Mood Worsening in Spring in Women with Depression and Tree-Pollen Allergy

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DESCRIPTION (provided by applicant): This is a resubmission of our R21 proposal with revisions on the number of participants, inclusion of men and changes in cytokine profile based on the reviewers' suggestions. Seasonal spring peaks in depression and suicide have been consistently reported, but poorly understood. We hypothesize that allergic reactions to tree pollen (which robustly peaks in spring) in vulnerable individuals would result in secretion of certain cytokines which could affect brain function and contribute to triggering depressive episodes in patients with Major Depression or Bipolar Disorder. This hypothesis is based on the association between depression and allergy and the worsening in mood after administration of cytokines for experimental or therapeutic purposes. Our long-term objectives are to pursue this hypothesis at epidemiological, clinical cohort, animal and cellular levels. The specific aims of this project is to 1) evaluate the relationship between a positive immunoglobulin E (IgE) anti-tree-pollen and springtime worsening in mood in patients with recurrent mood disorders and 2) explore a quantitative relationship between certain markers of local or system inflammation and the severity of depressive symptoms in IgE anti-tree-pollen patients. In this study, 50 participants (male=15, female=35) with positive anti-tree-pollen specific IgE and 50 control participants will be enrolled. We will compare changes in depression scores and decompensation between the two groups. We will also correlate mood changes with changes in biological markers. We expect that worsening in mood in the specific IgE positive group will be greater than in control participants, and that worsening in depression will correlate with allergic cytokine activation in the specific IgE positive group. The theoretical novelty of the proposal is the concept of a vulnerability-trigger pair, i.e. an antibody (IgE anti-tree-pollen) and an allergen (i.e., tree-pollen) when coupled results in cytokine release which further mediate depression exacerbation in individuals with a vulnerability for mood disorders. If this model is confirmed in a future larger study which will be designed based on the results of this preliminary application, this may open new therapeutic targets and interventions to address currently neglected predisposing, precipitating and perpetuating factors in recurrent mood disorders.