Yuri Milaneschi1, Femke Lamers2, Mariska Bot2, Madeleine L Drent3, Brenda W J H Penninx2. 1. Department of Psychiatry, EMGO Institute for Health and Care Research and Neuroscience Campus Amsterdam, VU University Medical Center/GGZ ingest, Amsterdam, The Netherlands. Electronic address: y.milaneschi@ggzingeest.nl. 2. Department of Psychiatry, EMGO Institute for Health and Care Research and Neuroscience Campus Amsterdam, VU University Medical Center/GGZ ingest, Amsterdam, The Netherlands. 3. Department of Internal Medicine, Endocrine Section, VU University Medical Center, Department of Clinical Neuropsychology, Faculty of Psychology and Education, VU University, Neuroscience Campus Amsterdam, Amsterdam, The Netherlands.
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.
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 depressedpatients, 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.
Authors: Carla M Patist; Nicolas J C Stapelberg; Eugene F Du Toit; John P Headrick Journal: Cogn Affect Behav Neurosci Date: 2018-12 Impact factor: 3.282
Authors: A M Lasserre; M-P F Strippoli; J Glaus; M Gholam-Rezaee; C L Vandeleur; E Castelao; P Marques-Vidal; G Waeber; P Vollenweider; M Preisig Journal: Mol Psychiatry Date: 2016-10-11 Impact factor: 15.992
Authors: Yuri Milaneschi; Femke Lamers; Wouter J Peyrot; Bernhard T Baune; Gerome Breen; Abbas Dehghan; Andreas J Forstner; Hans J Grabe; Georg Homuth; Carol Kan; Cathryn Lewis; Niamh Mullins; Matthias Nauck; Giorgio Pistis; Martin Preisig; Margarita Rivera; Marcella Rietschel; Fabian Streit; Jana Strohmaier; Alexander Teumer; Sandra Van der Auwera; Naomi R Wray; Dorret I Boomsma; Brenda W J H Penninx Journal: JAMA Psychiatry Date: 2017-12-01 Impact factor: 21.596