Complementary Chronotherapeutics for Pregnancy and Postpartum Depression

描述(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，并损害儿童的生长发育和神经认知发育。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，特别是考虑到卡介苗的安全性和有效性有限。 有记录的孕妇和哺乳期妇女的治疗方案。在以前的工作中，我们发现，与正常对照(NC)孕妇或产后妇女相比，妊娠期抑郁症患者(DP)的褪黑素节律提前(移位)，而产后DP的褪黑素节律延迟(移位)。在这一新的应用中，我们将测试这样的假设，即通过适当的时机唤醒治疗和光线治疗的组合来纠正这些潜在的昼夜节律紊乱可以达到抗抑郁的效果。我们预计治疗将有选择性地发挥作用：对于有相位提前节律的妊娠DP，我们假设早醒疗法(EWT：醒到03：00小时，然后睡眠到07：00小时)加上晚上(PM)明亮的白光(BWL)，它延迟了褪黑素的节律，比晚睡疗法(LWT：从21：00-01：00小时睡眠，然后醒来)加早晨(AM)BWL，它会使褪黑素节律相位提前，从而更能改善情绪。相反，在产后延迟节律的产后DP中，我们假设LWT+AM BWL使褪黑素节律提前，比EWT+PM BWL更能改善情绪，后者使它们延迟。这些结合的时间生物学疗法是互补的，因为觉醒疗法可以加速和增强光照疗法的抗抑郁效果，而光照疗法可能需要长达10周的时间才能显示出对妊娠DP的疗效，而光照疗法可以维持唤醒疗法的抗抑郁效果，这些效果往往在随后的睡眠后消失。虽然这些联合治疗在其他情绪障碍方面已经证明了安全性和有效性，但它们还没有应用于怀孕和产后的MD。我们将在家中观察EWT+PM BWL与LWT+AM BWL对孕期和产后DP患者情绪、尿褪黑素和睡眠/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，我们的目标是开发产后MD的创新替代干预措施，潜在地改变女性情绪和其他具有昼夜节律紊乱的疾病的治疗方法。

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.