Mast cells' involvement in inflammation pathways linked to depression: evidence in mastocytosis

Abstract

Converging sources of evidence point to a role for inflammation in the development of depression, fatigue and cognitive dysfunction. More precisely, the tryptophan (TRP) catabolism is thought to play a major role in inflammation-induced depression. Mastocytosis is a rare disease in which chronic symptoms, including depression, are related to mast cell accumulation and activation. Our objectives were to study the correlations between neuropsychiatric features and the TRP catabolism pathway in mastocytosis in order to demonstrate mast cells' potential involvement in inflammation-induced depression. Fifty-four patients with mastocytosis and a mean age of 50.1 years were enrolled in the study and compared healthy age-matched controls. Depression and stress were evaluated with the Beck Depression Inventory revised and the Perceived Stress Scale. All patients had measurements of TRP, serotonin (5-HT), kynurenine (KYN), indoleamine 2,3-dioxygenase 1 (IDO1) activity (ratio KYN/TRP), kynurenic acid (KA) and quinolinic acid (QA). Patients displayed significantly lower levels of TRP and 5-HT without hypoalbuminemia or malabsorption, higher IDO1 activity, and higher levels of KA and QA, with an imbalance towards the latter. High perceived stress and high depression scores were associated with low TRP and high IDO1 activity. In conclusion, TRP metabolism is altered in mastocytosis and correlates with perceived stress and depression, demonstrating mast cells' involvement in inflammation pathways linked to depression.

Masitinib for treatment of severely symptomatic indolent systemic mastocytosis: a randomised, placebo-controlled, phase 3 study

“…Depression and asthenia are potential psychiatric manifestations of mast cell activation and can have a negative influence on the wellbeing of patients with systemic mastocytosis. 1,2,22,23 Thus, the improvement in endpoints, such as the Fatigue Impact Scale and Hamilton Rating Scale for Depression (non-significant), and their associated 4R75% and 3R75% composite endpoints is indicative that masitinib can positively affiect neuropsychiatric manifestations of systemic mastocytosis. These efficacy data confirm observations from related phase 2 studies (appendix p 20).…”

Masitinib for treatment of severely symptomatic indolent systemic mastocytosis: a randomised, placebo-controlled, phase 3 study

“…Depression and asthenia are potential psychiatric manifestations of mast cell activation and can have a negative infl uence on the wellbeing of patients with systemic mastocytosis. 1,2,22,23 Thus, the improvement in endpoints, such as the Fatigue Impact Scale and Hamilton Rating Scale for Depression (non-signifi cant), and their associated 4R75% and 3R75% composite endpoints is indicative that masitinib can positively aff ect neuropsychiatric manifestations of systemic mastocytosis. These effi cacy data confi rm observations from related phase 2 studies (appendix p 20).…”

Mast Cells in the Developing Brain Determine Adult Sexual Behavior

“…We here demonstrate that sex-specific organization of the POA and resultant male-typical sexual behavior depends upon a surprising cellular player--the mast cell. Mast cells populate the brains of many species, including humans (18), but the possibility that mast cells are important to human brain development was discounted due to their sparseness.…”