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Linking atypical depression and insulin resistance-related disorders via low-grade chronic inflammation: Integrating the phenotypic, molecular and neuroanatomical dimensions
Open accessAbstract
Insulin resistance (IR) and related disorders, such as T2DM, increase the risk of major depressive disorder (MDD) and vice versa. Current evidence indicates that psychological stress and overeating can induce chronic low-grade inflammation that can interfere with glutamate metabolism in MDD as well as insulin signaling, particularly in the atypical subtype. Here we first review the interactive role of inflammatory processes in the development of MDD, IR and related metabolic disorders. Next, we describe the role of the anterior cingulate cortex in the pathophysiology of MDD and IR-related disorders. Furthermore, we outline how specific clinical features of atypical depression, such as hyperphagia, are more associated with inflammation and IR-related disorders. Finally, we examine the regional specificity of the effects of inflammation on the brain that show an overlap with the functional and morphometric brain patterns activated in MDD and IR-related disorders.
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“symptoms of increased appetite, energy balance disturbances and hypersomnia, which are shared between atypical MDD and metabolic diseases including obesity, the metabolic syndrome and diabetes mellitus15,257.”
From Comorbidity between major depressive disorder and physical diseases: a comprehensive review of epidemiology, mechanisms and management (2023) · cites this paper as [257]
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Self-citation
Metadata
- Authors
- Sen, Z. D., Danyeli, L. V., Woelfer, M., Lamers, F., Wagner, G., Sobanski, T., & Walter, M.
- Affiliations
- Jena University Hospital (DE)
- Leibniz Institute for Neurobiology (DE)
- Amsterdam University Medical Centers (NL)
- Corresponding author
- Walter, Martin
- Venue
- Brain, Behavior, and Immunity
- Publisher
- Elsevier BV
- Published
- 2021-03
- Volume
- 93
- Pages
- 335-352
- ISSN
- 0889-1591 (ISSN-L)
- OpenAlex
- W3114780798
- Cited by
- 65
- References
- 305
- Citations by year
- 2026: 12 · 2025: 22 · 2024: 9 · 2023: 11 · 2022: 4 · 2021: 6
- FWCI
- 0.43
- Type
- journal article
- Language
- en
- Open access
- green
- research.vumc.nl
- Licence
- Locations
- Brain Behavior and Immunity (publishedVersion)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion, other-oa)
- Pure Amsterdam UMC (submittedVersion, cc-by)
- Informationszentrum Lebenswissenschaften (ZB MED) (submittedVersion, cc-by-nc-nd)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Funders
- Horizon 2020
- Deutsche Forschungsgemeinschaft
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- atypical depression, insulin resistance, low-grade inflammation, major depressive disorder, type 2 diabetes, hyperphagia, anterior cingulate cortex, glutamate metabolism, insulin signaling, psychological stress, neuroinflammation, brain morphometry
- MeSH terms
- Depression, Major Depressive Disorder, Humans, Inflammation, Insulin, Insulin Resistance
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