title: The association between leptin and depressive symptoms is modulated by abdominal adiposity.
abstract: BACKGROUND
  Evidence for a role of leptin in depression is limited and conflicting. Inconclusive findings may be explained by the complex effect of obesity on leptin signaling. In particular, both hyperleptinemia due to leptin resistance in obese persons as well as low leptin in lean persons can imply that low leptin biological signaling is associated with an increased risk of significant depressive symptoms. We tested whether the relationship between leptin and depressive symptoms is modulated by abdominal adiposity in two population-based studies.
  
  
  METHODS
  Data were from 851 participants (65-94 years) of the InCHIANTI Study and 1064 (26-93 years) of the Baltimore Longitudinal Study of Aging (BLSA). Plasma concentrations of leptin, waist circumference and depressive symptoms via the Center for Epidemiological Studies-Depression scale (CES-D) were assessed. In longitudinal InCHIANTI analyses onset of depressed mood (CES-D≥20) was evaluated over a 9-year follow-up.
  
  
  RESULTS
  In pooled cross-sectional analyses the interaction between leptin and waist circumference was significantly associated with CES-D scores ((log)leptin-by-waist interaction p=0.01). Also in longitudinal analyses, the (log)leptin-by-waist interaction term significantly (p=0.04) predicted depressed mood onset over time; depressed mood risk was especially increased for high levels of both leptin and waist circumference.
  
  
  CONCLUSIONS
  The present findings suggest that low leptin signaling rather than low leptin concentration is a risk factor for depression. Future studies should develop proxy measures of leptin signaling by combining information on abdominal adiposity and leptin level to be used for clinical and research applications.
authors.affiliation: Department of Psychiatry and EMGO Institute for Health and Care Research, VU University Medical Center/GGZ inGeest, Amsterdam, The Netherlands; Longitudinal Studies Section, Translational Gerontology Branch, National Institute on Aging, Baltimore, MD, USA. Electronic address: y.milaneschi@ggzingeest.nl.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Milaneschi
authors.affiliation: Department of Medical Humanities and Social Sciences, Florida State University College of Medicine, Tallahassee, FL, USA; Laboratory of Population Science, National Institute on Aging, Baltimore, MD, USA.
authors.forename: Angelina R
authors.initials: AR
authors.lastname: Sutin
authors.affiliation: Department of Geriatrics Florida State University College of Medicine, Tallahassee, FL, USA.
authors.forename: Antonio
authors.initials: A
authors.lastname: Terracciano
authors.affiliation: Longitudinal Studies Section, Translational Gerontology Branch, National Institute on Aging, Baltimore, MD, USA; Laboratory of Cardiovascular Sciences, Human Cardiovascular Studies Unit, National Institute on Aging, Baltimore, MD, USA; Department of Internal Medicine, University of Genova, Genova, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Canepa
authors.affiliation: Longitudinal Studies Section, Translational Gerontology Branch, National Institute on Aging, Baltimore, MD, USA.
authors.forename: Kristofer S
authors.initials: KS
authors.lastname: Gravenstein
authors.affiliation: Longitudinal Studies Section, Translational Gerontology Branch, National Institute on Aging, Baltimore, MD, USA; Laboratory of Clinical Investigation, National Institute on Aging, Baltimore, MD, USA.
authors.forename: Josephine M
authors.initials: JM
authors.lastname: Egan
authors.affiliation: Department of Psychiatry and EMGO Institute for Health and Care Research, VU University Medical Center/GGZ inGeest, Amsterdam, The Netherlands.
authors.forename: Nicole
authors.initials: N
authors.lastname: Vogelzangs
authors.affiliation: University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Jack M
authors.initials: JM
authors.lastname: Guralnik
authors.affiliation: Geriatric Unit, ASF, Florence, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Bandinelli
authors.affiliation: Department of Psychiatry and EMGO Institute for Health and Care Research, VU University Medical Center/GGZ inGeest, Amsterdam, The Netherlands.
authors.forename: Brenda W J H
authors.initials: BW
authors.lastname: Penninx
authors.affiliation: Longitudinal Studies Section, Translational Gerontology Branch, National Institute on Aging, Baltimore, MD, USA.
authors.forename: Luigi
authors.initials: L
authors.lastname: Ferrucci
mesh_terms: D050153:Abdominal Fat / Q000503:physiopathology*; D050154:Adiposity / Q000502:physiology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003430:Cross-Sectional Studies; D003863:Depression / Q000097:blood* / Q000503:physiopathology; D005260:Female; D006801:Humans; D020738:Leptin / Q000097:blood*; D008297:Male; D008875:Middle Aged; D055105:Waist Circumference / Q000502:physiology*; D055815:Young Adult
chemical_list: D020738:Leptin
keywords: Abdominal adiposity; Aging; Depression; Leptin; Obesity