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Author Notes:

Helen S. Mayberg, MD, mailing address: Emory University, Dept of Psychiatry, 101 Woodruff Circle, WMB 4313, Atlanta, GA 30322, hmayber@emory.edu, phone: (404) 727-6740, fax: (404) 727-6743.

We thank the treating psychotherapists: Sheethal Reddy, PhD, Patrick Sylvers, PhD, Lorie Ritschel, PhD, Meredith Jones, PhD, Mary Heekin, LCSW, Maryrose Gerardi, PhD, and Jill Rosenberg, LCSW; treating physicians: Ebrahim Haroon, MD, Jeffrey Rakofsky, MD, Dylan Wint, MD, Corey Beck, MD; clinical coordinators: Ronald Chismar, Melanie Galanti, Rachelle Gibson, Lauren Marx, Melissa McKenzie, and Tanja Mletzko; Blinded Raters: Margo Aaron, Yara Betancourt, Cristina Velasquez Delgado, Novall Khan, Ximena Marincic, and Christopher Vaughan; and the imaging team: Rebecca DeMayo, Eundria Hill, Kiseung Choi, Justin Rajendra for their contributions.

Complete list of disclosures available in full text.


Research Funding:

This study was supported by NIH grants R01 MH073719 (HSM); T32 GM08695 (CLM); K23 MH086690 (BWD); K23 MH077869 (PEH).


  • Science & Technology
  • Life Sciences & Biomedicine
  • Neurosciences
  • Psychiatry
  • Neurosciences & Neurology
  • Antidepressant medication
  • biomarker
  • depression
  • psychotherapy
  • subcallosal cingulate
  • superior temporal sulcus

Pretreatment Brain States Identify Likely Nonresponse to Standard Treatments for Depression


Journal Title:

Biological Psychiatry


Volume 76, Number 7


, Pages 527-535

Type of Work:

Article | Post-print: After Peer Review


Background: Treatment approaches for major depressive disorder (MDD) result in approximately one third of patients achieving remission after a first treatment. Added treatment generally improves remission rates, but approximately one third of all patients fail to respond after several treatments (sequential monotherapies or combined treatment). A pretreatment biomarker could help identify these patients. Overactivity of the subcallosal cingulate has been associated with failure of response to treatment in MDD, and it is a potential candidate for such a biomarker. Methods: Investigators enrolled 82 patients with MDD currently not receiving treatment in a two-phase treatment study. Patients underwent a fluorodeoxyglucose positron emission tomography scan. After scanning, patients were randomly assigned to 12 weeks of treatment with either escitalopram or cognitive-behavioral therapy (CBT). Patients not achieving remission after 12 weeks of initial treatment were treated with an additional 12 weeks of escitalopram plus CBT. Subcallosal cingulate metabolism was compared between patients who failed to achieve a response and patients who achieved remission as a result of either phase one or phase two treatment. This analysis was followed by a whole-brain analysis making the same comparison. Results: After two phases of treatment (24 weeks), 36 patients were identified as remitters, 6 patients were responders, and 9 patients were nonresponders. Subcallosal cingulate metabolism was significantly higher in nonresponders than remitters. In the follow-up wholebrain analysis, increased superior temporal sulcus activity was also associated with nonresponse to two treatments. Conclusions: Patients with MDD who fail to achieve remission as a result of CBT or escitalopram, either alone or in combination, have a distinct brain metabolic pattern compared with patients who achieve remission as a result of CBT, escitalopram, or their combination.

Copyright information:

© 2014 Society of Biological Psychiatry.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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