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Cited by 118Deep Brain Stimulation and Movement DisordersTreatment of Major DepressionObsessive-Compulsive Spectrum Disorders

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A longitudinal study on deep brain stimulation of the medial forebrain bundle for treatment-resistant depression

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Fenoy, Albert J., Schulz, Paul E., Selvaraj, Sudhakar, Burrows, Christina L., Zunta-Soares, Giovanna, Durkin, Kathryn, Zanotti-Fregonara, Paolo, Quevedo, Joao, Soares, Jair C.·2018·Translational Psychiatry
DOI 10.1038/s41398-018-0160-4PMC PMC5986795
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Abstract

Abstract Deep brain stimulation (DBS) to the superolateral branch of the medial forebrain bundle (MFB) has been reported to lead to rapid antidepressant effects. In this longitudinal study, we expand upon the initial results we reported at 26 weeks (Fenoy et al., 2016), showing sustained antidepressant effects of MFB DBS on six patients with treatment-resistant depression (TRD) over 1 year. The Montgomery-Åsberg Depression Rating Scale (MADRS) was used as the primary assessment tool. Deterministic fiber tracking was used to individually map the target area; analysis was performed to compare modulated fiber tracts between patients. Intraoperatively, upon stimulation at target, responders reported immediate increases in energy and motivation. An insertional effect was seen during the 4-week sham stimulation phase from baseline (28% mean MADRS reduction,p = 0.02). However, after 1 week of initiating stimulation, three of six patients had a > 50% decrease in MADRS scores relative to baseline (43% mean MADRS reduction,p = 0.005). One patient withdrew from study participation. At 52 weeks, four of remaining five patients have > 70% decrease in MADRS scores relative to baseline (73% mean MADRS reduction,p = 0.007). Evaluation of modulated fiber tracts reveals significant common orbitofrontal connectivity to the target region in all responders. Neuropsychological testing and18F-fluoro-deoxyglucose-positron emission tomography cerebral metabolism evaluations performed at baseline and at 52 weeks showed minimal changes and verified safety. This longitudinal evaluation of MFB DBS demonstrated rapid antidepressant effects, as initially reported by Schlaepfer et al. (2013), and supports the use of DBS for TRD.

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Crossref · 10.1038/s41398-018-0160-4

