Longitudinal Study on the Sustainability of Transcranial Magnetic Stimulation Protocols - Biomarkers

Despite advances in the effective treatment of major depressive disorder using repetitive transcranial magnetic stimulation (rTMS), the processes that determine a patient's response trajectory remain poorly understood. Currently, there are no validated clinical or neurophysiological markers that can identify factors predicting the durability of the response to rTMS at the individual level. This constitutes a major limitation for planning individualised treatments and highlights the need for precision medicine approaches and reliable biomarkers to predict the long-term efficacy of TMS-based interventions, thereby enabling more informed clinical decisions and optimised resource allocation. rTMS is assumed to work by inducing neuroplasticity on multiple levels of the nervous system, ranging from modulating neurotransmitter release to changing structural and functional brain circuits. While rTMS likely acts as a universal modulator of neuroplasticity, the exact mechanisms are not fully established, especially regarding long-term durability. The LONGISTIM-BIO study ("Longitudinal Study on the Durability of Transcranial Magnetic Stimulation Protocols - Biomarkers") aims to explore the duration of the treatment effect following an initial response to a course of TMS treatment and examines potential neurophysiological and clinical/sociodemographic predictors associated with the trajectories of the treatment effect. More explicitly, it examines neuroplasticity as a biomarker of treatment response durability, and explores its association with heart-brain-coupling (HBC), a physiological marker of rTMS target engagement, as well as inflammation, as measured by a blood test (white blood cells, C-reactive protein (CRP)). During this study, participants undergo an rTMS treatment as per standard clinical care. They receive daily sessions of 20Hz rTMS targeting the left dorsolateral prefrontal cortex during which the heart rate will be recorded. Before the first rTMS session, after the last session, and one month after the last session, the severity of depression is evaluated using both the MADRS and the PHQ-8 questionnaire. At the one-month follow-up, the effectiveness of the course is determined by a 50% improvement in the MADRS score. Following the 1-month follow-up visit, if meeting the inclusion criteria, patients will receive bi-weekly assessments of depression severity (PHQ-8 as primary and MADRS self-rated questionnaire as secondary outcome). If two consecutive PHQ-8 questionnaires are pathological (score ≥10), a new rTMS course is scheduled with the shortest delay possible. During this new course of treatment, participation in the study includes: * a blood draw prior to the first TMS session * 4 magnetic resonance imaging (MRI) scans: #1 before the course of treatment, #2 at the end of the course, #3 one month after the end of the treatment, and #4 upon the expected date of relapse. Patients will again be monitored using self-report questionnaires (PHQ-8 and MADRS-SR) every 2 weeks until a relapse occurs.