A predictive coding framework for understanding major depression
Open accessAbstract
Predictive coding models of brain processing propose that top-down cortical signals promote efficient neural signaling by carrying predictions about incoming sensory information. These "priors" serve to constrain bottom-up signal propagation where prediction errors are carried via feedforward mechanisms. Depression, traditionally viewed as a disorder characterized by negative cognitive biases, is associated with disrupted reward prediction error encoding and signaling. Accumulating evidence also suggests that depression is characterized by impaired local and long-range prediction signaling across multiple sensory domains. This review highlights the electrophysiological and neuroimaging evidence for disrupted predictive processing in depression. The discussion is framed around the manner in which disrupted generative predictions about the sensorium could lead to depressive symptomatology, including anhedonia and negative bias. In particular, the review focuses on studies of sensory deviance detection and reward processing, highlighting research evidence for both disrupted generative predictions and prediction error signaling in depression. The role of the monoaminergic and glutamatergic systems in predictive coding processes is also discussed. This review provides a novel framework for understanding depression using predictive coding principles and establishes a foundational roadmap for potential future research.
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Mood disorders are typically managed with medications acting on the monoaminergic and glutamatergic systems.
“mood disorders are typically managed with medications acting on the monoaminergic and glutamatergic systems”
From Predictive coding in neuropsychiatric disorders: a systematic transdiagnostic review. (2025) · cites this paper as Gilbert et al., 2022
The “Antidepressant Drugs and Predictive Processes” section says most approved antidepressants target the monoaminergic system and describes ketamine and esketamine as glutamatergic treatment options for depression. It does not establish that glutamatergic medications are *typically* used, or that this treatment pattern applies to mood disorders broadly rather than major depression. (LLM, conf=0.88)
Experimental — accuracy not yet measuredMonoaminergic and glutamatergic systems play a critical role in mood, behavioral, and cognitive regulation, including predictive performance.
“both playing a critical role in mood, behavioral, and cognitive regulation, including predictive performance (Gilbert et al., 2022; Goulty et al., 2023; Pal, 2021; Sanacora et al., 2008).”
From Predictive coding in neuropsychiatric disorders: a systematic transdiagnostic review. (2025) · cites this paper as Gilbert et al., 2022
The Monoaminergic Drugs section links monoamines to emotion, behavior, and cognition, while the Glutamatergic Drugs section links glutamate signaling to mood disorders and possible roles in predictive coding. But the Conclusion says further work is needed to understand how these systems support predictive signaling; the paper does not establish that both play a critical role in predictive performance generally. Page numbers are unavailable in our copy. (LLM, conf=0.84)
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- Authors
- Gilbert, J. R., Wusinich, C., & Zarate, C. A.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Gilbert, Jessica R.
- Venue
- Frontiers in Human Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2022-03-03
- Volume
- 16
- Pages
- 787495-787495
- ISSN
- 1662-5161 (ISSN-L)
- PMC
- PMC8927302
- OpenAlex
- W4214927613
- Cited by
- 38
- References
- 128
- Citations by year
- 2026: 16 · 2025: 9 · 2024: 9 · 2023: 2 · 2022: 1 · 2021: 1
- FWCI
- 0.73
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Human Neuroscience (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Keywords
- major depressive disorder, predictive coding, reward prediction error, anhedonia, negative cognitive bias, top-down prediction, monoaminergic systems, glutamatergic system, electrophysiology, neuroimaging
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