THE MEDIODORSAL THALAMIC NUCLEUS IN SCHIZOPHRENIA

描述：(摘自申请者的摘要)精神分裂症是一种常见的， 毁灭性的疾病，最常导致终生残疾。尽管 该病的细胞和分子病理生理学研究进展 仍然不为人知。在这个辅导式职业发展奖中，候选人将 检验丘脑内侧背侧投射神经元的一般假设 精神分裂症患者核团(MDTN)异常，这种异常是 与MDTN基因表达模式的改变有关。 最近的尸检研究报告说，MDTN的体积较小， 精神分裂症受试者的神经元和神经胶质细胞比 正常受试者。这些研究的结果提出了以下几点 将在拟议的研究中解决的问题：1)减少 精神分裂症常见的MDTN的神经元数量和体积，以及 对疾病的诊断特异性？2)哪些神经元亚群是 受影响的局部回路神经元或投射到前额叶的神经元 皮质？3)MDTN基因表达的变化与什么相关，以及 这些异常的潜在原因？4)这些发现是 这种疾病的病理生理学或它们是慢性治疗的结果 抗精神病药物？ 在调查这些问题时，这位儿童精神病学家候选人将 根据学习计划在1)严格的行为中培养技能 人类尸检研究，2)体视学技术， 免疫组织化学和原位杂交，以及3)分析 精神疾病中组织特异性基因表达的模式。最后，他 将学习如何使用非人类灵长类动物的临床现象模型 了解人类疾病和治疗方法。要获得这些技能，请访问 匹兹堡大学，由大卫·A·刘易斯教授和大卫·A·刘易斯教授指导 帕特·R·莱维特，将使候选人能够开始调查 首发精神障碍的发育病理生理学 在童年和青春期。

DESCRIPTION: (Adapted from applicant's abstract) Schizophrenia is a common, devastating illness, which most often leads to life long disability. Despite recent advances, the cellular and molecular pathophysiology of this illness remains unknown. In this mentored career development award, the candidate will test the general hypothesis that projection neurons in the mediodorsal thalamic nucleus (MDTN) are abnormal in schizophrenia, and that this abnormality is associated with alterations in the pattern of gene expression in the MDTN. Recent postmortem studies have reported that the MDTN is smaller in size and has fewer neurons and glial cells in subjects with schizophrenia compared to normal subjects. The results of these studies have raised the following questions that will be addressed in the proposed studies: 1) Is a decrease in neuronal number and volume of the MDTN common in schizophrenia, and is it diagnostically specific to the illness? 2) Which neuronal subpopulations are affected- local circuit neurons or neurons that project to the prefrontal cortex? 3) What alterations in MDTN gene expression are associated with, and potentially causal to these abnormalities? 4) Are these findings part of the pathophysiology of the illness or are they the result of chronic treatment with antipsychotic medications? While investigating these questions, the candidate, a child psychiatrist, will under take a program of study to develop skills in 1) the conduct of rigorous human postmortem studies, 2) the techniques of stereology, immunohistochemistry, and in situ hybridization, and 3) the analysis of patterns of tissue specific gene expression in psychiatric disease. Finally, he will learn how to use a nonhuman primate model of clinical phenomena to understand human disease and treatment. Acquiring these skills at the University of Pittsburgh, under the mentorship of Professors David A. Lewis and Pat R. Levitt, will enable the candidate to launch a career investigating the developmental pathophysiology of psychiatric disorders which have their onset in childhood and adolescence.