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Photograph of boy crying by David Shankbone.

A new kind of SAD?

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Seasonal Affective Disorder (SAD) is the name given to a pattern of depressive episodes that are associated with a particular time of year.

Fall and winter are the times of year that are most often associated with SAD, and the common explanation is that some individuals are more sensitive to the shorter and darker days characteristic of autumn and winter months.

However, a new study by Guzman, et al. [Guzman A, Tonelli LH, et al. Mood-worsening with high-pollen-counts and seasonality: A preliminary report. J Affective Disorders. 01-AUG-2007; 101(1-3):269–74], suggests that there may be a “non-winter” form of SAD that is driven not by short days or long nights, but rather by elevated levels of pollen in the air! While this is only a small preliminary study, this idea of pollen-driven SAD should be of interest to people with mast cell-related disorders.

The authors explain their rationale for expecting pollen counts to be associated with depressive episodes: "Pollen induces a strong inflammatory response of the respiratory tract in allergic individuals, and inflammatory triggers have been associated with acute worsening of mood in healthy individuals.... We hypothesize that pollen-related worsening of mood will predict a greater seasonality of mood."

Simmering summer SAD?

And if this weren't intriguing enough, the article mentions, in passing, that there is a kind of summer SAD that may be driven by high temperatures. Now, there's a form of SAD that many of us with mast cell-related disorders understand all too well!

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Nasal symptoms and sleep

Photograph of sleeping baby by Paul Sapiano.

Of course, this isn‘t the first study to make a connection between mood changes and the effects of mast cell degranulation. At the 2008 Annual Meeting of the American Academy of Allergy Asthma & Immunology (AAAAI), Dr. Jean Bousquet talked about the effect that nasal allergies (allergic rhinitis) have on sleep, noting, “Sleep disturbances in patients with chronic disorders constitute a factor that contributes to exacerbate symptoms, complicate management, and affect mood and quality of life.” Reference [Bousquet J. Sleep and allergic rhinitis. AAAAI Annual Meeting. Philadelphia, PA.: 2008; unpublished paper provided as handout at session, “Allergic Rhinitis and Sleep Disorders: Evidence for the Relationship and Impact of Therapy,” part of workshop on Allergic Rhinitis and the Relationship to Other Diseases. 3/14/08.].

In his research Bousquet found that the worse a person‘s nasal allergies were, the more likely they were to report both daytime sleepiness and lower quality-of-life scores.

Now people with mast cell-related disorders may or may not have symptoms similar to those observed in nasal allergies, but given that so many of us are prone to systemic symptoms of mast cell degranulation, it‘s not a stretch to infer that those symptoms help to fragment sleep (that is, causing us to wake up more frequently during the night) and make us feel both less rested and more miserable.

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Depression in mastocytosis

Moving away from the literature on allergies, in his 2004 paper on urticaria pigmentosa, Brockow, et al. [Brockow, K. Urticaria pigmentosa. Immunol Allergy Clin N Am. 2004; 24(2): 287–316], observed that “Patients with systemic mastocytosis sometimes experience neuropsychiatric abnormalities. Altered cognitive functions, such as poor attention, irritability, impaired memory, personality change and depression, have been seen in association with mastocytosis.”

However, within the medical literature on mastocytosis, while depression is often mentioned as a symptom, it appears that researchers differ as to whether they think that depression is a symptom of the disease process or whether they feel that it occurs more often in reaction to the fact of having this rare and sometimes-difficult condition.

In 2005, Dr. Dean Metcalfe [Metcalfe DD. Regulation of normal and neoplastic human mast cell development in mastocytosis. Trans Am Clin Climatol Assoc. 2005; 116:185–203], discussing mastocytosis patients, commented, “Some patients present with neurologic or neuropsychiatric manifestations, including alterations in cognitive abilities, or depression. The etiology of such symptoms is unclear, although mediator-induced hypotensive effects on the brain or a mixed organic brain syndrome, or both, have been hypothesized.”

But in his 2006 paper Dr. Joseph Butterfield [Butterfield J. Systemic mastocytosis: Clinical manifestations and differential diagnosis. Immunol Allergy Clin N Am. 2006; 26(3):487–513] comments, “Psychiatric complaints in patients with SM [systemic mastocytosis] are widely divergent. Some symptoms, such as depression, can be explained by the emotional distress, disability and helplessness caused by other symptoms of SM, whereas other psychiatric symptoms, such as episodes of rage, impaired attention and memory, amnesia, crying spells, anger, and fatigue, may escape easy explanation.”

In a recent paper by Deolano, et al. [Deolano D, Alvareztwose I, et al. Safety and effectiveness of immunotherapy in patients with indolent systemic mastocytosis presenting with Hymenoptera venom anaphylaxis. J Allergy Clin Immunol. 2008; 121(2): 519–526], in a table delineating the clinical characteristics of mastocytosis patients, they note that some of their patients demonstrated neuropsychiatric symptoms, with which they included “concentration difficulties, irritability, insomnia, anxiety, depression,” although they made no inferences as to whether or not they are more symptomatic of chronic illness in general or of mastocytosis in particular.

