• Juan F Gálvez, Zafer Keser, Benson Mwangi, Amna A Ghouse, Albert J Fenoy, Paul E Schulz, Marsal Sanches, Joao Quevedo, Sudhakar Selvaraj, Prashant Gajwani, Giovana Zunta-Soares, Khader M Hasan, and Jair C Soares.
• UT Center of Excellence on Mood Disorders, The University of Texas Health Science Center at Houston, Houston, TX, USA; Department of Psychiatry, Pontificia Universidad Javeriana School of Medicine, Bogotá, Colombia. Electronic address: Juan.F.GalvezFlorez@uth.tmc.edu.
• Prog. Neuropsychopharmacol. Biol. Psychiatry. 2015 Apr 3; 58: 59-70.

IntroductionDespite a wide variety of therapeutic interventions for major depressive disorder (MDD), treatment resistant depression (TRD) remains to be prevalent and troublesome in clinical practice. In recent years, deep brain stimulation (DBS) has emerged as an alternative for individuals suffering from TRD not responding to combining antidepressants, multiple adjunctive strategies and electroconvulsive therapy (ECT). Although the best site for TRD-DBS is still unclear, pilot data suggests that the medial forebrain bundle (MFB) might be a key target to accomplish therapeutic efficacy in TRD patients.ObjectiveTo explore the anatomic, electrophysiologic, neurocognitive and treatment data supporting the MFB as a target for TRD-DBS.ResultsThe MFB connects multiple targets involved in motivated behavior, mood regulation and antidepressant response. Specific phenomenology associated with TRD can be linked specifically to the superolateral branch (sl) of the MFB (slMFB). TRD patients who received DBS-slMFB reported high response/remission rates with an improvement in functioning and no significant adverse outcomes in their physical health or neurocognitive performance.DiscussionThe slMFB is an essential component of a network of structural and functional pathways connecting different areas possibly involved in the pathogenesis of mood disorders. Therefore, the slMFB should be considered as an exciting therapeutic target for DBS therapy to achieve a sustained relief in TRD patients.ConclusionThere is an urgent need for clinical trials exploring DBS-slMFB in TRD. Further efforts should pursue measuring baseline pro-inflammatory cytokines, oxidative stress, and cognition as possible biomarkers of DBS-slMFB response in order to aid clinicians in better patient selection.Copyright © 2014 Elsevier Inc. All rights reserved.

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