Alternative Treatments for Premenstrual Dysphoric Disorder

经前焦虑症（PMDD）是一种列在DSM-IV中的致残性抑郁症，影响5-8%的女性。如果不及时治疗，PMDD可能发展为重度抑郁症。至少有40%的妇女对提供的药物没有反应，产生了有问题的副作用，或寻求慢性药物治疗以外的选择来治疗这种定期疾病。以前，我们独立管理睡眠和光行为疗法，从基本的昼夜节律生物学的发现，以改善PMDD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，我们计划共同管理唤醒疗法，然后进行光治疗，这是一种新的替代方法，以前从未在PMDD中尝试过，尽管它在其他情绪障碍中表现出疗效。这些潜在的补充治疗具有唤醒疗法的优点，可以加速光治疗的抗抑郁作用的开始，这在2周黄体期的相对短暂症状期间是一个关键的益处，而光治疗保持了唤醒疗法的其他短暂作用的益处，这些作用通常在随后的睡眠后丧失。我们的主要目的是研究这些干预措施对情绪的影响，其次是对昼夜节律的影响，以检验关键时间的时间疗法通过纠正褪黑激素和睡眠中的相位紊乱来改善情绪的假设。由于我们发现，与无症状的卵泡期、月经周期相比较，PMDD中褪黑激素节律在有症状的黄体期是相延迟的（移后的），我们假设，用晚醒疗法（LWT：睡眠21：00-01：00 h，然后醒来）加早晨明亮的白色光（BWL）来推进褪黑激素节律将比用早醒疗法（EWT：醒来，然后睡眠03：00-07：00 h）加晚上BWL来延迟PMDD患者的情绪改善更多。结果的措施是情绪，尿褪黑激素，睡眠/活动的PMDD受试者。这些研究将确定是否创新，替代，结合时间生物学干预，针对特定的潜在昼夜节律异常，可以在PMDD的情绪受益。结果可能会影响其他抑郁症与时间生物学障碍和其他妇女的情绪障碍。

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.