Ongoing Projects

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:

• the specificity of the familial aggregation of bipolar disorder, major depressive disorder, and substance use disorders;
• the impact of comorbid psychiatric conditions, including substance dependence, on the familial transmission of mood disorders;
• the mechanisms of the association between bipolar disorder and comorbid conditions through the investigation of patterns of transmission of these disorders in families;
• a large number of potential risk or protective factors of mood and substance use disorders.

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:

• to test the validity of postulated psychopathological, neuropsychological and biological endophenotypes of mood disorders;
• to determine the contribution of genetic determinants to these endophenotypes.

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.

Recent publications

• Vandeleur C.L., Strippoli M-P.F., Castelao E., Gholam-Rezaee M, Ferrero F, et al. The Lausanne-Geneva cohort study of offspring of parents with mood disorders: methodology, findings, current sample characteristics, and perspectives. Social Psychiatry and Psychiatric Epidemiology 2017; 52:1041-1058.
• Vandeleur C.L., Merikangas K.R., Strippoli M-P.F., Castelao E., Preisig M. Specificity of psychosis, mania and major depression in a contemporary family study. Molecular Psychiatry 2014; 19: 209-213.
• Vandeleur C.L., Rothen S., Gholam-Rezaee M., Castelao E., Vidal S., et al. Mental disorders in offspring of parents with bipolar and major depressive disorders. Bipolar Disorders 2012; 14: 641-653.
• Vidal S., Vandeleur C.L., Rothen S., Gholam-Rezaee M., Castelao E., et al. Risk of mental disorders in children of parents with alcohol or heroin dependence: A controlled high risk study. European Addiction Research 2012; 18:253-264.

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:

• What is the prevalence of psychiatric disorders in a random sample of residents of the city of Lausanne?
• What is the prevalence and what are the genetic, metabolic and environmental determinants of cardiovascular risk factors and cardiovascular disorders?
• What are the mechanisms of the associations between psychiatric and cardiovascular disorders in this population?

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.