Lay summary

Background: Cardio-vascular diseases (CVD), their well established risk factors (CVRF) and mental disorders are common and co-occur more frequently than would be expected by chance. However, the pathogenetic mechanisms and course determinants of both CVD and mental disorders have only partially been identified. In particular, the mechanisms underlying their association still need to be elucidated. Several non-mutually exclusive hypotheses have been suggested to explain this association: a) mental disorders could increase vulnerability to CVD through damaging health behavior including smoking, poor diet, sedentary lifestyle or the side effects of psychotropic drugs; b) CVD or its treatment could promote the development of mental disorders; or c) mental disorders and CVD/CVRF could share pathogenetic mechanisms, such as metabolic processes or genes.

The primary aim of the cohort proposal is to follow-up a large population-based sample, which underwent a comprehensive somatic, psychiatric and genetic investigation in order to prospectively assess the complex association between CVD, CVRF and mental disorders.

Data collection at follow-up surveys will include: 1) the course of the conditions related to CVD or mental disorders observed at baseline; 2) the incidence of conditions related to CVD or mental disorders during the follow-up; 3) supplementary data on relevant phenotypes that were not part of the baseline investigation; and 4) the evaluation of candidate variables which could be either mediators of a causal relationship or shared factors underlying the association between mental disorders and CVD/CVRF. This list includes biological (genetic, inflammatory, hormonal), clinical (persistent pain, sleep disorders), behavioral (nutrition, physical activity, smoking, alcohol and drug consumption, coping style) and environmental factors (major life-events, social support). The collection of this follow-up information is crucial for the establishment of the dynamic relationship between CVD/CVRF and mental disorders. Specifically, it will allow us to address:

Three main study questions: 1) Do mental disorders increase vulnerability to CVRF and CVD? 2) Do CVRF and CVD or their drug treatment promote the development of mental disorders? 3) Do CVRF/CVD and mental disorders share common pathogenetic processes?

Methods: The project combines a comprehensive follow-up of CVRF and CVD with a psychiatric exam in all subjects of the original CoLaus sample (n = 6'738). The somatic investigation includes a shortened questionnaire on CVRF, CV events and new CVD since baseline and measurements of the same clinical and biological variables in the fasting state as at baseline. Data on the cause of death will be collected from the Swiss National Death Registry. The comprehensive psychiatric investigation employs contemporary epidemiological methods. In addition, screening for subjective and objective cognitive impairment is performed in subjects older than 65 years. This first follow-up of the sample has started in 2009 and is progressing rapidly. We expect that by spring 2013, 5000 subjects will have participated at the physical and 4000 subjects at the psychiatric evaluation.

Major achievements: Analyses of the data from the baseline evaluations and the recently assessed cytokines have yielded more than 80 papers in high impact factor peer-reviewed scientific journals. A first set of epidemiological articles have provided highly relevant results from the public health perspective, whereas a second set of articles, based on genetic data (GWAS), have contributed, in combination with data from other studies, to a better insight into potential new determinants involved in the pathogenesis of complex diseases.

Expected value of the project: The combined CoLaus/PsyCoLaus sample provides a unique opportunity to obtain prospective data on the interplay between CVRF/CVD and mental disorders, overcoming limitations of previous research by bringing together a comprehensive investigation of both CVRF and mental disorders as well as a large number of biological variables and a genome-wide genotype assessment in subjects recruited from the general population. With the recent rapid progress in identifying genetic markers for complex diseases, we anticipate that numerous genetic markers for the index diseases in this study will also be used to inform us on the mechanisms of the associations between CVD/CVRF and mental disorders, as well as to predict risk for the development of these conditions.. A better understanding of the psychological, physiological and behavioral links underlying these conditions will result in the development of more specific and efficient strategies of prevention and treatment for both psychiatric and CVD/CVRF, two major elements of burden of disease.