Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Functional connectivity changes with rapid remission from moderate-to-severe major depressive disorder

Xiaoqian Xiao, View ORCID ProfileBrandon S. Bentzley, Eleanor J. Cole, Claudia Tischler, Katy H. Stimpson, Dalton Duvio, View ORCID ProfileJames H. Bishop, Danielle D. DeSouza, View ORCID ProfileAlan Schatzberg, View ORCID ProfileCorey Keller, Keith D. Sudheimer, View ORCID ProfileNolan R. Williams
doi: https://doi.org/10.1101/672154
Xiaoqian Xiao
1Department of Psychiatry & Behavioral Sciences, Stanford University, Palo Alto, California, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Brandon S. Bentzley
1Department of Psychiatry & Behavioral Sciences, Stanford University, Palo Alto, California, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Brandon S. Bentzley
Eleanor J. Cole
1Department of Psychiatry & Behavioral Sciences, Stanford University, Palo Alto, California, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Claudia Tischler
1Department of Psychiatry & Behavioral Sciences, Stanford University, Palo Alto, California, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Katy H. Stimpson
1Department of Psychiatry & Behavioral Sciences, Stanford University, Palo Alto, California, USA
3Department of Psychology, Palo Alto University, Palo Alto, California, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Dalton Duvio
1Department of Psychiatry & Behavioral Sciences, Stanford University, Palo Alto, California, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
James H. Bishop
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for James H. Bishop
Danielle D. DeSouza
2Department of Neurology & Neurological Sciences, Stanford University, Palo Alto, California, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Alan Schatzberg
1Department of Psychiatry & Behavioral Sciences, Stanford University, Palo Alto, California, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Alan Schatzberg
Corey Keller
1Department of Psychiatry & Behavioral Sciences, Stanford University, Palo Alto, California, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Corey Keller
Keith D. Sudheimer
1Department of Psychiatry & Behavioral Sciences, Stanford University, Palo Alto, California, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Nolan R. Williams
1Department of Psychiatry & Behavioral Sciences, Stanford University, Palo Alto, California, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Nolan R. Williams
  • For correspondence: nolanw@stanford.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

Abstract

Major depressive disorder (MDD) is prevalent and debilitating, and development of improved treatments is limited by insufficient understanding of the neurological changes associated with disease remission. In turn, efforts to elucidate these changes have been challenging due to disease heterogeneity as well as limited effectiveness, delayed onset, and significant off-target effects of treatments. We developed a form of repetitive transcranial magnetic stimulation of the left dorsolateral prefrontal cortex (lDLPFC) that in an open-label study was associated with remission from MDD in 90% of individuals in 1-5 days (Stanford Accelerated Intelligent Neuromodulation Therapy, SAINT). This provides a tool to begin exploring the functional connectivity (FC) changes associated with MDD remission. Resting-state fMRI scans were performed before and after SAINT in 18 participants with moderate-to-severe, treatment-resistant MDD. FC was determined between regions of interest defined a priori by well-described roles in emotion regulation. Following SAINT, FC was significantly decreased between subgenual cingulate cortex (sgACC) and 3 of 4 default mode network (DMN) nodes. Significant reductions in FC were also observed between the following: DLPFC-striatum, DLPFC-amygdala, DMN-amygdala, DMN-striatum, and amygdala-striatum. Greater clinical improvements were correlated with larger decreases in FC between DLPFC-amygdala and DLPFC-insula, as well as smaller decreases in FC between sgACC-DMN. Greater clinical improvements were correlated with lower baseline FC between DMN-DLPFC, DMN-striatum, and DMN-ventrolateral prefrontal cortex. The multiple, significant reductions in FC we observed following SAINT and remission from depression support the hypothesis that MDD is a state of hyper-connectivity within these networks, and rapid decoupling of network nodes may lead to rapid remission from depression.

Significance statement Major depressive disorder is common and debilitating. It has been difficult to study the brain changes associated with recovery from depression, because treatments take weeks-to-months to become effective, and symptoms fail to resolve in many people. We recently developed a type of magnetic brain stimulation called SAINT. SAINT leads to full remission from depression in 90% of people within 5 days. We used SAINT and functional magnetic resonance imaging to determine how the brain changes with rapid remission from depression. We found changes in areas of the brain associated with emotion regulation. This provides a significantly clearer picture of how the non-depressed brain differs from the depressed brain, which can be used to develop rapid and effective treatments for depression.

