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: 9890007
• 负责人: Jonathan E Posner
• 金额: $ 64.29万
• 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/9890007
• 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 environment; 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; Patient Self-Report; 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

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.

项目摘要 这种新的R01旨在研究选择性5-羟色胺再摄取抑制剂（SSRI）抗抑郁药的影响 在前两个 生活年。胎儿接触抗抑郁药是一个关键的公共卫生问题，因为处方 在过去30年中，孕妇的SSRIS增加了4-8倍，但它们对胎儿的影响 神经发育仍然未知。尽管对母亲来说很安全有效，但很容易 越过plapeta并进入胎儿大脑，可能会改变5-HT在 胎儿时期。这种胎儿暴露是否转化为对后代的长期影响尚不清楚。这 医师和孕妇面临的选择同样不清楚，因为中止SSRI并离开 未经治疗的孕产妇抑郁症可能会删除母亲和儿童的后果。解决 这些问题更明确地与舍布鲁克大学（加拿大魁北克）合作与 开发新的出生队列并测试SSRI和孕产妇抑郁症对后代的影响 神经发育。我们将注册患有（n = 250）的孕妇，没有（n = 125） 他们的头三个月，并评估其抑郁症状和药物使用的过程 剩余的怀孕。根据怀孕的结论，我们将知道婴儿是否暴露于SSRI； 该暴露的数量（剂量）和定时（三个月）；以及遗产抑郁的长度和严重程度 在并发期间。当婴儿为1个月时，我们将进行MRI扫描和EEG评估 旧，然后纵向跟随后代，重复的脑电图以及情感的行为度量 通过生命的头两年进行调节，以测试大脑结构或连通性的任何异常 确定在1个月时会产生发育后果。我们还将检查产后的影响 家庭环境，每月监测父母（母亲和父亲）抑郁症状， 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的影响分开，并表征 妊娠SSRI效应的家庭环境。如果资助，我们将构成最大的队列测试大脑和 胎儿抗抑郁药暴露至今的行为结果。调查结果将在临床上有用，无论如何 他们的方向。如果我们发现胎儿暴露于胎儿的后代中有重大的大脑或行为问题 抗抑郁药，女性可以针对其他药物治疗和抑郁症的非药物治疗 这对母子可能是安全的。如果我们没有发现不良影响，那么这将使 安全使用SSRI，并有可能提高合规性。