Procurement and Characterization of Postmortem Brain Tissue

人类大脑收集核心（HBCC）的使命是深入了解精神障碍的原因和机制。为了能够进行这项研究，我们从有和没有精神疾病的死者身上获得了脑组织。研究结果将有助于我们更好地了解精神疾病中的脑功能障碍，并开发新的治疗方法和预防策略。 我们通过北方和中央弗吉尼亚州以及哥伦比亚特区的医学检查办公室（MEO）获得大脑。我们的工作人员被告知MEO可能的捐赠，我们联系死者的近亲，以获得捐赠整个大脑，血液样本，头皮和头发的小样本的同意。死者的近亲或家属无需支付任何费用。允许捐赠对家庭也没有直接好处。捐赠完全是自愿的。 我们通过从我们收到的任何材料中删除他/她的姓名和所有识别信息来保护死者的机密性，并仅用数字标记所有样本和从中获得的信息。我们的工作人员将亲属的同意录音，作为捐赠的正式记录，并与MEO安排收集组织。我们试图通过与家人的面谈和在获得近亲的书面授权后公布的医疗记录来获得有关死者的医疗和精神病史的进一步信息。我们将接受捐赠，即使近亲不希望回答后续问题。 我们不会向死者的亲属或家属提供任何个人研究结果，也不会对死者的死因发表任何评论。如果家属对死者有进一步的问题，请直接与MEO联系。 我们现在收集了来自1,003名受试者的脑组织。 从2014年8月20日起，我们通过DC和北方和中央VA医学检查办公室收集了74个大脑。本年内所收集的样本，按诊断分类如下： 焦虑症 1 双相情感障碍 4 非精神科对照 4 重度抑郁症 3 神经障碍 8 精神分裂 2 药物滥用 2 其他 6 在确诊过程中 44 我们的研究重点是阐明精神分裂症和情绪障碍的细胞和分子病理生理学。对精神疾病中遗传成分的进一步了解可能会提高诊断能力，并有望导致新的治疗方法。死后人脑研究受到标本质量和数量的限制。 通过与NIH和校外研究人员的合作，我们已经启动了以下分子和遗传学研究来解决这些问题： - 使用微阵列表达研究的数百名精神障碍患者的背外侧前额叶皮层、海马和硬脑膜中的全基因组表达模式。 - 在数百名精神障碍受试者和对照个体中使用背外侧前额叶和前扣带皮层的RNA和全基因组测序的基因表达模式和与遗传变异的关联。 - 使用染色质免疫沉淀（ChIP）和大规模并行DNA测序（Chipseq），对来自荧光激活细胞分选（FACS）神经元和非神经元群体的精神分裂症受试者和对照者的背外侧前额叶和前扣带皮层的顺式调节表观基因组作图。 - 使用具有高通量测序的转座酶可降解染色质测定（ATAC-seq），从分选的（FACS）神经元和非神经元细胞全面鉴定精神分裂症受试者和对照者的背外侧前额叶和前扣带皮层中的活性基因调控元件，ATAC-seq是一种用于全基因组绘制染色质可及性的方法。 - 使用Taqman测定法，改变背外侧前额叶皮质中的锥体细胞和星形胶质细胞群体中的miRNA表达（200名受试者，对照和精神分裂症患者）。 - 使用三叉神经节、血液、血管和硬脑膜组织通过RNA测序在偏头痛中绘制生物活性脂质和RNA表达。 - 通过RNA测序绘制自杀抑郁症和双相情感障碍受试者膝下前扣带皮层的基因表达图。

The mission of Human Brain Collection Core (HBCC) is to gain insight into the causes and mechanisms of mental disorders. To be able to conduct this research, we obtain brain tissues from deceased individuals with and without psychiatric disorders. The results will help us better understand brain dysfunction in mental disorders and develop new therapies and preventive strategies. We obtain brains through the Medical Examiners Offices (MEOs) of Northern and Central Virginia and the District of Columbia. Our personnel are notified of potential donations by MEOs and we contact the next-of-kin of the decedent to obtain consent for donation of the entire brain, blood samples, a small sample of scalp and hair. There is no cost to the next-of-kin or the decedent's family. There is also no direct benefit to the family for allowing the donation. The donation is strictly voluntary. We protect confidentiality of the decedent by removing his/her name and all identifying information from any materials we receive, and label all samples and the information derived from them only with a number. Our personnel audiotape the next-of-kin's consent as an official record of the donation, and make arrangements with the MEOs to collect the tissues. We try to obtain further information about the decedent's medical and psychiatric history through interviews with the family and released medical records, after obtaining written authorization from the next-of-kin. We will accept a donation even if the next-of-kin does not wish to answer follow-up questions. We do not provide any individual research results to the next-of-kin or the families or comments about the cause of death. The families are directed to contact the MEOs directly if they have further questions about the decedent. Our collection consists now of brain tissues from 1,003 subjects. From August 20, 2014, we collected 74 brains through the DC and Northern and Central VA Medical Examiners Offices. The breakdown by diagnosis for the tissues collected during this year is as follows: Anxiety disorder 1 Bipolar disorder 4 Non-psychiatric controls 4 Major Depressive Disorder 3 Neurological disorders 8 Schizophrenia 2 Substance abuse 2 Other 6 In the process of determining diagnosis 44 The major focus of our studies is elucidating the cellular and molecular pathophysiology of schizophrenia and mood disorders. Improved understanding of a genetic component in in mental illness may enhance diagnostic abilities and hopefully, lead to new treatments. Postmortem human brain studies are limited by the quality and quantity of the specimens. Through collaborations with NIH and extramural investigators, we have initiated the following molecular and genetic studies to address these questions: -Whole genome expression patterns in the dorsolateral prefrontal cortex, hippocampus and dura in several hundred individuals with mental disorders using microarray expression studies. -Gene expression patterns and associations with genetic variants using RNA and whole genome sequencing of dorsolateral prefrontal and anterior cingulate cortices in several hundred subjects with mental disorders and control individuals. -Cis regulatory epigenome mapping of the dorsolateral prefrontal and anterior cingulate cortices of subjects with schizophrenia and controls from the fluorescence-activated cell sorted (FACS) neuronal and non-neuronal populations using chromatin immunoprecipitation (ChIP) with massively parallel DNA sequencing (Chipseq). -Comprehensive identification of active gene regulatory elements in the dorsolateral prefrontal and anterior cingulate cortices of subjects with schizophrenia and controls from sorted (FACS) neuronal and non-neuronal cells using an Assay for Transposase-Accessible Chromatin with high throughput sequencing (ATAC-seq), a method for mapping chromatin accessibility genome-wide. -Alterations of miRNA expression in pyramidal and astrocyte cell populations in the dorsolateral prefrontal cortex (200 subjects, controls and schizophrenia) using Taqman assays. -Mapping bioactive lipids and RNA expression by RNA-sequencing in migraine headaches using trigeminal ganglia, blood, blood vessels and dura tissues. -Mapping gene expression by RNA-sequencing in the subgenual anterior cingulate cortex of subjects with depression who committed suicide and in bipolar disorder.