Complementary Chronotherapeutics for Pregnancy and Postpartum Depression

描述（由申请人提供）：怀孕和产后重度抑郁症 (MD) 对母亲及其家庭有残疾影响，并损害孩子的生长和神经认知发育。迫切需要对其发病机制进行研究，最终目的是开发新的治疗策略，特别是考虑到其安全性和有效性有限 记录了孕妇和哺乳期妇女的治疗方案。在之前的工作中，我们证明，与正常对照（NC）孕妇或产后妇女相比，怀孕抑郁症患者（DP）的褪黑激素节律存在相位超前（提前），而产后 DP 的褪黑激素节律存在相位延迟（晚移）。在这个新应用中，我们将测试这样一个假设：通过适当定时的唤醒疗法和光治疗相结合来纠正这些潜在的昼夜节律紊乱，可以达到抗抑郁效果。我们期望治疗能够选择性地发挥作用：对于阶段性超前节律的妊娠期 DP，我们假设早醒治疗（EWT：醒来直至 03:00 小时，然后睡眠直至 07:00 小时）加上晚间 (PM) 亮白光 (BWL)（相位延迟褪黑激素节律）比晚醒疗法（LWT：从 21:00 到 01:00 睡觉，然后醒来）加早晨 (AM) 更能改善情绪。 BWL，它使褪黑激素节律提前。相比之下，在具有相位延迟节律的产后 DP 中，我们假设 LWT 加 AM BWL（相位提前褪黑激素节律）比 EWT 加 PM BWL（相位延迟）更能改善情绪。这些组合的时间生物学治疗是互补的，因为唤醒疗法可以加速和增强光治疗的抗抑郁作用，这种作用可能需要长达 10 周的时间才能在妊娠 DP 中显现出疗效，而光治疗可以维持唤醒疗法的抗抑郁作用，而这种作用通常在随后的睡眠后消失。尽管这些联合治疗已在其他情绪障碍中证明了安全性和有效性，但尚未应用于妊娠期和产后MD。我们将研究 EWT 加 PM BWL 与 LWT 加 AM BWL 对孕妇和产后家庭 DP 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转化方法，我们的目标是为产后 MD 开发创新的替代干预措施，有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.