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Atypical Features in Depression Are a Hallmark of an Increased Cardio- Metabolic Risk

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Atypical Features in Depression Are a Hallmark of an Increased Cardio- Metabolic Risk Unicentre CH-1015 Lausanne http://serval.unil.ch RYear : 2017 WHEN THE HEART ACHES: ATYPICAL FEATURES IN DEPRESSION ARE A HALLMARK OF AN INCREASED CARDIO- METABOLIC RISK Lasserre Aurélie Lasserre Aurélie, 2017, WHEN THE HEART ACHES: ATYPICAL FEATURES IN DEPRESSION ARE A HALLMARK OF AN INCREASED CARDIO-METABOLIC RISK Originally published at : Thesis, University of Lausanne Posted at the University of Lausanne Open Archive http://serval.unil.ch Document URN : urn:nbn:ch:serval-BIB_D212DDC309D30 Droits d’auteur L'Université de Lausanne attire expressément l'attention des utilisateurs sur le fait que tous les documents publiés dans l'Archive SERVAL sont protégés par le droit d'auteur, conformément à la loi fédérale sur le droit d'auteur et les droits voisins (LDA). A ce titre, il est indispensable d'obtenir le consentement préalable de l'auteur et/ou de l’éditeur avant toute utilisation d'une oeuvre ou d'une partie d'une oeuvre ne relevant pas d'une utilisation à des fins personnelles au sens de la LDA (art. 19, al. 1 lettre a). A défaut, tout contrevenant s'expose aux sanctions prévues par cette loi. Nous déclinons toute responsabilité en la matière. Copyright The University of Lausanne expressly draws the attention of users to the fact that all documents published in the SERVAL Archive are protected by copyright in accordance with federal law on copyright and similar rights (LDA). Accordingly it is indispensable to obtain prior consent from the author and/or publisher before any use of a work or part of a work for purposes other than personal use within the meaning of LDA (art. 19, para. 1 letter a). Failure to do so will expose offenders to the sanctions laid down by this law. We accept no liability in this respect. Département de psychiatrie Centre d'épidémiologie psychiatrique et de psychopathologie WHEN THE HEART ACHES: ATYPICAL FEATURES IN DEPRESSION ARE A HALLMARK OF AN INCREASED CARDIO-METABOLIC RISK Thèse de doctorat MD - PhD présentée à la Faculté de biologie et de médecine de l’Université de Lausanne par Aurélie LASSERRE Médecin diplômée de la Confédération Helvétique Jury Prof. Brigitte Santos-Eggimann, présidente et répondante MD-PhD Prof. Martin Preisig, directeur de thèse Prof. Philippe Conus, expert Prof. Femke Lamers, experte Lausanne 2017 3 4 All the fruits of scientific work, in epidemiology or other disciplines, are at best only tentative formulations of a description of nature, even when the work itself is carried out without mistakes. Kenneth J. Rothman, 2005 5 6 Remerciements Ce travail a été soutenu par une bourse du programme national MD-PhD de l’Académie suisse des sciences médicales et du Fonds national suisse de la recherche scientifique (323530_151479), l’École suisse de santé publique + et le Département de psychiatrie du Centre hospitalier universitaire vaudois et de l’Université de Lausanne. Je tiens aussi à remercier toutes les personnes sans qui ce travail n’aurait pas pu exister : Tou·te·s les participant·e·s à l’étude CoLaus, qui ont donné de leur temps et de leur personne à plusieurs reprises, ainsi que les investigatrices et investigateur de CoLaus et de PsyCoLaus pour leur précieux travail de documentation. Un immense merci à mes chères et chers collègues du CEPP ; Caroline, Jenni, Sonia, Mehdi, Marie, Enrique, Gioia, Christine, Jessica, Dominique, Sirak, Giorgio, Joachim et Flore pour leur chaleureux accueil au sein de l’équipe, leurs précieuses collaborations, relectures, discussions, analyses et surtout les cafés ! Merci aussi à l’équipe de recherche du côté de CoLaus ; Peter, Pedro et Helena. Et bien sûr, toute ma reconnaissance à Martin, pour m’avoir fait confiance, pour sa disponibilité, son soutien et son enseignement! Un grand merci à la professeure Brigitte Santos-Eggimann, pour son temps et ses encouragements aux débuts, qui m’ont, entre autres, aidé à obtenir la bourse du programme MD- PhD. Merci aussi à mes expert·e·s de thèse, les professeur·e·s Femke Lamers et Philippe Conus, pour leur disponibilité, leur intérêt et leurs bons conseils tout au long de ce travail. J’aimerai aussi beaucoup remercier mes chères et chers ancien·ne·s collègues de l’IUMSP, avec qui tout a commencé : Arnaud Chiolero, Pascal Bovet, Nadia Danon-Hersch, Murielle Bochud et Fred Paccaud, qui m’ont transmis avec une immense générosité leur passion pour l’épidémiologie. Merci aussi à Jean-Nicolas Despland, Gilles Ambesin, Sylvie Berney et Stéphane Duriaux grâce à qui j’ai pu poursuivre ma formation clinique en parallèle à ce travail, avec toujours beaucoup de plaisir. Milles mercis pour les bons moments et les encouragements à mes chères et chers ami·e·s qui étaient à mes côtés durant cette période pas toujours simple; Marie, Denis, Isabelle, Guillaume, Gaëlle, Daniel, Joëlle, Laurent, Tatjana, Stéphane, Abigaël, Jessica, Catherine, Yaël, Philippe, Lyne, Natacha, Sylvain, Lucy, Helena, Eric et les autres. Enfin, rien de tout cela n’aurait été possible sans mes parents, mes tantes, mes grands-tantes, mes grands-mères, ainsi que Lise, Alexandre et Louis, que je remercie du fond du cœur pour leur soutien inconditionnel. Un merci tout particulier aux grands-parents d’Adèle, pour leur amour et leur temps avec elle. Et bien sûr un infini merci à mon très cher Thomas, présent à chaque instant. 