MooDS: Systematic Investigation of the Molecular Causes of Major Mood Disorders and Schizophrenia

Affective disorders and schizophrenia are among the major causes of illness related disability worldwide. Their course is predominantly chronic or recurrent and is associated with an increased mortality. The Integrated Genome Research Network (IG) MooDs aims to explain the causative factors contributing to affective disorders and schizophrenia. It will build upon the previous work of the applicants, which has included the collection of large and well characterised patient samples, molecular genetic studies and the first genome wide association studies.

These genetic studies will be expanded in IG MooDs with the aim of identifying responsible genes with greater certainty. Genomewide association studies will be performed in substantially enlarged patient samples, with total sample sizes of 1500 patients for all 3 investigated illnesses (unipolar and bipolar affective disorder and schizophrenia) being the aim. New statistical methods will be developed and applied for the interpretation of genome wide association data. With the aid of methods from the field of bioinformatics, genome wide information concerning biological pathways will be incorporated into the analyses, and the explanatory power of the genomewide association studies will be further improved.

Detailed illness- related data from a large number of patients will be brought together in a diagnosis-comprehensive databank (MooDS Phenome Database). This will permit investigation of the significance of illness associated genes to clinical presentation, course of illness, response to medication and long-term prognosis. The pathophysiology of the investigated illnesses will be systematically explained on the basis of the genetic findings, which will involve the use of various approaches. At an experimental level, the most up to date methods will identify and characterise the interaction partners of the involved genes, while the establishment of animal models will allow the provision of a detailed functional explanation. The affected pathways will be further characterised through the application of systems-biology approaches and placed in a wider functional context. The significance of the illness associated genes to brain morphology and function will be investigated through the use of imaging techniques.