Parsing the Heterogeneity of Neural Functioning in Postpartum Depression

项目概述(由申请人提供)：产后抑郁障碍(PPD；包括严重和轻度抑郁症)构成公共健康危机，对妇女、其子女和家庭有潜在的长期不良后果。由机制提供信息的预防战略对今后减少发病率至关重要。关于产后抑郁的潜在神经机制以及这些机制如何影响产妇护理，目前还缺乏信息。我们的研究团队已经开始发现PPD的可能神经生物标记物，包括对恐惧面孔的背内侧前额叶皮质(DmPFC)活动减少和对奖励的非持续性腹侧纹状体反应。此外，杏仁核对婴儿哭泣的活动减少与母亲的敏感度降低有关。为响应NIMH战略计划目标1)“促进在大脑和行为科学中发现精神障碍的原因”，以及PA-07-081：“妇女在孕期和产后期的心理健康”，我们的目标是阐明神经活动与情绪刺激、产后抑郁和母体敏感性扰动之间的假定联系。为响应NIMH战略计划目标：2)“绘制精神疾病轨迹图以确定何时、何地和如何干预”，我们的目标是阐明产后情感神经功能的发育途径，以便能够及早识别(即孕前)易受伤害的妇女，并为个性化的预防和干预计划提供信息。在这项申请中，我们建议通过前瞻性的数据收集，对PPD的神经基础进行首批测试之一，这些测试与年轻女性的子女护理相关，对这些年轻女性来说，精神病史、心理社会功能和自己的育儿经历是已知的。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；R01 MH056630)的广泛资源来提供发育背景，以解析产后情感神经功能的异质性。在拟议工作期间怀孕的180名18岁及18岁以上的合格女孩将从PGS抽样(n=2 451)中招募，从5-8岁起每年跟踪调查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个月的母婴互动数据：1)PPD+既往重度或轻度抑郁症史；2)PPD+无抑郁史；以及3)无抑郁史的健康产后对照组。因此，我们将利用一个难得的机会来阐明产后抑郁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.