Remitted major depression is characterized by reduced prefrontal cortex reactivity to reward loss
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Background Major depression (MDD) is characterized by anhedonia. Although a growing body of literature has linked anhedonia in MDD to reduced frontostriatal activity during reward gains, relatively few studies have examined neural responsivity to loss, and no studies to date have examined neural responses to loss in euthymic individuals with a history of MDD.Methods An fMRI monetary incentive delay task was administered to 19 participants with remitted MDD (rMDD) and 19 never depressed controls. Analyses examined group activation differences in brain reward circuitry during monetary loss anticipation and outcomes. Secondary analyses examined the association between self-reported rumination and brain activation in the rMDD group.Results Compared to controls, the rMDD group showed less superior frontal gyrus activation during loss anticipation and less inferior and superior frontal gyri activation during loss outcomes (cluster corrected p's<.05). Ruminative Responses Scale scores were negatively correlated with superior frontal gyrus activation (r=-.68, p=.001) during loss outcomes in the rMDD group.Limitations Replication with a larger sample is needed.Conclusions Euthymic individuals with a history of MDD showed prefrontal cortex hypoactivation during loss anticipation and outcomes, and the degree of superior frontal gyrus hypoactivation was associated with rumination. Abnormal prefrontal cortex responses to loss may reflect a trait-like vulnerability to MDD, although future research is needed to evaluate the utility of this functional neural endophenotype as a prospective risk marker.
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MDD patients generally exhibit reduced sensitivity to reward, reflected by reduced ventral CSTC loop activation in the orbitofrontal cortex, anterior cingulate and ventral striatum to reward and loss receipt/anticipation.
“MDD patients generally exhibit reduced sensitivity to reward; this cognitive blunting is reflected by reduced ventral CSTC loop activation in the orbitofrontal cortex, anterior cingulate and ventral striatum to reward and loss receipt/anticipation (Smoski et al., 2011; Chantiluke et al., 2012; Schiller et al., 2013; Admon et al., 2015; Manelis et al., 2016).”
From Cortico-striatal-thalamic loop circuits of the salience network: A central pathway in psychiatric disease and treatment (2016) · cites this paper as Schiller et al., 2013
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- Authors
- Schiller, C. E., Minkel, J., Smoski, M. J., & Dichter, G. S.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Duke Medical Center (US)
- Corresponding author
- Schiller, Crystal Edler
- Venue
- Journal of Affective Disorders
- Publisher
- Elsevier BV
- Published
- 2013-11
- Volume
- 151
- Issue
- 2
- Pages
- 756-762
- ISSN
- 0165-0327 (ISSN-L)
- PMC
- PMC3797197
- OpenAlex
- W2013504061
- Cited by
- 89
- References
- 40
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 4 · 2023: 4 · 2022: 7 · 2021: 6 · 2020: 8 · 2019: 7 · 2018: 7 · 2017: 8 · 2016: 10 · 2015: 10 · 2014: 6
- FWCI
- 4.75
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Affective Disorders (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (K23 MH081285, R21 MH094781, K23 MH087754, T32 MH093315)
- National Alliance for Research on Schizophrenia and Depression
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Keywords
- anhedonia, prefrontal cortex, superior frontal gyrus, rumination, monetary incentive delay task, depression vulnerability, frontostriatal circuits
- MeSH terms
- Adult, Depressive Disorder, Major, Major Depressive Disorder, Female, Humans, Magnetic Resonance Imaging, Male, Motivation, Prospective Studies, Reward, Prefrontal Cortex, Young Adult
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