Mood Worsening in Spring in Patients with Recurrent Depression and Tree-Pollen Al

描述（由申请人提供）：这是我们R21提案的重新提交，根据评审员的建议对参与者数量、纳入男性以及细胞因子谱的变化进行了修改。抑郁症和自杀的季节性春季高峰一直有报道，但知之甚少。我们假设，易受伤害的个体对树花粉的过敏反应（在春季达到高峰）会导致某些细胞因子的分泌，这些细胞因子可能会影响大脑功能，并导致重度抑郁症或双相情感障碍患者的抑郁发作。这一假设是基于抑郁症和过敏症之间的关联，以及出于实验或治疗目的给予细胞因子后情绪恶化。我们的长期目标是在流行病学，临床队列，动物和细胞水平上追求这一假设。本项目的具体目的是：1）评估免疫球蛋白E（IgE）抗树花粉阳性与复发性心境障碍患者春季情绪恶化之间的关系; 2）探索IgE抗树花粉患者中某些局部或系统炎症标志物与抑郁症状严重程度之间的定量关系。在本研究中，将招募50名抗树花粉特异性IgE阳性的参与者（男性=15，女性=35）和50名对照参与者。我们将比较两组之间抑郁评分和失代偿的变化。我们还将把情绪变化与生物标志物的变化联系起来。我们预期特异性IgE阳性组的情绪恶化将大于对照组，并且抑郁症的恶化将与特异性IgE阳性组的过敏性细胞因子激活相关。该提议的理论新奇是免疫性触发对的概念，即抗体（IgE抗树花粉）和过敏原（即，树花粉）在偶联时导致细胞因子释放，其进一步介导易患情绪障碍的个体的抑郁恶化。如果这个模型在未来的一项更大规模的研究中得到证实，该研究将根据这一初步应用的结果进行设计，这可能会开辟新的治疗靶点和干预措施，以解决目前被忽视的复发性情绪障碍的诱发因素，诱发因素和持久因素。

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.