Despite its high morbidity and mortality, treatment-resistant depression (TRD) in adolescents was little known in terms of its neurobiology and how the medication affects it.

For a study, researchers compared the baseline brain volumetric differences between healthy adolescents (n=30), adolescents with major depressive disorder (MDD) (n=19), and adolescents with TRD (n=34) using automated segmentation in FreeSurfer. Transcranial magnetic stimulation (TMS) was administered to the left dorsolateral prefrontal cortex for 6 weeks, either actively (n=18) or sham (n=7), for a combined subsample of teenagers with TRD. Ten teenagers who had active TMS treatment took part in the open-label experiment. Participants in a randomized controlled experiment received active treatment (n=8) or sham treatment (n=7) for the remaining teens.

When compared to healthy adolescents, adolescents with TRD and MDD showed smaller caudal anterior cingulate cortex volumes (TRD: −3%, P=.030; MDD: −.03%, P=.041) and decreased total amygdalas (TRD and MDD: -5%, P=.032, respectively). In teenagers with TRD, 6 weeks of active TMS increased the volume of the stimulated left dorsolateral prefrontal cortex (+.4%, P=.026) and the total amygdala (+4%, P<.001).

The amygdala volumes were decreased in the group of teenagers with MDD and TRD. The volumetric result could be normalized by TMS, which increases the likelihood that TMS impacts the frontolimbic neurostructure in adolescents with TRD. TMS also seemed to have an advantageous impact close to the stimulation location.