Role of Allopregnanolone in Mediating the Adverse Effects of Psychosocial Stress

描述（由申请人提供）：情绪障碍，如焦虑和抑郁，在女性中的发病率是男性的两倍。 此外，女性易患与卵巢激素水平波动相关的情绪障碍，包括经前焦虑障碍、产后抑郁症和激素替代疗法引起的负面情绪。 这些疾病的一个诱发因素可能是长期暴露于社会心理压力源和身体活动增加。主应力轴。 这些情绪障碍在女性中的发生因其他不良健康后果的存在而复杂化。 值得注意的是，进食障碍，如情绪化进食和肥胖，与情感障碍高度共病，在被诊断患有情绪障碍的个体中存在类似的神经生物学系统破坏。 该提案的长期目标是阐明孕激素调节应激轴和多巴胺能（5-HT）系统破坏的机制，这两者都与女性情绪和饮食障碍的病因学有关。 该提案的中心目标是暗示异孕烯醇酮（ALLO），一种特定的孕酮，水平的破坏作为一个关键的球员在系统的破坏与情感障碍的情绪和压力轴反应特性的增加。 第一个目的是评估孕激素如何调节社会引起的情绪反应和食欲的变化。第二个目的是确定ALLO和相关行为表型的变化是否是由于应激诱导的活动。 我们将利用行为学相关的心理社会压力模型，采用激素和药理学手段来评估情绪行为和对高热量饮食的偏好。 公共卫生相关性：女性对情绪和饮食失调的易感性是男性的两倍，包括焦虑、抑郁、肥胖和情绪化饮食。研究心理社会压力干扰卵巢激素作用的机制，将有助于发展以焦虑为基础的女性精神病理学。

DESCRIPTION (provided by applicant): The incidence of mood disorders, such as anxiety and depression, in women is twice that in men. Moreover, women are susceptible to a distinct group of mood disorders that are associated with fluctuations in ovarian hormone levels, including premenstrual dysphoric disorder, postpartum depression, and hormone replacement therapy induced negative mood. A precipitating factor in these disorders may be chronic exposure to psychosocial stressors and increased activation of the body?s primary stress axis. The occurrence of these mood disorders in women is complicated by the presence of other adverse health outcomes. Notably, eating disorders, such as emotional eating and obesity, are highly co-morbid with affective disorders, having similar disruptions in neurobiological systems present within individuals diagnosed with mood disorders. The long-term objective of the proposal is to elucidate the mechanisms by which progestagens modulate the disruption of stress axis and the serotonergic (5HT) system, both of which have been implicated in the etiology of mood and eating disorders in women. The central goal of this proposal is to implicate the disruption of allopregnanolone (ALLO), a specific progesterone, levels as a critical player in the disruption of systems associated with increased emotional and stress axis reactivity characteristic of affective disorders. The first aim is to evaluate how progestagens modulate socially induced changes in emotional reactivity and appetite. The second aim is to determine whether changes in ALLO and associated behavioral phenotypes are due to stress-induced activity. We will make use of an ethologically relevant model of psychosocial stress, employing hormonal and pharmacological means to assess emotional behavior and preference for a high calorie diet. PUBLIC HEALTH RELEVANCE: Women are twice as susceptible as men to mood and eating disorders, including anxiety, depression, obesity, and emotional eating. Studying the mechanisms by which psychosocial stress disrupts the actions of ovarian hormones will speak to the development of anxiety-based psychopathology in women.