Procurement and Characterization of Postmortem Brain Tissue

目前，人类大脑收集核心(HBCC)资源包括患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)、精神分裂症和分裂情感障碍(186)、药物滥用(81)、严重抑郁障碍(256)、其他精神诊断(123)、神经障碍(52)、未诊断(63)。 数据库中的主题总数为1598个。从2018年10月1日到2019年7月31日，我们通过华盛顿特区和退伍军人管理局北部和中部验尸官办公室收集了61个大脑。 每次诊断的病例数： 2例ADHD 1例自闭症 1例双相情感障碍 1个控件 4重度抑郁障碍 2神经科 5物质使用障碍 1个未确定 44个待定 其他资源包括： -从数百名精神障碍患者和对照组的背侧前额叶皮质(DLPFC)、海马体、前扣带回皮质(ACC)和膝下前扣带回皮质(SgACC)以及硬脑膜构建的cDNA库 -来自DLPFC、海马体和硬脑膜的微阵列表达和基因分型数据(可在DBGaP Access ID：phs000979.v2.p2上公开获得) -放在载玻片上的冰冻切片(14微米厚)(来自32名精神分裂症患者和63名对照的DLPFC)， -福尔马林固定的单侧大脑半球冠状切片(约15毫米厚)，来自15名对照组，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。 -来源于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、核糖核酸测序和芯片测序(乙酰化和甲基化标记)数据(公开可在DBGaP Access ID：phs000979.v2.p2、CommonMind Consortium门户网站和心理编码资源页面：http://resource.psychencode.org/)获得 -来自膝下ACC的200人、来自上颞回的219人和来自背侧前扣带的311人的RNA测序数据将很快提供。 我们与神经生物库(NBB)共享信息。我们的病例清单可以通过神经生物库网站(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。我们实施了向ICD10代码的转换，使我们的诊断定义可以轻松地与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NBB和研究人员能够轻松地获得这些区域。 与去年同期相比，去年索取组织/数据的请求数量有所增加。自HBCC成立以来，我们已经向调查人员分发了180多个获批项目的样本和数据，其中大多数是在过去两年内。去年，我们回应了25项组织申请和6项关于拨款申请的支持函请求。 仍在进行或在过去一年已发起的组织分发请求如下： 1.利用SnRNA-seq技术定位帕金森病相关人脑组织基因表达 2.单核转录图谱以确定炎症对儿童早期小脑蠕虫的影响 3.7q11.23 CNV(Williams综合征和Dup7)患儿的染色质构象分析 4.来自人脑组织的单个神经元中与精神相关的结构变体在整个转录组中的影响。 5.自闭症谱系障碍患者的异常蛋白S-亚硝酸化 6.精神分裂症高炎症与低炎症患者免疫细胞浸润的识别和特征 7.人类口语脑回路的分子和细胞图谱 8.围产期选择性5-羟色胺再摄取抑制物(SSRI)暴露对神经发育和情绪行为的影响 9.阿片类药物使用者多巴胺D2和D1的表达 10.血液常规处理及血液临床标本DNA提取 11.炎症标志物的酶联免疫吸附试验研究进展 12.开发转运蛋白的PET放射性配体 13.探索严重精神疾病的非蛋白质编码转录本 14.抑郁症患者脑血管微损伤的调查 15.控制脑型疟疾病例的大脑 16.出生后和成人神经前体细胞单个核的RNA序列 17.精神分裂症和双相情感障碍患者疾病和脑区域特征的大规模基因表达分析 18.酒精依赖患者脑内甲基化的综合研究 19.自杀后5-羟色胺神经元中FKBP5的表达。 20.中脑多巴胺神经元群之间年龄相关的分子差异 21.破译非编码基因调控元件在人脑中的作用 22.多发性硬化症的突触损害 23.黑质、蓝斑和中缝背侧的单细胞特征 24.成人脑内未成熟神经元的定性和定量分析 25.开发一种食欲素受体的PET放射配基。

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.