7 Résumé La dépression et les maladies cardiovasculaires représentent deux enjeux majeurs de santé publique en raison du grand nombre de personnes atteintes et de leur impact sur la qualité de vie. Ces troubles coexistent chez les mêmes individus plus souvent que ce que le hasard voudrait, pourtant les mécanismes qui sous-tendent cette association ne sont que peu compris. Compte tenu de l'hétérogénéité de la dépression, l’évaluation détaillée des symptômes, de la temporalité et des sous-types de la dépression semble être une piste vers une meilleure compréhension de ces mécanismes. Dans ce contexte, les objectifs de ce travail étaient (1) d’examiner l’effet des différents sous-types de dépression sur les facteurs de risque cardio-vasculaires métaboliques et (2) d’évaluer la mortalité associée à différentes caractéristiques de la dépression. Parmi les habitants de Lausanne âgés de 35 à 66 ans, un échantillon randomisé de 3719 personnes (étude PsyCoLaus) a accepté de se soumettre à des investigations physiques et psychiatriques étendues, cela à deux reprises à cinq ans d’intervalle. Des modèles linéaires généralisés ont permis d’analyser ces données. Les participants ayant présenté une dépression atypique au début de l’étude prenaient plus de poids, augmentaient plus leur tour de taille, et présentaient un taux plus élevé d’obésité et de syndrome métabolique à la fin du suivi que les participants sans dépression, indépendamment d’un grand nombre de facteurs confondants. Ce même groupe de participants a aussi présenté une plus grande augmentation de sa glycémie à jeûn, indépendamment de sa prise de poids. Enfin, les sujets qui présentaient une dépression lors de la première investigation étaient plus à risque de décéder durant les cinq années du suivi que les autres. Ces résultats soulignent la nécessité pour le chercheur comme pour le clinicien, d'évaluer en détail les divers aspects de la dépression, en particulier les caractéristiques atypiques, et de considérer leurs possibles conséquences métaboliques. 8 Summary Depression and cardiovascular diseases represent two major issues of public health due to the large number of people affected and their heavy consequences on quality of life. They are known to coexist in the same individuals more frequently than what would be expected by chance, but the mechanisms underlying this association still need to be elucidated. Given the heterogeneity of depression, studying symptoms, courses or subtypes in detail rather than depression as a whole is likely to be a more promising approach to better understand these mechanisms. Accordingly, the aims the present work were to (1) assess the prospective associations between depression subtypes at baseline and the subsequent changes in metabolic cardio-vascular risk factors, and (2) determine the association of clinical and course characteristics of depressive disorders with all- cause mortality over a 5-year follow-up period. A randomly selected sample of 3719 persons aged 35 to 66 years from the population of Lausanne (PsyCoLaus) agreed to participate in thorough physical and psychiatric assessments at baseline and, five years later, at a follow-up visit. Generalized linear models were used. Participants with the atypical subtype of depression at baseline, compared to the never depressed, presented a higher increase of body mass index, waist, as well as a higher incidence of obesity and metabolic syndrome after five years, independently of a large range of known possible confounders. This same group had also a higher increase of fasting plasma glucose. Moreover, survival analyses showed that participants with a current episode of depression at baseline were at a higher risk of dying during the five following years than the never depressed. These results emphasize the need for assessing in detail the various characteristics of depression, in particular the atypical subtype, in research as well as in clinical settings and to consider their metabolic consequences. 9 10 Table of contents INTRODUCTION 13 Depression and cardiovascular diseases, two public health priorities 13 Some historical landmarks of the definition of depression 15 Major depressive disorder, atypical and melancholic features, according to DSM-5 20 Depression and cardiovascular
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