PROJECT: JTC2013: AnxBio

Anxiety disorders are the most common mental disorders within the EU and cause considerable disability due to high prevalence (14%), early onset and chronic nature. The currently used, poorly targeted drugs are ineffective because of addiction, tolerance, and poor efficacy. Consequently, better anxiolytics are needed, and their development requires understanding of the molecular mechanisms of anxiety, which currently remain largely unknown. Our goal is to identify the major biological pathways and biomarkers for anxiety disorders using a well-established mouse model and a human patient sample. Our mouse model, the social defeat, allows investigation of gene-environment interactions, known to be important in anxiety disorders. Using the most current massively parallel sequencing and proteomics methods we will analyze the miRNAs and their mRNA targets, gene expression differences and proteome dynamics related to increased anxiety in brain and blood cells in the mouse. In parallel, we will perform gene expression and methylome profiling from blood cells of human patients. We will integrate these data with bioinformatics analysis to find altered regulatory networks and will form hypotheses, which we will test in functional studies in mice and samples from patients. This multidisciplinary project will increase understanding of the genetic and neurobiological basis of anxiety, and will provide targets for the development of improved anxiolytics and biomarkers for anxiety disorders.