The effects of melancholic features on the efficacy of high-frequency rTMS in adolescents and young adults with major depressive disorder.

Objective: This research examined the effects of neuronavigated high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) on adolescents and young adults with major depressive disorder (AYA-MDD) with melancholic features. It also explored neuroimaging differences between melancholic (MD) and non-melancholic (NMD) AYA-MDD subtypes.

Method: Forty-four AYA-MDD participants (14 MD, 30 NMD) underwent 10 daily HF-rTMS sessions over two weeks. Resting-state fMRI scans were conducted pre- and post-treatment on 35 individuals (13 MD). The default mode network (DMN) was analyzed via independent component analysis (ICA). Depressive symptoms were measured using the HDRS-17 and three dimensions: somatic disturbances (SoD), core mood/anhedonia (CMA), and insomnia.

Result: SoD and insomnia improved significantly by week 1, while CMA showed improvement after two weeks. No between-group outcome differences were found. MD patients had baseline hyperactivity in the right frontal gyrus and hypoactivity in the right precuneus compared to healthy controls (HC). NMD patients showed right frontal gyrus hyperactivity and right cuneus hypoactivity relative to HC. MD patients also had greater right frontal gyrus activity and lower right precuneus activity than NMD patients. Post-treatment, MD patients exhibited increased left precuneus/cuneus activity, while NMD patients showed reduced left middle frontal gyrus/right angular gyrus activity. No correlations emerged between brain regions and HDRS-6 reduction.

Conclusion: Melancholic features may delay early HF-rTMS response, necessitating at least two weeks of treatment for core symptom relief. While pre/post-treatment brain changes differed between groups, DMN posterior region modulation appears central to rTMS therapeutic effects.