Prepubertal Stress, Windows of Risk & Sex Bias for Affective Disturbance

青春期前的压力，风险之窗

基本信息

批准号：
8522236
负责人：
C. Neill NEILL EPPERSON
金额：
$ 115.2万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-08-06 至 2017-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8522236
关键词：
Adrenal Glands Adult Affective Aging Anxiety Disorders Autoimmune Diseases Behavioral Model Bipolar Disorder Brain Cardiovascular Diseases Caring Childhood Disease Dissociation Epigenetic Process Female Funding Gender Goals Gonadal Steroid Hormones Hormonal Hypothalamic structure Individual Life Longevity Maintenance Major Depressive Disorder Medical Migraine Molecular Models Mood Disorders Names Obesity Onset of illness Outcome Ovarian Parents Perimenopause Pituitary Gland Postpartum Period Pregnancy Psychophysiology Puberty Relapse Reporting Research Research Personnel Resources Risk Sex Bias Sex Characteristics Steroids Stress Subgroup Substance Use Disorder System Time Woman behavioral health biological adaptation to stress depressive symptoms early experience experience male molecular modeling neuroimaging neuropsychiatry premenstrual dysphoric disorder prepuberty programs reproductive reproductive neuroendocrinology response sex

项目摘要

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. Further, an important dissociation has been reported for a subgroup of women who experience early life adversity but do not present with adult disease, suggesting that there may be resiliency factors important in disease protection or amelioration. In fact, the availability of a caring and stable parent or guardian has been shown to be one of the most important aspects that distinguish between positive and negative outcomes in abused individuals. We propose that one vital contributor to the increased risk for major depressive disorder (MOD) in women, and propensity for other affective disturbances at specific reproductive time points, is the programming effect of prepubertal adversity on dysregulation of hypothalamic pituitary adrenal (HPA) activity and ovarian steroid responsiveness across the lifespan. It is well documented that from puberty to the late perimenopause, MOD and several anxiety disorders are more common in females than males. Moreover, periods of hormonal flux across the female lifespan are associated with increased risk for affective disturbance: the premenstrum (premenstrual dysphoric disorder), the postpartum (onset/relapse bipolar disorder, MOD), and the perimenopause (depression symptoms and MDD. The goal of the scientific Projects in this SCOR proposal is to determine how the experience of prepubertal adversity reprograms the brain toward stress dysregulation, and how this intersects with periods of dynamic hormonal flux across the life span, including pregnancy (Projects I & III) and aging (Projects II & III). In addition, mechanistic epigenetic studies will examine sex differences in response to stress during this sensitive window of brain maturation (Project III). SCOR funding would harness the respective expertise of Drs. Epperson and Bale in behavioral and molecular models of stress and reproductive neuroendocrinology, psychophysiology, and neuroimaging, to create the Penn Center for the Study of Sex and Gender in Behavioral Health. The Center would provide an intellectual platform with important resources to encourage established investigators, and their mentees, to consider sex and gender as crucial factors in their research.

描述（由申请人提供）：已经很好地确定，儿童逆境是成人情感障碍的最有效的预测因素之一，尤其是在女性中。此外，已经报道了一群经历早期生命逆境但不患有成人疾病的妇女子组的重要解离，这表明可能存在对疾病保护或改善重要的弹性因素。实际上，已证明有关怀和稳定的父母或监护人的可用性是区分受虐待个体的正面和负面结果的最重要方面之一。我们建议，有一个至关重要的因素导致妇女重大抑郁症（MOD）的风险增加，而在特定生殖时间点上对其他情感障碍的倾向是编程效应的倾向在整个生命周期中，下丘脑垂体肾上腺（HPA）活性和卵巢类固醇反应性的前后逆境。有充分的文献证明，从青春期到晚期围栏，MOD和几种焦虑症在女性中比男性更常见。此外，整个女性寿命的激素通量时期与情感障碍的风险增加有关：前体内（经前烦躁不安），产后（起床/复发性双极障碍，模式）和临时性症状（抑郁症状和MDD）在该评分症状上的脑力训练的目标。失调，以及在整个生命周期中与动态荷尔特的时期相交，包括怀孕（项目I＆III）和衰老（项目II和III）。生殖神经内分泌学，心理生理学和神经影像学，以创建宾夕法尼亚州行为健康中的性别和性别研究中心。该中心将为一个重要的资源提供一个重要的资源，以鼓励既定的研究人员及其受训者将性和性别视为研究中的关键因素。