SEASONALITY OF DEPRESSION AND AIRBORNE ALLERGENS

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH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 中心，不一定是研究者的机构。 冬季型季节性情感障碍（SAD）被广泛接受。然而，复发性情绪障碍最常见的是在春季和秋季失代偿。此外，在春季，全球范围内有一个强劲且高度重复的自杀高峰（Petridou et al. 2002，Maes et al. 1993）。这个春季抑郁症和自杀高峰的原因尚不清楚。因为（a）某些细胞因子（例如，血液化学物质，如干扰素-？[IFN-?])导致抑郁症（Pollmacher等，2002，赖兴贝格等，2001），（B）鼻粘膜中的过敏反应引起肥大细胞、嗜酸性粒细胞和其它单核细胞释放细胞因子，和（c）树花粉浓度在春季急剧上升，我们假设，在复发性情绪障碍的受试者中，花粉IgE抗体将与春季抑郁症恶化有关，与秋季豚草有类似的关系。炎症引起抑郁作用的一种可能机制是在过敏性炎症期间分泌的某些细胞因子（例如，IL-4、IFN-γ），色氨酸（TRP）是一种血液中的化学物质，血清素是由色氨酸产生的，而犬尿氨酸（KYN）是一种有毒的化合物。先前的研究表明，a）急性TRP消耗伴随着情绪恶化（Delgado等1990），B）在实验范例中细胞因子水平与情绪恶化直接相关（赖兴贝格等2001），和c）由治疗性IFN施用诱导的TRP/KYN比率的降低与抑郁症正相关（Capuron等2003）。季节性过敏是一种常见的疾病。Arbes等人（2005年）报告称，54%的国家健康和营养检查调查（NHANES II和III）参与者至少有一种过敏原的皮肤点刺试验呈阳性。几项研究表明抑郁症与季节性过敏之间存在联系（Timonen et al. 2002，2003，Marshal et al. 2002）。鉴于自杀/抑郁高峰和树花粉高峰的时间“邻近”，我们探索了自杀和树花粉暴露之间的流行病学关联，并报告了在树花粉暴露高峰期间和之后女性自杀的增加（Postolache et al. 2005）。我们的长期目标是确定炎症介导的触发抑郁症代偿失调和自杀高峰在春季使用同心圆的方法与临床，流行病学，死后脑组织和动物研究。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：与无过敏原特异性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峰期与树花粉前间期的抑郁评分增加更大。假设1b：IgE抗花粉阳性受试者在暴露于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：探索过敏性炎症的某些标志物（例如，过敏相关细胞因子、TRP/KYN比率）和IgE抗花粉阳性受试者中抑郁症状的严重程度。假设2a：从花粉高峰前到花粉高峰间隔的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间隔的抑郁评分变化与IL-4、IL-13和IFN-γ血液水平的变化呈正相关。假设2c：从峰前到峰花粉间隔的抑郁评分的变化将与TRP/KYN比值负相关。

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.