Darren L Clark1, Frank P MacMaster2, Elliot C Brown3, Zelma H T Kiss4, Rajamannar Ramasubbu5. 1. Department of Psychiatry, University of Calgary, Calgary, AB, Canada; Department of Clinical Neuroscience, University of Calgary, AB, Canada; Mathison centre for Mental Health Research and Education, TRW building, Room 4D64, 3280 Hospital Drive NW, Calgary, Alberta, T2N 4Z6 Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada. Electronic address: dlclark@ucalgary.ca. 2. Department of Psychiatry, University of Calgary, Calgary, AB, Canada; Mathison centre for Mental Health Research and Education, TRW building, Room 4D64, 3280 Hospital Drive NW, Calgary, Alberta, T2N 4Z6 Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada; Department of Radiology, University of Calgary, Calgary, AB, Canada; Child and Adolescent Imaging Research (CAIR) Program, Alberta Children's Hospital, 2888 Shaganappi Trail NW, Calgary, Alberta, T3B 6A8 Canada. Electronic address: fmacmast@ucalgary.ca. 3. Department of Psychiatry, University of Calgary, Calgary, AB, Canada; Department of Clinical Neuroscience, University of Calgary, AB, Canada; Mathison centre for Mental Health Research and Education, TRW building, Room 4D64, 3280 Hospital Drive NW, Calgary, Alberta, T2N 4Z6 Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Neuroscience Research Center, Berlin, Germany. Electronic address: elliot.c.brown@gmail.com. 4. Department of Clinical Neuroscience, University of Calgary, AB, Canada; Mathison centre for Mental Health Research and Education, TRW building, Room 4D64, 3280 Hospital Drive NW, Calgary, Alberta, T2N 4Z6 Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada. Electronic address: zkiss@ucalgary.ca. 5. Department of Psychiatry, University of Calgary, Calgary, AB, Canada; Department of Clinical Neuroscience, University of Calgary, AB, Canada; Mathison centre for Mental Health Research and Education, TRW building, Room 4D64, 3280 Hospital Drive NW, Calgary, Alberta, T2N 4Z6 Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada. Electronic address: rramasub@ucalgary.ca.
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 (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.
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.
Authors: Matti Gärtner; Anne Weigand; Milan Scheidegger; Mick Lehmann; Patrik O Wyss; Andreas Wunder; Anke Henning; Simone Grimm Journal: Eur Arch Psychiatry Clin Neurosci Date: 2022-01-12 Impact factor: 5.760