Cited by 1,073Regulation of Appetite and ObesityEating Disorders and BehaviorsAdipokines, Inflammation, and Metabolic Diseases

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Depression and obesity: evidence of shared biological mechanisms

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Milaneschi, Yuri, Simmons, W. Kyle, van Rossum, Elisabeth F. C., Penninx, Brenda WJH·2019·Molecular Psychiatry

DOI 10.1038/s41380-018-0017-5

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Abstract

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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Major depression recurrence is associated with differences in obesity-related traits in women, but not in men
Bannert, U., Siewert‐Markus, U., Klinger-König, J., Grabe, H. J., Stracke, S., Dörr, M., Völzke, H., Markus, M. R. P., Töpfer, P., & Ittermann, T. (2024) · European Psychiatry · doi:10.1192/j.eurpsy.2024.1764 · Cited by 5
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Unraveling the Metabolic and Microbiome Signatures in Fecal Samples of Pregnant Women with Prenatal Depression
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Activation of Hippocampal IR/IRS-1 Signaling Contributes to the Treatment with Zuogui Jiangtang Jieyu Decoction on the Diabetes-Related Depression
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Influential
Association Between Weight‐Adjusted Waist Index and Depressive Symptoms Among Middle‐Aged and Older Adults: Evidence From Two Prospective Longitudinal Cohort Studies
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The Association Between Childhood Trauma, Emotional Dysregulation, and Depressive Symptoms’ Severity in Patients with Obesity Seeking Bariatric Surgery
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The Association Between Obesity and Depressive Symptoms: Mediation by C-Reactive Protein and Neutrophil-to-Lymphocyte Ratio
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“CRP, a well-known acute-phase protein, is elevated during inflammatory responses and has been directly associated with the pro-inflammatory state observed in both obesity and depression [ 1].”
Influential
BMI mediates the causal relationship between depression and the risk of Rheumatoid arthritis: The results from NHANES 2003 to 2018 and the Mendelian studies
Li, H., Li, P., Dai, Y., Zhao, C. T., & Li, L. (2025) · Medicine · doi:10.1097/md.0000000000043027 · Cited by 2
“[15,16] The primary factors involve negative emotions stimulating the release of glucocorticoids and insulin, resulting in heightened appetite.”
Exploring the influence of psychological factors on the comorbidity of dental caries and obesity in adolescents from the perspective of the oral-gut-brain axis
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González-Palacios, P., Ramírez, V., Muros, J. J., González-Domenech, P., Baca, M. Á., Monteagudo, C., & Rivas, A. (2025) · Journal of Affective Disorders · doi:10.1016/j.jad.2025.120410 · Cited by 2
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Beyond BMI: Finding critical body adiposity indices for dual-threat prediction of depression and mortality in stroke survivors
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735. Immunometabolic Dysregulation in Depression Predates Illness Onset and is Associated With Lower Brain Gray Matter Volume
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Impact of duration of untreated illness on clinical and physical measures in early adult patients with major depressive disorder: a large-scale cross-sectional study
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Background
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Overgewicht en obesitas bij volwassenen en kinderen
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Central Serotonin/Noradrenaline Transporter Availability and Treatment Success in Patients with Obesity
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“We also observed an overall significant positive correlation between BMI and BDI in line with cross-sectional and metaanalyses, which indicates that obesity is a risk factor for the development of depression and vice versa, depression triggers excessive weight gain leading to obesity [40,41].”
Background
Psychological Aspects, Physical Activity Levels and Overweight Concerns: A Cross-Over Study of Brazilian Adolescents
Santana, K. S., Fonseca, S. J., Queiroz, C., de Oliveira, A. J., Machado, S., & Neto, G. D. A. M. (2022) · Clinical Practice and Epidemiology in Mental Health · doi:10.2174/17450179-v18-e221020-2022-15 · Cited by 2
Pandemi Döneminde Bireylerin Sezgisel Yeme Davranışı, Depresyon ve Beden Kütle İndeksi Arasındaki İlişkinin Değerlendirilmesi
ÖNAL, D., & Okudu, C. (2023) · Haliç Üniversitesi Sağlık Bilimleri Dergisi · doi:10.48124/husagbilder.1160327 · Cited by 2

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
ORCID: Milaneschi, Yuri
Simmons, W. Kyle
Penninx, Brenda WJH
Venue: Molecular Psychiatry
Publisher: Springer Science and Business Media LLC
Published: 2018-02-16
Volume: 24
Issue: 1
Pages: 18-33
ISSN: 1359-4184 (ISSN-L)
1476-5578
DOI: 10.1038/s41380-018-0017-5
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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Depression and obesity: evidence of shared biological mechanisms

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