Effect of intrinsic patterns of functional brain connectivity in moderating antidepressant treatment response in major depression
Open accessAbstract
OBJECTIVE: Major depressive disorder is associated with aberrant resting-state functional connectivity across multiple brain networks supporting emotion processing, executive function, and reward processing. The purpose of this study was to determine whether patterns of resting-state connectivity between brain regions predict differential outcome to antidepressant medication (sertraline) compared with placebo. METHODS: Participants in the Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care (EMBARC) study underwent structural and resting-state functional MRI at baseline. Participants were then randomly assigned to receive either sertraline or placebo treatment for 8 weeks (N=279). A region of interest-based approach was utilized to compute functional connectivity between brain regions. Linear mixed-model intent-to-treat analyses were used to identify brain regions that moderated (i.e., differentially predicted) outcomes between the sertraline and placebo arms. RESULTS: Prediction of response to sertraline involved several within- and between-network connectivity patterns. In general, higher connectivity within the default mode network predicted better outcomes specifically for sertraline, as did greater between-network connectivity of the default mode and executive control networks. In contrast, both placebo and sertraline outcomes were predicted (in opposite directions) by between-network hippocampal connectivity. CONCLUSIONS: This study identified specific functional network-based moderators of treatment outcome involving brain networks known to be affected by major depression. Specifically, functional connectivity patterns of brain regions between and within networks appear to play an important role in identifying a favorable response for a drug treatment for major depressive disorder.
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Studies of late-life depression showed increased FCS in the inferior parietal lobule and parahippocampal gyrus and decreased FCS in the somatosensory and motor cortices compared to HCs.
“Similar to the alteration patterns in our results, studies of late-life depression showed increased FCS in the inferior parietal lobule and parahippocampal gyrus and decreased FCS in the somatosensory and motor cortices compared to HCs [69].”
From Mapping neurophysiological subtypes of major depressive disorder using normative models of the functional connectome (2023) · cites this paper as [69]
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- Authors
- Chin Fatt, C. R., Jha, M. K., Cooper, C. M., Fonzo, G., South, C., Grannemann, B., Carmody, T., Greer, T. L., Kurian, B., Fava, M., McGrath, P. J., Adams, P., McInnis, M., Parsey, R. V., Weissman, M., Phillips, M. L., Etkin, A., & Trivedi, M. H.
- Affiliations
- Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas (Chin Fatt, Jha, Cooper, South, Grannemann, Carmody, Greer, Kurian, Trivedi); Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York (Jha); Department of Psychiatry and Behavioral Sciences and Stanford Neurosciences Institute, Stanford University, Stanford, Calif. (Fonzo, Etkin); Mental Illness Research, Education, and Clinical Center, Veterans Affairs Palo Alto Health Care System, Palo Alto, Calif. ...
- VA Palo Alto Health Care System (US)
- ORCID
- Venue
- American Journal of Psychiatry
- Published
- 2020-02-01
- Volume
- 177
- Issue
- 2
- Pages
- 143-154
- ISSN
- 0002-953X (ISSN-L)
- 1535-7228
- OpenAlex
- W2973556437
- Cited by
- 125
- References
- 49
- Citations by year
- 2026: 11 · 2025: 16 · 2024: 24 · 2023: 16 · 2022: 24 · 2021: 15 · 2020: 16 · 2019: 3
- FWCI
- 8.43
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- American Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Veterans Affairs
- Abbott Laboratories
- Bristol-Myers Squibb
- Eli Lilly and Company
- Pfizer
- AstraZeneca
- GlaxoSmithKline
- Sanofi
- Massachusetts General Hospital
- Biogen
- CeNeRx
- Pharmavite
- University of Pittsburgh
- Sunovion
- National Alliance for Research on Schizophrenia and Depression
- Vanda Pharmaceuticals
- Jazz Pharmaceuticals
- Hersh Foundation
- Amarin Corporation
- ACADIA Pharmaceuticals
- Orexigen Therapeutics
- Avanir Pharmaceuticals
- Cerecor
- Supernus Pharmaceuticals
- American Society of Clinical Psychopharmacology
- FORUM Pharmaceuticals
- Belvoir Media Group
- Vistagen Therapeutics
- Dainippon Sumitomo Pharma
- Eisai
- Servier
- H. Lundbeck A/S
- Stony Brook University
- Allergan
- Amarin Pharma
- Takeda Pharmaceuticals International
- National Institute of Mental Health (U01MH092250, U01MH092221)
- National Institute on Drug Abuse
- National Center for Complementary and Alternative Medicine
- NIH Clinical Center
- Janssen Research and Development
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
- Keywords
- major depressive disorder, resting-state functional connectivity, antidepressant response, sertraline, placebo response, default mode network, frontoparietal network, hippocampal connectivity, treatment moderators, treatment outcome prediction
- MeSH terms
- Adolescent, Adult, Aged, Antidepressive Agents, Brain, Major Depressive Disorder, Depressive Disorder, Major, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Neural Pathways, Predictive Value of Tests, Treatment Outcome, Sertraline, Young Adult, Functional Neuroimaging
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