The present project aims at identifying DNA methylation determinants of ketamine response in patients with depression and anxiety in comorbidity. We hypothesize that acute ketamine may induce rapid changes of DNA methylation at selected genetic loci, and that the epigenetic… Leggi tutto reprogramming at specific genes plays a key role in the fast and sustained antidepressant effect of the drug. To challenge our hypothesis, the collaboration between the two research units involved will allow the complimentary integration of clinical and preclinical studies, including innovative genome-wide techniques together with the use of a well-validated model of mood and anxiety disorders. Taking together, the results of the present project promise to highlight epigenetically-driven changes correlated with behavioral response to ketamine. Indeed, the combined results of this effort will give more insight into the basic mechanisms mediating the rapid antidepressant effect, and will help the identification of new targets for the development of faster and better treatments. Moreover, the project will also aim at assessing whether pre-existing differences of epigenetic signature in patients before ketamine treatment may have validity in the prediction of the response to the drug. This would be of help in the personalization of the treatment of mood and anxiety disorders.