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，增加 新母亲的发病率和死亡率（包括自杀），并导致婴儿/儿童的不良后果。电流 治疗往往不能产生恢复或耐受性差，许多孕妇寻求非- 药物治疗或放弃治疗时，非药物的选择是不可用的。孕妇和 经历昼夜节律失调的新妈妈患围产期抑郁症的风险增加。 本精神障碍非药物干预的疗效临床试验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 对于寻求抑郁症门诊治疗的孕妇，无论是否有焦虑。pic是 多组分治疗包括明亮的光疗法、睡眠相位提前和睡眠稳定/限制，其针对昼夜节律和睡眠-觉醒行为的研究领域标准（RDoC）结构。为了增加样本量和多样性并加速招募，本研究将在临床结构不同且已试点PIC干预的4家研究中心进行。这项研究将招募在怀孕第三个三个月期间被诊断为重度抑郁症的孕妇。我们将患者随机分配至： (a)常规治疗（UC，n = 110）或（B）PIC + UC（n = 110）。PIC + UC将出现妊娠和产后 这些药物组合物将通过个性化的方法进行管理，以根据每个患者的个人昼夜节律和睡眠时间优化干预。基线评估后，将在5天内开具PIC处方 专门的临床访视：妊娠晚期3次，产后2次。UC将包括 药物和/或心理治疗。将在两组中对UC进行量化，以评价 PIC + UC和UC组。两组的情绪将通过盲法临床医生访谈和患者自我评估进行测量。 次报告.将通过评价副作用/不良事件来评估PIC干预的安全性特征。 重要的是，这项研究还将检查PIC假设工作和测试的目标机制 昼夜节律目标对改善情绪症状的中介作用。参与者将佩戴手腕 在妊娠第28 - 40周和产后第2 - 6周期间连续进行腕动计/光监测，以评估 光暴露和估计睡眠时间和持续时间。昼夜节律时相（用唾液暗光测量 褪黑激素起效）将在妊娠期间（约30周妊娠）的基线，妊娠36周， 产后第6周。探索性的目的将研究婴儿睡眠行为与 母体的昼夜节律和与PIC未来传播相关的因素。如果干预有效， 围产期PIC可能会改变临床实践，并由于高患病率而对公共卫生产生重大影响。 围产期抑郁症和焦虑症，情绪障碍对母亲及其子女的负面影响， 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.