Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 109, Issue 30, Pages 12248-12253Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1202835109
Keywords
adipose tissue; adipokines; tail suspension test; forced swim test; dexamethasome suppression test
Categories
Funding
- National Alliance for Research on Schizophrenia and Depression Independent Investigator Award
- National Institutes of Health [MH096251, MH076929]
- [DK76902]
- [DK55758]
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Depression is a debilitating mental illness and is often comorbid with metabolic disorders such as type 2 diabetes. Adiponectin is an adipocyte-derived hormone with antidiabetic and insulin-sensitizing properties. Here we show that adiponectin levels in plasma are reduced in a chronic social-defeat stress model of depression, which correlates with decreased social interaction time. A reduction in adiponectin levels caused by haploinsufficiency results in increased susceptibility to social aversion, anhedonia, and learned helplessness and causes impaired glucocorticoid-mediated negative feedback on the hypothalamic-pituitary-adrenal (HPA) axis. Intracerebroventricular (i.c.v.) injection of an adiponectin neutralizing antibody precipitates stress-induced depressive-like behavior. Conversely, i.c.v. administration of exogenous adiponectin produces antidepressant-like behavioral effects in normal-weight mice and in diet-induced obese diabetic mice. Taken together, these results suggest a critical role of adiponectin in depressive-like behaviors and point to a potential innovative therapeutic approach for depressive disorders.
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