Parsing the Heterogeneity of Neural Functioning in Postpartum Depression

产后抑郁症（PPD，包括重度和轻度抑郁症）是一种公共卫生危机，对妇女、她的孩子和家庭有潜在的长期不良后果。有机制依据的预防战略对未来降低发病率至关重要。关于产后抑郁症的潜在神经机制以及这些机制如何影响产妇护理的信息缺乏。我们的研究小组已经开始发现PPD的假定神经生物标志物，包括对恐惧面孔的背内侧前额叶皮层（DMPFC）活动减少和对奖励的非持续腹侧纹状体反应。此外，杏仁核对婴儿哭声的活动减少与母亲对婴儿哭声的敏感性降低有关。为了响应NIMH战略计划目标1)“促进大脑和行为科学的发现，以推动对精神障碍原因的研究”，以及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、产后抑郁症和产妇敏感性扰动之间的假定联系。为了响应NIMH战略计划的目标：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育途径，以便及早识别（即孕前）弱势妇女，并为个性化的预防和干预计划提供信息。在这项应用中，我们建议通过前瞻性数据收集，对已知精神病史、社会心理功能和自己的育儿经历的年轻女性进行与照顾后代相关的PPD神经基础的首批测试之一。为此，我们利用多个pi的专业知识和纵向匹兹堡女孩研究（PGS; R01 MH056630）的广泛资源，提供发育背景来分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（n=2,451），该样本从5-8岁开始每年进行10年的跟踪调查。我们将获得三个亚组妇女产后3个月情感神经活动和3个月和6个月母婴互动数据：1)PPD +既往有严重或轻微抑郁史；2) PPD +无抑郁史；3)健康的产后对照组，无抑郁史。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亲敏感性的损害。

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. PUBLIC HEALTH RELEVANCE: PROJECT NARRATIVE RELEVANCE TO PUBLIC HEALTH Postpartum depressive disorders affect more than one in seven American women annually and can lead to deficits in maternal caregiving that are associated with long-term, adverse consequences for the developing child. By examining brain activity to emotional stimuli in mothers for whom psychosocial background was documented through a 10-year prospective study, we will be able to characterize the neural basis of postpartum depression and maternal caregiving within a developmental context. In so doing, we aim to identify women most at risk for postpartum depression and/or impaired caregiving before pregnancy, and thus facilitate preventive identification and treatment for postpartum depression.