Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 May 1;81(9):807-814.
doi: 10.1016/j.biopsych.2015.10.023. Epub 2015 Nov 17.

Leptin Dysregulation Is Specifically Associated With Major Depression With Atypical Features: Evidence for a Mechanism Connecting Obesity and Depression

Yuri Milaneschi  1 , Femke Lamers  2 , Mariska Bot  2 , Madeleine L Drent  3 , Brenda W J H Penninx  2
Affiliations

Leptin Dysregulation Is Specifically Associated With Major Depression With Atypical Features: Evidence for a Mechanism Connecting Obesity and Depression

Yuri Milaneschi et al. Biol Psychiatry. .

Abstract

Background: Obesity-related dysregulation of leptin signaling (e.g., hyperleptinemia due to central functional resistance) may affect mood. However, evidence for leptin dysregulation in major depressive disorder (MDD) is conflicting. Inconclusive findings may be attributable to heterogeneity of MDD, aggregating biologically different subtypes. We examined the relationship of leptin with MDD, its common subtypes (typical and atypical), and clinical features.

Methods: The sample consisted of participants (aged 18 to 65 years) from the Netherlands Study of Depression and Anxiety with current (n = 1062) or remitted (n = 711) MDD and healthy control subjects (n = 497). Diagnoses of MDD and subtypes were based on DSM-IV symptoms. Additional symptoms were measured with the Inventory of Depressive Symptomatology. Blood levels of leptin and adiposity indexes (body mass index and waist circumference) were assessed.

Results: As compared to control subjects, higher leptin was associated with the atypical MDD subtype both for remitted (n = 144, odds ratio = 1.53, 95% confidence interval = 1.16-2.03, p = .003) and current (n = 270, odds ratio = 1.90, 95% confidence interval = 1.51-2.93, p = 5.3e-8) cases. This association was stronger for increasing adiposity levels (leptin by body mass index interaction, p < .02), strengthening the hypothesis of the involvement of leptin resistance. No association with leptin was found for overall MDD or the typical subtype. Among currently depressed patients, higher leptin was associated with key symptoms identifying the atypical subtype, such as hyperphagia, increased weight, and leaden paralysis.

Conclusions: Leptin dysregulation (resistance) may represent an underlying mechanism connecting obesity and MDD with atypical features. Development of treatment effectively targeting leptin resistance may benefit patients with atypical depression characterized by obesity-related metabolic alterations.

Keywords: Atypical; Epidemiology; Heterogeneity; Leptin; Major depression; Obesity.

PubMed Disclaimer

Comment in

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

Publication types

-