Complementary Chronotherapeutics for Pregnancy and Postpartum Depression

描述（由申请人提供）：妊娠和产后重度抑郁症（MD）对母亲及其家庭有致残作用，并损害儿童的生长和神经认知发育。迫切需要研究其发病机制，最终目的是开发新的治疗策略，特别是考虑到药物的安全性和有效性有限， 在妊娠期和哺乳期女性中记录的治疗选择。在以前的工作中，我们表明，怀孕抑郁症患者（DP）有相位提前（移位早），而产后DP有相位延迟（移位晚）褪黑激素节律与正常对照（NC）孕妇或产后妇女相比。在这个新的应用中，我们将测试的假设，纠正这些潜在的昼夜节律紊乱与适当的时间唤醒疗法和光治疗的组合实现抗抑郁作用。我们期望治疗选择性地起作用：在具有相位提前节律的妊娠DP中，我们假设早醒疗法（EWT：醒来直到03：00 h，然后睡觉直到07：00 h）加上夜晚（PM）明亮的白色光（BWL）（其相位延迟褪黑激素节律）将比晚醒疗法（LWT：从21：00-01：00 h睡觉，然后醒来）加上早晨（AM）BWL（其相位提前褪黑激素节律）更多地改善情绪。相比之下，在产后DP与相位延迟的节奏，我们假设，LWT加AM BWL，相位提前褪黑激素的节奏，将改善情绪比EWT加PM BWL，相位延迟。这些组合的时间生物学治疗是互补的，因为唤醒治疗可以加速和增强光治疗的抗抑郁作用，光治疗可能需要长达10周才能在妊娠DP中显示疗效，而光治疗可以维持唤醒治疗的抗抑郁作用，这些作用通常在随后的睡眠后丧失。尽管这些联合治疗在其他情绪障碍中表现出安全性和有效性，但它们尚未应用于妊娠和产后MD。我们将研究EWT加PM BWL与LWT加AM BWL对妊娠和产后DP在家中的情绪、尿褪黑激素和睡眠/觉醒周期的影响。通过这种针对潜在的时间生物学异常的翻译方法，我们的目标是为产后MD开发创新的替代干预措施，可能改变女性情绪和其他昼夜节律紊乱疾病的治疗方法。

DESCRIPTION (provided by applicant): Pregnant and postpartum major depression (MD) has disabling effects on the mother and her family, and impairs growth and neurocognitive development of the child. Investigation into its pathogenesis, with the ultimate aim of developing new treatment strategies, is needed urgently, particularly given the limited safety and efficacy of treatment options documented in pregnant and in lactating women. In previous work, we demonstrated that pregnant depressed patients (DP) had phase-advanced (shifted-earlier), whereas postpartum DP had phase-delayed (shifted-later) melatonin rhythms compared with normal control (NC) pregnant or postpartum women. In this new application we will test the hypothesis that correcting these underlying circadian rhythm disturbances with a combination of appropriately-timed wake therapy and light treatment achieves antidepressant effects. We expect treatments to act selectively: In pregnant DP with phase- advanced rhythms, we hypothesize that early wake therapy (EWT: wake until 03:00 h, followed by sleep until 07:00 h) plus evening (PM) bright white light (BWL), which phase-delay melatonin rhythms, will improve mood more than late wake therapy (LWT: sleep from 21:00-01:00 h, followed by wake) plus morning (AM) BWL, which phase-advance melatonin rhythms. In contrast, in postpartum DP with phase-delayed rhythms, we hypothesize that LWT plus AM BWL, which phase-advance melatonin rhythms, will improve mood more than EWT plus PM BWL, which phase-delay them. These combined chronobiological treatments are complementary in that wake therapy can hasten and potentiate the antidepressant effects of light treatment that may take up to 10 weeks to show efficacy in pregnant DP, while light treatment can sustain the antidepressant effects of wake therapy that often are lost after subsequent sleep. Although these combined treatments have demonstrated safety and efficacy in other mood disorders, they have not been applied to pregnant and postpartum MD. We will examine the effects of EWT plus PM BWL vs. LWT plus AM BWL on mood, urinary melatonin and the sleep/wake cycle in pregnant and postpartum DP at home. By this translational approach targeted to underlying chronobiological abnormalities, we aim to develop innovative alternative interventions for puerperal MD, potentially transforming treatment approaches for women's mood and other disorders with circadian rhythm disturbances.