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、性唤醒和情绪的神经生物系统。因此，ELA代表了一种环境事件，改变了贯穿各种精神病理的基本机制。月经相关情绪障碍(MRMD)，包括经前焦虑症(PMDD)，定义为在月经周期的黄体期周期性地重复出现情感和躯体/疼痛症状和损害。MRMD与ELA的高发生率相关，并代表了一种精神病理学模型，其病理生理基础与ELA有关。这项应用的主要目标是测试行为干预对MRMD有效性的预测因素和生物行为机制。基于正念的压力减轻(MBSR)是一种有前景的干预措施，有证据表明对压力、唤醒和情绪的有益调节。根据有证据表明，患有ELA的MRMD妇女比没有ELA的MRMD妇女有更严重的症状、应激反应失调和更高的疼痛敏感性，我们假设MBSR将有效地减轻MRMD妇女的症状、功能障碍和疼痛敏感性，特别是在那些患有ELA的妇女中。我们的次要目标是检查生物、心理和社会介质的有效性，从而促进我们对MRMD和其他ELA发生率较高的疾病的病理生理机制的理解，并帮助确定治疗靶点。符合MRMD预期标准的120-130名妇女将被随机分为8周MBSR计划或8周健康教育计划(HEP)对照组(根据ELA和基线经前抑郁严重程度分层)。主要的结果衡量标准是：1)在整个干预过程中对经前抑郁症状进行前瞻性评估；2)功能损害；3)对冷加压痛的敏感性。如果主要结果的假设得到支持，将检查涉及经前焦虑、易怒和总症状严重程度的次要结果测量，以及对热痛程序(索引中枢疼痛处理)的时间总和的敏感度。在实验室(干预前后)，MBSR疗效的预测生物介质将在静息和精神应激时进行评估：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)；以及4)心脏自主控制(压力感受器反射敏感性)。治疗效果的预测心理中介因素是：1)特质正念；2)接受；3)沉思，在干预前、干预中点和干预后进行评估。在为期8周的干预之后，将对妇女进行为期6个月的跟踪，以评估受益结果的可持续性。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3个月和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.