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

项目摘要 这种新的R 01旨在研究选择性5-羟色胺再摄取抑制剂（SSRI）抗抑郁药的作用 怀孕期间妇女使用药物对后代大脑和前两个月认知发育的影响 多年的生活。胎儿暴露于抗抑郁药是一个关键的公共卫生问题，因为处方药 在过去的30年里，孕妇的SSRI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SSRIs被认为对母亲安全有效， 穿过胎盘进入胎儿大脑，可能改变5-HT在胎儿发育过程中的重要神经营养作用。 胎儿期这种胎儿暴露是否会对后代产生长期影响仍不清楚。的 医生和孕妇面临的选择也同样不清楚， 母亲的抑郁症如果得不到治疗，会对母亲和孩子产生有害的后果。解决 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）合作， 开发一个新的出生队列，并测试SSRI和母亲抑郁暴露对后代的影响 神经发育我们将招募患有（n=250）和没有（n=125）抑郁症的孕妇， 他们的头三个月，并评估他们的抑郁症状和药物使用的过程中， 剩余妊娠到妊娠结束时，我们将知道婴儿是否暴露于SSRIs; 暴露的数量（剂量）和时间（妊娠期）;以及母亲抑郁的时间和严重程度 在同期。我们将在婴儿1个月时进行MRI扫描和EEG评估 然后用重复的脑电图以及情绪的行为测量纵向跟踪后代 通过生命的头两年来测试大脑结构或连接是否有任何异常， 在1个月时识别出具有发育后果。我们还将研究产后的影响， 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， 更明确地将药物的影响与抑郁症暴露分开，并描述 家庭环境对妊娠期SSRI的影响。如果获得资助，我们将形成最大的队列测试大脑， 胎儿抗抑郁药暴露的行为结果。结果将提供临床信息，无论 他们的方向。如果我们发现在胎儿期暴露于 抗抑郁药，妇女可以直接向其他药物和非药物治疗抑郁症 对母亲和孩子来说可能更安全如果我们没有发现不良影响，那么这将为 安全使用SSRIs，并可能增加依从性。

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.