Appetite changes reveal depression subgroups with distinct endocrine, metabolic, and immune states

Mol Psychiatry. 2020 Jul;25(7):1457-1468. doi: 10.1038/s41380-018-0093-6. Epub 2018 Jun 13.


There exists little human neuroscience research to explain why some individuals lose their appetite when they become depressed, while others eat more. Answering this question may reveal much about the various pathophysiologies underlying depression. The present study combined neuroimaging, salivary cortisol, and blood markers of inflammation and metabolism collected prior to scanning. We compared the relationships between peripheral endocrine, metabolic, and immune signaling and brain activity to food cues between depressed participants experiencing increased (N = 23) or decreased (N = 31) appetite and weight in their current depressive episode and healthy control participants (N = 42). The two depression subgroups were unmedicated and did not differ in depression severity, anxiety, anhedonia, or body mass index. Depressed participants experiencing decreased appetite had higher cortisol levels than subjects in the other two groups, and their cortisol values correlated inversely with the ventral striatal response to food cues. In contrast, depressed participants experiencing increased appetite exhibited marked immunometabolic dysregulation, with higher insulin, insulin resistance, leptin, CRP, IL-1RA, and IL-6, and lower ghrelin than subjects in other groups, and the magnitude of their insulin resistance correlated positively with the insula response to food cues. These findings provide novel evidence linking aberrations in homeostatic signaling pathways within depression subtypes to the activity of neural systems that respond to food cues and select when, what, and how much to eat. In conjunction with prior work, the present findings strongly support the existence of pathophysiologically distinct depression subtypes for which the direction of appetite change may be an easily measured behavioral marker.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Appetite* / immunology
  • C-Reactive Protein / analysis
  • Depression / blood
  • Depression / classification
  • Depression / immunology*
  • Depression / metabolism*
  • Female
  • Ghrelin / blood
  • Humans
  • Hydrocortisone / analysis
  • Inflammation / blood
  • Inflammation / complications
  • Inflammation / immunology
  • Insulin / blood
  • Insulin / metabolism
  • Insulin Resistance
  • Interleukin 1 Receptor Antagonist Protein / blood
  • Interleukin 1 Receptor Antagonist Protein / immunology
  • Interleukin-6 / blood
  • Interleukin-6 / immunology
  • Leptin / blood
  • Male
  • Middle Aged
  • Saliva / chemistry
  • Young Adult


  • Ghrelin
  • Insulin
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-6
  • Leptin
  • C-Reactive Protein
  • Hydrocortisone