Depression is the most common psychiatric disease with an overall prevalence of 6-10% in Europe. Depression has an impact on the community that is greater than that of many chronic physical diseases. It is considered by the WHO to become the leading cause of disability worldwide. Current treatment strategies with pharmacotherapy or psychotherapy are associated with a significant clinical response and improvement in 50-60% of patients and with a full recovery in only 30-40%. Thus, at least in one third of the patients’ current treatment options do not lead to a full recovery of depression. In contrast to the high prevalence and burden of mood disorders, there is still a limited knowledge on the pathophysiology of depression or bipolar disease and on possible alternative ways for treatment. Beside changes in neurotransmitters, genetic and environmental factors, an involvement of the immune system has been discussed in recent years. Activation of the immune system during immune treatment or chronic autoimmune diseases was found to be associated with a significant increase in depressive symptoms. In addition immune activation or immune suppression has been observed in patients with depression or bipolar disorders. Thus interactions between the immune system and the brain might be important for the pathophysiology of mood changes or mood disorders and may offer a new field of interest to develop alternative treatment strategies. In this context the INFLAME-D project will adopt a multi-disciplinary and translational approach to decipher the psychoimmunological mechanisms involved in the pathophysiology of depression and to assess whether any of them are shared with bipolar disorders. In different translational projects, basic and clinical researchers will try to detect immune changes in patients and animals suffering from primary psychiatric mood disorders as depression or bipolar disease or with depression induced by immune therapy and will assess the involvement of these changes in the development of depression. This project will allow the identification of biomarkers for the diagnosis and prognosis of depression as well as the development of innovative treatment strategies.