Depression in mastocytosis patients: A symptom, not a reaction

Patients with mastocytosis have many psychological manifestations of their disease.  They include low attention span, difficulty concentrating, forgetfulness, depression, poor motivation, susceptibility to stress, irritability and anxiety.  Depression is the most common, and often the most significant, neuropsych complaint among this population.  Depression is found in 40-70% of mastocytosis patients, compared to 7% in the general population, 14-25% in advanced diabetes patients and 10-50% in advanced cancer patients.  Recent research has found that depression in mastocytosis patients is not a function of the physical impact of the disease, but is instead an intrinsic part of the pathology. 

Identification of depression frequency in mastocytosis patients is frustrated by the use of the Hamilton Depression Scale, a common tool for rating the severity of symptoms.  The scale uses indicators like insomnia, muscular pain, headache and GI trouble, all of which can present in mastocytosis in the absence of more traditional depressive symptoms, like depressive mood, anxiety, guilt and psychomotor retardation.   The most thorough study on this topic found that depression in mastocytosis patients was found to have two general groups of symptoms: “anxiety-depression” and “sleep disturbances.” 

Mild to moderate depression was found to occur in 56% of mastocytosis patients interviewed, while severe depression occurred in only 8%.  Insomnia was very common in both groups.  Psychomotor retardation (slowing down of thoughts and physical processes), GI symptoms and weight loss were rare in both groups.  Those severely depressed experienced impairment in work and activities (97%), depressed mood (95%), anxiety (83%), and guilt (61%.)  Genital symptoms, early insomnia and suicide ideation were found regularly in this group, while general bodily symptoms and anxiety were less common.  Mild-moderate depression was characterized by more late insomnia and anxiety. 

Mastocytosis was found to have a specific pattern of depression distinct from other chronic diseases, including diabetes.  The high frequency of suicide ideation indicates that risk of suicide attempt is much higher in mastocytosis patients than in the general population.  Slowing down of thoughts and physical processes and loss of insight were very rare in this population.  Severely depressed patients had more impairment of sexuality.  This study also found mild-moderately depressed patients to more frequently be hypochondriacs, defined here as apprehension about bodily sensation or health state not supported clinically.  (Note: I personally find it frustrating that hypochondria is a considered symptom here, but it is a standard part of the scale they used, so I understand its inclusion.  I know we have all personally suffered through doctors telling us our concerns were invalid, when they were in fact occult.  Nevertheless, it was a finding of the study so I’m reporting it here.)

A French study evaluated the effect of masitinib treatment on depression in mastocytosis patients.  Masitinib is a tyrosine kinase inhibitor that act on mast cells.  It interacts with the KIT and Lyn receptors.  It is primarily used in veterinary medicine, but has shown efficacy in human patients with cutaneous mastocytosis.  Depression was significantly improved in 75% of patients.  50% of patients improved, with 25% finding remission. 

Previous studies have shown that depression in cancer and diabetes patients is related to poor quality of life.  Interestingly, the data in this study demonstrated that for mastocytosis patients, depression does not improve with a better quality of life.  However, the effect of masitinib on mast cells improves depression in these people.  It is believed that this is effected by two pathways: blocking of mast cell secreted mediators in the brain and by reducing the number of mast cells in parts of the brain associated with emotion.

The overwhelming prevalence of depression in mastocytosis patients indicates a systemic brain involvement, likely through mast cell released mediators such as serotonin or substance P.  Recent findings suggest that mast cells are important in the mechanisms regulating emotion.  It has also been noted that anxiety and negative emotionality are common to diseases mediated by mast cells, including asthma, rheumatoid arthritis and multiple sclerosis.  Mast cells have also been shown to evoke hypothalamic-pituitary-adrenal responses by releasing histamine and corticotropin-releasing hormone.  This axis (HPA) is involved heavily in the biology of mood disorders, such as anxiety and bipolar disorders.  This means that these disorders are, at least partly, due to mast cell activity in the brain.

Importantly, this study found that physical symptoms, including pain, were NOT a function of depression but instead due to mastocytosis.  “In mastocytosis, depression does not seem to be related to physical related symptoms or severity and therefore should be considered an endogenous manifestation.”

The takeaway of this study, and others, is that neuropsychiatric features found in mast cell patients are intrinsic to the disease.  These symptoms are NOT reactions to the physical symptoms.  They also are not related to quality of life.  Use of medication that directly impacts proliferation of mast cells has been seen to reduce these symptoms.

Sources:

Moura DS, Sultan S, Georgin-Lavialle S, Pillet N, Montestruc F, et al. (2011) Depression in Patients with Mastocytosis: Prevalence, Features and Effects of Masitinib Therapy. PLoS ONE 6(10): e26375. doi:10.1371/journal.pone.0026375

Cowen PJ (2010) Not fade away: the HPA axis and depression. Psychological Medicine 40: 1–4.

Nautiyal KM, Ribeiro AC, Pfaff DW, Silver R (2008) Brain mast cells link the immune system to anxiety-like behavior. Proc Natl Acad Sci U S A 105:18053–18057.