Development Psychopharmacology

描述(申请人提供)：围产期精神病学的最新研究 治疗几乎完全集中在抗抑郁药上。然而， 引入抗惊厥药物和非典型抗精神病药物，这些药物不会 阻碍排卵，为女性提供了新的治疗选择 双相情感障碍、精神分裂症和其他精神疾病。这个 这些疾病的表现通常发生在育龄期间； 然而，这些药物的临床生殖安全数据(以及 发展)是有限的，积累起来很慢。因此，有一个紧急情况 需要定义产科结局和功能性中枢神经系统暴露的数据 这些化合物。 目前的研究结合了自然的临床调查和详细的 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 包括抗惊厥药物和非典型抗精神病药物的预期文献 暴露，通过收集脐带评估胎盘通过 采乳采血、哺乳暴露及血清的护理 婴儿，以及在发生以下情况时通过收集羊水进行产前暴露 羊膜穿刺术。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难度，临床 这项研究与动物研究相辅相成，使用大鼠作为研究的模型 婴儿中枢神经系统暴露。给予固定剂量的非典型抗精神病药物或 对怀孕和新生的哺乳水坝都有抗惊厥作用， 后代对中枢神经系统的暴露将通过比较 母体大脑和血液中的浓度，以及子代大脑、血液和 其他纸巾。将通过以下方式评估中枢神经系统暴露的功能影响 体外5-羟色胺和多巴胺转运体及受体分析。 这项研究超越了以往研究的专属焦点 抗抑郁药包括非典型抗精神病药物和抗惊厥药物，以及 首次提供了婴儿中枢神经系统暴露的一瞥。这样的信息将是 与临床决策相关，因为精神病学家努力治疗严重的 围产期疾病，同时将婴儿接触降至最低。这些研究程序 将进一步适用于未来研究其他类别的研究 精神类药物。

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.