Relationships between Neuroactive Steroids, GABA and Glutamate MRS and Connectivity of the Default Mode Network in Postpartum Depression

项目摘要 产后抑郁症是分娩最常见的并发症之一。未经治疗的产后抑郁症 可能会对母亲和孩子的福祉产生实质性的不利影响，对孩子的牙齿产生负面影响- 具有持久后果的动力、行为和情绪的发展。其潜在的病理生理学基础 产后抑郁症在很大程度上是未知的，这为开发改进的治疗方法制造了障碍。整体而言 本研究的目的是确定GABA能和谷氨酸能神经活性类固醇的关系， 女性大脑皮质GABA和GLU浓度与默认模式网络静息-状态功能连接 产后抑郁症与健康产后和非产后妇女的对比。我们的中心假设是 持续的高幅度神经活性类固醇暴露，然后在怀孕期间和之后停用- 产期与低幅度神经活性类固醇暴露/停用月经周期，是 与默认模式网络内不同的皮质GABA和GLU浓度及其 与网络静息状态功能连通性的相关性，以及女性与 没有产后抑郁症。本研究是对54例健康围产期对照的前瞻性观察研究。 54例产后抑郁症妇女和54例围产期抑郁症的横断面检查结果比较 处于月经周期卵泡期的健康女性。将观察围产期情绪数据和血液样本。 两次产前和两次产后学习访问。健康产后妇女与产后妇女的比较 产后抑郁症将接受单功能磁共振成像和磁共振波谱扫描 而处于月经周期卵泡期的健康妇女将完成一次研究访问，包括 情绪、血液和神经成像测量。这项研究将检验默认模式休息状态功能的差异 跨组连接性(目标1)，跨组GABA和谷氨酸浓度差异(目标2)，对应 光谱与静止态功能连接性之间的关系(目标3)，并探索光谱- 产后抑郁症的复制、静息状态功能连接、神经活性类固醇激素和抑郁(探索性) 目标1)。最后，一半患有产后抑郁症的妇女将在成功后完成第二次成像治疗 产后抑郁治疗(探索性目标2)测定GABA、谷氨酸和静息功能状态 与治疗相关的必然性变化。然后，该数据可以作为预测的客观指标 对现有药物治疗的反应，确定新的产后特异性治疗靶点，并测量 新开发的治疗方法的潜在疗效。

Project Summary Postpartum depression is one of the most common complications of childbirth. Untreated postpartum depression can have substantial adverse effects on the well-being of the mother and child, negatively impacting child cog- nitive, behavioral, and emotional development with lasting consequences. The underlying pathophysiology of postpartum depression is largely unknown, creating an obstacle to developing improved treatments. The overall goal of this study is to determine the relationships between GABAergic and glutamatergic neuroactive steroids, cortical GABA and GLU concentrations and default mode network resting-state functional connectivity in women with postpartum depression versus healthy postpartum and non-postpartum women. Our central hypothesis is that high sustained amplitude neuroactive steroid exposure then withdrawal during the pregnancy and the post- partum period versus the low brief amplitude neuroactive steroid exposure/withdrawal of the menstrual cycle, is associated with differential cortical GABA and GLU concentrations within the default mode network and their correlation to network resting state functional connectivity, with further differences between women with and without postpartum depression. This study is a prospective observational study of 54 healthy peripartum comparison women and 54 peripartum women with postpartum depression in comparison to a cross-sectional examination of 54 healthy women in the follicular stage of the menstrual cycle. Peripartum mood data and blood specimens will be ob- tained at 2 antepartum and 2 postpartum study visits. Healthy postpartum comparison women and women with post- partum depression will undergo a single functional MRI and magnetic resonance spectroscopy scan in the postpartum period while healthy women in the follicular phase of the menstrual cycle will complete a single study visit including mood, blood and neuroimaging measures. The study will examine differences in default mode resting state functional connectivity across groups (Aim 1), differences in GABA and glutamate concentrations across groups (Aim 2), corre- lations between spectroscopy and resting-state functional connectivity (Aim 3) and explore correlations of spectros- copy, resting-state functional connectivity, neuroactive steroids and depression in postpartum depression (Exploratory Aim 1). Finally, half of the women with postpartum depression will complete a second imaging session after successful postpartum depression treatment (Exploratory Aim 2) to determine GABA, glutamate and resting-state functional con- nectivity changes associated with treatment. This data can then serve as an objective index against which to predict response to current pharmacotherapies, identify new postpartum-specific therapeutic targets and measure po- tential efficacy of newly developed treatments.