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Depression and obesity: evidence of shared biological mechanisms
Open accessAbstract
Depression and obesity are common conditions with major public health implications that tend to co-occur within individuals. The relationship between these conditions is bidirectional: the presence of one increases the risk for developing the other. It has thus become crucial to gain a better understanding of the mechanisms responsible for the intertwined downward physiological spirals associated with both conditions. The present review focuses specifically on shared biological pathways that may mechanistically explain the depression-obesity link, including genetics, alterations in systems involved in homeostatic adjustments (HPA axis, immuno-inflammatory activation, neuroendocrine regulators of energy metabolism including leptin and insulin, and microbiome) and brain circuitries integrating homeostatic and mood regulatory responses. Furthermore, the review addresses interventional opportunities and questions to be answered by future research that will enable a comprehensive characterization and targeting of the biological links between depression and obesity.
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“Additionally, psychological factors like un-healthy coping mechanisms may play a role in the development and maintenance of obesity whilst also possibly impacting on mental health (Milaneschi et al., 2019; Lopresti and Drummond, 2013).”
BackgroundDreimüller, N., Lieb, K., Tadić, A., Engelmann, J., Wollschläger, D., & Wagner, S. (2019) · Journal of Affective Disorders · doi:10.1016/j.jad.2019.06.067 · Cited by 60
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Pistis, G., Milaneschi, Y., Vandeleur, C. L., Lasserre, A. M., Penninx, B. W. J. H., Lamers, F., Boomsma, D. I., Hottenga, J., Marques-Vidal, P. M., Vollenweider, P., et al. (2021) · Translational Psychiatry · doi:10.1038/s41398-021-01236-7 · Cited by 58
“MDD include (1) mood reactivity and at least two of the following four symptoms: (2) increase in appetite or significant weight gain, (3) hypersomnia, (4) leaden paralysis, and (5) interpersonal rejection sensitivity.”
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“It is one of the most severe metabolic disorder conditions, which generally develop due to improper energy intake versus energy workout [3–7], stress [8], sedentary lifestyle [9], alcohol consumption [10], depression [11], insufficient nutritional knowledge about the food supplements, and then, ultimately these leads…”
BackgroundMood‐related central and peripheral clocks
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The relationship between depression and relative fat mass (RFM): A population-based study
Zhu, X., Yue, Y., Li, L., Zhu, L., Cai, Y., & Shu, Y. (2024) · Journal of Affective Disorders · doi:10.1016/j.jad.2024.04.031 · Cited by 60
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“But psychiatric diseases also seem to share some pathophysiological brain pathways in common with those leading to weight gain and its metabolic complications, thereby creating a kind of vicious circle where each of the pathways influences the risk for the other [21].”
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The metabolome-wide signature of major depressive disorder
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“Such fi ndings not only indicate pathway dysregulations that contribute to depression symptomatology development-but also help explain why comorbidities like metabolic syndrome [4], obesity [5], diabetes [6]) and cardiovascular disease [7] occur more often in depressed than non-depressed persons.”
Self-citationThe microbiota: a key regulator of health, productivity, and reproductive success in mammals
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“, altered sleep and increased fatigue) in ways that are bidirectional and mutually-reinforcing (Luppino et al., 2010; Milaneschi et al., 2019).”
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Astrocytes in Post-traumatic Stress Disorder
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“Generally, therapeutic strategies are aimed at neurons (monoamine hypothesis [156], hypercortisolism hypothesis [157], BDNF hypothesis [158], and myo-inositol hypothesis [159]).”
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Auricular transcutaneous vagus nerve stimulation modulates the heart-evoked potential
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“An ever increasing body of evidence reports that systems involved in homeostatic adjustments such as the neuroendocrine, the immuno-inflammatory and the energy metabolism (insulin and leptin) are greatly altered both in psychiatric and metabolic disorders (Milaneschi et al., 2019).”
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Metadata
- Authors
- Milaneschi, Y., Simmons, W. K., van Rossum, E. F. C., & Penninx, B. W.
- Affiliations
- Amsterdam Neuroscience (NL)
- Laureate Institute for Brain Research (US)
- Corresponding author
- Penninx, Brenda WJH
- Venue
- Molecular Psychiatry
- Published
- 2018-02-16
- Volume
- 24
- Issue
- 1
- Pages
- 18-33
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- OpenAlex
- W2793219717
- Semantic Scholar
- 68e357daebf4d3c206fe34e3d98835cf2e71eb1c
- Cited by
- 1,073
- References
- 209
- Citations by year
- 2026: 128 · 2025: 216 · 2024: 180 · 2023: 181 · 2022: 147 · 2021: 108 · 2020: 59 · 2019: 44 · 2018: 9
- FWCI
- 7.69
- Type
- journal article
- Language
- en
- Open access
- green
- pure.amsterdamumc.nl
- Licence
- other-oa
- www.springer.com/tdm (tdm)
- Locations
- Molecular Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion, other-oa)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Social Sciences › Psychology › Clinical Psychology › Eating Disorders and Behaviors
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- depression, obesity, bidirectional comorbidity, hypothalamic-pituitary-adrenal axis, inflammation, leptin, insulin, gut microbiota, energy metabolism, neuroendocrine regulation, brain circuits, genetic risk factors
- MeSH terms
- Brain, Depression, Major Depressive Disorder, Depressive Disorder, Energy Metabolism, Female, Homeostasis, Humans, Hypothalamo-Hypophyseal System, Inflammation, Insulin, Male, Obesity, Pituitary-Adrenal System, Leptin, Melanocortins, Microbiota
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