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Fig. 1 Study protocol. DBS, deep brain stimulation; SE, side effects; PET, positron emission tomography; Hz, Hertz; us, microseconds; V, volts; MADRS, Montgomery-Åsburg Depression Rating Scale, HAM-A, Hamilton Anxiety Scale; YMRS, Young Mania Rating Scale; CGI, Clinical Global Impressions
Fig. 1 Study protocol. DBS, deep brain stimulation; SE, side effects; PET, positron emission tomography; Hz, Hertz; us, microseconds; V, volts; MADRS, Montgomery-Åsburg Depression Rating Scale, HAM-A, Hamilton Anxiety Scale; YMRS, Young Mania Rating Scale; CGI, Clinical Global ImpressionsCC BY · PubMed Central
Fig. 2 MADRS scores recorded over time. Initiation = bilateral DBS ON at t = 4w OFF following MADRS assessment. End-sham = 4w OFF. DBS initiation begun after End-Sham assessment. Mean % change MADRS baseline–12 w ON = 64%; mean % change MADRS baseline–52 w = 73%. MADRS, Montgomery-Åsburg Depression Rating Scale. Insert: Chronology of > 50% treatment response by month ( ±) for each patient for 12 months
Fig. 2 MADRS scores recorded over time. Initiation = bilateral DBS ON at t = 4w OFF following MADRS assessment. End-sham = 4w OFF. DBS initiation begun after End-Sham assessment. Mean % change MADRS baseline–12 w ON = 64%; mean % change MADRS baseline–52 w = 73%. MADRS, Montgomery-Åsburg Depression Rating Scale. Insert: Chronology of > 50% treatment response by month ( ±) for each patient for 12 monthsCC BY · PubMed Central
Fig. 3 Representation of active cathodal contacts in two planes for each of the six patients presented in this series, superimposed upon the deterministic tractography-defined target of the medial forebrain bundle for Patient 1; this is presented on adaptations of stereotactic atlas slices from Schaltenbrand and Wahren50. a H.v. 4.5, axial view b F.p. 3.0, Coronal view. STN = subthalamic nucleus; RN = red nucleus; SNr = substantia nigra; Mmt = mammillothalamic tract; Fx = fornix; V3 = 3rd ventricle
Fig. 3 Representation of active cathodal contacts in two planes for each of the six patients presented in this series, superimposed upon the deterministic tractography-defined target of the medial forebrain bundle for Patient 1; this is presented on adaptations of stereotactic atlas slices from Schaltenbrand and Wahren50. a H.v. 4.5, axial view b F.p. 3.0, Coronal view. STN = subthalamic nucleus; RN = red nucleus; SNr = substantia nigra; Mmt = mammillothalamic tract; Fx = fornix; V3 = 3rd ventricleCC BY · PubMed Central
Fig. 4 Depiction of modulated fiber tracts (assuming an isotropic model) from active cathodal contacts in patients #1–#6. Chronological order of implantation. Significant orbitofrontal connectivity to the MFB target region seen in all responder patients but minimally seen in the non-responder Patient no. 3
Fig. 4 Depiction of modulated fiber tracts (assuming an isotropic model) from active cathodal contacts in patients #1–#6. Chronological order of implantation. Significant orbitofrontal connectivity to the MFB target region seen in all responder patients but minimally seen in the non-responder Patient no. 3CC BY · PubMed Central

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Research works printed but not linked: 1

  1. Russo, S. J. & Nestler, E. J. The brain reward circuitry in mood disorders. Nat. Rev. Neurosci. 14, 609–625 (2013). · DOI · Paper page

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Metadata

Authors
Fenoy, A. J., Schulz, P. E., Selvaraj, S., Burrows, C. L., Zunta-Soares, G., Durkin, K., Zanotti-Fregonara, P., Quevedo, J., & Soares, J. C.
Affiliations
The University of Texas Health Science Center at Houston (US)
Corresponding author
Fenoy, Albert J.
ORCID
Venue
Translational Psychiatry
Publisher
Springer Science and Business Media LLC
Published
2018-06-04
Volume
8
Issue
1
Pages
111-111
ISSN
2158-3188 (ISSN-L)
DOI
10.1038/s41398-018-0160-4
PMC
PMC5986795
OpenAlex
W2805696691
Cited by
118
References
54
Citations by year
2026: 6 · 2025: 11 · 2024: 19 · 2023: 15 · 2022: 17 · 2021: 24 · 2020: 16 · 2019: 9 · 2018: 1
FWCI
8.49
Type
journal article
Language
en
Open access
Licence
Locations
  • Translational Psychiatry (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • Medtronic
  • John S. Dunn Foundation
  • National Institutes of Health (UL1TR000371)
  • National Center for Advancing Translational Sciences
Topics
  • Health Sciences › Medicine › Clinical Neurology › Deep Brain Stimulation and Movement Disorders
  • Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
  • Social Sciences › Psychology › Clinical Psychology › Obsessive-Compulsive Spectrum Disorders
Keywords
deep brain stimulation, medial forebrain bundle, treatment-resistant depression, deterministic fiber tracking, sham stimulation, brain glucose metabolism
MeSH terms
Adult, Female, Humans, Longitudinal Studies, Male, Medial Forebrain Bundle, Middle Aged, Motivation, Neuropsychological Tests, Psychiatric Status Rating Scales, Texas, Treatment Outcome, Deep Brain Stimulation, Positron-Emission Tomography, Young Adult, Depressive Disorder, Treatment-Resistant

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