Reversing Impact of Childhood Adversity on MDD & Cognitive Decline in Menopause

扭转童年逆境对抑郁症的影响

• 批准号: 8797776
• 负责人: C. Neill NEILL EPPERSON
• 金额: $ 32万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-30 至 2016-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8797776
• 关键词: Address; Adult; Adverse effects; Affect; Age; Aging; Alcohol consumption; Animals; Behavior; Biological Assay; Body mass index; Brain; Brain region; C-reactive protein; Childhood; Cognition; Cognitive; Cognitive aging; Cohort Studies; Data; Data Quality; Dementia; Development; Digit structure; Education; Endocrine system; Estradiol; Event; Functional disorder; Funding; Future; Health; Hippocampus (Brain); Hormones; Household; Hypogonadism; Immune system; Impaired cognition; Imprisonment; Incidence; Inflammation; Inflammatory; Interleukin-1; Interleukin-6; Investigation; Life; Life Stress; Life Style; Link; Longevity; Major Depressive Disorder; Measures; Mediating; Memory; Menopause; Mental Depression; Mental disorders; Mood Disorders; Moods; Mothers; Neuraxis; Ovarian; Ovarian hormone; Patient Self-Report; Performance; Peripheral; Pharmacotherapy; Postmenopause; Prefrontal Cortex; Premenopause; Production; Psychosocial Stress; Publishing; Questionnaires; Recording of previous events; Regulation; Relapse; Relative (related person); Reporting; Research; Research Activity; Research Personnel; Risk; Sampling; Serum; Sex Characteristics; Sexual abuse; Sleep; Smoking Status; Social support; Socioeconomic Status; Staging; Stress; Stress and Coping; Substance abuse problem; TNF gene; Testing; Time; Violence; Waxes; Woman; Women' s Health; base; biobehavior; cognitive change; cohort; cytokine; diet and exercise; divorce/separation; emotional abuse; emotional neglect; executive function; experience; inflammatory marker; nonhuman primate; physical abuse; physical neglect; processing speed; public health relevance; reproductive hormone; resilience; response; senescence

 DESCRIPTION (provided by applicant): It is well established that childhood adversity is one of the most potent predictors of adult affective disorders, particularly among women. Similarly, stress has been linked with poor cognitive aging, although the importance of the developmental stage at which such events occur is not as clear. Stress modulation of both immune and endocrine systems, directly or through their central nervous system targets, is one possible mechanism by which childhood adversity impacts both cognition and mood. In response to this RFA, we propose to utilize data collected during the 14-year long Penn Ovarian Aging Study (POAS, PI: E. Freeman) to address critical questions regarding the reversibility of early life adversity impact on risk for major depressive disorder (MDD) and sub-optimal cognitive aging, with a particular focus on the menopause transition during which reproductive hormone changes unmask vulnerability to depression and cognitive complaints in many women. Using data from the POAS cohort, we recently reported a 2-fold increased risk of new onset MDD during the menopause transition among women with a history of two or more adverse childhood experiences (ACEs). Likewise, we published the first confirmation that menopause exerts an age-independent effect on immediate and delayed verbal recall and have recently obtained preliminary evidence that ACEs may contribute an additional adverse effect in some cognitive domains. While these findings suggest an intriguing and important interaction between childhood adversity and risk for depression and cognitive decline with menopause, it would be a lost opportunity for women's health, and potentially sex difference research in affective disorders and dementia, to not utilize this cohort further to identify factors that mediate, exacerbate and/or ameliorate the negative impact of childhood adversity on mood and cognition. Moreover, there are few opportunities as rich as this to explore these factors in the presence of well-characterized ovarian hormone fluctuations over an important transition period in women's lives. This RFA is perfectly timed as funding would enable us to 1) utilize the existing biobehavioral data from the POAS cohort to determine the extent of the impact of childhood adversity on timing of depression onset, slope of the decline in cognition and trajectory of ovarian senescence; 2) conduct comprehensive assessments of life-long adversity to address whether specific "clusters" of adversity and/or a "double-hit" is necessary to observe the impact of early life stress; 3) collect more robust measures of cognition, particularly those related to executive functions and affect regulation as these are common concerns among menopausal women, and prefrontal cortex and hippocampal brain regions are a primary target of stress hormones and neuro-inflammation, and finally to 4) test the hypothesis that inflammation mediates, at least in part, the relationship between childhood adversity and the emergence of MDD and cognitive decline in the context of declining estradiol production. The extensive expertise of this collaborative group of investigators and the quality of data from the POAS cohort will insure successful completion of the proposed analyses/research activities to inform development of future studies targeting the reversible biobehavioral factors identified during the course of this 2-year R01 funding.

 描述（由适用提供）：众所周知，儿童期广告是成人情感障碍，尤其是女性中最潜在的预测因素之一。同样，压力与认知衰老差有关，尽管发生此类事件的发育阶段的重要性并不清楚。免疫系统和内分泌系统的压力调节，直接或通过其中枢神经系统目标是一种可能的机制，童年广告都会影响认知和情绪。为了应对此RFA，我们建议利用在宾夕法尼亚州卵巢衰老研究（POAS，PI：E。Freeman）期间收集的数据，以解决有关早期生活广告对重大抑郁症（MDD）风险的可逆性影响（MDD）的可逆性（MDD）的关键问题（MDD），并以优秀的认知能力对许多依赖的转变，并且在这种情况下的依赖性依赖于抑郁症，这是在这种情况下的转变，而在这种情况下，这种依赖的转变是在这种情况下的抑郁症。 女性。使用来自POAS队列的数据，我们最近报告说，在具有两种或以上不良童年经历（ACES）病史的女性中，在更年期过渡期间，新发作MDD的风险增加了2倍。同样，我们发表了第一个确认，即更年期对直接和延迟的言语召回产生了与年龄无关的影响，并且最近获得了初步的证据，即尽管这些发现表明，这些发现表明儿童抑郁症和抑郁症的风险和认知能力下降的风险和认知能力下降之间具有有趣而重要的互动，这将是对妇女的健康和潜在的性行为的机会，而不是妇女的健康疾病，并且是对妇女的健康研究的机会，而不是艾滋病，并且有效果的疾病，而效果的疾病则是进一步的，艾滋病的竞争力是富有的，并且是效果的疾病。确定介导，加剧和/或改善儿童广告对情绪和认知的负面影响的因素。此外，在妇女生活中重要的过渡时期，在有良好的卵巢马内波动的情况下，很少有机会探索这些因素。此RFA的时间很好，因为资金将使我们能够达到1）利用POAS队列中现有的生物行为数据来确定儿童广告发作的影响程度，卵巢感受的认知下降和轨迹轨迹的斜率；对终身广告进行全面评估，以解决广告和/或“双重打击”是否需要观察早期生活压力的影响； 3）收集更强大的认知措施，尤其是与执行功能相关的认知措施，因为这些是绝经妇女的普遍关注点，而前额叶皮层和海马大脑区域是压力激素和神经炎症的主要目标，以及神经炎症的主要目标，最后是4），至少在炎症中，炎症的差异是在炎症中的发展，至少是在炎症中介导的，并且在炎症之间的发展，在炎症之间，在某种程度上宣传了宣传的关系。雌二醇生产下降的背景。这个合作研究者的广泛专业知识以及POAS队列的数据质量将确保成功完成拟议的分析/研究活动，以告知针对这项两年R01资金过程中确定的可逆生物行为因素的未来研究。