Procurement and Characterization of Postmortem Brain Tissue

目前，人类大脑收集核心（HBCC）资源包括来自具有以下诊断的个人的大脑（括号中列出的受试者数量）：双相情感障碍（152），非精神对照（311），精神分裂症和情感性精神障碍（186），物质滥用（81），重度抑郁症（256），其他精神病诊断（123），神经系统疾病（52），未确诊（63） 数据库中的受试者总数为1598例。从2018年10月1日到2019年7月31日，我们通过DC和北方和中央VA医学检查办公室收集了61个大脑。 每种诊断的病例数： 2例ADHD 1自闭症 1例双相情感障碍 1控制 4重度抑郁症 2例神经系统疾病 5物质使用障碍 1个未确定 44个待决 其他资源包括： - 从来自数百名患有精神障碍的受试者和对照的背外侧前额叶皮层（DLPFC）、海马、前扣带皮层（ACC）和膝下前扣带皮层（sgACC）以及硬脑膜构建的cDNA文库 - 来自DLPFC、海马和硬脑膜的微阵列表达和基因分型数据（可在dbGAP登录ID：phs000979.v2.p2处公开获得） - 固定在载玻片上的冷冻切片（14 μ m厚）（来自32名精神分裂症患者和63名对照的DLPFC）， - 来自15名对照、10名精神分裂症患者、5名重度抑郁症患者、4名双相情感障碍患者的单个半球的福尔马林固定冠状切片（约15 mm厚）。 - 来自死后硬脑膜的成纤维细胞：450 -400名受试者的DLPFC的全基因组测序、RNA测序和芯片测序（乙酰化和甲基化标记）数据（可在dbGAP登录ID：phs000979.v2.p2、CommonMind Consortium门户网站和PsychEncode资源页面：http：//resource.psychencode.org/上公开获得） - 来自膝下前扣带回的200个个体、来自上级颞回的219个个体和来自背侧前扣带回的311个个体的RNA测序数据将很快可用。 我们与Neurobiobank（NBB）共享信息。我们的病例清单可以通过Neurobiobank网站（https：//neurobiobank.nih.gov/）进行搜索。我们从NMS获得了数百个样本的详细定量电子毒理学数据，并与NBB分享。我们实现了向ICD 10代码的过渡，使我们的诊断定义可以轻松与NBB共享。我们已经统一了HBCC中可用的大脑区域/标本的命名和报告，目的是使这些领域易于NBB和研究人员使用。 与去年同期相比，去年要求提供组织/数据的数量有所增加。自HBCC成立以来，我们已向研究人员分发了180多个批准项目的样本和数据，其中大部分是在过去两年中。在过去的一年里，我们已经回应了25个组织和6个请求支持赠款申请的信件请求。 仍在进行中或去年已启动的组织分发请求为： 1. 利用snRNA-seq技术定位帕金森病相关脑区的基因表达 2. 单核转录组学分析确定炎症对儿童早期小脑蚓部的影响 3. 7 q11.23 CNVs儿童（威廉姆斯综合征和Dup 7）的染色质构象分析 4. 来自人脑组织的单个神经元内精神病学相关结构变异的转录组范围效应。 5. 自闭症谱系障碍中蛋白质S-亚硝基化的异常 6. 精神分裂症高炎症与低炎症病例中免疫细胞浸润的识别和表征 7. 人类口语脑回路的分子和细胞分析 8. 围产期暴露于选择性5-羟色胺再摄取抑制剂（SSRI）对神经发育和情绪行为的影响。 9. 阿片类药物依赖者多巴胺D2和D1的表达 10. 血液常规处理和血液临床样本DNA提取 11. 炎症标志物的ELISA开发 12. 转运蛋白PET放射性配体的研制 13. 重性精神疾病非蛋白质编码转录本的研究 14. 抑郁症患者脑血管微损害的研究 15. 控制脑型疟疾病例的大脑 16. 来自出生后和成年人神经祖细胞的单个核的RNA seq 17. 精神分裂症和双相情感障碍疾病和脑区特征的大规模基因表达分析 18. 酒依赖患者脑内甲基化的综合研究 19. FKBP 5在自杀中5-羟色胺神经元中的表达。 20. 中脑多巴胺神经元群之间的突触相关分子差异 21. 人类大脑中非编码基因调控元件的作用 22. 多发性硬化的突触损伤 23. 黑质、蓝斑和中缝背核的单细胞特征 24. 成人脑内未成熟神经元的定性定量分析 25. 开发食欲素受体的PET放射性配体。

Currently, the Human Brain Collection Core (HBCC) resources include brains from individuals with the following diagnoses (numbers of subjects listed in parentheses): Bipolar disorder (152), Non-psychiatric controls (311), Schizophrenia and schizoaffective disorder (186), Substance Abuse (81), Major depressive disorder (256), Other psychiatric diagnoses (123), Neurological disorders (52), Not diagnosed (63). The total number of subjects in the database is 1598. From Oct 1, 2018, until July 31, 2019 we collected 61 brains through the DC and Northern and Central VA Medical Examiners Offices. Number of cases per diagnosis: 2 ADHD 1 Autism 1 Bipolar Disorder 1 Control 4 Major depressive disorder 2 Neurological 5 Substance use disorder 1 Undetermined 44 pending Other resources include: -cDNA libraries constructed from dorsolateral prefrontal cortex (DLPFC), hippocampus, anterior cingulate cortex (ACC) and subgenual anterior cingulate cortex (sgACC), and dura from hundreds of subjects with psychiatric disorders and controls -microarray expression and genotyping data (publicly available at dbGAP accession ID: phs000979.v2.p2) from DLPFC, hippocampus and dura -frozen sections (14 um thick) mounted on slides (DLPFC from 32 patients with schizophrenia and 63 controls), -formalin-fixed coronal slices (approximately 15 mm thick) of a single hemisphere from 15 controls, 10 patients with schizophrenia, 5 with major depression, 4 with bipolar disorder. -Fibroblasts derived from postmortem dura: 450 -Whole genome sequencing, RNA sequencing, and Chip-sequencing (acetylation and methylation