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

青春期前的压力，风险之窗

• 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
• 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

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）：众所周知，童年逆境是成年情感障碍最有效的预测因素之一，尤其是在女性中。此外，有报道称，一组早期经历生活逆境但未出现成年疾病的妇女存在重要的分离，这表明在疾病保护或改善中可能存在重要的弹性因素。事实上，是否有一个关心和稳定的父母或监护人是区分受虐者的积极和消极结果的最重要的方面之一。我们认为，在特定的生殖时间点，女性患重度抑郁症（MOD）的风险增加以及其他情感障碍倾向的一个重要因素是编程效应