SEASONALITY OF DEPRESSION AND AIRBORNE ALLERGENS

抑郁症和空气过敏原的季节性

• 批准号: 7951165
• 负责人: TEODOR T POSTOLACHE
• 金额: $ 2.45万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7951165
• 关键词: Acute; Allergens; Allergic; Allergic Reaction; Ambrosia; Animals; Antibodies; Autopsy; Blood; Cells; Chemicals; Clinical; Clinical Research; Computer Retrieval of Information on Scientific Projects Database; Depression and Suicide; Enzyme Activation; Epidemiology; Exposure to; Funding; Goals; Grant; Hypersensitivity; IgE; Inflammation; Institution; Interferons; Interleukin-13; Interleukin-4; Kynurenine; Link; Marshal; Mediating; Mononuclear; Mood Disorders; Moods; National Health and Nutrition Examination Survey; Participant; Poison; Pollen; Production; Recurrence; Reporting; Research; Research Personnel; Resources; Seasonal Affective Disorder; Serotonin; Severities; Skin; Source; Structure of mucous membrane of nose; Suicide; Symptoms; Testing; Therapeutic; Tryptophan; United States National Institutes of Health; Woman; airborne allergen; anti-IgE; brain tissue; cytokine; depression; depressive symptoms; eosinophil; falls; indoleamine; mast cell; tree pollen

