SEASONALITY OF DEPRESSION AND AIRBORNE ALLERGENS

抑郁症和空气过敏原的季节性

基本信息

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
项目类别：
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

项目摘要

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.

该子项目是利用该技术的众多研究子项目之一资源由 NIH/NCRR 资助的中心拨款提供。子项目及研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金，因此可以在其他 CRISP 条目中表示。列出的机构是对于中心来说，它不一定是研究者的机构。冬季型季节性情感障碍（SAD）已被广泛接受。然而，复发性情绪障碍最常见于春季和秋季失代偿。此外，春季期间，全球范围内会出现强劲且高度重复的自杀高峰（Petridou 等人，2002 年；Maes 等人，1993 年）。今年春季抑郁症和自杀高峰的原因尚不清楚。因为 (a) 治疗性和实验性施用某些细胞因子（例如血液化学物质，如干扰素-? [IFN-?]）会导致抑郁症（Pollmacher 等人，2002 年，Reichenberg 等人，2001 年），(b) 过敏反应在鼻粘膜中，引起肥大细胞、嗜酸性粒细胞和其他单核细胞释放细胞因子，并且（c）树花粉浓度在春季急剧上升，我们假设在患有反复出现的情绪障碍，特异性抗树花粉 IgE 抗体的存在与春季抑郁症恶化有关，与秋季豚草也有类似的关系。炎症引起抑郁症的一种可能机制是过敏性炎症期间分泌的某些细胞因子（例如 IL-4、IFN-α）激活酶（吲哚胺 2,3 脱氧酶 [IDO]），从而“脱轨”色氨酸 (TRP)（一种用于制造血清素的血液化学物质）会转化为犬尿氨酸 (KYN)（一种有毒化合物）。先前的研究表明，a) 急性 TRP 耗竭伴随着情绪恶化 (Delgado et al. 1990)，b) 实验范式中细胞因子水平与情绪恶化直接相关 (Reichenberg et al. 2001)，以及 c) TRP/TRP 的降低治疗性 IFN 给药诱导的 KYN 比率与抑郁症呈正相关（Capuron 等人，2003）。季节性过敏是一种常见病症。阿贝斯等人。 (2005) 报告称，54% 的国家健康和营养检查调查（NHANES II 和 III）参与者的至少一种过敏原的皮肤点刺测试呈阳性。多项研究表明抑郁症和季节性过敏之间存在联系（Timonen 等人，2002 年、2003 年；Marshal 等人，2002 年）。鉴于自杀/抑郁高峰和树木花粉高峰的时间“邻近”，我们探讨了自杀与树木花粉暴露之间的流行病学关联，并报告在高峰树花粉暴露期间和之后女性自杀率增加（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，确定春季抑郁症失代偿和自杀高峰的炎症介导触发因素。具体目标 1：评估复发性情绪障碍受试者中 IgE 抗花粉阳性与春季和/或秋季情绪恶化之间的关系。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，IgE 抗树花粉阳性受试者在树花粉峰值期间与树花粉前间隔期间的抑郁评分增加更大。假设 1b：IgE 抗花粉阳性受试者在接触花粉期间与之前的失代偿率将高于对照受试者的失代偿率。具体目标2：探讨IgE抗花粉阳性受试者中某些过敏性炎症标志物（例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：抑郁评分从花粉高峰期到花粉高峰期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抑郁评分的变化将与血液中 IL-4、IL-13 和 IFN-α 水平的变化呈正相关。假设 2c：抑郁评分从花粉高峰期到花粉高峰期的变化与 TRP/KYN 比率呈负相关。