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

Darren L. Clark, Frank P. MacMaster, Elliot C. Brown, Zelma H.T. Kiss, Rajamannar Ramasubbu

Research output: Contribution to journalArticle


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 (HDRS). 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 HDRS scores in all TRD patients (p = 0.018), and predicted both HDRS reduction (p = 0.002) and 6-month response outcome in MDD-TRD patients (p = 0.013). Neither baseline glutamine nor glutamine/glutamate ratio significantly related to outcome or 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.

Original languageEnglish
Pages (from-to)90-94
Number of pages5
JournalJournal of affective disorders
Publication statusPublished - Apr 1 2020



  • Anterior cingulate cortex
  • Deep brain stimulation
  • Glutamate
  • Glutamine
  • Magnetic resonance imaging
  • Treatment-resistant depression

ASJC Scopus subject areas

  • Clinical Psychology
  • Psychiatry and Mental health

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