17.4 Noninvasive Brain Stimulation for Adolescent Treatment-Resistant Depression

Objectives: New data from our group's ongoing research, with high frequency repetitive transcranial magnetic stimulation (rTMS), will be reviewed. This presentation will also survey extant literature focused on transcranial direct current stimulation (tDCS) and rTMS for adolescent treatment-resistant depression (TRD). Methods: Adolescents (n = 10) with TRD received up to 30 sessions of 10-Hz rTMS at 120 percent motor threshold, with 3,000 pulses per session applied to the left dorsolateral prefrontal cortex. Treatment localization was guided by MRI. Scalp locations with a standard 5-cm rule and Beam F3 methods were assessed for comparisons to the MRI-guided technique. Proton magnetic resonance spectroscopy scans of the anterior cingulate cortex and the left dorsolateral prefrontal cortex were collected at 3T with 8-cm3 voxels. Results: Depression severity as assessed with the Children's Depression Rating Scale-Revised improved from baseline over the course of treatment and at 6-month follow-up visits. The MRI-guided approach for treatment localization was feasible and efficient. Mean Euclidean distances between MRI-guided location and 5-cm rule location and MRI-guided location and the Beam F3 methods were different (p = 0.006). In the anterior cingulate and left dorsolateral prefrontal cortices, the glutamine to glutamate ratio increased over time with a statistically significant increase in the anterior cingulate cortex (p = 0.04). Glutamine/glutamate ratios increased in conjunction with depressive symptom improvement. Systematic reviews of tDCS suggest that sessions are safe and tolerable in adolescents, whereas studies of TRD are lacking. Conclusions: Our results suggest that 5-cm rule, Beam F3, and MRI-guided localization approaches in adolescents may yield different locations for stimulation. High-frequency rTMS applied to the left dorsolateral prefrontal cortex may modulate glutamate neurochemistry in adolescents with TRD. Future work with tDCS might offer a more accessible, cost-effective option. Given the potential family burden of daily rTMS treatments, future research efforts also should focus on baseline predictive biomarkers for patient selection and dosing strategies.