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.

摘要 这项转化研究的广泛目标是确定母亲抑郁症治疗是否影响 心室发育通过全面的超声心动图测量后立即 出生和时间。医学治疗母亲抑郁症的决定是具有挑战性的， 仔细考虑风险与收益。选择性5-羟色胺再摄取抑制剂（SSRIs）是一种 目前，10-13%的孕妇服用这类抗抑郁药。人际 心理治疗（IPT）是一种替代性非药物治疗，已显示出对轻度至 严重的抑郁症母亲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， 环境可使个体易患心血管疾病。到目前为止，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 和斑马鱼，其中母亲抑郁症作为一个促成因素被消除。流行病学报告 如果SSRIs影响心脏发育，而母亲抑郁仍然是一个问题， 混杂因素因此，关键是要确定这些心室的结果后，SSRI暴露， 动物模型转化为人类，如果在非药物治疗中观察到类似的结果， 治疗母亲抑郁症为了解决这些问题，一个儿科专家合作小组 （新生儿血流动力学、心脏病学和心脏重症监护）和精神病学将招募母亲 没有抑郁症和母亲抑郁症治疗SSRIs或IPT和他们的后代。我们将 应用已在新生儿和儿童中验证的先进超声心动图技术 人口追求两个具体目标：（1）测量产妇抑郁症的影响， 出生后即刻、1周龄和1岁时对后代心室大小的处理;以及（2） 量化母亲抑郁及其治疗对子代心室功能的影响， 出生时、1周时和1岁时。因为心脏大小和心室功能很重要 许多成人和儿童疾病的预后预测因子，这项研究将提供重要的答案 一个及时的高度相关的临床问题