Intervention for Menstrual Mood Disorders & Early Life Abuse: Biopsych Mechanisms

描述（由申请人提供）：早期生活虐待（ELA）影响调节压力、觉醒和情绪的神经生物学系统。因此，ELA代表了一种环境事件，改变了跨越各种精神病理学的基本机制。月经相关情绪障碍（mrmd），包括经前烦躁不安障碍（PMDD），是指在月经周期的黄体期反复出现情感和躯体/疼痛症状和损害。mrmd与ELA的高发率相关，并代表了一种精神病理学模型，其病理生理基础与ELA相关。本应用程序的主要目的是测试mrmd行为干预效果的预测因子和生物行为机制。正念减压（MBSR）是一种很有前途的干预方法，有证据表明它对压力、觉醒和情绪的调节有益。我们假设，基于有ELA的MRMD女性比没有ELA的MRMD女性有更严重的症状、应激反应失调和更大的疼痛敏感性的证据，正念减压疗法将有效地减轻MRMD女性的症状、功能损伤和疼痛敏感性，特别是对ELA患者。我们的第二个目标是研究生物心理社会介质的疗效，从而提高我们对MRMD和其他高ELA发病率疾病的病理生理机制的理解，并帮助确定治疗靶点。120-130名符合MRMD预期标准的女性将被随机分配（根据ELA和基线经前抑郁严重程度分层）到8周的正念减压计划组或8周的健康教育计划（HEP）对照组。主要结局指标是：1)在整个干预过程中对经前抑郁症状进行前瞻性评估；2)功能障碍；3)对冷压疼痛敏感。如果主要结果的假设得到支持，次要结果测量包括经前焦虑、易怒和总症状严重程度以及对热痛过程时间总和的敏感性（索引中枢疼痛处理）将被检查。在实验室（干预前和干预后），将在静息和精神应激反应中评估正念减压疗法疗效的预测生物介质：1)交感神经系统（血压、心率、血浆去甲肾上腺素和肾上腺素）；2)下丘脑-垂体-肾上腺（血浆ACTH和皮质醇）；3)炎症（血浆IL-6）；4)心脏自主控制（压力感受器反射敏感性）。预测治疗效果的心理调节因子有：1)特质正念；2)验收;3)反刍，在干预前、干预中、干预后进行评估。在8周的干预之后，将对女性进行为期6个月的随访，以评估有益结果的可持续性。结果将与干预阶段相同：每日症状评分、功能和疼痛敏感性（在第3个月和第6个月进行测试）以及依从性。

DESCRIPTION (provided by applicant): Early life abuse (ELA) impacts neurobiological systems that regulate stress, arousal and emotion. As such, ELA represents an environmental event altering fundamental mechanisms that cut across a variety of psychopathologies. Menstrually related mood disorders (MRMDs), including premenstrual dysphoric disorder (PMDD), are defined by the cyclic recurrence of affective and somatic/pain symptoms and impairment during the luteal phase of the menstrual cycle. MRMDs are associated with high rates of ELA and represent a model of psychopathology whose pathophysiologic underpinnings are linked to ELA. The primary objective of this application is to test predictors and biobehavioral mechanisms of efficacy of a behavioral intervention for MRMDs. Mindfulness based stress reduction (MBSR) is a promising intervention with evidence for beneficial modulation of stress, arousal and emotion. We hypothesize, based on the evidence that MRMD women with ELA have more severe symptoms, dysregulation in stress reactivity, and greater pain sensitivity than MRMD women without ELA, that MBSR will be efficacious in reducing symptoms, functional impairment and pain sensitivity in women with MRMD, especially in those with ELA. Our secondary objective is to examine biopsychosocial mediators of efficacy, thus advancing our understanding of pathophysiological mechanisms in MRMD and other disorders with high rates of ELA and aiding in the identifying therapeutic targets. 120-130 women meeting prospective criteria for a MRMD will be randomized (stratified on ELA and baseline premenstrual depression severity) to either the 8-week MBSR program or to an 8-week Health Education Program (HEP) Control Group. Primary outcome measures are: 1) premenstrual depression symptomatology assessed prospectively throughout the intervention; 2) functional impairment; and 3) sensitivity to cold pressor pain. If hypotheses for primary outcomes are supported, secondary outcome measures involving premenstrual anxiety, irritability and total symptom severity as well as sensitivity to the temporal summation of heat pain procedure (indexing central pain processing) will be examined. In the laboratory (before and after the intervention), predicted biological mediators of MBSR efficacy will be assessed at rest and in response to mental stress: 1) sympathetic nervous system (blood pressure, heart rate, plasma norepinephrine and epinephrine); 2) hypothalamic-pituitary-adrenal (plasma ACTH and cortisol); 3) inflammatory (plasma IL-6); and 4) cardiac autonomic control (baroreceptor reflex sensitivity). Predicted psychological mediators of treatment efficacy are: 1) trait mindfulness; 2) acceptance; and 3) rumination, assessed before, at the mid-point, and after the intervention. Following the 8 week intervention, women will be followed for 6 months to assess sustainability of beneficial outcomes. Outcomes will be as for the intervention phase: daily symptom ratings, function and pain sensitivity (tested at months 3 and 6), as well as adherence.