Baseline glymphatic efficiency is associated with plasma BDNF changes following rTMS: an exploratory biomarker study...

Brain-derived neurotrophic factor (BDNF) has been proposed as a potential biological correlate of repetitive transcranial magnetic stimulation (rTMS). However, its relationship with clinical and cognitive outcomes in mood disorders remains unclear. In this prospective exploratory pre-post study, 28 adults with major depressive disorder or bipolar disorder underwent 12 sessions of high-frequency left dorsolateral prefrontal cortex (DLPFC) rTMS while continuing pharmacological treatment. Assessments included Hamilton Rating Scale for Depression (HDRS-24), Wisconsin Card Sorting Test (WCST), plasma BDNF, and baseline glymphatic efficiency (diffusion tensor image analysis along the perivascular space (DTI-ALPS)). Over the study period, HDRS-24 scores and WCST perseverative errors decreased, whereas the number of WCST categories completed did not significantly change at the group level; peripheral plasma BDNF also increased. Greater BDNF change ratios were associated with higher baseline ALPS indices and with individual variability in WCST categories completed, but not with changes in depressive symptoms or perseverative errors. Given the uncontrolled design, these longitudinal changes should be interpreted as associations observed over time rather than treatment effects attributable to rTMS. Baseline glymphatic efficiency may therefore reflect an individual biological characteristic associated with neurotrophic responsiveness to rTMS. These exploratory findings require replication in larger controlled studies using standard clinical protocols.