PROJECT: JTC2013: INFLAME-D

Role of inflammation and related processes in the development, phenomenology and treatment of depression

Abstract

Depression is the most common psychiatric disease with an overall prevalence of 6-10% in Europe. Recent WHO-data point out that mood disorders represent a leading cause for global years lived with disability. However, despite the frequency and substantial health and economic burden of mood disorders, there is only a limited knowledge on the pathophysiology of depression, risk and resilience factors as well as alternative ways for treatment. Beside the classical ?neurotransmitter model?, recent research indicates that cytokines and other immune factors are associated with mood changes and that immune-to-brain interactions might be relevant for future treatment strategies. Markers of impaired cellular immunity (decreased natural killer cell cytotoxicity) and inflammation (elevated IL-6, TNF-? and CRP) have been associated with uni- or bipolar depression. Further strong evidence for a role of cytokines and other inflammatory factors in the pathophysiology of depression comes from data obtained with the model of Interferon-alpha (IFN-?) therapy. In this context, the ?INFLAME-D? project aims to combine clinical and basic research investigations in order to get more information about the possible role of inflammation and related processes in the development, phenomenology and treatment of depression. The main objectives of the INFLAME-D project are to decipher the psychoimmunological underlying mechanisms of depression and to assess whether any of them are shared with bipolar disorders. For this purpose, four specific scientific tasks have been developed. The first task aims at investigating the risk and resiliency factors for IFN-?-induced depression in medically ill patients and to evaluate the influence of antidepressant (pre-) treatment on immunological factors during IFN-?-induced depression. The second task aims at assessing behavioural and molecular changes induced by INF-? treatment in mice. In a third task, we will assess the involvement of inflammatory and related metabolic processes in the phenomenology, treatment responsiveness and risk of relapse of idiopathic unipolar and bipolar depressive disorders and determine the mechanisms underlying these effects. Finally the task four aims at determining the role of metabolic alterations in inflammation and its subsequent mood effects in laboratory rodents.

Keywords

affective disorders, Pharmacology, Behavioural methodologies, (epi)genetic approaches, aetiology, Clinical trial, treatment, rsik factors, resilience, inflammatory system

Call topic

Mental Disorders

Proposed runtime

2014 - 2018

Project team

Martin Schaefer (Coordinator)
Germany (BMBF)
Lucile Capuron
France (ANR)
Annamaria Cattaneo
Italy (MOH)
Astrid Friebe
Germany (BMBF)
Marion Leboyer
France (ANR)