Understanding the Relationship Between Environmental Endocrine Disrupting Chemicals, Neuropsychiatric Outcomes, and Related Biological Processes in Depression

了解环境内分泌干扰化学物质、神经精神结果和抑郁症相关生物过程之间的关系

• 批准号: 10739590
• 负责人: Jessica A Harder
• 金额: $ 24.48万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2028-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10739590
• 关键词: Address; Adverse effects; Affect; Age; Animal Model; Awareness; Behavior; Biological; Biological Markers; Biological Process; Biometry; Brain; Brain-Derived Neurotrophic Factor; C-reactive protein; Chemical Exposure; Chemicals; Child; Childhood; Clinical; Cognition; Cognition Disorders; Cognitive; Collaborations; Competence; Data; Data Collection; Development Plans; Dimensions; Disease; Educational workshop; Elderly; Emotional; Endocrine Disruptors; Environment; Environmental Exposure; Environmental Impact; Environmental Pollutants; Estradiol; Estrogens; Exposure to; Female; Food Packaging; Foundations; Genes; Goals; Gonadal Steroid Hormones; Grant; Growth Factor; Health; Hormonal; Hormones; Impaired cognition; Individual; Inflammation; Inflammatory; Interleukin-6; Intervention; Knowledge; Life; Life Style; Literature; Major Depressive Disorder; Measures; Mediating; Mediation; Mediator; Menopause; Mental Depression; Mentorship; Methods; Methylation; Mood Disorders; Moods; Outcome; Outcome Measure; Pathway interactions; Patients; Pharmaceutical Preparations; Plastics; Postmenopause; Predisposition; Public Health; Public Policy; Qualifying; Recording of previous events; Research; Research Personnel; Risk; Role; Series; Serum; Severities; Standardization; Statistical Methods; Symptoms; Synaptic plasticity; TNF gene; Testing; Testosterone; Therapeutic Intervention; Training; Urine; Vulnerable Populations; Woman; Work; affective disturbance; career development; chemical association; cognitive function; cognitive performance; cognitive testing; cohort; consumer product; cytokine; depressive symptoms; disorder risk; early life exposure; experience; human old age (65+); inflammatory marker; interest; laboratory experience; lifestyle intervention; middle age; mood symptom; neurobehavioral; neuropsychiatric disorder; neuropsychiatric symptom; neuropsychiatry; neurotrophic factor; neurotropic; novel; older women; phthalates; pre-clinical; prenatal; primary outcome; profiles in patients; programs; recruit; sex; symposium; symptomatology; urinary

Environmental endocrine disrupting chemicals (EDCs) are associated with multiple adverse health effects. Early- life exposures alter neurobehavioral trajectories, with increased risk for depression and poorer cognitive functioning in childhood. However, very few studies have evaluated the effects of EDC exposure in later life despite ongoing exposure. Patients with a history of major depression (MDD) are at increased risk for neuropsychiatric symptoms such as low mood and cognitive dysfunction and this risk is further elevated in women during the menopausal and post-menopausal period. Preclinical and clinical evidence suggests that EDCs affect a number of biological variables implicated in mood and cognitive disorders, including inflammatory biomarkers, brain-derived neurotrophic factor (BDNF), and sex hormones. The proposed study seeks to better understand how EDCs affect mood and cognition in postmenopausal women with and without depression. We propose to evaluate 1) the association between EDCs and neuropsychiatric symptoms (mood and cognition) in postmenopausal women with MDD and without mood disorders (healthy controls; HC), 2) the relationship between EDCs and biological variables including inflammatory cytokines like C-reactive protein, interleukin-6, and tumor necrosis factor-α, BDNF, and sex hormones including estradiol and testosterone, and 3) whether the biological variables of interest mediate any potential association of EDCs with neuropsychiatric outcomes. We will leverage ongoing data collection of an existing study of postmenopausal women including depression rating scale scores and detailed cognitive assessment data, as well as serum cytokine, BDNF, and sex hormone levels. Urinary bisphenols and a suite of 16 phthalate metabolites will be measured in 75 MDD and 75 HC subjects. Urine will be collected at 2 timepoints (at recruitment and 1 month later), then pooled for EDC assessment. Regression and statistical methods for mixtures will be used to assess relationships between individual EDCs and their mixtures with neuropsychiatric outcomes and biomarkers. Mediation analysis will explore the direct and indirect effect of EDCs on outcome measures via the biological variables. Career development plan goals include gaining competency in the interpretation of environmental exposures and inflammatory data and in biostatistics, especially mixture methods of analysis. Training goals will be met by coursework, workshops/seminars, conferences, lab experience, readings, and mentorship. Training experiences will mostly take place at Harvard- affiliated BWH and HSPH. This project will identify emotional and cognitive effects and relevant biological effects of EDCs in a population vulnerable to neuropsychiatric symptoms. Enhanced mechanistic understanding will allow novel interventions targeting contributory biological variables, such as lifestyle changes or medications that reduce inflammation, increase BDNF, and regulate sex hormones to mitigate adverse effects of EDCs. Increased awareness of neuropsychiatric implications of EDC exposures may also guide public policy changes that regulate or reduce their omnipresence in consumer products and the environment.

环境内分泌干扰化学物质（EDC）与多种不良健康效应有关。早期的- 生活暴露改变神经行为的轨迹，抑郁症的风险增加和认知较差 在童年时期。但是，很少有研究评估EDC暴露在以后的生活中的影响 尽管持续曝光。患有严重抑郁史（MDD）的患者的风险增加 神经精神科症状，例如情绪低落和认知功能障碍，这种风险进一步升高 妇女在绝经期和绝经后时期。临床前和临床证据表明 EDC会影响情绪和认知障碍中实施的许多生物变量，包括炎症 生物标志物，脑衍生的神经营养因子（BDNF）和性激素。拟议的研究试图更好 了解EDC如何影响有或没有抑郁症的绝经后妇女的情绪和认知。我们 评估1）EDC与神经精神症状（情绪和认知）之间的关联 绝经后妇女患有MDD并且没有情绪障碍（健康对照； HC），2） 在EDC和生物学变量之间 和肿瘤坏死因子-α，BDNF和性激素，包括雌二醇和睾丸激素，以及3）是否是否 感兴趣的生物学变量介导了EDC与神经精神疗法的任何潜在关联。我们 将利用现有的绝经后妇女研究（包括抑郁评级）的现有研究的数据收集 量表得分和详细的认知评估数据以及血清细胞因子，BDNF和性激素水平。 将在75个MDD和75名HC受试者中测量尿双酚和16个邻苯二甲酸酯代谢产物的套件。 尿液将在2个时间点（在招聘和1个月后）收集，然后进行汇总进行EDC评估。 混合物的回归和统计方法将用于评估单个EDC之间的关系 以及它们与神经精神病学结果和生物标志物的混合物。调解分析将探讨直接和 通过生物学变量，EDC对结果度量的间接影响。职业发展计划目标包括 在解释环境暴露和炎症数据以及生物统计学方面具有能力 特别是混合分析方法。课程，研讨会/研讨会将实现培训目标， 会议，实验室经验，阅读和精神训练。培训经验主要是在哈佛大学进行 会员BWH和HSPH。该项目将确定情绪和认知效应以及相关的生物学效应 EDC在容易受到神经精神症状的人群中的影响。增强的机械理解将会 允许针对促进生物学变量的新颖干预措施，例如生活方式的改变或药物 减少炎症，增加BDNF并调节性恐怖，以减轻EDC的不良影响。增加 EDC暴露对神经精神含义的意识也可能指导规范的公共政策变化 或减少他们在消费产品和环境中的万能。