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The winter-type of Seasonal Affective Disorder (SAD) is widely accepted. However, recurrent mood disorders most commonly decompensate in spring and fall. Moreover, during spring there is a robust and highly replicated suicide peak worldwide (Petridou et al. 2002, Maes et al. 1993). The cause of this spring depression and suicide peak is unknown. Because (a) therapeutic and experimental administration of certain cytokines (e.g., blood chemicals, such as interferon-? [IFN-?]) results in depression (Pollmacher et al. 2002, Reichenberg et al. 2001), (b) allergic reactions in the nasal mucosa cause cytokine release from mast cells, eosinophils, and other mononuclear cells, and (c) tree-pollen concentration rises dramatically in spring, we hypothesize that in subjects with recurrent mood disorders the presence of specific anti-tree-pollen IgE antibodies will be associated with worsening depression in spring and a similar relationship with ragweed in fall. One possible mechanism of the depression-causing effect of inflammation is the activation of an enzyme (indoleamine 2,3 deoxygenase [IDO]) by certain cytokines secreted during allergic inflammation (e.g., IL-4, IFN-?), which "derails" tryptophan (TRP), a blood chemical from which serotonin is made, into production of kynurenine (KYN), a toxic compound. Previous studies show that a) acute TRP depletion is accompanied by mood worsening (Delgado et al 1990), b) cytokine levels directly correlate with mood worsening in experimental paradigms (Reichenberg et al. 2001), and c) the decrease of the TRP/KYN ratio induced by the therapeutic IFN administration positively correlates with depression (Capuron et al. 2003). Seasonal allergy is a common condition. Arbes et al. (2005) reported that 54% of National Health and Nutrition Examination Surveys (NHANES II and III) participants had a positive skin prick test for at least one allergen. Several studies show a link between depression and seasonal allergy (Timonen et al. 2002, 2003, Marshal et al. 2002). Given the temporal "vicinity" of suicide/depression peaks and tree-pollen peaks, we explored an epidemiologic association between suicide and tree-pollen exposure and reported an increase in suicide in women during and after peak-tree-pollen exposure (Postolache et al. 2005). Our long-term goal is to identify inflammation-mediated triggers for depression decompensation and suicide peak in spring using a concentric approach with clinical, epidemiological, postmortem brain tissue, and animal studies. Specific aim 1: To assess the relationship between positive IgE anti-pollen and spring and/or fall mood worsening in subjects with recurrent mood disorders. Hypothesis 1a: IgE anti-tree-pollen positive subjects will have a greater increase in depression scores during the peak- vs. pre-tree-pollen intervals compared with subjects with no allergen specific IgE antibodies (Phadiatop negative control subjects). Hypothesis 1b: The rate of decompensation during vs. before exposure to pollen will be greater in IgE anti-pollen positive subjects than the rate of decompensation in control subjects. Specific aim 2: To explore a quantitative relationship between certain markers of allergic inflammation (e.g., allergy related cytokines, TRP/KYN ratio) and the severity of depressive symptoms in IgE anti-pollen positive subjects. Hypothesis 2a: The change in depression scores from pre-peak to peak pollen intervals will positively correlate with changes in allergy symptom scores. Hypothesis 2b: The change in depression scores from pre-peak to peak pollen intervals will positively correlate with the changes in blood levels of IL-4, IL-13, and IFN-?. Hypothesis 2c: The change in depression scores from pre-peak to peak pollen intervals will negatively correlate with TRP/KYN ratios.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 冬季类型的季节性情感障碍(SAD)被广泛接受。然而，反复发作的情绪障碍最常见的是在春季和秋季失代偿。此外，在春季，全世界出现了一个强劲的、高度重复的自杀高峰(Petridou等人。2002年，Maes等人。1993年)。造成这一春季抑郁和自杀高峰的原因不明。因为(A)某些细胞因子的治疗性和试验性给药(例如，血液化学物质，如干扰素-？[干扰素-？])导致抑郁(Pollmacher等人2002年，Reichenberg等人。)，(B)鼻黏膜过敏反应导致肥大细胞、嗜酸性粒细胞和其他单核细胞释放细胞因子，以及(C)树花粉浓度在春季急剧上升，我们假设在反复出现情绪障碍的受试者中，特异性抗树花粉IgE抗体的存在将与春季恶化的抑郁有关，并与秋季的豚草有类似的关系。炎症导致抑郁的一个可能机制是在变态反应性炎症过程中分泌的某些细胞因子(如IL-4、干扰素-β)激活一种酶(吲哚胺2，3脱氧酶[IDO])，使色氨酸(Trp)--一种制造5-羟色胺的血液化学物质--脱轨，产生一种有毒化合物犬尿氨酸(KYN)。以前的研究表明，a)急性Trp耗竭伴随着情绪恶化(Delgado等人，1990)，b)在实验范式中，细胞因子水平与情绪恶化直接相关(Reichenberg等人)。C)治疗性应用干扰素引起的Trp/Kyn比率的降低与抑郁呈正相关(Capuron等人)。2003年)。季节性过敏是一种常见的疾病。阿贝斯等人。(2005)报告说，54%的国家健康和营养调查(NHANES II和III)参与者至少有一种过敏原皮肤点刺试验呈阳性。几项研究表明抑郁和季节性过敏之间存在联系(Timonen等人。2002年、2003年，Marshal等人。2002年)。考虑到自杀/抑郁峰和树花粉峰的时间“邻近”，我们探索了自杀和树花粉暴露之间的流行病学联系，并报告了在峰-树花粉暴露期间和之后女性自杀率的增加(Postolache等人。2005)。我们的长期目标是通过临床、流行病学、死后脑组织和动物研究的同心方法，确定炎症介导的抑郁失代偿和春季自杀高峰期的触发因素。具体目的1：评估反复发作的情绪障碍患者中IgE抗花粉抗体阳性与春季和/或秋季情绪恶化的关系。假设1a：与没有过敏原特异性IgE抗体的受试者(Phadiatop阴性对照受试者)相比，抗树花粉抗体阳性的受试者在高峰期与受试者在受试者的抑郁评分上有更大的增加。假设1b：IgE抗花粉阳性受试者在接触花粉期间的失代偿率将高于对照组受试者的失代偿率。具体目的2：探讨IgE抗花粉阳性受试者某些过敏性炎症标志物(如过敏相关细胞因子、Trp/Kyn比值)与抑郁症状严重程度之间的定量关系。假设2a：从花粉高峰前到花粉高峰期间抑郁评分的变化将与过敏症状评分的变化呈正相关。假设2b：从花粉高峰前到花粉高峰期间抑郁评分的变化将与血液中IL-4、IL-13和干扰素-1水平的变化呈正相关。假设2c：从花粉高峰期前到高峰期，抑郁得分的变化将与Trp/Kyn比率负相关。