Neuropsychiatric features of mast cell disease: Part 2 of 2

Mast cell activation can induce neuropsychiatric symptoms. Degranulation has been linked previously to headache. It is possible that peptidergic and cholinergic neurons receive mast cell mediators and that this plays a role in headache pathology.  TNF is speculated to participate in depression.  Histamine may cause memory deficits, although there is conflicting information on this topic. Some patients have improvement in neuropsychiatric symptoms with antihistamines.

Mastocytosis patients who have GI and neuropsychiatric symptoms often have low serum serotonin.  Tryptophan is a precursor to serotonin. Plasma tryptophan is also often low in mastocytosis patients, while plasma IDO1 (indoleamine-2,3-dioxygenase 1) activity is higher. IDO1 breaks down tryptophan through an alternate pathway that does not form serotonin. In this pathway, IDO1 breaks down tryptophan, forming kynurenic acid and quinolinic acid.  The accumulation of these substances could explain the fatigue and cognitive impairment in mastocytosis patients.  Low tryptophan and low serotonin in this population were associated with perceived stress and depression.

Treatment of neuropsychiatric symptoms in mast cell patients can include a variety of medications.   SSRI medications can reduce fatigue and depression in some inflammation models.  Some mast cell patients take these medications, usually with low starting doses in case mast cell degranulation in these people has conversely led to higher serotonin levels.  Bupropion, SNRIs and tricyclic medications are also commonly used for depressive symptoms in many chronic illness populations.

Some tricyclic antidepressants have antihistamine properties, with doxepin being a common choice.  Another tricyclic, amitriptyline, can inhibit release of mast cell mediators. Mianserin and mirtazapine can be prescribed for insomnia but also have antihistamine properties. Aprepitant could potentially be used in treatment of depression and cognitive impairment in mastocytosis and MCAS patients. Prochloperazine also decreases mast cell mediator release. Amantadine has improved depression and fatigue symptoms in multiple sclerosis patients. Inhibition of TNF with infliximab has improved depression in patients with high levels of inflammation.

Kynurenic acid, formed in the alternate tryptophan breakdown pathway described above, can block acetylcholine receptors, causing neurologic symptoms.  A7 agonists like nicotine could potentially overcome this effect.  Quinolinic acid binds at the NMDA receptor, cause neurologic symptoms.  Ketamine, an NMDA antagonist, can produce significant improvements in depressive symptoms in treatment resistant depression. As quinolinic acid is typically present in higher levels than kynurenic acid in mastocytosis patients, ketamine might offer a treatment for these patients with depression and high perceived stress.

Masitinib, a tyrosine kinase inhibitor, was shown to decrease depression, anxiety and cognitive difficulties in a significant amount of mastocytosis patients. Mindful meditation may also help patients to lessen activation caused by psychological stress and therefore decreasing biological stress.

References:

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.

3 Responses

  1. K. Hendricks April 16, 2016 / 12:17 am

    Very interesting. I’m awaiting the results of neuropsych testing prompted by memory loss, language issues, and migraines. I also suffer from insomnia. I have wondered why I have adverse reactions to ssri or any type of medication that alters serotonin levels or reuptake. I feel like it is related to my mast cell activation but I haven’t been able to find much about it.

  2. Jorunn Johnsen April 17, 2016 / 6:43 am

    What is bad, is that most Health care proff. even dont know nothing at all about this. So therefore ie. children get poiseon medication in sted of antihistamin,Ketotifen, Neuroprotek . I am so tired of tell People With masto or/and masto suspect issues to read and ,understand this.

  3. Michelle Dellene April 22, 2016 / 11:13 am

    Another great post. I’ve been wondering too if I have too little or too much serotonin. Whenever I tried SSRIs I would get extremely ill and they always seemed to make me worse, not better but from what I understand too much or too little can cause the same symptoms. When I started on quercetin it felt like my serotonin levels were finally leveling out where they should be and the difference in my mood disorder was apparent to myself and my family within just a few days.

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