Major depression (or MDD) in adolescents is a major public health problem. MDD affects
approximately 15% of adolescents; it is associated with impairment in social, family, and
academic functioning, and it is a major risk factor for suicide - a leading cause of death in
adolescents . Unfortunately, there is a paucity of treatment options for this age group.
Selective serotonin reuptake inhibitors (SSRIs) are the only class of medications approved
for treating MDD in adolescents, but rates of remission following treatment with SSRIs are
only 30 to 45 percent. Cognitive behavior therapy is associated with similar remission rates
and access is limited. Most adolescents will require more than one therapeutic intervention
in order to achieve full symptom control. Collectively, there is overwhelming evidence that
additional treatment options are urgently needed to improve outcomes for teens with MDD. One
novel treatment for adolescent MDD is repetitive transcranial magnetic stimulation (rTMS).
Studies in children have been limited (a total of 23 cases). This is surprising given the
evidence suggesting younger adult subjects with MDD respond better to rTMS (56% response
rate) than older subjects. This limited experience with rTMS for adolescent MDD represents a
substantial gap in the knowledge, recently recognized in publications calling for further
study of rTMS in adolescent depression. Most importantly, the mechanism of action of rTMS in
adolescent MDD is not well understood. The objective of this application is to develop an
understanding of the brain alterations associated with the positive clinical changes that
occur with rTMS in adolescent MDD. Such knowledge will provide the basis for pursuing rTMS
for adolescent MDD as a rational therapeutic technique.
Specific Aim: To compare the effect of rTMS on DLPFC glutamate concentration in adolescent
MDD. The investigators hypothesize an increase (normalization to controls) in DLPFC glutamate
after three weeks of rTMS. Furthermore, the change in glutamate concentration will correlate
with a change in MDD symptoms.