Development Psychopharmacology

描述（由申请人提供）：围产期精神病的最新研究 治疗几乎完全集中在抗抑郁药上。但 采用抗惊厥药和非典型抗精神病药， 抑制排卵，为患有以下疾病的妇女提供了新的治疗选择： 躁郁症、精神分裂症和其他精神疾病。的 这些疾病的表现往往发生在育龄期; 然而，这些药物（以及 发展）是有限的，积累缓慢。因此，有一个紧迫的 需要定义产科结局和功能性CNS暴露的数据， 这些化合物。 目前的研究结合了自然主义的临床调查， 动物研究，提供新的产科结局数据和科学依据 比较不同药物对中枢神经系统的影响。临床研究 包括抗惊厥药和非典型抗精神病药的前瞻性文件 暴露，通过采集脐带评估胎盘通过 血液、通过采集母乳和哺乳期血清进行的哺乳期暴露 婴儿和产前接触通过收集羊水的情况下， 子宫穿刺术。每年将获得儿科记录，以监测儿童 发展里程碑 考虑到量化人脑暴露的困难， 研究补充了动物研究，使用大鼠作为研究模型， 婴儿CNS暴露。给予固定剂量的非典型抗精神病药，或 对妊娠和新分娩的母乳喂养母鼠都有抗惊厥作用， 将通过比较以下动物的药物水平来确定后代CNS暴露： 母体脑和血液中的浓度，以及后代脑、血液和 其他组织。CNS暴露的功能影响将通过以下方式进行评估： 离体血清素和多巴胺转运蛋白和受体分析。 这项研究超越了以往研究的唯一重点， 抗抑郁药，包括非典型抗精神病药和抗惊厥药，以及 提供了婴儿中枢神经系统暴露的第一个一瞥。此类信息将 与临床决策有关，因为精神科医生奋进治疗严重的 围产期疾病，同时尽量减少婴儿接触。这些研究程序 将进一步适用于未来的研究调查其他类 精神病药物。

DESCRIPTION (Provided by applicant): Recent studies of perinatal psychiatric treatment have focused almost exclusively upon antidepressants. However, the introduction of anticonvulsants and atypical antipsychotics, which do not impede ovulation, has provided new treatment alternatives for women with bipolar disorder, schizophrenia, and other psychiatric illnesses. The presentation of these disorders often occurs during the childbearing years; however, clinical reproductive safety data for these medications (and those in development) is limited and slow to accumulate. As such, there is an urgent need for data defining both obstetrical outcome and functional CNS exposure for these compounds. The current study combines a naturalistic clinical investigation with detailed animal studies to provide novel obstetrical outcome data and a scientific basis for comparing CNS effects of individual medications. The clinical study includes prospective documentation of anticonvulsant and atypical antipsychotic exposures, assessment of placental passage via collection of umbilical cord blood, lactational exposure via collection of breast milk and serum of nursing infants, and prenatal exposure via collection of amniotic fluid in the event of amniocentesis. Pediatric records will be obtained annually to monitor child developmental milestones. Considering the difficulty of quantifying human brain exposure, the clinical study is complemented with an animal study using the rat as a model to study infant CNS exposure. Administering a fixed dose of an atypical antipsychotic or anticonvulsant to both pregnant and newly delivered breast-feeding dams, offspring CNS exposure will be determined by comparing medication levels in maternal brain and blood with concentrations in offspring brain, blood, and other tissues. The functional impact of CNS exposure will be assessed by ex-vivo serotonin and dopamine transporter and receptor analysis. This study moves beyond the exclusive focus of previous studies upon antidepressants to include atypical antipsychotics and anticonvulsants, and provides the first glimpse into infant CNS exposure. Such information will be relevant to clinical decision-making as psychiatrists endeavor to treat severe peripartum illness while minimizing infant exposure. These study procedures will furthermore be applicable to future research investigating other classes of psychotropic medications.