To our knowledge, this is the first study to examine the relationship between allergen-specific IgE positivity (allergic sensitization) and a worsening of depression scores during peak pollen periods in patients with recurrent mood disorders. Two primary hypotheses of the study were confirmed. First, allergen-specific IgE status was associated with a greater increase in depressive scores during exposure to aeroallergens (p = 0.01). Second, the exacerbation of allergic symptoms correlated significantly with a worsening in the depression scores (p = 0.02).
When stratified by diagnoses, the difference was seen only in bipolar depression. Although neuroimmune system dysregulation has previously been suggested to play a role in bipolar disorder (24
), to our knowledge, this is the first study to link allergens, allergy, and bipolar depression.
Our current results are consistent with our previous studies reporting behavioral and neuroimmune changes in laboratory animals sensitized and exposed to aeroallergens (51
). Of particular importance, increased gene expression for Th2 cytokines overexpressed in sensitized and exposed rodents (53
) was also found overexpressed in victims of suicide as compared with individuals who died of other causes (54
Since symptoms of allergies, especially upper respiratory allergies, impair quality of life (7
), psychological distress associated with allergic exacerbation may appear to be the logical link between worsening in mood and exposure to allergens. However, in our study, after adjustment for allergy symptom severity (measure of physical discomfort), the changes in depression scores remained significant. The findings of our current study suggest that worsening of depression in sensitized individuals during peak pollen seasons is not related only to severity of physical symptoms in allergic reaction, thus unlikely to be a mere reaction to a physical illness or methodological artifact (57
). CRP values were included in the multivariable model as an overall surrogate of inflammation. The significant negative relationship between changes in CRP and changes in certain depression scores between high pollen and low pollen conditions is unprecedented, unexpected, and for a better understanding would require replication in larger samples with measurement of inflammatory mediators and markers of physical health.
Exacerbation in bipolar disorder has also been linked to photoperiodic changes (58
); therefore, it could be theoretically possible that changes in mood ratings from low to high pollen season can be accounted for by the difference in photoperiod and result in a spurious relationship between allergy and depression. However, our results being robust to adjustment to order of visit (with implicit differences in photoperiod) reduced the possibility of the observed association being secondary to change in daylength.
Limitations of our study include non-random order of high versus low pollen visit and lack of information on meteorological condition of the days patients were evaluated (however, patients were not interviewed during rainy days when pollen counts would be low). A major limitation is not evaluating health behaviors of the participants. Although our data suggest a biological, probably immunological, relationship between allergen exposure, allergy, and depression, we did not measure cytokines locally or systemically. The levels of total IgE were not measured, and would have been potentially interesting to evaluate relationships between total IgE and medications, and depression scores. Finally, we excluded those patients who had suicidal ideations, were psychotic, or were using illicit drugs, potentially reducing generalizability of our results.
Our study had considerable strengths which included substantiation of diagnoses by standardized tools (SCID); measurement of symptoms by rater with semistructured scales previously used in seasonal depression (SIGH-SAD, HIGH-SAD); determination of allergen-specific IgE status by state-of-the-art laboratory evaluation; and finally, careful coupling between sensitivity and exposure.
In conclusion, as hypothesized, from low to high pollen exposure, worsening of depression scores was positively associated with allergic sensitization even after adjustment for changes in allergy symptoms. These results, if replicated in larger and better designed studies, suggest a potential for developing personalized interventions to prevent a specific (i.e., allergen-induced) form of environmentally driven exacerbation of mood disorders, in particular in patients with bipolar disorder. Future studies should focus on patients with bipolar I disorder in larger numbers, randomize the order of visit and mood ratings, and measure potential molecular mediators in plasma as well as nasal secretions.