To study the genetics of Affective Disorders at the molecular level using the candidate gene strategy (mainly association and sib-pair methods) with relevant DNA polymorphic markers.
To use molecular genetics to validate diagnostic subclassifications of affective disorders (phenotypic heterogeneity): from genotype to phenotype.
To delineate gene-psychosocial environment interactions through different cultural settings across European centers.
To consolidate and exploit a large European data bank of genetic, familial, clinical, psychosocial and psychopharmacological data available for Affective Disorders.
The understanding of genetic aspects of depression has benefited from recent findings with DNA markers. Affective disorders have been the subject of numerous studies using molecular genetics, covering a significant part of the genome. Most recent work suggests that several chromosomal regions may play a role in the etiology of Bipolar Affective Disorder. These regions of interest include genes on chromosomes 18, 21, 4, 5, 11 and X but have not yet been finally confirmed.
The main objective of this project is to test these hypotheses as well as new promising results in a powerful sample of patients with Bipolar and Unipolar depression recruited for association studies, in the framework of BIOMED1 collaborative project (EC Concerted Action on Affective Disorders: interaction between genetic and psychosocial vulnerability factors - Contract No BMH1-CT-92-1217 (1993-1996) - project leader: Prof. J. Mendlewicz). Genetic markers will be tested in a large European sample of patients and controls, already available for psychiatric genetic studies. This data bank of more than 1300 individuals with DNA available will be exploited in order to reach the main objective. This objective can only be achieved through a large scale multidisciplinary and multicenter effort. Eight European centers will collaborate in this research project. The large data base already available from these centers will allow rapid large scale investigations of genetic markers.
Selected genetic markers potentially involved in the genetic transmission of Affective Disorders (from association studies) will also be investigated through complementary strategies using sib-pair and linkage methods. Specific modes of inheritance such as anticipation and mutations (Trinucleotide Repeat Expansions) will also be studied in families and unrelated patients recruited for the project.
In addition, the quantitative effects of some relevant psychosocial vulnerability factors on gene expression will be evaluated through association, sib-pair and linkage analyses. This integrative approach offers the opportunity to properly explore the multifactorial aspects of mood disorders.
Affective disorders are highly prevalent and are associated with severe social disability and considerable mortality both with major economic impact. Etiology and risk factors of these disorders are not well known. Therefore, progress in psychiatric genetics and understanding of gene-psychosocial interactions could be of great benefit for public health.
Funding SchemeCSC - Cost-sharing contracts
EH10 5HF Edinburgh