Development Psychopharmacology

描述（由申请人提供）：围产期精神病学的最新研究

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.