Relationships Between Changes in Sustained Fronto-Striatal Connectivity and Positive Affect in Major Depression Resulting From Antidepressant Treatment
Open accessAbstract
OBJECTIVE Deficits in positive affect and their neural bases have been associated with major depression. However, whether reductions in positive affect result solely from an overall reduction in nucleus accumbens activity and fronto-striatal connectivity or the additional inability to sustain engagement of this network over time is unknown. The authors sought to determine whether treatment-induced changes in the ability to sustain nucleus accumbens activity and fronto-striatal connectivity during the regulation of positive affect are associated with gains in positive affect. METHOD Using fMRI, the authors assessed the ability to sustain activity in reward-related networks when attempting to increase positive emotion during performance of an emotion regulation paradigm in 21 depressed patients before and after 2 months of antidepressant treatment. Over the same interval, 14 healthy comparison subjects underwent scanning as well. RESULTS After 2 months of treatment, self-reported positive affect increased. The patients who demonstrated the largest increases in sustained nucleus accumbens activity over the 2 months were those who demonstrated the largest increases in positive affect. In addition, the patients who demonstrated the largest increases in sustained fronto-striatal connectivity were also those who demonstrated the largest increases in positive affect when controlling for negative affect. None of these associations were observed in healthy comparison subjects. CONCLUSIONS Treatment-induced change in the sustained engagement of fronto-striatal circuitry tracks the experience of positive emotion in daily life. Studies examining reduced positive affect in a variety of psychiatric disorders might benefit from examining the temporal dynamics of brain activity when attempting to understand changes in daily positive affect.
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Chronic SSRI administration in depressed patients improves self-reported depression severity and negative affective bias, and these improvements strongly correlate with increases in nucleus accumbens activity and nucleus accumbens-prefrontal connectivity.
“There is limited evidence of the effect of antidepressants on these measures of reward circuit function, but it has been shown that improvements in self-reported depression severity and negative affective bias are improved with chronic SSRI administration in depressed patients and are strongly correlated with increases in NAc activity and NAc-PFC connectivity [249].”
From Plasticity of synapses and reward circuit function in the genesis and treatment of depression (2023) · cites this paper as [249]
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- Authors
- Heller, A. S., Johnstone, T., Light, S. N., Peterson, M. J., Kolden, G. G., Kalin, N. H., & Davidson, R. J.
- Affiliations
- University of Wisconsin–Madison (US)
- Venue
- American Journal of Psychiatry
- Published
- 2013-02
- Volume
- 170
- Issue
- 2
- Pages
- 197-206
- ISSN
- 0002-953X (ISSN-L)
- 1535-7228
- PMC
- PMC3563751
- OpenAlex
- W2123335103
- Cited by
- 161
- References
- 42
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 7 · 2023: 8 · 2022: 11 · 2021: 32 · 2020: 5 · 2019: 12 · 2018: 13 · 2017: 12 · 2016: 11 · 2015: 19 · 2014: 8 · 2013: 13
- FWCI
- 9.41
- Type
- journal article
- Language
- en
- Open access
- Locations
- American Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- CentAUR (University of Reading) (acceptedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Swinburne figshare (Swinburne University of Technology) (submittedVersion)
- Funders
- National Institute of Mental Health (P50MH069315, P50MH084051, R01MH043454)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P30HD003352)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- major depressive disorder, positive affect, antidepressant treatment, nucleus accumbens, frontostriatal connectivity, sustained neural activity, emotion regulation, negative affect, temporal dynamics of brain activity
- MeSH terms
- Venlafaxine Hydrochloride, Affect, Antidepressive Agents, Biological Availability, Brain Mapping, Cyclohexanols, Depressive Disorder, Major, Major Depressive Disorder, Female, Fluoxetine, Frontal Lobe, Humans, Magnetic Resonance Imaging, Male, Nerve Net, Nucleus Accumbens, Psychiatric Status Rating Scales, Reward, Visual Cortex, Treatment Outcome, Sickness Impact Profile, Diagnostic and Statistical Manual of Mental Disorders
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