The DOI matches its Crossref record; 316 of the 318 references it cites were found in a registry or an index.
Potential roles of zinc in the pathophysiology and treatment of major depressive disorder
Abstract
Incomplete response to monoaminergic antidepressants in major depressive disorder (MDD), and the phenomenon of neuroprogression, suggests a need for additional pathophysiological markers and pharmacological targets. Neuronal zinc is concentrated exclusively within glutamatergic neurons, acting as an allosteric modulator of the N-methyl D-aspartate and other receptors that regulate excitatory neurotransmission and neuroplasticity. Zinc-containing neurons form extensive associational circuitry throughout the cortex, amygdala and hippocampus, which subserve mood regulation and cognitive functions. In animal models of depression, zinc is reduced in these circuits, zinc treatment has antidepressant-like effects and dietary zinc insufficiency induces depressive behaviors. Clinically, serum zinc is lower in MDD, which may constitute a state-marker of illness and a risk factor for treatment-resistance. Marginal zinc deficiency in MDD may relate to multiple putative mechanisms underlying core symptomatology and neuroprogression (e.g. immune dysfunction, monoamine metabolism, stress response dysregulation, oxidative/nitrosative stress, neurotrophic deficits, transcriptional/epigenetic regulation of neural networks). Initial randomized trials suggest a benefit of zinc supplementation. In summary, molecular and animal behavioral data support the clinical significance of zinc in the setting of MDD.
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“In a double-blinded, placebo controlled prospective trial, involving 489 postmenopausal elderly women, there was no effect of hormone therapy and calcitriol, either individually or in combination, on depression (55).”
From Effects of zinc, vitamin D, and their co-supplementation on mood, serum cortisol, and brain-derived neurotrophic factor in patients with obesity and mild to moderate depressive symptoms: A phase II, 12-wk, 2 × 2 factorial design, double-blind, randomized, placebo-controlled trial (2020) · cites this paper as [55]
In the citing paper
“Observational studies show an association between low zinc dietary intake or low zinc status and depression in adults or elderly subjects [189,190,191].”
From Vitamins and Minerals for Energy, Fatigue and Cognition: A Narrative Review of the Biochemical and Clinical Evidence (2020) · cites this paper as [189]
In the citing paper
“Moreover, although the proof of its implications in the oxidative mechanisms is pretty solid, some animal models studies contradicted the clinical findings [285] and therefore, there is still a need for the determination of the real benefits for the copper therapy in patients with depression [288].”
From Oxidative Stress Implications in the Affective Disorders: Main Biomarkers, Animal Models Relevance, Genetic Perspectives, and Antioxidant Approaches (2016) · cites this paper as [288]
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Metadata
- Authors
- Swardfager, W., Herrmann, N., McIntyre, R. S., Mazereeuw, G., Goldberger, K., Cha, D. S., Schwartz, Y., & Lanctôt, K. L.
- Affiliations
- Toronto Rehabilitation Institute (CA)
- University of Toronto (CA)
- University Health Network (CA)
- Sunnybrook Research Institute (CA)
- Corresponding author
- Lanctôt, Krista L.
- Venue
- Neuroscience & Biobehavioral Reviews
- Publisher
- Elsevier BV
- Published
- 2013-06
- Volume
- 37
- Issue
- 5
- Pages
- 911-929
- ISSN
- 0149-7634 (ISSN-L)
- OpenAlex
- W2087435407
- Cited by
- 116
- References
- 318
- Citations by year
- 2026: 7 · 2025: 7 · 2024: 6 · 2023: 7 · 2022: 3 · 2021: 2 · 2020: 9 · 2019: 8 · 2018: 9 · 2017: 10 · 2016: 14 · 2015: 15 · 2014: 12 · 2013: 7
- FWCI
- 2.01
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Neuroscience & Biobehavioral Reviews (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- zinc, major depressive disorder, neuroprogression, treatment-resistant depression, NMDA receptor, glutamatergic neurons, excitatory neurotransmission, neuroplasticity, zinc supplementation, serum zinc, dietary zinc deficiency, mood regulation, oxidative stress, immune dysfunction, monoamine metabolism, stress response dysregulation, epigenetic regulation
- MeSH terms
- Animals, Major Depressive Disorder, Humans, Synaptic Transmission, Neurons, Zinc, Receptors, N-Methyl-D-Aspartate
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