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Early diagnosis, treatment and prevention of mood disorders targetting the activated inflammatory response system

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Immune dysfunction linked to mood disorders

Accumulating evidence suggests that the neural and immune systems are tightly intertwined. With this mind, European researchers investigated the novel hypothesis that immune dysfunction could be the triggering event in mood disorders.

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An abnormal immune activation is emerging as central to the development of mood disorders. A chronic state of inflammation in certain brain areas involved in mood regulation could cause mood imbalance, as a result of hormonal or metabolic disturbance. For example, immune activation could impair the catabolism of tryptophan, an important precursor of the neurotransmitter serotonin. The EU-funded MOODINFLAME study was designed to test the underlying hypothesis that many mood or psychiatric disorders are triggered by increased susceptibility to inflammation. Their objective was to study immune dysfunction in psychiatric patients and mouse models of disease and develop brain and blood scans for assessing immune dysfunction. Large number of patient samples were analysed. Results linked mood disorder with increased numbers of monocytes expressing both pro- and anti-inflammatory genes as well as high levels of pro-inflammatory cytokines. All this data validated the overall immune dysfunction pattern in patients with mood disorders. Interestingly, an activated state of monocytes negatively determined the outcome of anti-depressant therapy. Work in animal models of depressive-like behaviour further corroborated these findings. Animals exhibited activated inflammatory responses and an abnormal tryptophan metabolism. Scientists identified three major pathways that were implicated in the aberrant immune-endocrine interface. This abnormal communication led to structural and functional deficits of important brain regions. Regarding therapeutic strategies, part of the MOODINFLAME work entailed the screening of various non-steroid anti-inflammatory drugs in the animal models. The PSYCH-AID project, which is an EU-funded continuation project of MOODINFLAME will continue the investigation of such drugs in patients with mood disorders. Overall, the outcome of the study has the potential to change the way psychiatric disorders are treated. The generated diagnostic tools will be of enormous help down this path, facilitating the screening of patients with mood disorders for immune dysregulation.

Keywords

Inflammation, immune dysregulation, lymphocytes, mood disorders, tryptophan, serotonin, psychiatric, monocytes, pro-inflammatory, cytokines, anti-depressant, non-steroid anti-inflammatory drugs

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