Parsing the Heterogeneity of Neural Functioning in Postpartum Depression

描述（由申请人提供）：项目概述产后抑郁症（PPD;包括重度和轻度抑郁症）构成了一种公共卫生危机，对妇女、其子女和家庭可能产生长期不良后果。根据机制制定的预防战略对今后减少发病率至关重要。关于PPD的潜在神经机制以及这些机制如何影响母体生育的信息非常缺乏。我们的研究团队已经开始发现PPD的假定神经生物标志物，包括背内侧前额叶皮层（DMPFC）对恐惧面孔的活动减少和腹侧纹状体对奖励的不持续反应。此外，杏仁核对婴儿哭声的反应减弱与母亲敏感性降低有关。为了响应NIMH战略计划目标1）“促进大脑和行为科学的发现，以推动对精神疾病原因的研究”和PA-07-081：“怀孕和产后妇女的心理健康”，我们的目标是阐明神经活动与情绪刺激，PPD和母体敏感性扰动之间的假定联系。为了响应NIMH战略计划目标：2）“绘制精神疾病轨迹以确定何时，何地以及如何干预”，我们的目标是阐明产后情感神经功能的发展途径，以便早期识别（即怀孕前）脆弱的女性，并为个性化的预防和干预计划提供信息。在本申请中，我们建议通过前瞻性数据收集，对与年轻女性的后代护理相关的PPD神经基础进行第一次测试，这些年轻女性的精神病史，心理社会功能和自己的育儿经验是已知的。为此，我们利用多个PI的专业知识和匹兹堡女孩纵向研究（PGS; R 01 MH 056630）的广泛资源，提供发展背景来解析产后情感神经功能的异质性。将从PGS样本（n= 2 451）中招募180名年龄在18岁及以上、在拟议工作期间怀孕的合格女孩，从5-8岁开始每年随访10年。我们将获得三个亚组妇女产后3个月的情感神经活动和3个月和6个月的母婴间期数据：1）PPD +既往重度或轻度抑郁症史; 2）PPD +无抑郁症史; 3）健康产后对照组，无抑郁症史。因此，我们将利用一个难得的机会来阐明PPD的神经特征和发育背景下母体敏感性的损害。

DESCRIPTION (provided by applicant): PROJECT SUMMARY Postpartum depressive disorders (PPD; including major and minor depression) constitute a public health crisis with potentially long-term, adverse consequences for the woman, her child and family. Prevention strategies informed by mechanisms are critical to future reduction in morbidity. There is a dearth of information about the underlying neural mechanisms of PPD and how these impact on maternal caregiving. Our investigative team has begun to uncover putative neural biomarkers of PPD including reduced dorsomedial prefrontal cortex (DMPFC) activity to fearful faces and unsustained ventral striatal response to reward. Furthermore, reduced amygdala activity to infant cry was associated with reduced maternal sensitivity. In response to NIMH strategic plan objective 1) 'To promote discovery in the brain and behavioral sciences to fuel research on the causes of mental disorders', and PA-07-081: 'Women's Mental Health in Pregnancy and the Postpartum Period', we aim to elucidate the putative link between neural activity to emotional stimuli, PPD, and perturbations in maternal sensitivity. In response to NIMH strategic plan objective: 2) 'To chart mental illness trajectories to determine when, where, and how to intervene,' we aim to elucidate developmental pathways to postpartum affective neural functioning to enable early identification (i.e. pre-pregnancy) of vulnerable women, and inform personalized prevention and intervention programs. In this application, we propose to conduct one of the first tests of the neural underpinnings of PPD that are relevant to care of the offspring in young women for whom psychiatric history, psychosocial functioning, and own parenting experience are known, via prospective data collection. To this end, we leverage the expertise of multiple PIs and the extensive resources of the longitudinal Pittsburgh Girls Study (PGS; R01 MH056630) to provide the developmental context to parse the heterogeneity in postpartum affective neural functioning. One hundred and eighty eligible girls aged 18 years and older, who become pregnant during the period of the proposed work, will be recruited from the PGS sample (n=2,451), that has been followed annually for 10 years since ages 5-8 years. We will acquire 3-month postpartum affective neural activity and 3- and 6-month mother-infant interactional data in three sub-groups of women: 1) PPD + past history of major or minor depression; 2) PPD + no history of depression; and 3) Healthy postpartum controls with no history of depression. We will thus capitalize on a rare opportunity to elucidate the neural signature of PPD and impairments in maternal sensitivity within a developmental context.