Cited by 32Treatment of Major DepressionFunctional Brain Connectivity StudiesNeurotransmitter Receptor Influence on Behavior

Intrinsic reward circuit connectivity profiles underlying symptom and quality of life outcomes following antidepressant medication: a report from the iSPOT-D trial

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Fischer, Adina S., Holt-Gosselin, Bailey, Fleming, Scott L., Hack, Laura M., Ball, Tali M., Schatzberg, Alan F., Williams, Leanne M.·2021·Neuropsychopharmacology

Abstract

There is a critical need to better understand the neural basis of antidepressant medication (ADM) response with respect to both symptom alleviation and quality of life (QoL) in major depressive disorder (MDD). Reward neurocircuitry has been implicated in QoL, the neural basis of MDD, and the mechanisms of ADM response. Yet, we do not know whether change in reward neurocircuitry as a function of ADM is associated with change in symptoms and QoL. To address this gap in knowledge, we analyzed data from 128 patients with MDD who participated in the iSPOT-D trial and were assessed with functional neuroimaging pre- and post-ADM treatment (randomized to sertraline, venlafaxine-XR, or escitalopram). 58 matched healthy controls were scanned at the same time points. We quantified functional connectivity (FC) of reward neurocircuitry using nucleus accumbens (NAc) seed regions of interest, and then characterized how changes in FC relate to symptom response (primary outcome) and QoL response (secondary outcome). Symptom responders showed an increase in NAc-dorsal anterior cingulate cortex (ACC) FC relative to non-responders (p < 0.001) which was associated with improvement in physical QoL (p < 0.0003), and a decrease in NAc-inferior parietal lobule FC relative to controls (p < 0.001). QoL response was characterized by increases in FC between NAc-ventral ACC for environmental, NAc-thalamus for physical, and NAc-paracingulate gyrus for social domains (p < 0.001). Symptom responders to sertraline were distinguished by a decrease in NAc-insula FC (p < 0.001) and to venlafaxine-XR by an increase in NAc-inferior temporal gyrus FC (p < 0.005). Findings suggest that change in reward neurocircuitry may underlie differential ADM response profiles with respect to symptoms and QoL in depression.

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  • Increases in nucleus accumbens-prefrontal connectivity correlate with reduced symptom severity and quality-of-life measurements in SSRI-responsive patients compared with unresponsive controls.

    “Similar increases in NAc-PFC connectivity correlate with reduced symptom severity and quality-of-life measurements in SSRI-responsive patients compared to unresponsive controls [250].”

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  1. Greenberg T, Fournier JC, Stiffler R, Chase HW, Almeida JR, Aslam H, et al. Reward related ventral striatal activity and differential response to sertraline versus pla- cebo in depressed individuals. Mol Psychiatry. 2020;25:1526-36.

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Authors
Fischer, A. S., Holt-Gosselin, B., Fleming, S. L., Hack, L. M., Ball, T. M., Schatzberg, A. F., & Williams, L. M.
Affiliations
Stanford Medicine (US)
Corresponding author
  • Fischer, Adina S.
  • Williams, Leanne M.
Venue
Neuropsychopharmacology
Published
2020-11-23
Volume
46
Issue
4
Pages
809-819
ISSN
  • 0893-133X (ISSN-L)
  • 1740-634X
OpenAlex
W3106776454
Cited by
30
References
57
Citations by year
2026: 1 · 2025: 5 · 2024: 11 · 2023: 6 · 2022: 3 · 2021: 3 · 2020: 1
FWCI
1.90
Type
journal article
Language
en
Open access
Locations
  • Neuropsychopharmacology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (R01 MH101496)
Topics
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords
major depressive disorder, antidepressant response, functional connectivity, nucleus accumbens, quality of life, symptom response, sertraline, venlafaxine, escitalopram, dorsal anterior cingulate cortex, inferior parietal lobule, thalamus, insula, inferior temporal gyrus, paracingulate gyrus
MeSH terms
Antidepressive Agents, Major Depressive Disorder, Humans, Magnetic Resonance Imaging, Quality of Life, Reward, Citalopram

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