Competing Interest Statement

Dr. Bentzley receives consulting payments from Owl Insights.

Footnotes

  • ↵# Co-first authors

  • NRW and KDS have filed intellectual property on the methodology discussed in this manuscript.

  • Reformatted for new submission

  • Abbreviations

    AI
    anterior insula
    BLA
    basolateral amygdala
    CMA
    centromedian amygdala
    dACC
    dorsal anterior cingulate cortex
    DLPFC
    dorsolateral prefrontal cortex
    DMN
    default mode network
    exeS
    executive striatum
    FC
    functional connectivity
    HAMD
    Hamilton Depression Rating Scale
    Ins
    insula
    limS
    limbic striatum
    MADRS
    Montgomery Asberg Depression Rating Scale
    MDD
    major depressive disorder
    SA
    superficial amygdala
    sgACC
    subgenual anterior cingulate cortex
    SN
    salience network
    VLPFC
    ventrolateral prefrontal cortex.
    Preceding r
    right
    preceding l
    left.
  • Copyright 
    The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
    Back to top
    PreviousNext
    Posted June 18, 2020.
    Download PDF
    Email

    Thank you for your interest in spreading the word about bioRxiv.

    NOTE: Your email address is requested solely to identify you as the sender of this article.

    Enter multiple addresses on separate lines or separate them with commas.
    Functional connectivity changes with rapid remission from moderate-to-severe major depressive disorder
    (Your Name) has forwarded a page to you from bioRxiv
    (Your Name) thought you would like to see this page from the bioRxiv website.
    CAPTCHA
    This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
    Share
    Functional connectivity changes with rapid remission from moderate-to-severe major depressive disorder
    Xiaoqian Xiao, Brandon S. Bentzley, Eleanor J. Cole, Claudia Tischler, Katy H. Stimpson, Dalton Duvio, James H. Bishop, Danielle D. DeSouza, Alan Schatzberg, Corey Keller, Keith D. Sudheimer, Nolan R. Williams
    bioRxiv 672154; doi: https://doi.org/10.1101/672154
    Reddit logo Twitter logo Facebook logo LinkedIn logo Mendeley logo
    Citation Tools
    Functional connectivity changes with rapid remission from moderate-to-severe major depressive disorder
    Xiaoqian Xiao, Brandon S. Bentzley, Eleanor J. Cole, Claudia Tischler, Katy H. Stimpson, Dalton Duvio, James H. Bishop, Danielle D. DeSouza, Alan Schatzberg, Corey Keller, Keith D. Sudheimer, Nolan R. Williams
    bioRxiv 672154; doi: https://doi.org/10.1101/672154

    Citation Manager Formats

    • BibTeX
    • Bookends
    • EasyBib
    • EndNote (tagged)
    • EndNote 8 (xml)
    • Medlars
    • Mendeley
    • Papers
    • RefWorks Tagged
    • Ref Manager
    • RIS
    • Zotero
    • Tweet Widget
    • Facebook Like
    • Google Plus One

    Subject Area

    • Clinical Trials
    Subject Areas
    All Articles
    • Animal Behavior and Cognition (4672)
    • Biochemistry (10338)
    • Bioengineering (7658)
    • Bioinformatics (26299)
    • Biophysics (13501)
    • Cancer Biology (10672)
    • Cell Biology (15412)
    • Clinical Trials (138)
    • Developmental Biology (8487)
    • Ecology (12805)
    • Epidemiology (2067)
    • Evolutionary Biology (16830)
    • Genetics (11382)
    • Genomics (15469)
    • Immunology (10601)
    • Microbiology (25166)
    • Molecular Biology (10205)
    • Neuroscience (54383)
    • Paleontology (399)
    • Pathology (1667)
    • Pharmacology and Toxicology (2889)
    • Physiology (4334)
    • Plant Biology (9235)
    • Scientific Communication and Education (1586)
    • Synthetic Biology (2554)
    • Systems Biology (6773)
    • Zoology (1461)