Postmortem Human Brain Collection (Supplement to MH67996)

描述(申请人提供)：应NIMH(神经科学和基础行为科学部，Douglas Meinecke博士)的要求，本补充申请对应于03年和04年资助的“严重抑郁症中的海马体萎缩(RO1 MH 67996；PI：C.斯托克迈尔)”。继续和扩大组织收集的补充支持请求是作为RO1 63187(06/01/02-11/30/05)的一部分授予Gregory Ordway博士的补充死后脑收集资金(NOT-MH-01-010)的延伸，以及在此之前向PI提供11年的NIMH收集资金。神经影像和尸检脑研究为重度抑郁障碍(MDD)的海马区病理提供了证据。据推测，海马神经纤维层的减少是MDD海马区组织病理学的微观基础。为了实现父母代号为1(MH 67996)的特定目标，要求提供补充资金，用于1)在尸检时收集人脑组织，2)从近亲和医疗记录中获得足够的临床信息，以便对需求侧管理-IV精神障碍进行回顾评估。在知情书面同意的情况下，从在生命的最后两周内患有严重抑郁发作的受试者和年龄、性别、死后间隔和组织pH值匹配的精神正常对照组受试者身上寻找脑组织。这些抑郁的受试者在死亡时不会接受抗抑郁药或抗精神病药物的治疗，所有受试者的神经学和神经病理必须是正常的。患有MDD的受试者目前必须没有酒精或精神活性物质使用障碍的共病Axis I诊断。MDD的存在或不存在是由共识诊断确定的，该诊断基于从所有DSM IV精神障碍结构化临床访谈(SCID)的所有受试者的近亲收集的医疗记录和数据。按照目前的收集速度，在未来两年内，每年收集6-8名MDD患者和大约10名正常对照患者将能够实现所资助的具体目标。目前美国国立卫生研究院向C.斯托克迈尔博士、G.奥德韦博士、G.Rajkowska博士、R.Duman博士、B.Karolewicz博士和M.Austin博士提供的资金完全依赖于这一脑组织补充材料，以更好地了解主要精神疾病的细胞和分子病理生理学。

DESCRIPTION (provided by applicant): At the request of NIMH (Division of Neuroscience and Basic Behavioral Science, Dr. Douglas Meinecke), this Supplemental application corresponds to Funded Years 03 and 04 of "Hippocampal Atrophy in Major Depression (RO1 MH 67996; PI: C. Stockmeier). The request for Supplemental support to continue and expand tissue collection is an extension of Supplemental Postmortem Brain Collection funding (NOT-MH-01- 010) awarded to Dr. Gregory Ordway as part of RO1 63187 (06/01/02 -11/30/05), and 11 years of NIMH funding for collection to the PI prior to that. Neuroimaging and postmortem brain studies provide evidence for hippocampal pathology in major depressive disorder (MDD). It is hypothesized that a decrease in hippocampal neuropil, in response to diminished markers of neural growth and synaptic connection, resulting in an increase in neuronal and glial density, is the microscopic basis for the histopathology of the hippocampus in MDD. To meet the Specific Aims of the parent RO1 (MH 67996), supplemental funds are requested for the collection of 1) human brain tissue at autopsy and 2) sufficient clinical information from next-of-kin and medical records for retrospective assessment of DSM-IV psychiatric disorders. With informed written consent, brain tissue is sought from subjects suffering a major depressive episode in the last two weeks of life and psychiatrically-normal control subjects matched for age, gender, postmortem interval arid tissue pH. These depressed subjects will not be receiving antidepressant or antipsychotic treatment at the time of death and all subjects must be neurologically and neuropathologically normal. Subjects with MDD must have no current co-morbid Axis I diagnosis of an alcohol or psychoactive substance use disorder. The presence or absence of MDD is determined by consensus diagnosis based on medical records and data gathered from next-of-kin of all subjects with the Structured Clinical Interview for DSM IV Psychiatric Disorders (SCID). At current collection rates, the collection of 6-8 subjects with MDD and about 10 normal control subjects per year for the next two years will permit achievement of the funded specific aims. Current NIH funding to Drs.C. Stockmeier, G. Ordway, G. Rajkowska, R. Duman, B. Karolewicz and M. Austin depends solely on this Supplement for brain tissue to better understanding of the cellular and molecular pathophysiology of the major mental illnesses.