PERIL AND PLEASURE: AN RDOC-INSPIRED EXAMINATION OF THREAT RESPONSES AND REWARD PROCESSING IN ANXIETY AND DEPRESSION: Neighborhood Characteristics and Mental Health
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As a step toward addressing limitations in the current psychiatric diagnostic system, the National Institute of Mental Health recently developed the Research Domain Criteria (RDoC) to stimulate integrative research-spanning self-report, behavior, neural circuitry, and molecular/genetic mechanisms-on core psychological processes implicated in mental illness. Here, we use the RDoC conceptualization to review research on threat responses, reward processing, and their interaction. The first section of the manuscript highlights the pivotal role of exaggerated threat responses-mediated by circuits connecting the frontal cortex, amygdala, and midbrain-in anxiety, and reviews data indicating that genotypic variation in the serotonin system is associated with hyperactivity in this circuitry, which elevates the risk for anxiety and mood disorders. In the second section, we describe mounting evidence linking anhedonic behavior to deficits in psychological functions that rely heavily on dopamine signaling, especially cost/benefit decision making and reward learning. The third section covers recent studies that document negative effects of acute threats and chronic stress on reward responses in humans. The mechanisms underlying such effects are unclear, but the fourth section reviews new optogenetic data in rodents indicating that GABAergic inhibition of midbrain dopamine neurons, driven by activation of the habenula, may play a fundamental role in stress-induced anhedonia. In addition to its basic scientific value, a better understanding of interactions between the neural systems that mediate threat and reward responses may offer relief from the burdensome condition of anxious depression.
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Dysfunction of reward networks, especially in reward valuation, effort valuation, action selection, preference-based decision making, and reward learning, is a central process perpetuating depression.
“Neurobiological findings suggest that dysfunction of reward networks (especially in reward valuation, effort valuation, action selection, preference-based decision making, and reward learning) is a central process perpetuating depression [7,8].”
From Behavioral Activation and Depression Symptomatology: Longitudinal Assessment of Linguistic Indicators in Text-Based Therapy Sessions (2021) · cites this paper as [8]
Anxiety and depression can be conceptualized along partially distinct biobehavioral dimensions of positive and negative affect domains.
“Recent efforts to integrate advances in neuroscience with clinical psychiatry suggest that anxiety and depression can be conceptualized along partially distinct biobehavioral dimensions of positive and negative affect domains7, 8”
From Upregulating the positive affect system in anxiety and depression: Outcomes of a positive activity intervention: <scp>Taylor et al.</scp> (2017) · cites this paper as [8]
The current findings have clinical implications for emerging dimensional classification systems wherein the positive affect system is hypothesized to play a role across various forms of psychopathology, including anxiety and depression.
“The current findings have clinical implications for emerging dimensional classification systems wherein the positive affect system is hypothesized to play a role across various forms of psychopathology, including anxiety and depression7, 8.”
From Upregulating the positive affect system in anxiety and depression: Outcomes of a positive activity intervention: <scp>Taylor et al.</scp> (2017) · cites this paper as [8]
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- Authors
- Dillon, D. G., Rosso, I. M., Pechtel, P., Killgore, W. D. S., Rauch, S. L., & Pizzagalli, D. A.
- Affiliations
- Harvard University (US)
- Corresponding author
- Dillon, Daniel G.
- ORCID
- Venue
- Depression and Anxiety
- Publisher
- Hindawi Limited
- Published
- 2013-10-21
- Volume
- 31
- Issue
- 3
- Pages
- 233-249
- ISSN
- 1091-4269 (ISSN-L)
- PMC
- PMC3951656
- OpenAlex
- W2159359129
- Cited by
- 209
- References
- 156
- Citations by year
- 2026: 12 · 2025: 10 · 2024: 24 · 2023: 17 · 2022: 16 · 2021: 25 · 2020: 17 · 2019: 16 · 2018: 16 · 2017: 19 · 2016: 12 · 2015: 19 · 2014: 6
- FWCI
- 1.26
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Depression and Anxiety (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- AstraZeneca
- Servier
- National Institute of Mental Health (K99MH094438, R01MH101521, R01MH095809, R01MH068376, R21MH078979, R01MH096987)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Keywords
- threat response, reward processing, anxiety, depression, Research Domain Criteria, serotonergic system, amygdala, frontal cortex, midbrain, anhedonia, dopamine signaling, cost-benefit decision making, reward learning, chronic stress, habenula, GABAergic inhibition, optogenetics, anxious depression
- MeSH terms
- Animals, Anxiety Disorders, Brain, Depressive Disorder, Fear, Humans, Reward
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