Psychiatry, Institute of Medical Science, Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, CanadaSection of Psychiatry, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, ItalySection of Psychiatry, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, ItalyDepartment of Biomedical Sciences, Division of Neuroscience and Clinical Pharmacology, University of Cagliari, Cagliari, ItalySection of Psychiatry, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, ItalyUnit of Clinical Psychiatry, University Hospital Agency of Cagliari, Cagliari, ItalyDepartment of Biomedical Sciences, Division of Neuroscience and Clinical Pharmacology, University of Cagliari, Cagliari, ItalyCentro Nazionale delle Ricerche (CNR) Institute of Neuroscience - Cagliari, National Research Council, Cagliari, ItalySection of Psychiatry, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, ItalyUnit of Clinical Psychiatry, University Hospital Agency of Cagliari, Cagliari, ItalyDepartment of Pharmacology, Dalhousie University, Halifax, NS, CanadaDepartment of Biomedical Sciences, Division of Neuroscience and Clinical Pharmacology, University of Cagliari, Cagliari, ItalyCentro Nazionale delle Ricerche (CNR) Institute of Neuroscience - Cagliari, National Research Council, Cagliari, ItalySection of Psychiatry, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, ItalyUnit of Clinical Psychiatry, University Hospital Agency of Cagliari, Cagliari, ItalyIntroductionTreatment-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).MethodsThis 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.ResultsrTMS 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).DiscussionrTMS 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.https://www.frontiersin.org/articles/10.3389/fpsyt.2025.1584673/fullrTMSdepressiontreatment-resistanceBDNFsuicidalityneuroplasticity
spellingShingle Enrico Ginelli
Lucia Sanna
Pasquale Paribello
Pasquale Paribello
Ulker Isayeva
Ulker Isayeva
Giorgio Corona
Clement C. Zai
Clement C. Zai
Daniela Manca
Maria Novella Iaselli
Roberto Collu
Federica Pinna
Federica Pinna
Maria Scherma
Maria Scherma
Mirko Manchia
Mirko Manchia
Mirko Manchia
Paola Fadda
Paola Fadda
Bernardo Carpiniello
Bernardo Carpiniello
Impact of repetitive transcranial magnetic stimulation on clinical and cognitive outcomes, and brain-derived neurotrophic factor levels in treatment-resistant depression
Frontiers in Psychiatry
rTMS
depression
treatment-resistance
BDNF
suicidality
neuroplasticity
title Impact of repetitive transcranial magnetic stimulation on clinical and cognitive outcomes, and brain-derived neurotrophic factor levels in treatment-resistant depression
title_full Impact of repetitive transcranial magnetic stimulation on clinical and cognitive outcomes, and brain-derived neurotrophic factor levels in treatment-resistant depression
title_fullStr Impact of repetitive transcranial magnetic stimulation on clinical and cognitive outcomes, and brain-derived neurotrophic factor levels in treatment-resistant depression
title_full_unstemmed Impact of repetitive transcranial magnetic stimulation on clinical and cognitive outcomes, and brain-derived neurotrophic factor levels in treatment-resistant depression
title_short Impact of repetitive transcranial magnetic stimulation on clinical and cognitive outcomes, and brain-derived neurotrophic factor levels in treatment-resistant depression
title_sort impact of repetitive transcranial magnetic stimulation on clinical and cognitive outcomes and brain derived neurotrophic factor levels in treatment resistant depression
topic rTMS
depression
treatment-resistance
BDNF
suicidality
neuroplasticity
url https://www.frontiersin.org/articles/10.3389/fpsyt.2025.1584673/full
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