Neuropsychiatric features of mast cell disease: Part 1 of 2

The fact that psychiatric symptoms occur as a function of mast cell disease on the nervous system is common knowledge to patients but less acknowledged by providers.  A significant population of mast cells is found in the brain in close association with both blood vessels and nerve cells.  Mast cells are present in large numbers in the hypothalamus, which regulates stress response, emotion and cognition; the amygdales, near the pituitary gland; and the thalamus.  Lesions and structural changes in the thalamus have previously been associated with altered perception of pain and emotional reactivity.

One study found that in a group of 88 patients with indolent systemic mastocytosis (ISM) and cutaneous mastocytosis (CM), 75% reported depressive symptoms.  In another study, a group of 288 mastocytosis patients had a prevalence of 60% depressive and anxiety-type symptoms.  The depressive symptoms seen most often in mastocytosis patients are affective and cognitive symptoms (depressed mood, low motivation, feelings of guilt and failure; and anxio-somatic symptoms (physical and mental effects of anxiety, insomnia).  Psychomotor difficulties (slowing of thought processes and/or neurologic control of movement) and lack of insight were rare in these patients.

Depression is often assessed using the Hamilton Depression Rating Scale.  This tool may not be ideal for use in mast cell patients because the somatic symptoms correlated with depression are often the same as physical symptoms of mast cell disease.  When excluding symptoms that could be from mastocytosis rather than depression, patients still had a high prevalence of sadness and loss of motivation.

One mastocytosis cohort reported 38.6% had cognitive impairment of some kind. Inability to focus and pay attention is the cognitive symptom most commonly reported by mastocytosis patients.  This was not linked to depression, age, education or staging of mastocytosis.  Importantly, it was also independent of amount of antihistamine use.  Memory impairment was also not related to age or education.  Cognitive difficulties were found to be much more prevalent in mastocytosis patients than in other chronic disease populations.

Fatigue is a common neuropsychiatric symptom for mast cell patients and has been seen in populations with both mastocytosis and mast cell activation syndrome.  Patients who have moderate to severe fatigue often experience pain and cognitive deficits.  The level of fatigue can be disabling as it makes it difficult to focus or perform even simple tasks.

35% of mastocytosis patients in one study reported 35% had either acute or chronic headaches.  37.5% had migraines, while 17.2% had tension type headaches.  Headache patients often reported episodic flushing or itching at the time of the headache. In the migraine group, 66% experienced aura symptoms.  Overall, 39% of patients in this group with or without migraines experienced aura symptoms, usually visual.

Exaggeration of the stress response could explain neuropsychiatric symptoms in mast cell patients. In one population, 42% of patients perceived their stress level to be high. Persistent stress response could lead to negative emotions.  These symptoms could be reinforced by mast cell hyperactivity in the brain, which can affect stress response, emotionality and cognition.


Georgin-Lavialle S, et al. Mastocytosis in adulthood and neuropsychiatric disorders. Translational Resarch 2016; x:1-9.

Georgin-Lavialle S, et al. Leukocyte telomere length in mastocytosis: correlations with depression and perceived stress. Brain Behav Immun 2014; 35: 51-57.

Moura DS, et al. Neuropsychological features of adult mastocytosis. Immunol Allergy Clin North Am 2014; 34(2): 407-422.

Moura DS, et al. Depression in patients with mastocytosis: prevalence, features and effects of masitinib therapy. PLoS One 2011, 6: e.26375.

Moura DS, et al. Evidence for cognitive impairment in mastocytosis: prevalence, features and correlations to depression. PLoS One 2012, 7: e.39468.

Smith JH, et al. Neurologic symptoms and diagnosis in adults with mast cell disease. Clin Neurol Neurosurg 2011, 113: 570-574.

13 Responses

  1. Elizabeth Metcalf April 15, 2016 / 12:37 am

    Great blog post & i’m so happy to see the neuropsych particulars discussed. I’m looking forward to more information to share with my mental health providers. Thanks as well for the references!


  2. Moí Alayne April 15, 2016 / 1:16 am

    Would you please add me to your email list please?
    Im seeing my neuro tomorrow and she never paid attention when I say exactly how you describe how we feel, think, migraines, ITCH, depression, etc.
    I’m going to show her this and if I have to beg her to read it.
    Whatever happens, thank you.

  3. Pam April 15, 2016 / 6:33 am

    Lisa, I love this blog. I recently told my husband that I cannot seem to focus for a very long time when watching a tv program or a movie. I had never read or heard of this being part of the cognitive part of Mastocytosis. Even in a conversation at times I have a problem at times paying attention because I get distracted by something else. I am also fatigued often and the last six months have had more pain than I have had in the 7-8 years since diagnosis. Some of the others I have known about and most do not have those symptoms, except short term memory and word recall has been a big one. All this to say, I am so very thankful to find out that these symptoms are often due to Mastocytosis. Knowing the probable source helps so much. Thank you, my friend, for the time you spend, and the care and knowledge/research you impart to us. ❤️

  4. becca April 15, 2016 / 8:29 am

    I’m not quite able to grasp the significance of the studies since you don’t mention control groups.

    • Lisa Klimas April 15, 2016 / 10:18 am

      There weren’t control groups. They were reporting on cohorts of mastocytosis patients.

  5. Lina Bihari Andersson April 15, 2016 / 11:41 am

    Please put me on your mailing list.

  6. Carole April 15, 2016 / 1:49 pm


    This information is incredibly helpful. I am dealing with all of these issues right now and have not had much success in getting answers. I have learned more from you than anyone. Thank you!!

  7. lori April 15, 2016 / 1:57 pm

    Thank you Lisa. I would like to show this to my Doctors.
    You Rock!

  8. Diana April 15, 2016 / 4:27 pm

    Thank you for devoting so much of your time to give us information we need. I was diagnosed with MCAD 3 years ago. I am in my 60’s. I have a chronic tryptase level of 22.8. I have anxiety, fatigue and the usual Mast cell symptoms. I take 4 24 hour 180 mg Allegras, 2 Pepcids, 1625 mg Aspirin and 20 mg of montelukast per day. I also take 240 mg of a beta-blocker for A-fib, an anticoagulant and 10 mg Ditropan for IC – 25 mg Nortriptylene and 1.5 mg Klonopin. I sometimes feel like a

  9. Diana April 15, 2016 / 4:43 pm

    Thank you for the articles. Many of us do need this sort of evidence. I take lots of meds for MCAD/Masto. My tryptase is chronically >25. I have usual flushing and abdominal problems. I am surprised I can think at all. I really have to fight to do so. Today was the most difficult trying to function cognitively. I was so embarrassed when I just couldn’t seem to “get it”. I am a Ph.D. in my 60s. No one understood… this produces more anxiety and depression. I have calmed down a little, thanks to your study references.

  10. Michelle Dellene April 15, 2016 / 7:27 pm

    My neurologist was the one who explained to me that my chronic migraines and psychiatric symptoms were caused by my mast cell disease. I guess I’m lucky. He totally gets it. He put me on cyproheptadine and it is like a miracle drug for me. Adding quercetin boosted my mood as well. The two combined seem to be doing far more for me than any other traditional psychiatric or migraine medications ever did, which makes sense since it’s the disease causing it all. Thanks for confirming what I’ve already learned!

  11. Pam April 15, 2016 / 11:48 pm

    Thanks you so much!!!!

  12. Cherry April 17, 2016 / 8:48 am

    Thank you for this! I’ve always suspected something like this. I have had the problem that my symptoms were thought to be only psychiatric while actually I was suffering dysautonomia and mast cell activation syndrome.

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