Intrinsic reward circuit connectivity profiles underlying symptom and quality of life outcomes following antidepressant medication: a report from the iSPOT-D trial
Open accessAbstract
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].”
From Plasticity of synapses and reward circuit function in the genesis and treatment of depression (2023) · cites this paper as [250]
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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.
- ORCID
- Venue
- Neuropsychopharmacology
- Published
- 2020-11-23
- Volume
- 46
- Issue
- 4
- Pages
- 809-819
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC8027440
- 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
- bronze
- doi.org
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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