Antiglucocorticoid Therapy in Bipolar Depression with Mi

双相抑郁症的抗糖皮质激素治疗

• 批准号: 7312900
• 负责人: HUSSEINI K MANJI
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF MENTAL HEALTH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7312900
• 关键词: Antiglucocorticoid; Therapy; Bipolar; Depression; Mi

The focus of this study is to elucidate the efficacy of a glucocorticoid receptor antagonist, mifepristone, on the affective and cognitive symptom profile that characterizes treatment resistant bipolar depression. Patients with bipolar depression often have indices of hypercortisolism, which potentially contribute to central nervous system dysfunction responsible for the cognitive and affective abnormalities in bipolar disorder. Recent data reveal that mifepristone is capable of ameliorating the mood and thought disturbances of psychotic depression. Clinical responsiveness to mifepristone in bipolar depression would implicate cortisol and an abnormal hypothalamic-pituitary axis (HPA) axis directly in mood abnormalities and specific cognitive deficits in bipolar depression. A detailed dissection of the HPA axis in bipolar patients should identify a distinctive mifepristone -responsive pathophysiological subtype based on neuroendocrine profile. Patients, in addition to careful clinical evaluation, will be carefully evaluated by physiologic stimuli that probe discreet aspects of HPA axis organization including diurnal rhythm, pulsatile secretion, feedback responsiveness to cortisol, and pituitary responsiveness to corticotrophin releasing hormone challenge. Patients will also receive formal neuropsychological and psychophysiological testing of various components of information processing, including those that are cortisol-dependent and associated with bipolar illness.

本研究的重点是阐明糖皮质激素受体拮抗剂米非司酮对治疗抵抗性双相抑郁症特征的情感和认知症状的功效。双相抑郁症患者通常有皮质醇增多症的症状，这可能会导致中枢神经系统功能障碍，从而导致双相情感障碍的认知和情感异常。最近的数据表明，米非司酮能够改善精神病性抑郁症的情绪和思维障碍。双相抑郁症对米非司酮的临床反应表明皮质醇和异常的下丘脑-垂体轴（HPA）轴直接与双相抑郁症的情绪异常和特定认知缺陷有关。对双相情感障碍患者 HPA 轴的详细解剖应根据神经内分泌特征确定独特的米非司酮反应性病理生理学亚型。除了仔细的临床评估之外，还将通过生理刺激来仔细评估患者，这些刺激探查 HPA 轴组织的谨慎方面，包括昼夜节律、脉动分泌、对皮质醇的反馈反应性以及垂体对促肾上腺皮质激素释放激素挑战的反应性。患者还将接受信息处理各个组成部分的正式神经心理学和心理生理学测试，包括那些依赖皮质醇和与双相情感障碍相关的部分。