Personalized Integrated Chronotherapy for Perinatal Depression

围产期抑郁和焦虑是常见的、严重的、经常重叠的疾病，它们会增加 新母亲的发病率和死亡率(包括自杀)，并导致婴儿/儿童结局不佳。当前 治疗往往无法产生恢复或耐受性差，许多孕妇寻求非 药物治疗或在非药物治疗方案不可用时放弃治疗。期盼的和 经历昼夜节律失调的新妈妈患围产期抑郁症的风险更高。 这项非药物干预精神障碍的确证疗效临床试验R01寻求 测试个性化综合时间疗法(PIC)干预是否可以改善治疗结果 适用于因抑郁症而寻求门诊治疗的孕妇，无论是否患有焦虑。PIC是一种 针对昼夜节律和睡眠-觉醒行为的研究领域标准(RDoC)结构的多组分治疗包括强光治疗、睡眠相提前和睡眠稳定/限制。为了增加样本量和多样性，加速招募，这项研究将在临床结构不同的4个地点进行，这些地点已经试行了PIC干预。这项研究将招募怀孕第三个月被诊断为严重抑郁障碍的孕妇。我们将随机将患者分为以下两组： (A)常规护理(UC，n=110)或(B)PIC UC(n=110)。图片UC将有怀孕和产后 将通过量身定制的个性化方法进行管理，以根据每个患者的个人生物钟和睡眠时间来优化干预。在基线评估后，将在5年内开出PIC 专门的临床访问：3次在妊娠晚期，2次在产后。统一通信将包括 药物和/或心理治疗。将对两组的UC进行量化，以评估 图UC和UC组。两组的情绪将通过临床医生的盲访和患者的自我评估来衡量。 报告情况。将通过评估副作用/不良事件来评估PIC干预的安全性。 重要的是，这项研究还将检查假设PIC工作和测试的目标机制 昼夜节律指标在改善情绪症状中的中介作用。参赛者将佩戴手腕 在孕期28-40周和产后2-6周期间，动作图/光监测仪持续监测 并估计睡眠时间和持续时间。昼夜节律(用唾液暗光测量 (褪黑激素开始)将在怀孕期间(~30周)、36周时、 在产后6周。探索性目标将检查婴儿睡眠行为和 母体昼夜节律和与未来PIC传播相关的因素。如果这种干预是有效的， 由于PIC的高患病率，围产期PIC可能改变临床实践，并对公共卫生产生重大影响 围产期抑郁和焦虑，情绪障碍对母亲和孩子的负面影响，以及 需要为患有围产期情绪障碍的妇女提供有效的、新颖的非药物疗法。

Perinatal depression and anxiety are common, serious, and frequently overlapping disorders that increase morbidity and mortality in new mothers (including suicide) and result in poor infant/child outcomes. Current therapies often fail to produce recovery or are poorly tolerated, and many pregnant women seek non- pharmacologic therapy or forgo treatment when non-pharmacologic options are not available. Expectant and new mothers who experience circadian rhythm dysregulation are at increased risk for perinatal depression. This Confirmatory Efficacy Clinical Trial of Non-Pharmacological Interventions for Mental Disorders R01 seeks to test whether a Personalized Integrated Chronotherapy (PIC) intervention can improve treatment outcomes for pregnant patients seeking outpatient treatment for depression, with or without anxiety. PIC is a multicomponent treatment consisting of bright light therapy, sleep phase advance, and sleep stabilization/restriction that targets the Research Domain Criteria (RDoC) constructs of circadian rhythms and sleep-wake behavior. To increase sample size and diversity and accelerate recruitment, this study will be performed at 4 sites that differ in clinical structure and that have piloted the PIC intervention. The study will enroll expectant mothers diagnosed with major depressive disorder during 3rd trimester of pregnancy. We will randomize patients to either: (a) usual care (UC, n = 110) or (b) PIC+UC (n = 110). PIC+UC will have pregnancy and postpartum components and will be administered via a personalized approach tailored to optimize the intervention based on each patient’s individual circadian and sleep timing. After a baseline assessment, PIC will be prescribed during 5 dedicated clinical visits: three during 3rd trimester of pregnancy and 2 in the postpartum period. UC will consist of medication and/or psychotherapy. UC will be quantified in both groups to evaluate differences between the PIC+UC and UC groups. Mood will be measured in both groups by blinded clinician interview and patient self- report. The safety profile of the PIC intervention will be assessed by evaluation of side effects/adverse events. Importantly, the study will also examine the target mechanisms by which PIC is hypothesized to work and test the mediation effects of the circadian targets on improvement in mood symptoms. Participants will wear wrist actigraphy/light monitors continuously during weeks 28-40 of pregnancy and postpartum weeks 2-6 to assess light exposure and to estimate sleep timing and duration. Circadian phase (measured with salivary dim light melatonin onset) will be measured at baseline during pregnancy (~30 weeks’ gestation), at 36 weeks’ gestation, and at postpartum week 6. Exploratory aims will examine associations between infant sleep behavior and maternal circadian rhythms and factors relevant to future dissemination of PIC. If this intervention is effective, perinatal PIC could change clinical practice and have major public health impact due to the high prevalence of perinatal depression and anxiety, the negative effects of mood disorders on mothers and their children, and the need to provide effective, novel, non-pharmacologic therapies for women with perinatal mood disorders.