Effects of intermittent Theta Burst Stimulation and adjunctive D-Cycloserine on GABA levels in the medial Prefrontal Cortex

Motivation: Non-invasive brain stimulation is an evidenced based treatment for major depression. Change in GABA in the medial prefrontal cortex (mPFC) has been suggested as a mechanism of antidepressant effect of brain stimulation, including intermittent Theta Burst Stimulation (iTBS). Goal(s): Investigate the effect of iTBS combined with adjunctive D-Cycloserine on magnetic resonance spectroscopy measured GABA levels in the mPFC. Approach: Participants were randomized to receive adjunctive D-Cycloserine or placebo in addition to two weeks of iTBS treatment, with assessments at baseline and after two weeks of intervention. Results: There was no effect of iTBS, adjunctive D-Cycloserine or responder status on GABA levels. Impact: This study provides evidence of dissociation between GABA change and clinical response following the delivery of intermittent Theta Burst Stimulation (iTBS) in major depression. The antidepressant effects of iTBS may not rely on change in GABA within the mPFC.