Mood disorders and substance use disorders are major public health issues. Given the serious consequences of mood disorders, particularly in the presence of comorbidity, and the severe problems caused by addiction to psychoactive substances, it is necessary to identify premorbid risk factors for these disorders and early events that begin in childhood and adolescence.
Over the past thirty years many family studies have demonstrated the familial aggregation of psychiatric disorders for both mood disorders and disorders related to substance use. As a consequence of this observation, the so-called high risk studies focus on the biological offspring of affected patients. This experimental design has the enormous advantage of allowing the prospective follow-up of children at high risk of developing diseases their parent(s) are affected with and description of the early natural history of these disorders.
The major objectives of the study are to investigate:
Participants of this controlled family study are adults with mood disorders (unipolar or bipolar) or substance use disorders. Affected probands with at least one child in the age range of 6.0 to 17.9 years were consecutively recruited from the inpatient and outpatient facilities of the psychiatric departments of Lausanne and Geneva between 1996 and 2004. Comparison probands were recruited from the orthopedic departments of the same inpatient and outpatient clinical settings in Lausanne and Geneva. During recruitment, the probands were asked permission to include their first-degree relatives. The prospective nested study «high risk» includes probands, their offspring and the biological co-parents of the offspring of interest. More specifically, the "high risk" study investigates psychopathology among the offspring of affected probands.
A total of 207 probands (81 with bipolar and 64 with unipolar disorders respectively, and 62 comparison probands) and 566 relatives (201 spouses and 365 children aged 6 to 17.9 years at recruitment) are part of the Lausanne-Geneva family study. Participants are interviewed each third year by psychiatrists or masters-level psychologists. Diagnostic information is obtained using the validated French translation of the Diagnostic of Interview for Genetic Studies (DIGS). They also complete self-reported questionnaires on personality traits, life events, and the familial and professional environment.
The main strength of the Lausanne-Geneva family study is the assessment of probands, offspring and co-parents altogether. This is extremely rare and allows us to consider the effect of affected probands on the psychopathology of their offspring as well as the effect of psychiatric disorders of the co-parent on children.
The Lausanne-Geneva family study has been enlarged to study endophenotypes of mood disorders. The National Center of Competence in Research – Synapsy, created in 2010 and funded by the Swiss National Science Foundation, is a joint venture between psychiatry and neurobiology with the aim to better understand the origins of psychic and cognitive disorders in order to improve their diagnosis and treatment. Synapsy research projects are organized around two main research axes. The first concerns the biological factors that influence development, from conception to the first years of life, in view of identifying the genes that could affect vulnerability to mental illnesses. The second concerns the environmental factors associated with life experience which could leave an imprint in the brain. The aim of the project Mood disorders of the second axis is to identify specific clinical and functional phenotypes which will be the starting point to investigate neurobiological mechanisms of psychopathology.
The endophenotype concept is one promising approach to overcome the current difficulties of defining valid phenotypes for mental disorders. This concept is based on the assumption that the number of genes involved in the variations of endophenotypes (i.e. measureable components unseen by the unaided eye along the pathway between disease and distal genotype) are fewer than those involved in mental disorders as a whole. Moreover, a series of postulated endophenotypes for mood disorders include clinical features, such as anhedonia and anxiety, cognitive performance, stress parameters as well as neurophysiological and neurobiological characteristics that can be studied in both humans and animals.
Accordingly, the specific goals of this project are:
The Lausanne-Geneva family study (including 200 new probands) is very particular in that it involves individuals who have been very thoroughly and extensively assessed, offering a unique opportunity to test endophenotypes.
The inclusion of both unipolar and bipolar mood disorders as well as the availability of assessments of individuals with other diagnoses will allow us to test the specificity of particular endophenotypes for both unipolar and bipolar mood disorders. The assessment of first-degree relatives in combination with the availability of control families will allow us to test the familial aggregation (the specific endophenotype is more prevalent among the relatives of affected probands compared to the relatives of unaffected probands) and cosegregation patterns of specific endophenotypes (the specific endophenotype is more prevalent among the affected relatives of affected probands compared to the unaffected relatives of affected probands). In addition, the comparison of the prevalence of specific endophenotypes between first-degree relatives of probands with a mood disorder and those of probands with other disorders will provide additional information on the specificity of the assessed endophenotypes.
Cardiovascular disorders and psychiatric disorders are highly prevalent in the general population. Epidemiological studies suggest that both pathologies often occur together. Several studies have shown that patients with coronary artery disease frequently suffer from depressive disorders and that, conversely, the presence of depressive disorders may increase the cardiovascular risk. Another potential mechanism of association would be that the expression of psychiatric and cardiovascular disorders is due to a common cause. Few studies that try to answer these questions have combined objective physical exams with a psychological evaluation based on direct interviews with trained and experienced psychologists.
The Colaus|PsyCoLaus study aims to answer the following questions:
The participants of Colaus|PsyColaus (6'733 participants aged 35.0-74.9 years at recruitment) underwent the somatic investigation between 2003 and 2006 including an interview, a physical exam and blood sampling. Between 2004 and 2008 3'727 participants aged 35.0-64.9 years were interviewed by psychologists using the validated French translation of the Diagnostic of Interview for Genetic Studies (DIGS). They also completed questionnaires on migraine, personality, and stress factors. The 2 follow-up exams were performed between 2009 and 2017. A total of 5120 persons accepted to participate at least once in the psychiatric investigation.
The Colaus|PsyColaus project, funded by the Swiss National Science Foundation, will be pursued to continue somatic and psychiatric investigations during a new follow-up period (2018-2020).
Because participants have had in-depth investigations for cardiovascular diseases, cardiovascular risk factors and psychiatric disorders, the Colaus|PsyColaus study is unique worldwide and helps to better understand the links between these two types of pathologies.
The European project “Linked2Safety” uses the expertise specifically developed during the CoLaus|PsyCoLaus project, along with expertise from other countries around Europe. The CEPP is involved in the pilot phases necessary for the validation of this project.
Linked2Safety is an FP7 project funded by the European Commission under the area of ICT for health. The vision of the project is to advance clinical practice by providing healthcare professionals with an innovative and efficient tool facilitating access to homogenous and anonymized health records.
The Linked2Safety project aims to build a secure, extensible platform with medical and clinical data from the enlarged Europe. The aggregated and anonymized data will aim to support sound decision-making, towards the effective organization and execution of clinical trials, allowing health carers and medical scientists to easily submit their own query and get homogenized access to high-quality medical data. This will allow analysis of all the available data of the subjects, such as genetic, environmental and their medical history during a clinical trial, leading to the identification of the phenotypic and genotypic factors that are associated with specific adverse events and thus early detection of potential patients’ safety issues. The selection of subjects for clinical trials will also be made possible with better collaboration between sites.
The Linked2Safety project reassures compliance with the European and national legislations, with regard to the publication, access to and reuse of patients’ personal and healthcare data. Furthermore a demonstration of the use of the Linked2Safety framework will be shown through the implementation of a set of Research Showcases (showcases specific to scientific questions). Through the use of the project, a step-by-step cookbook will be created describing the Linked2Safety methodology.
Complete list of Colaus/PsyColaus publications :