Rostral anterior cingulate glutamate predicts response to subcallosal deep brain stimulation for resistant depression

Abstract Background : Deep brain stimulation (DBS) of the subcallosal cingulate (SCC) provided benefit for treatment-resistant depression (TRD) in open-label studies but failed in a recent randomized sham-controlled trial. Informed patient selection, based on reliable biomarkers, is needed to optimize outcome. We investigated if rostral anterior cingulate (rACC) glutamate/glutamine concentration could serve as a potential biomarker of response. Methods : Sixteen adults with TRD (Major Depression; MDD = 14; Bipolar Depression; BD =2) underwent proton magnetic resonance spectroscopy using a short-echo proton spectroscopy with a voxel placed in the rACC, prior to DBS. Improvement in depression was assessed using the 17-item Hamilton Rating Scale for Depression (HRSD). Glutamate and glutamine concentrations at baseline in the rACC were examined in relation to clinical outcomes at six months. Results : Lower baseline glutamate predicted significant reduction in HRSD scores in all patients (p=0.018), and predicted both HDRS reduction (p=0.002) and 6-month response outcome in MDD patients (p=0.013). Neither baseline glutamine, nor glutamine/glutamate ratio significantly related to outcome nor symptom improvement. Limitations : Our study was limited by sample size, though it is large for a DBS study. We measured from a single voxel in the brain, so we cannot be certain our findings are specific to the rACC. Conclusions : These preliminary results suggest that baseline rACC-glutamate concentration could serve as a response-predictive biomarker for SCC-DBS, particularly in patients with resistant major depression. If our findings are replicated and validated, rACC-glutamate may provide a basis to prospectively select TRD patients to improve likelihood of response to SCC-DBS.