Ovarian Effects on Intrinsic Connectivity and the Affective Enhancement of Memory

卵巢对内在连通性和记忆情感增强的影响

• 批准号: 9240048
• 负责人: Lisa Feldman Barrett
• 金额: $ 68.62万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-03-23 至 2022-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9240048
• 关键词: Address; Affect; Affective; Affective Symptoms; Brain; Cognition; Data; Diagnosis; Disease; Emotional; Emotions; Equipment and supply inventories; Estrogens; Event; Exhibits; Galvanic Skin Response; Group Structure; Hormonal; Hormones; Hydrocortisone; Individual; Ingestion; Intervention; Lead; Life; Luteal Phase; Measures; Memory; Menstrual cycle; Mental Depression; Mood Disorders; Ovarian; Ovarian hormone; Patient Self-Report; Pharmacology; Phase; Physiological; Post-Traumatic Stress Disorders; Predisposition; Prevention; Progesterone; Public Health; Research; Rest; Retrieval; Risk; Risk Management; Sex Characteristics; Stress; Symptoms; Testing; Time; Trauma; Woman; base; biological adaptation to stress; depressive symptoms; experience; heart rate variability; memory retrieval; men; mood symptom; negative affect; negative emotional state; negative mood; pill; response; stress reactivity; targeted treatment; traumatic event

It is well established that women exhibit a significantly higher rate of affective disorders than men do. This difference is particularly strong in post-traumatic stress disorder, where women are more than twice as likely to experience PTSD than men. Recent evidence suggests that women’s susceptibility to PTSD varies with their levels of ovarian hormones. During the luteal phase, when progesterone is elevated, women are more than three times as likely to develop PTSD symptoms after trauma. Similarly, women are twice as likely as men to be diagnosed with depression, and depressive symptoms also vary by menstrual phase. Both of these disorders involve alterations of memory, stress responses, and resting connectivity in the brain’s intrinsic networks. In PTSD, individuals experience intrusive memories of traumatic events, while individuals with depression show a marked negative retrieval bias. Stress-evoked release of the stress hormone cortisol is also elevated in both disorders. Similarly, resting connectivity between the default mode network, a group of structures engaged during the retrieval of memories, and the salience network, a group of structures involved in processing emotion, is elevated in individuals suffering from both disorders. Recent research indicates that affective memory, stress responsiveness, and resting connectivity are all influenced by changes in ovarian hormone levels. Negative memories acquired during the progesterone-rich luteal phase are better retained than during other menstrual phases. Increased progesterone is also associated with increased stress-evoked cortisol secretion. Similarly, ingestion of progesterone pills increases the connectivity between key nodes of default and salience networks. No study to date, however, has assessed the influence of changes in ovarian hormones on inter-network connectivity over the menstrual cycle. We hypothesize that changes in hormone levels over the menstrual cycle produce natural windows of vulnerability to traumatic life events, during which changes in the connectivity of the brain facilitate stress responses and enhance memory for negative experiences. To test this hypothesis, we will measure resting connectivity, stress hormone levels, physiological responses, and memory for negative material learned at hormonally distinct phases of the menstrual cycle. We predict that connectivity between resting and default mode networks will be at highest levels during the luteal phase, and that material learned in a negative emotional state will be best retained during the luteal phase. Additionally, we predict that the amount of connectivity between these two networks will significantly predict the enhancement of memory by negative affect, as well as the physiological response to negative mood induction. The results of this study could help to identify periods of maximum vulnerability trauma, thus facilitating prevention, as well as point to new and more targeted drug treatments.

众所周知，女性患情感障碍的比率明显高于男性。这种差异在创伤后应激障碍中尤为明显，女性患创伤后应激障碍的可能性是男性的两倍多。最近的证据表明，女性对创伤后应激障碍的易感性随其卵巢激素水平而变化。在黄体期，当黄体酮升高时，女性在创伤后出现PTSD症状的可能性是正常人的三倍多。同样，女性被诊断为抑郁症和抑郁症的可能性是男性的两倍