A team of European researchers led by Dr. Yuri Milaneschi (Amsterdam UMC) has published a new study in JAMA Psychiatry exploring the role of energy homeostasis in the pathophysiology and heterogeneity of Major Depressive Disorder (MDD).
The study hypothesises that disruptions in biological pathways regulating energy balance may contribute to the complex mechanisms underlying MDD. Specifically, these disruptions were hypothesised to drive a distinct clinical profile characterised by symptoms such as increased sleep and appetite, which reflect energy-saving and intake responses.
“These findings mark an exciting step in the emerging field of metabolic psychiatry.”
To investigate this, the researchers developed a polygenic score representing genetic predisposition to alterations in energy homeostasis. This score was derived by integrating data from the latest and largest genome-wide association studies (GWAS) on metabolic, interoceptive, and motivational traits. It was then applied to over 5,000 individuals from two major psychiatric cohorts: CoLaus|PsyCoLaus (Switzerland) and NESDA (Netherlands).
The findings revealed that, among 15 depressive symptoms, the polygenic score was specifically associated with increased appetite and sleep during an MDD episode. This suggests a biologically distinct depression subtype linked to energy regulation mechanisms.
Dr. Milaneschi: “By understanding energy regulation’s role in depression, we could potentially develop more targeted and effective interventions for a substantial portion of patients.”
Pistis G., Strippoli M.F., van Dalfsen J.H., Vaucher, J., Kutalik, Z., Vollenweider, P., Penninx, B.W.J.H., Preisig, M., and Milaneschi, Y. The Role of Energy Homeostasis in Depression Pathophysiology and Its Heterogeneity. JAMA Psychiatry. Published online August 06, 2025. doi:10.1001/jamapsychiatry.2025.1858