Neuroanatomical predictors of response to subcallosal cingulate deep brain stimulation for treatment-resistant depression

Neuroanatomical predictors of response to subcallosal cingulate deep brain stimulation for treatment-resistant depression

J Psychiatry Neurosci 2020;45(1):45-54 | PDF | Appendix

Tejas Sankar, MDCM; M. Mallar Chakravarty, PhD; Natasha Jawa, MSc; Stanley X. Li, MSc; Peter Giacobbe, MD; Sidney H. Kennedy, MD; Sakina J. Rizvi, PhD; Helen S. Mayberg, MD; Clement Hamani, MD, PhD; Andres M. Lozano, MD, PhD

Background: Deep brain stimulation targeting the subcallosal cingulate gyrus (SCG DBS) improves the symptoms of treatment-resistant depression in some patients, but not in others. We hypothesized that there are pre-existing structural brain differences between responders and nonresponders to SCG DBS, detectable using structural MRI.

Methods: We studied preoperative, T1-weighted MRI scans of 27 patients treated with SCG DBS from 2003 to 2011. Responders (n = 15) were patients with a > 50% improvement in Hamilton Rating Scale for Depression score following 12 months of SCG DBS. Preoperative subcallosal cingulate gyrus grey matter volume was obtained using manual segmentation by a trained observer blinded to patient identity. Volumes of hippocampus, thalamus, amygdala, whole-brain cortical grey matter and white matter volume were obtained using automated techniques.

Results: Preoperative subcallosal cingulate gyrus, thalamic and amygdalar volumes were significantly larger in patients who went on to respond to SCG-DBS. Hippocampal volume did not differ between groups. Cortical grey matter volume was significantly smaller in responders, and cortical grey matter:white matter ratio distinguished between responders and nonresponders with high sensitivity and specificity.

Limitations: Normalization by intracranial volume nullified some between-group differences in volumetric measures.

Conclusion: There are structural brain differences between patients with treatment-resistant depression who respond to SCG DBS and those who do not. Specifically, the structural integrity of the subcallosal cingulate gyrus target region and its connected subcortical areas, and variations in cortical volume across the entire brain, appear to be important determinants of response. Structural MRI shows promise as a biomarker in deep brain stimulation for depression, and may play a role in refining patient selection for future trials.


Sumitted Oct. 31, 2018; Revised Mar. 20, 2019; Accepted Apr. 8, 2019; Published online Sept. 17, 2019

Affiliations: From the Division of Neurosurgery, University of Alberta, Edmonton, Alberta, Canada (Sankar); the Department of Psychiatry, McGill University, Montreal, Quebec, Canada (Chakravarty); the Department of Biological and Biomedical Engineering, McGill University, Montreal, Quebec, Canada (Chakravarty); the Division of Neurosurgery, University of Toronto, Toronto, Ontario, Canada (Jawa, Li, Hamani, Lozano); the Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada (Giacobbe, Kennedy, Rizvi); and the Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, United States (Mayberg).

Funding: T. Sankar’s work on this manuscript was supported by a Canadian Institutes of Health Research (CIHR) fellowship award. A. Lozano was supported by a Canada Research Chair in Neuroscience and the R.R. Tasker Chair in Functional Neurosurgery.

Competing interests: M. Chakravarty is a member of the JPN editorial board; he was not involved in the decision-making on this manuscript. P. Giacobbe and S. Kennedy have received honoraria from St. Jude Medical, Inc. H. Mayberg has received consulting and intellectual property fees from St. Jude Medical, Inc. C. Hamani is a consultant for St. Jude Medical, Inc. A. Lozano is a consultant to Medtronic, Inc., St. Jude Medical, Inc., and Boston Scientific, Inc.; serves on the scientific advisory board of Ceregene, Codman, Neurophage, Aleva and Alcyone Life Sciences; is co-founder of Functional Neuromodulation Inc.; and holds intellectual property in the field of deep brain stimulation. T. Sankar, N. Jawa, S. Li and S. Rizvi report no biomedical financial interests or other conflicts of interest.

Contributors: T. Sankar, C. Hamani and A. Lozano designed the study. T. Sankar, N. Jawa, S. Li, P. Giacobbe, S. Kennedy and S. Rizvi acquired the data, which T. Sankar, M. Chakravarty, P. Giacobbe, S. Kennedy and H. Mayberg analyzed. T. Sankar, M. Chakravarty, S. Kennedy and S. Rizvi wrote the article, which all authors reviewed. All authors approved the final version to be published and can certify that no other individuals not listed as authors have made substantial contributions to the paper.

DOI: 10.1503/cjs.180207

Correspondence to: T. Sankar, Division of Neurosurgery, Department of Surgery, University of Alberta; 2D Department of Surgery, Walter C. Mackenzie Health Sciences Centre, 8440-112 Street NW, Edmonton, AB, T6G 2B7; tsankar@ualberta.ca