Alternative Treatments for Premenstrual Dysphoric Disorder

经前烦躁不安症（PMDD）是一种列在DSM-IV中的致残抑郁症，影响了5-8%的经期妇女，需要创新的替代治疗方法。如果不及时治疗，经前不悦症会发展为重度抑郁症。在提供药物治疗的情况下，至少40%的女性没有反应，出现了有问题的副作用，或者寻求慢性药物治疗以外的其他选择。以前，我们独立实施睡眠和光行为疗法，将基础昼夜生物学的发现转化为改善经前不悦症女性的健康。为了响应开发新型联合疗法的呼吁，在本提案中，我们计划联合使用清醒疗法和光照疗法，这是一种新的替代方法，此前从未在PMDD中尝试过，尽管它在其他情绪障碍中已被证明有效。这些潜在的补充疗法的优点是，清醒疗法加速了光照疗法抗抑郁效果的发作，这在2周黄体期相对短暂的症状中是至关重要的益处，而光照疗法保持了光照疗法在随后睡眠后通常失去的短暂效果的益处。我们的主要目的是检查这些干预措施对情绪的影响，其次是对昼夜节律的影响，以验证关键时间疗法通过纠正褪黑激素和睡眠的相位紊乱来改善情绪的假设。由于我们发现在经前抑郁症中，有症状的黄体与无症状的卵泡月经周期相比较，褪黑激素节律延迟（移后），我们假设通过晚醒治疗（LWT：睡眠21:00-01:00小时，然后醒来）和早晨明亮的白光（BWL）来促进褪黑激素节律，比早醒治疗（EWT：醒来，然后睡觉03:00-07:00小时）和晚上BWL更能改善经前抑郁症患者的情绪。结果测量是情绪，尿褪黑素，PMDD受试者的睡眠/活动。这些研究将确定针对特定潜在昼夜节律异常的创新、替代、联合时间生物学干预是否能使经前抑郁症患者的情绪受益。研究结果可能会影响其他伴有时间生物学障碍的抑郁症和其他女性情绪障碍。

Innovative, alternative treatments are needed for Premenstrual Dysphoric Disorder (PMDD), a disabling depressive disorder listed in DSM-IV, affecting 5-8% of menstruating women. Left untreated, PMDD can progress to major depression. Offered medication, at least 40% of women do not respond, develop problematic side-effects or seek options other than chronic pharmacological treatment for this periodic illness. Previously we independently administered sleep and light behavioral therapies, translating discoveries from basic circadian biology to improve the health of women with PMDD. In response to a call for the development of novel combination therapies, in this proposal we plan to co-administer wake therapy followed by light treatment, a novel alternative approach, never before tried in PMDD, despite its demonstrated efficacy in other mood disorders. These potentially complementary treatments have the advantage of wake therapy hastening the onset of the antidepressant effects of light treatment, a crucial benefit during the relatively short-lived symptoms of the 2-week luteal phase, whereas light treatment maintains the benefit of the otherwise transitory effects of wake therapy often lost after subsequent sleep. Our primary aim is to examine the effects of these interventions on mood, and secondarily on circadian rhythms, to test the hypothesis that critically-timed chronotherapy improves mood by correcting phase disturbances in melatonin and sleep. As we found that in PMDD melatonin rhythms were phase-delayed (shifted-later) in the symptomatic luteal compared with the asymptomatic follicular, menstrual cycle phase, we hypothesize that advancing melatonin rhythms with late wake therapy (LWT: sleep 21:00-01:00 h, followed by wake) plus morning bright white light (BWL) will improve mood in PMDD patients more than delaying them with early wake therapy (EWT: wake, then sleep 03:00-07:00 h) plus evening BWL. Outcome measures are mood, urinary melatonin, sleep/activity in PMDD subjects. These studies will determine whether innovative, alternative, combined chronobiological interventions, targeted to specific underlying circadian rhythm abnormalities, can benefit mood in PMDD. The results may impact other depressive disorders with chronobiological disturbances and other women¿s mood disorders.