The leptin hypothesis of depression: a potential link between mood disorders and obesity?

Curr Opin Pharmacol. 2007 Dec;7(6):648-52. doi: 10.1016/j.coph.2007.10.010. Epub 2007 Nov 26.


The adipose-derived hormone leptin is well known for its function in the control of energy homeostasis. Recent studies suggest a novel role for this adipokine in the regulation of mood and emotion. Low levels of leptin have been found to be associated with depressive behaviors in rodents and humans. Pharmacological studies indicate that leptin has antidepressant-like efficacy. Both leptin insufficiency and leptin resistance may contribute to alterations of affective status. Identifying the key brain regions that mediate leptin's antidepressant activity and dissecting its intracellular signal transduction pathways may provide new insights into the pathogenesis of depression and facilitate the development of novel therapeutic strategies for the treatment of this illness.

Publication types

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

MeSH terms

  • Animals
  • Biogenic Monoamines / physiology
  • Depression / physiopathology*
  • Depression / psychology*
  • Humans
  • Hypothalamo-Hypophyseal System / drug effects
  • Hypothalamo-Hypophyseal System / physiology
  • Leptin / pharmacology
  • Leptin / physiology*
  • Mood Disorders / physiopathology*
  • Mood Disorders / psychology*
  • Nerve Growth Factors / physiology
  • Obesity / physiopathology*
  • Obesity / psychology*
  • Pituitary-Adrenal System / drug effects
  • Pituitary-Adrenal System / physiology
  • Receptors, Leptin / physiology


  • Biogenic Monoamines
  • Leptin
  • Nerve Growth Factors
  • Receptors, Leptin