SSRI Exposure and Ventricular Development from Bench to Bedside: A Prospective Study to Determine if Maternal Depression Treatment Impacts Offspring Cardiac Development

SSRI 暴露和心室发育（从实验室到临床）：一项前瞻性研究，以确定母亲抑郁治疗是否影响后代心脏发育

• 批准号: 10636635
• 负责人: Sarah Elizabeth Haskell
• 金额: $ 36.01万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10636635
• 关键词: 1 year old; Address; Adult; Affect; Animal Model; Animals; Antidepressive Agents; Birth; Cardiac; Cardiac Myocytes; Cardiology; Cardiovascular Diseases; Cardiovascular system; Childhood; Congenital Heart Defects; Critical Care; Data; Depressed mood; Development; Dimensions; Disease; Echocardiography; Epidemiology; Exposure to; Fetal Development; Fetus; Frequencies; Future; Genetic; Gestational Age; Growth; Health; Human; Imaging Techniques; Impairment; Individual; Infant; Investigation; Knowledge; Left; Long-Term Effects; Measurement; Measures; Medical; Mental Depression; Monitor; Mothers; Mus; Myocardial; Neonatal; Newborn Infant; Nonpharmacologic Therapy; Outcome; Pediatrics; Performance; Pharmacological Treatment; Physiological; Pilot Projects; Population; Pre-Clinical Model; Predictive Value; Pregnant Women; Prospective Studies; Psychiatry; Public Health; Recommendation; Reporting; Research; Research Design; Risk; Selective Serotonin Reuptake Inhibitor; Serotonin; Sertraline; Signal Transduction; Structure; Techniques; Time; Translating; United States; Ventricular; Ventricular Function; Woman; Work; Zebrafish; antepartum depression; bench to bedside; cardiogenesis; cardiovascular health; clinically relevant; detection sensitivity; expectation; fetal; health of the mother; heart dimension/size; heart function; hemodynamics; indexing; infancy; inhibitor therapy; innovation; insight; interpersonal therapy; intrauterine environment; maternal depression; offspring; outcome prediction; perinatal mental health; peripartum depression; persistent pulmonary hypertension; pharmacologic; policy implication; postnatal; prenatal exposure; recruit; risk prediction; translational goal; translational study; treatment risk

ABSTRACT The broad goal of this translational study is to determine if maternal depression treatment affects ventricular development through comprehensive echocardiography measurements immediately after birth and over time. The decision to medically treat maternal depression is challenging and includes careful consideration of the risks versus benefits. Selective serotonin reuptake inhibitors (SSRIs) are a class of antidepressants currently prescribed to 10-13% of pregnant women. Interpersonal psychotherapy (IPT) is an alternative non-pharmacologic treatment that has shown efficacy in mild to severe depression. Treatment of maternal depression is not only critical for the health of the mother and fetus but may impact overall health as research has shown that a deleterious intrauterine environment can predispose individuals to cardiovascular disease. To date, we have demonstrated both short- and long-term effects from SSRI exposure on ventricular size and cardiac function in mice and zebrafish where maternal depression is eliminated as a contributing factor. Epidemiologic reports continue to be conflicting if SSRIs influence cardiac development and maternal depression remains a confounding factor. Thus, it is critical to determine if these ventricular findings after SSRI exposure in animal models translate to humans and if similar findings are noted with non-pharmacologic treatment for maternal depression. To address these issues, a collaborative team of experts in pediatrics (neonatal hemodynamics, cardiology, and cardiac critical care) and psychiatry will recruit mothers without depression and with maternal depression treated with SSRIs or IPT and their offspring. We will apply advanced echocardiography techniques which have been validated in the newborn and pediatric populations to pursue two specific aims: (1) Measure the impact of maternal depression and its treatment on offspring ventricular size immediately after birth, at 1 week, and at 1 year of age; and (2) Quantify the impact of maternal depression and its treatment on offspring ventricular function following birth, at 1 week, and at 1 year of age. Because heart size and ventricular function are important predictors of outcomes in many adult and pediatric diseases, this study will provide important answers to a timely, highly-relevant clinical question.

抽象的 这项翻译研究的广泛目标是确定母体抑郁症治疗是否影响 通过全面的超声心动图测量，心室发展 出生和随着时间的流逝。医学治疗孕产妇抑郁症的决定具有挑战性，包括 仔细考虑风险与收益。选择性5-羟色胺再摄取抑制剂（SSRI）是一个 目前，抗抑郁药类别为10-13％的孕妇。人际关系 心理治疗（IPT）是一种替代性非药物治疗 严重的抑郁症。孕产妇抑郁症的治疗不仅对母亲的健康至关重要 和胎儿，但可能会影响整体健康，因为研究表明宫内有害 环境可以使个体患有心血管疾病。迄今为止，我们已经证明了 SSRI暴露对小鼠心室大小和心脏功能的短期和长期影响 斑马鱼被消除为促成因素的孕产妇抑郁症。流行病学报告 如果SSRIS影响心脏发展和母亲抑郁症仍然是一种 混杂因素。因此，至关重要的是确定SSRI暴露后这些心室发现是否在 动物模型转化为人类，如果有非药物治疗的发现类似发现 用于母亲抑郁症。为了解决这些问题，儿科专家的合作团队 （新生儿血液动力学，心脏病学和心脏重症护理），精神病学将招募母亲 没有抑郁症，用SSRI或IPT及其后代治疗的母亲抑郁症。我们将 应用在新生儿和小儿验证的高级超声心动图技术 追求两个具体目的的人群：（1）衡量产妇抑郁及其的影响 出生后，1周和1岁的后代心室大小治疗； （2） 量化母体抑郁及其治疗对后代心室功能的影响 出生，1周，1岁。因为心脏大小和心室功能很重要 预测许多成人和小儿疾病的结果，这项研究将提供重要答案 及时，高度相关的临床问题。