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

项目总结 这一新的R01旨在研究选择性5-羟色胺再摄取抑制剂(SSRI)的抗抑郁作用 妊娠期妇女用药对子代大脑和前两者认知发育的影响 生命中的岁月。胎儿接触抗抑郁药物是一个严重的公共卫生问题，因为处方 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 神经发育尚不清楚。尽管对母亲来说，SSRs被认为是安全有效的，但它很容易 穿过胎盘进入胎儿大脑，潜在地改变了5-羟色胺在胎盘发育过程中的重要神经营养作用 胎儿期。目前尚不清楚这种胎儿接触是否会对后代产生长期影响。这个 医生和孕妇面临的选择同样不明确，就像停止SSRI和离开一样 母亲抑郁得不到治疗可能会给母亲和孩子带来有害的后果。致信地址 这些问题更加明确，我们已经与加拿大魁北克舍布鲁克大学合作 建立新的出生队列，并测试SSRI和母亲抑郁暴露对后代的影响 神经发育。我们将招募有抑郁障碍的孕妇(n=250)和没有抑郁障碍的孕妇(n=125)。 并评估他们的抑郁症状和在过去三个月中的药物使用情况 剩下的怀孕。到怀孕结束时，我们将知道婴儿是否接触过SSRIs； 接触的数量(剂量)和时间(三个月)；以及产妇抑郁的持续时间和严重程度 在合并期间内。当婴儿1个月大时，我们将进行MRI扫描和EEG评估 然后用重复的脑电和情绪的行为测量对后代进行纵向跟踪 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个月时被确认具有发育后果。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，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的暴露分开，并表征 家庭环境对妊娠SSRI的影响。如果得到资助，我们将组成最大的测试大脑和 迄今为止胎儿服用抗抑郁药的行为结果。无论如何，这些发现都将在临床上提供信息。 他们的方向。如果我们发现暴露在胎儿体内的后代出现了严重的大脑或行为问题 抗抑郁药，女性可以针对抑郁症进行其他药物治疗和非药物治疗 这对母亲和孩子来说可能更安全。如果我们没有发现不利的影响，那么这将为 安全使用SSRI，并有可能提高遵从性。

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.