We report a statistically significant positive relationship between the changes in upper respiratory allergy symptoms and changes in the subject's depression scores over the spring from the low to high pollen periods. The results of the present study are consistent with those of previous research that has indicated an association between allergic disease and depression decompensation[7
]. This association is also consistent with our recent report that the induction of nasal inflammation results in depression-like behavior in animals[30
], and our animal data showing an increased expression of TH2 cytokines in the brain with sensitization and exposure to tree pollen[47
]. The data have not confirmed our working hypothesis that tree pollen specific IgE antibody positivity can predict the severity of mood worsening.
This finding may have resulted from the small number of tree pollen specific IgE positive individuals recruited at the time of this preliminary report. An alternate explanation might be represented by the unexpectedly large proportion of controls that developed allergic symptoms during the peak pollen period, despite being IgE anti-tree pollen negative. One can offer several speculative explanations for this observation. First, the nasal symptoms developed by subjects in the control group may reflect “non-allergic rhinitis”, a syndrome of unclear etiology. Non-allergic rhinitis is characterized by subjective hyperresponsiveness of the nasal mucosa to non-allergenic environmental triggers including changes in weather, irritants, or pollutants[48
]. Springtime is characterized by abrupt atmospheric changes, which may impact both nasal airways (sudden fluctuations in atmospheric pressure and temperature) and also airborne pollen counts (light, temperature, humidity, wind, etc). Second, it is possible that our control subjects could have been sensitive and exposed to other allergens that were in the air during the study, but not screened for by the Phadiatop test. Third, it has been recently suggested that some individuals, who develop nasal symptoms in the absence of serum IgE or a positive skin test to prevalent environmental allergen, may have a ‘local form’ of allergic disease involving IgE produced only in the nasal mucosa[49
]. Finally, exogenous proteases from pollens and other aeroallergens, which act on specific molecules such as protease-activated receptors (PARs), may cause inflammation by mechanisms other than IgE activation of effector cells[50
]. This is a variant of innate immunity but it is directed at multicellular parasites rather than unicellular organisms as would occur with the “classic” LPS-induced innate immune response[52
]. Yet, there is so far no solid evidence that such a mechanism is operative in human nasal disease.
Among the limitations of the study is the qualitative nature of the multi-allergen screen for assigning sensitization to aeroallergens. Because it only detects specific IgE antibody to 15 common environmental indoor and outdoor aeroallergens, the study participant may have been sensitive to an allergen other than these 15 aeroallergens. The order of the visits was not random. The allergic symptom assessments were performed as a self-report and did not use more accurate biological markers of upper airway allergic disease such as measures of inflammation with mediator release in nasal lavage or peripheral blood. These analyses are planned for future reports. Station level pollen counts only suggest individual exposure, but do not measure it precisely, particularly in participants' work and home microclimates. A questionnaire to screen all the subjects for past history of allergic rhinitis was not used.
In evaluating the association between severity of allergy symptoms and mood, the potential subjectivity in the measurements needs to be taken into consideration. For instance, a reporting style consistent with neuroticism could elevate the self-reported allergy and depression symptoms, and thus create a spurious relationship between them. The role of neuroticism in this relationship was examined in a recent publication[53
]. The authors identified an increased likelihood of allergic disease in individuals with major depression as well as in those with neuroticism as a personality trait. When accounting for gender, the relationship to allergic disease differed as well. In males, allergy was significantly associated with the presence of neuroticism but not with depression, while in the female group, allergic disease was strongly associated with depression but not to neuroticism. The study concluded that it is unlikely that neuroticism is associated with allergy-induced depression[53
]. Because “neuroticism” is considered a trait rather than a psychological state, its effects are minimized by measuring individual changes
in mood and allergy symptoms, rather than their absolute values
Allergies can influence mood by several potential mechanisms. There may be somatic changes such as discomfort caused by allergic inflammatory processes in the upper airway, that may affect well being. This situation may lead to other possible mediators affecting mood, such the use of medications such as antihistamines or vasoconstrictors, or disturbance of sleep caused by multiple factors including obstruction of the airways[49
]. The release of inflammatory mediators including cytokines is one likely mechanism that may promote the worsening in mood. This mood worsening can occur by either acting directly in the brain or through other pathways such as interactions with the HPA-axis and/or the IDO enzyme. Cytokines have been shown to induce depression and anxiety. Our findings relating allergic symptoms with depression scores may be explained in part by the release of cytokines during allergic reactions. In vitro
studies have shown that certain human polymorphisms increase the expression of cytokines including TNF-α[51
], and IFN-γ[47
]. In addition, certain cytokine polymorphisms increase susceptibility to allergic disease such as asthma[54
]. Moreover, allergic symptoms have been correlated with the amount of cytokines released during some allergic reactions[55
]. Thus it is possible that depression scores in some individuals may reflect the increased amount of cytokine release during allergic processes. This issue is a matter to be clarified with future investigations.
Despite its possible limitations, this study is the first to explore the relationship between sensitization to specific aeroallergens and the presence of depression decompensation during allergen exposure. In our previous manuscript[11
], allergy symptoms and mood changes were recorded from memory. The current study examined the severity of allergy symptoms in relationship to concurrently monitored depression severity. Our current result supports a relationship at a “state” rather than “trait” (i.e. vulnerability) level, a more optimistic alternative, as it implies possible triggering, and prophylactic potential. Obviously, causality, and direction of causality are not implied by our results, and would require experimental/interventional studies to see if exposure to aeroallergens triggers exacerbation of mood disorders in vulnerable patients. If confirmed in larger studies, the implications of our findings could be considerable. Clinicians should be particularly observant of those patients with a history of depression during the peak tree pollen period in the spring, which is temporally associated with a significant spring peak in suicide[39
]. Future studies should include replication of these findings and an examination of the mechanisms responsible for this reported relationship. Such studies may result in an informed search for novel pharmacological agents, and aeroallergen exposure reduction paradigms, which could reduce depression exacerbation with its concomitant suicide risk, related to recurrent mood disorders.