Effects of prenatal maternal depression and antidepressant exposures on offspring neurodevelopmental trajectories: A birth cohort study

产前母亲抑郁和抗抑郁药物暴露对后代神经发育轨迹的影响：出生队列研究

• 批准号: 10368921
• 负责人: Jonathan E Posner
• 金额: $ 63.4万
• 依托单位: NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-03-08 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10368921
• 关键词: Address; Adverse effects; Age; Amygdaloid structure; Anger; Antidepressive Agents; Behavior; Behavioral; Biological; Birth; Blood - brain barrier anatomy; Brain; Canada; Child; Classification; Clinical; Cognitive; Cohort Studies; Data; Data Collection; Depressive disorder; Development; Diffusion; Dorsal; Dose; Early Intervention; Electroencephalography; Enrollment; Environment; Equipment and supply inventories; Exposure to; Family; Family Characteristics; First Pregnancy Trimester; Frequencies; Fright; Functional Magnetic Resonance Imaging; Funding; Future; Goals; Home; Human; Impairment; Infant; Insula of Reil; Judgment; Laboratories; Length; Life; Live Birth; Long-Term Effects; MRI Scans; Magnetic Resonance Imaging; Mediating; Medical Records; Medical center; Mental Depression; Modeling; Mothers; Neurobiology; Pharmaceutical Preparations; Pharmacy facility; Phenotype; Physicians; Placenta; Postpartum Depression; Prefrontal Cortex; Pregnancy; Pregnant Women; Problem behavior; Psychotherapy; Public Health; Quebec; Records; Relative Risks; Research; Research Personnel; Rest; Rodent; Role; Selective Serotonin Reuptake Inhibitor; Serotonin; Severities; Shapes; Signal Transduction; Stable Populations; Structure; Temperament; Testing; Translating; Universities; Variant; Woman; affective disturbance; antepartum depression; antidepressant effect; base; behavior measurement; behavioral impairment; behavioral outcome; behavioral phenotyping; brain behavior; clinical practice; cognitive development; cohort; depressive symptoms; emotion regulation; epidemiology study; family influence; fetal; fetal blood; in utero; indexing; language impairment; magnetic resonance imaging/electroencephalography; maternal depression; multimodality; neurobehavioral; neurodevelopment; neurotropic; offspring; parental monitoring; postnatal; pre-clinical research; prenatal; prenatal exposure; risk benefit ratio; self-reported depression

PROJECT SUMMARY This new R01 aims to study the effects of selective serotonin reuptake inhibitor (SSRI) antidepressant medication use by women in pregnancy on their offspring’s brain and cognitive development in the first two years of life. Fetal exposure to antidepressants is a critical public health question because prescriptions of SSRIs to pregnant women have increased 4-8-fold over the last 30 years, yet their impact on fetal neurodevelopment remains unknown. Although considered safe and effective for the mother, SSRIs readily cross the placenta and into the fetal brain, potentially altering the important neurotropic role of 5-HT during the fetal period. Whether this fetal exposure translates to long-term effects on the offspring remain unclear. The choices facing physicians and pregnant women are similarly unclear, as discontinuing SSRI and leaving maternal depression untreated can have deleterious consequences for both mother and child. To address these questions more definitively, we have partnered with the University of Sherbrooke (Quebec, Canada) to develop a new birth cohort and test the effects of SSRI and maternal depression exposures on offspring neurodevelopment. We will enroll pregnant women with (n=250) and without (n=125) a depressive disorder in their first trimester, and assess the course of their depressive symptoms and medication usage over the remaining pregnancy. By conclusion of pregnancy, we will know whether the infant was exposed to SSRIs; the quantity (dose) and timing (trimester) of that exposure; and the length and severity of maternal depression during the concurrent period. We will perform an MRI scan and EEG assessment when the infant is 1 month old, and then longitudinally follow the offspring with repeated EEG, as well as behavioral measures of emotion regulation through the first two years of life to test whether any abnormalities in brain structure or connectivity identified at 1 month have developmental consequences. We will also examine the influence of the post-natal family environment, monitoring parental (maternal and paternal) depression symptoms monthly, and conducting two in-home assessments of family. These detailed longitudinal assessments will allow our study to more definitively separate effects of medication from depression exposure, and to characterize the influence of the family environment on gestational SSRI effects. If funded, we will form the largest cohort testing brain and behavioral outcomes of fetal antidepressant exposure to date. Findings will be clinically informative regardless of their direction. If we find significant brain or behavioral problems in offspring who were fetal exposed to antidepressants, women can be directed to other medication and non-medication treatments for depression that may be safer for mother and child. And if we find no adverse effects, then this will provide reassurance for the safe use of SSRIs, and potentially increase compliance as well.

项目概要 这种新的 R01 旨在研究选择性血清素再摄取抑制剂 (SSRI) 抗抑郁药的作用 怀孕期间妇女使用药物对其后代大脑和前两年认知发展的影响 胎儿接触抗抑郁药物是一个重要的公共卫生问题，因为 过去 30 年来，孕妇使用的 SSRIs 增加了 4-8 倍，但它们对胎儿的影响 尽管 SSRIs 被认为对母亲安全有效，但神经发育仍然未知。 穿过胎盘并进入胎儿大脑，可能改变 5-HT 在妊娠期间的重要神经营养作用 胎儿时期的这种暴露是否会对后代产生长期影响仍不清楚。 医生和孕妇面临的选择同样不明确，如停用 SSRI 并离开 未经治疗的产妇抑郁症可能会给母亲和孩子带来有害的后果。 为了更明确地回答这些问题，我们与舍布鲁克大学（加拿大魁北克省）合作， 建立一个新的出生队列并测试 SSRI 和母亲抑郁症暴露对后代的影响 我们将招募患有 (n=250) 和不患有 (n=125) 抑郁症的孕妇。 他们的前三个月，并评估他们的抑郁症状和药物使用情况的过程 通过妊娠结束，我们将知道婴儿是否接触过 SSRIs； 该暴露的数量（剂量）和时间（三个月）以及母亲抑郁症的持续时间和严重程度； 同期，我们将在婴儿 1 个月大时进行 MRI 扫描和脑电图评估。 老，然后纵向跟踪后代重复脑电图，以及情绪的行为测量 生命头两年的调节，以测试大脑结构或连接是否存在异常 我们还将检查出生后的影响。 家庭环境，每月监测父母（母亲和父亲）抑郁症状，以及 对家庭进行两次家庭评估这些详细的纵向评估将使我们的研究能够 更明确地将药物的影响与抑郁症暴露分开，并描述以下因素的影响： 如果获得资助，我们将组建最大的队列测试大脑和家庭环境对妊娠 SSRI 的影响。 无论如何，迄今为止胎儿接触抗抑郁药物的行为结果将具有临床信息。 如果我们发现胎儿接触过的后代有明显的大脑或行为问题。 抗抑郁药，可以指导女性接受其他药物和非药物治疗抑郁症 这对母亲和孩子来说可能更安全，如果我们没有发现任何不良影响，那么这将为母亲和孩子带来安心。 SSRIs 的安全使用，并可能提高依从性。