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And in the May paper by Hermine and 21 co-authors [Hermine O, Lortholary O, et al. Case-control cohort study of patients’ perceptions of disability in mastocytosis. PLoS ONE. 2008; 3(5):e2266], “Case-control cohort study of patients’ perceptions disability in mastocytosis,” depression is listed among the many manifestations of indolent mastocytosis. The authors comment, “Our results also confirmed the existence of number of previously described symptoms associated with mastocytosis, including fatigue (asthenia), anaphylaxis, sweating, flushing, pruritus, erythemateous crises, epigastric pain, diarrhea, nausea/vomiting, bone pain, headache, memory loss, difficulty with social interactions, reduced performance status, and depression.” They then add, “An important finding from this analysis was that psychological and neurological symptoms appear to be key contributors to disability in mastocytosis.”

In that study, 57% of patients reported depression, and a whopping 82% reported asthenia, which is a medical term for feelings of weakness and low energy. The authors add, “That depression is a common symptom of mastocytosis was confirmed by the finding that more than 70% of all mastocytosis patients had a Hamilton score >10.”

The authors assert that a Hamilton score greater than ten signifies someone who is disabled by depression — not someone who is mildly depressed.

They end by listing depression as one of the “symptoms significantly associated with mastocytosis.”

Depression in IA and MCAD

I was unable to find any references in the medical literature to the issue of depression in relation to either idiopathic anaphylaxis (IA) or mast cell activation disorder (MCAD). The neglect of IA, overall, in the existing literature is just one more thing to depress those of us with IA! But I suspect that much of what can be said about systemic mastocytosis applies to this other rare condition.

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Angioedema and depression

Photograph of Meredith P/woofiegrrl having angioedema.

In a 2006 paper on idiopathic recurrent angioedema (which is defined as having three or more episodes of angioedema [swelling of skin, mucous membranes, and/or internal organs] “within a period of six months to one year”), Frigas and Park [Frigas E, Park M. Idiopathic recurrent angioedema. Immunol Allergy Clin N Am. 2006; 26:739–751] list depression and chronic anxiety as being common symptoms among those for whom the problem is more severe.

Asthma, depression and death

On a more somber note, in a 1999 paper by Nagata, et al. [Nagata S, Irie M, Mishima N. Stress and asthma. Allergology International. 1999; 48(4):231–328], the authors noted that depression was one of the risk factors for having a fatal asthmatic attack. Even among children, depression was one of the psycho-social factors that seem important in differentiating the children who died from asthma to matched controls who did not.

That same paper cites another researcher, Miller, who “proposed the hypothesis that depression is associated with a shift towards increased peripheral and parasympathetic activity or cholinergic imbalance, leading to an exacerbation of pathophysiologic symptoms and culminating in sudden death from asthma.”

Interestingly, from our perspective, is the authors‘ further observation that “There are many clinical reports stating that an asthmatic attack is immediately preceded by emotional stress.” As if we did not already have first-hand awareness of the connection between stress and mast cell degranulation!

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Can depression make us less aware of an impending attack?

In her 2007 paper, “Anaphylaxis: Evidence-based long-term risk reduction in the community,” Dr. F. Estelle R. Simons [Simons FER. Anaphylaxis: Evidence-based long-term risk reduction in the community. Immunol Allergy Clin N Am. 2007; 27:231–248] points out not only the obvious point that people with mastocytosis, whether or not they display symptoms, are at increased risk for anaphylaxis, but also an important and more subtle issue: She lists depression as one of the coexisting conditions that can interfere with a person’s ability to recognize both their anaphylaxis triggers and the symptoms of an actual attack.

In other words, for us the issue is not just “is depression a symptom of mastocytosis or a reaction to having mastocytosis.” The bigger issue is: Can our depression interfere with our ability to learn to manage our disease and to recognize the telltale signs of an impending full-blown attack?

So what starts out as a seasonal disorder with a cute name leads us to much more troubling and important issues. Regardless of how or why we become depressed, how best can we manage those feelings so that they do not interfere with our well-being and our self-care?

Pediatric mast cell diseases and parental depression

One last related but just as important a point is made by Dr. Simons [Simons FER. Which infants are at increased risk for anaphylaxis? J Allergy Clin Immunol. 2007; 120(3):537–540] in another 2007 paper, “Which infants are at increased risk for anaphylaxis?” She notes that if the caregivers or parents of children prone to anaphylaxis are affected by depression, it may “impede recognition of anaphylaxis in the infant for whom they are responsible.”

This makes it even more important that parents of children with idiopathic anaphylaxis or mastocytosis deal constructively with their own reactions to their children‘s health conditions. Falling into depression could make it that much harder for a parent to protect his or her child from an incipient attack.

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An earlier version of this article appeared in the Spring 2008 issue of The Mastocytosis Chronicles, the quarterly newsletter of the Mastocytosis Society (TMS).

Page last updated: March 20, 2011

All information contained in this site is one layperson's interpretation of medical journal articles, textbooks, seminars, presentations, and other materials. Nothing that is stated here should carry more weight than the informed and considered opinions of your own highly trained and qualified medical caregivers. The author of this site is not a doctor and has absolutely no authority to prescribe or diagnose.

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