Glutamate: the master neurotransmitter and its implications in chronic stress and mood disorders
Open accessAbstract
This brief review article makes the argument that glutamate is deserving of its newfound attention within the neuroscience literature and that many directions of important research have yet to be explored. Glutamate is an excitatory neurotransmitter with several types of receptors found throughout the central nervous system, and its metabolism is important to maintaining optimal levels within the extracellular space. As such, it is important to memory, cognition, and mood regulation. The mechanisms by which chronic stress affect the glutamatergic system and neuroplasticity are outlined. Several implications for potential pharmacologic and non-pharmacologic interventions are discussed.
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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 Pal, 2021
The “Potential for Future Treatment > Antidepressant Medications” section (page not provided) reports that glutamatergic agents can reduce depressive symptoms and discusses approved esketamine. It mentions citalopram as a comparator, but does not establish that medications acting on both the monoaminergic and glutamatergic systems are typically used to manage mood disorders. (LLM, conf=0.85)
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 Pal, 2021
The Neuroplasticity section (page unavailable) says glutamate is important in cognition, learning, and mood, supporting the glutamatergic part of the claim. The passages do not establish the corresponding role of monoaminergic systems or address predictive performance. (LLM, conf=0.85)
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Predictive coding in neuropsychiatric disorders: a systematic transdiagnostic review.
Qela, B., Damiani, S., De Santis, S., Groppi, F., Pichiecchio, A., Asteggiano, C., Brondino, N., Monteleone, A. M., Grassi, L., Politi, P., et al. (2025) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2025.106020 · Cited by 26 · see citing works
“…mood disorders are typically managed with medications acting on the monoaminergic and glutamatergic systems, 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).”
- Authors
- Pal, M. M.
- Affiliations
- Lawton Public Schools (US)
- Corresponding author
- Pal, Mia Michaela
- Venue
- Frontiers in Human Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2021-10-29
- Volume
- 15
- Pages
- 722323-722323
- ISSN
- 1662-5161 (ISSN-L)
- PMC
- PMC8586693
- OpenAlex
- W3211063857
- Cited by
- 194
- References
- 25
- Citations by year
- 2026: 40 · 2025: 75 · 2024: 48 · 2023: 25 · 2022: 6
- FWCI
- 9.11
- 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)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- glutamate, glutamatergic system, chronic stress, mood disorders, neuroplasticity, glutamate receptors, glutamate metabolism, mood regulation, memory and cognition, pharmacological interventions, non-pharmacological treatment
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