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

神经活性类固醇、GABA 和谷氨酸 MRS 与产后抑郁症默认模式网络连通性之间的关系

• 批准号: 10579231
• 负责人: Kristina Marie Deligiannidis
• 金额: $ 57.87万
• 依托单位: FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-04 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10579231
• 关键词: Address; Adverse effects; Affect; Allopregnanolone; Anterior; Antidepressive Agents; Behavioral; Biological Markers; Blood; Blood specimen; Brain Chemistry; Brain region; Cessation of life; Child; Childbirth; Cognitive; Data; Dedications; Depressed mood; Development; Emotional; Estradiol; Event; Female; Functional Magnetic Resonance Imaging; Functional disorder; Future; Glutamates; Goals; Gonadal Steroid Hormones; Hamilton Rating Scale for Depression; Image; Lead; Magnetic Resonance Spectroscopy; Major Depressive Disorder; Measures; Mediator; Menstrual cycle; Mental Depression; Molecular; Moods; Mothers; National Institute of Mental Health; Neurosecretory Systems; Observational Study; Outcome; Perinatal; Personal Satisfaction; Pharmacotherapy; Plasma; Postpartum Depression; Postpartum Period; Postpartum Women; Prefrontal Cortex; Pregnancy; Prevalence; Research; Research Priority; Rest; Scanning; Selective Serotonin Reuptake Inhibitor; Severities; Spectrum Analysis; Suicide; Techniques; Testing; Visit; Withdrawal; Woman; antenatal; brain circuitry; cingulate cortex; cohort; gamma-Aminobutyric Acid; hormonal contraception; improved; indexing; neural circuit; neurochemistry; neuroimaging; neurosteroids; new therapeutic target; non-smoker; novel; predicting response; pregnenolone sulfate; proliferative phase Menstrual cycle; prospective; reproductive; tetrahydrodeoxycorticosterone; therapeutic target

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.

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 可能对母亲和孩子的福祉产生重大不利影响，对儿童的认知产生负面影响， 行为和情感的发展，并产生持久的后果。的基础病理生理学 产后抑郁症在很大程度上是未知的，这给开发更好的治疗方法造成了障碍。整体 本研究的目的是确定GABA能和多巴胺能神经活性类固醇之间的关系， 女性皮质GABA和GLU浓度与默认模式网络静息态功能连接 产后抑郁症患者与健康的产后和非产后妇女相比。我们的核心假设是 在怀孕期间和怀孕后， 分娩期与月经周期的低短暂幅度神经活性类固醇暴露/停药， 与默认模式网络内的不同皮层GABA和GLU浓度及其 与网络静息状态功能连接的相关性，以及女性与 没有产后抑郁症这项研究是一项前瞻性观察性研究，54例健康围产期比较 妇女和54名围产期妇女产后抑郁症相比，横断面检查54 处于月经周期卵泡期的健康女性。围产期情绪数据和血液标本将被观察到。 在2次产前和2次产后研究访视时获得。健康产后妇女与产后妇女的比较 产后抑郁症将在产后接受单一功能性MRI和磁共振波谱扫描 而处于月经周期卵泡期的健康女性将完成一次研究访视，包括 情绪血液和神经影像学指标该研究将检查默认模式静息状态功能的差异， 各组之间的连接性（目标1），各组之间GABA和谷氨酸浓度的差异（目标2）， 光谱和静息态功能连接之间的关系（目的3），并探索光谱的相关性， 产后抑郁症患者的拷贝、静息状态功能连接、神经活性类固醇和抑郁（探索性 目标1）。最后，一半患有产后抑郁症的女性在成功完成第二次成像后， 产后抑郁症治疗（探索性目标2），以确定GABA，谷氨酸和静息状态功能状态， 与治疗相关的死亡率变化。然后，这些数据可以作为预测的客观指标 对当前药物治疗的反应，确定新的产后特异性治疗靶点，并测量口服给药后的 新开发的治疗方法的潜在疗效。