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Prospective associations of major depressive disorder with atherosclerotic cardiovascular disease, cognitive impairment and mortality in the community

English title Prospective associations of major depressive disorder with atherosclerotic cardiovascular disease, cognitive impairment and mortality in the community
Applicant Vaucher Julien
Number 204523
Funding scheme Project funding (special)
Research institution Service de Médecine Interne Département de Médecine CHUV
Institution of higher education University of Lausanne - LA
Main discipline Mental Disorders, Psychosomatic Diseases
Start/End 01.01.2022 - 31.12.2025
Approved amount 908'000.00
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All Disciplines (3)

Discipline
Mental Disorders, Psychosomatic Diseases
Cardiovascular Diseases
Metabolic Disorders

Keywords (7)

Psy-colaus; Public Health; Cardiovascular risk factors; Genetics; Cardiovascular diseases; Epidemiology; Mental disorders

Lay Summary (French)

Lead
Etude des associations prospectives entre troubles dépressifs, maladies cardiovasculaires et déclin cognitif dans la population générale
Lay summary

Les troubles dépressifs sont fortement associés aux maladies cardiovasculaires et au déclin cognitif. Ces liens sont importants en termes de santé publique sachant la prévalence importante de ces trois maladies dans la population générale. Toutefois, les mécanismes qui sous-tendent ces liens n’ont pas été suffisamment étudiés, notamment au travers de mesures répétées dans le temps de facteurs pouvant expliquer leur survenue chez des mêmes individus. En conduisant un 4e suivi de l’étude CoLaus|PsyCoLaus (www.colaus-psycolaus.ch), nous allons collecter des données chez les participants les plus âgés de la cohorte (année de naissance entre 19300 et 1955), qui ont été recrutés initialement entre 2003 et 2006 parmi les habitants de la ville de Lausanne (Suisse). Ces participants qui ont, pour beaucoup, déjà participé à la plupart des suivis de l’étude ont été investigués de manière détaillées, au travers des multiples questionnaires sur leur état de santé, des examens physiques, des analyses de sang et d’urine, ainsi que par l’analyse d’une partie de leur génome. Un accent particulier a été porté à la récolte d’informations sur des facteurs originaux, comme l’activité physique, le sommeil, ou le degré d’inflammation présent dans l’organisme. De plus, un grand effort est effectué pour collecter et préciser les problèmes de santé que développent les participants, notamment les maladies cardiovasculaires et psychiatriques, ainsi que les troubles cognitifs. En combinant les données récoltées lors des précédents suivis avec celles de cette 5e phase de l’étude, nous allons étendre nos connaissances sur les associations complexes entre troubles dépressifs, maladies cardiovasculaires et déclin cognitif en : 1) établissant les associations dans le temps entre ces 3 entités ; et 2) en caractérisant le rôle de facteurs modifiables qui peuvent contribuer à leur genèse ou être des médiateurs de leur association. En utilisant cette approche originale et unique, nous serons à même de mieux comprendre les mécanismes induisant la survenue de ces maladies et la nature de leurs liens.

Direct link to Lay Summary Last update: 10.12.2021

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Associated projects

Number Title Start Funding scheme
189130 Associations between depression and obesity markers in adolescents and young adults in the community 01.10.2019 Project funding (special)

Abstract

Background: Major depressive disorder (MDD) has been consistently found to be prospectively associated with atherosclerotic cardiovascular diseases (ASCVD) and cognitive decline. Given the high lifetime-prevalence of MDD, its strong links with ASCVD and cognitive decline, two major disease burden, have major public health significance. However, the underlying mechanisms of these links have not been adequately studied with repetitive measures and simultaneous assessment of multiple mechanisms. Moreover, mechanisms are likely to vary across MDD subtypes, which have shown differential associations with cardiovascular risk factors (CVRF). Aim: To conduct a fourth follow-up (FU4) evaluation of our population-based cohort approximately 4 years after the last assessment to gain a better understanding of the associations of MDD with ASCVD, cognitive decline and death related to ASCVD and all-cause mortality as well as the role of factors that could be involved in these associations. Although rates of ASCVD or cognitive decline are still low, this follow up is likely to detect a steep increase of these outcomes. The proposed data collected at FU4 will allow us to address the following questions: 1) Does MDD or its subtypes (atypical, melancholic, unspecified) increase vulnerability to ASCVD (ischemic heart disease, stroke and peripheral artery disease), ASCVD death or all-cause mortality? 2) Does MDD or its subtypes increase vulnerability to subsequent cognitive decline (changes of cognitive test scores, minor cognitive impairment)? 3) Are sleep and activity patterns, inflammation, HPA axis regulation, diet and cardio-metabolic factors involved in the association of MDD or its subtypes and ASCVD or cognitive decline either as mediators of a causal relationship or as shared etiological factors? We hypothesize that both atypical and melancholic MDD are associated with ASCVD or cognitive decline, but that differential mechanisms may underlie these associations. Methods: We propose to perform a comprehensive 4th follow-up (FU4) of the elderly participants (year of birth 1930-1955; n=3881) of the CoLaus|PsyCoLaus cohort, which was randomly selected between 2003 and 2006 from the residents of the City of Lausanne. Participants underwent four thorough physical, biochemical and genetic (GWAS) evaluations of CVRF and ASCVD as well as comprehensive psychiatric assessments including a semi-structured diagnostic interview, cognitive tests and MRI. At the end of 2020, 9.5% of the cohort were deceased. FU3, which was slightly delayed by the covid pandemic will be completed by spring 2021. At each evaluation we have elicited information on behavioral, physiological, and metabolic factors that may be involved in the association between MDD and ASCVD. In addition, genetic information is available on all participants (Affymetrix GWAS). A particular focus was placed on actigraphy in combination with ecological momentary assessments, which provide an objective measure of activity and sleep patterns. FU4 (expected n=2100 for the physical and n=1600 for the psychiatric evaluations) will include the measures of previous assessments. For incident ASCVD, dementia or death, information will be elicited from medical records or from the Swiss National Death Registry. Interoperability of data is assured by integration into the Maelström meta-data catalogue through a SPHN driver project.Main expected outcome: The proposal will extend current knowledge on the complex associations of the heterogeneous category of MDD with ASCVD and cognitive decline by 1) establishing the specific prospective associations of subtypes of MDD with ASCVD cognitive decline, and 2) characterizing the role of modifiable factors involved therein, which will contribute to the development of more targeted strategies of prevention of both ASCVD and cognitive decline.Potential relevance: Our study has a series of unique and novel features including 1) comprehensive psychiatric phenotyping of the full range of mental disorders and subtypes of MDD in a prospective population-based cohort, 2) repetitive assessment of depressive episodes and their timing that can elucidate their dose-response relationship with ASCVD and cognitive decline, 3) repeated and simultaneous assessments of factors potentially involved in the association of MDD with ASCVD and cognitive decline enhancing our ability to characterize their independent roles, 4) availability of complementary genetic and familial aggregation data allowing us to triangulate causality by combining different approaches, and 5) combined objective measures of sleep and physical activity by actigraphy with subjective tracking of life context and emotional states that can characterize dynamic processes to supplement traditional clinical measures.
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