Altered Striatal Activation Predicting Real-World Positive Affect in Adolescent Major Depressive Disorder
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OBJECTIVE: Alterations in reward-related brain function and phenomenological aspects of positive affect are increasingly examined in the development of major depressive disorder. The authors tested differences in reward-related brain function in healthy and depressed adolescents, and the authors examined direct links between reward-related brain function and positive mood that occurred in real-world contexts. METHOD: Fifteen adolescents with major depressive disorder and 28 adolescents with no history of psychiatric disorder, ages 8-17 years, completed a functional magnetic resonance imaging guessing task involving monetary reward. Participants also reported their subjective positive affect in natural environments during a 4-day cell-phone-based ecological momentary assessment. RESULTS: Adolescents with major depressive disorder exhibited less striatal response than healthy comparison adolescents during reward anticipation and reward outcome, but more response in dorsolateral and medial prefrontal cortex. Diminished activation in a caudate region associated with this depression group difference was correlated with lower subjective positive affect in natural environments, particularly within the depressed group. CONCLUSIONS: Results support models of altered reward processing and related positive affect in young people with major depressive disorder and indicate that depressed adolescents' brain response to monetary reward is related to their affective experience in natural environments. Additionally, these results suggest that reward-processing paradigms capture brain function relevant to real-world positive affect.
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Across studies, over-recruitment of prefrontal cortex regions, including medial prefrontal cortex and dorsolateral prefrontal cortex, during reward processing has been interpreted as suggesting over-compensation for reduced striatal responses to rewards.
“Across studies, over-recruitment of PFC regions (mPFC, dlPFC) during reward processing has been interpreted as suggesting over-compensation for reduced striatal responses to rewards [104, 111, 112].”
From Prefrontal cortex and depression (2022) · cites this paper as [111]
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredIn a card-guessing task, depressed adolescents had potentiated mPFC (BA10) activation coupled with blunted ventral striatal activation to rewards.
“In a study using a card-guessing task, depressed adolescents had potentiated mPFC (BA10) activation (coupled with blunted ventral striatal activation) to rewards [111].”
From Prefrontal cortex and depression (2022) · cites this paper as [111]
The Method (Measures) describes a card-guessing reward task, and the Results (Depression-Related Differences in Neural Response to Reward) report greater medial BA10 activation during reward outcome alongside reduced caudate activation in depressed adolescents. The paper identifies the reduced-response region as the caudate, not specifically the ventral striatum; the Methods say the striatal region of interest encompassed both ventral striatum and adjacent caudate. Page numbers were not available in our copy. (LLM, conf=0.85)
Experimental — accuracy not yet measuredLower striatal and higher prefrontal responses to reward anticipation and outcome tracked with less daily positive affect and more depression in both typical and depressed adolescents.
“diminished striatal (and heightened prefrontal) responses to reward anticipation and outcome were associated with reports of lower daily positive affect and higher depression in both typically-developing and depressed adolescents [50,51].”
From Arrested development? Reconsidering dual-systems models of brain function in adolescence and disorders (2012) · cites this paper as [50]
In adolescents, more depressive symptoms and less daily positive affect have been linked to stronger PFC responses.
“greater depressive symptoms and lower daily positive affect have been associated with heightened PFC responses in adolescence [50,51].”
From Arrested development? Reconsidering dual-systems models of brain function in adolescence and disorders (2012) · cites this paper as [50]
Depression is associated with altered neural activity in the ventral striatum, which includes the nucleus accumbens.
“depression has been associated with altered neural activity in the ventral striatum (Epstein et al., 2006; Eshel and Roiser, 2010; Forbes et al., 2009; Monk et al., 2008.; Pizzagalli et al., 2009; Price and Drevets, 2010; Teicher et al., 2009), which includes the nucleus accumbens (NAcc)”
From Reduced nucleus accumbens reactivity and adolescent depression following early-life stress (2013) · cites this paper as Forbes et al., 2009
Reduced mesolimbic activity in MDD is found during reward anticipation and outcomes in both adults and children, and during reward learning.
“Reduced mesolimbic activity in MDD has been found during reward anticipation and outcomes in both adults and children [210,219-227] and during reward learning [206].”
From Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings (2012) · cites this paper as [220]
The few studies that have evaluated potential relations between mesolimbic neural activity and subjectively experienced reward or motivation to work for rewards have yielded promising initial results suggesting the external validity of laboratory-based measures of reward processes.
“The few studies that have evaluated potential relations between mesolimbic neural activity and subjectively experienced reward [220] or motivation to work for rewards [154] have yielded promising initial results suggesting the external validity of laboratory-based measures of reward processes”
From Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings (2012) · cites this paper as [220]
Structural and functional brain indices may be sufficiently stable within and across developmental periods to warrant treatment as susceptibility factors.
“Finally, structural and functional brain indices may be sufficiently stable within and across developmental periods (Caceres et al., 2009, Forbes et al., 2009, Hariri, 2009, Johnstone et al., 2005, Manuck et al., 2007, Miller et al., 2002, Miller et al., 2009, Wu et al., 2014, Zuo et al., 2010) to warrant treatment as susceptibility factors.”
From Adolescent neurobiological susceptibility to social context (2016) · cites this paper as Forbes et al., 2009
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- Authors
- Forbes, E. E., Hariri, A. R., Martin, S. L., Silk, J. S., Moyles, D. L., Fisher, P. M., Brown, S. M., Ryan, N. D., Birmaher, B., Axelson, D. A., & Dahl, R. E.
- Affiliations
- University of Pittsburgh (US)
- ORCID
- Venue
- American Journal of Psychiatry
- Published
- 2009-01
- Volume
- 166
- Issue
- 1
- Pages
- 64-73
- ISSN
- 0002-953X (ISSN-L)
- 1535-7228
- PMC
- PMC2701209
- OpenAlex
- W2138309161
- Cited by
- 582
- References
- 28
- Citations by year
- 2026: 16 · 2025: 24 · 2024: 23 · 2023: 31 · 2022: 31 · 2021: 38 · 2020: 27 · 2019: 45 · 2018: 39 · 2017: 36 · 2016: 54 · 2015: 33 · 2014: 47 · 2013: 42 · 2012: 30
- FWCI
- 11.41
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (P01MH041712, P01 MH 41712, R24MH067346, K01MH072837, K01MH074769)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- adolescent major depressive disorder, striatal activation, reward processing, positive affect, caudate nucleus, monetary rewards, reward anticipation, reward outcome, prefrontal cortex, ecological momentary assessment, functional MRI
- MeSH terms
- Adolescent, Affect, Age Factors, Caudate Nucleus, Child, Corpus Striatum, Depressive Disorder, Major, Major Depressive Disorder, Dominance, Cerebral, Female, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Motivation, Neurons, Oxygen, Prognosis, Reward, Social Environment, Prefrontal Cortex, Computers, Handheld
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