marks) data for DLPFC of 400 subjects (publicly available at dbGAP accession ID: phs000979.v2.p2, on the CommonMind Consortium portal and on the PsychEncode resource page: http://resource.psychencode.org/) -RNA sequencing data from 200 individuals from the subgenual ACC, 219 from the Superior Temporal Gyrus and 311 from the dorsal anterior cingulate will become available soon. We share information with Neurobiobank (NBB). Our inventory of cases can be searched through the Neurobiobank website (https://neurobiobank.nih.gov/). We obtain detailed quantitative electronic toxicological data from NMS on hundreds of our specimens and share them with NBB. We implemented a transition to ICD10 codes that makes our diagnostic definitions easily sharable with NBB. We have unified the naming and reporting of brain regions/specimens available in HBCC with the goal of making these fields easily available to NBB and investigators. The number of requests for tissue/data in the last year increased compared to the same period last year. We have distributed samples and data to investigators for more than 180 approved projects since the inception of the HBCC, most in the last 2 years. In the last year, we have responded to 25 requests for tissue and 6 requests for letters of support on grant applications. The tissue distribution requests that are still in progress or have been initiated in the last year are: 1. Mapping gene expression in Parkinsons Disease (PD)-relevant human brain regions by snRNA-seq 2. Single-Nuclei Transcriptomic Profiling to Determine the Impact of Inflammation on the Cerebellar Vermis During Early Childhood 3. Chromatin conformation analysis of Children with 7q11.23 CNVs (Williams Syndrome and Dup7) 4. Transcriptome-wide Effects of Psychiatrically-Relevant Structural Variants within Individual Neurons Derived from Human Brain Tissue. 5. Aberrant protein S-nitrosylation in autism spectrum disorders 6. Identifying and characterizing immune cell infiltration in high inflammation versus low inflammation cases of schizophrenia 7. Molecular and cellular profiling of spoken-language brain circuits in humans 8. The effects of perinatal selective serotonin reuptake inhibitor (SSRI) exposure on neurodevelopment and emotional behavior. 9. Dopamine D2 and D1 expression in opiate users 10. Routine Processing of Blood and DNA extraction from blood clinical samples 11. Elisa Development for Inflammatory Markers 12. Developing PET Radioligands for Translocator Protein 13. Exploring the non-protein coding transcripts in serious mental illness 14. Investigation of cerebrovascular micro-damage in major depressive disorder 15. Control brains for cerebral malaria cases 16. RNA seq of single nuclei from postnatal and adult human neural progenitor cells 17. Large-scale gene expression analysis of disease and brain region signatures in schizophrenia and bipolar disorder 18. A Comprehensive Study of Brain Methylation in Alcohol Dependent Patients 19. FKBP5 expression in serotonin neurons in suicide. 20. Age-associated molecular differences between midbrain dopamine neuron groups 21. Deciphering the role of non-coding gene regulatory elements in human brain 22. Synaptic damage in multiple sclerosis 23. Single cell characterization of nigra, ceruleus and dorsal raphe 24. Qualitative and quantitative analysis on immature neurons in the adult human brain 25. Developing a PET radioligand for the orexin receptors.