Major depressive disorder (MDD) affects approximately 15% of youth, half of who do not respond to standard treatment. One promising intervention is repetitive transcranial magnetic stimulation (rTMS). However, response is limited, highlighting the need to focus on biomarkers to predict treatment response.

To explore baseline biomarkers of response associated with rTMS treatment in adolescent MDD.

To determine the association between dorsolateral prefrontal cortex (DLPFC) glutamate levels, cortical thickness, and cerebral blood flow (CBF) with MDD symptomatology decrease after rTMS intervention.

Twenty-four MDD youth underwent 3 weeks of rTMS, baseline and post-intervention magnetic resonance imaging scans, and short echo proton magnetic resonance spectroscopy. Response was determined by a 50% reduction of depression scores.

Depressive symptoms decreased with rTMS (t = 8.304, P = 0.00). Glutamate levels differed significantly between responders and non-responders (t = 2.24, P = 0.0039), where higher glutamate changes were associated with a better response (r = 0.416, P = 0.038). Responders also exhibited thinner DLPFC (r = –0.797, P = 0.000) and lower CBF levels.

The development of biomarkers for rTMS represents a novel and encouraging technique for a personalized and effective treatment while reducing ineffective treatment costs and personal burden in adolescent MDD.

The authors have not supplied their declaration of competing interest.