Expert Review

Depression and obesity: evidence of shared biological mechanisms

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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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WKS’s contribution was supported by funding from the National Institute of Mental Health (K01MH096175) and National Institute of General Medical Services (P20GM109097). EFCvR is supported by a Vidi grant from the Netherlands Organization of Scientific Research NWO (grant number: 91716453) and an Erasmus MC research fellowship. BWJH’s contribution was supported by the EU FP7 MooDFOOD project grant agreement no. 613598.

Author information


  1. Department of Psychiatry, Amsterdam Neuroscience and Amsterdam Public Health Research Institute, VU University Medical Center, Amsterdam, The Netherlands

    • Yuri Milaneschi
    •  & Brenda WJH Penninx
  2. Laureate Institute for Brain Research, Tulsa, OK, USA

    • W. Kyle Simmons
  3. School of Community Medicine, The University of Tulsa, Tulsa, OK, USA

    • W. Kyle Simmons
  4. Department of Internal Medicine, Division of Endocrinology, Erasmus University Medical Center Rotterdam, and Obesity Center CGG, Rotterdam, The Netherlands

    • Elisabeth F. C. van Rossum


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Conflict of interest

WKS is listed as a co-inventor on a patent regarding appetite change in depression. BWJHP has received research funding (non-related to the work reported here) from Jansen Research and Boehringer Ingelheim. The remaining authors declare that they have no conflict of interest.

Corresponding author

Correspondence to Brenda WJH Penninx.