Procurement and Characterization of Postmortem Brain Tissue

目前，人脑收集中心(HBCC)分发了1209名患有以下诊断的个人的大脑组织(括号中列出的受试者数量)：注意力缺陷障碍(20例)；焦虑症(23例)；躁郁症(155例)、非精神控制(323例)、精神分裂症和分裂情感障碍(193例)、药物滥用(105例)、严重抑郁症(265例)、其他精神诊断(71例)、未确定(19例)；诊断待定(35例)。19例神经退行性疾病已转至NINDS。 从2019年10月1日到2020年8月11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31个大脑。对这些疾病的诊断仍在等待中。 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 -微阵列表达和基因分型数据(可在NIMH数据档案馆公开获得)(nda：来自DLPFC、海马体和硬脑膜的https://nda.nih.gov/edit_collection.html?id=3151) -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(可在CommonMind联盟门户网站上的nda：https://nda.nih.gov/edit_collection.html?id=3151)，和心理编码资源页面上公开获得：http://resource.psychencode.org/) -在nda(https://nda.nih.gov/edit_collection.html?id=3151).上还可以获得来自膝下部acc、219个上回和311个背侧前扣带的rna测序数据。 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200多个获批项目的样本和数据，其中大多数是在过去3年里。在过去的一年里，我们已经回复了32个关于组织或数据的请求。其中，5个被拒绝或取消。HBCC就赠款申请提供了5封支持信。 仍在进行或在过去一年已发起的组织分发请求如下： 1.与精神疾病相关的多巴胺能回路的功能基因组资源和整合模型 2.破译神经元和外周DNA甲基化在自杀和双相情感障碍中的作用 3.关于CMC案件的WGS补充资料 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.脑内酒精代谢的RNAScope 6.麦古恩-奥尔布赖特综合征和路易体痴呆患者的脑组织和GNAS基因分析。 7.将物质使用障碍的病例从HBCC转移到NIH大脑和组织存储库--加利福尼亚州，NIH神经生物库。 8.出生后和成年人类神经前体细胞的单核RNA测序 9.人类星状病毒脑炎的转录组 10.小区类型特定eQTL分析(数据请求) 11.单核RNA-SEQ丘脑背侧内侧区解剖优化的初步研究 12.迈阿密大学生物库的大脑移植 13.分析长期接触大麻引起的细胞类型转录变化 14.加州大学洛杉矶分校罕见癫痫和脑疾病组织库 15.人类皮质解剖学中性别差异的空间定向单细胞转录特征 16.创伤性脑损伤和反复头部撞击在CTE和多发性神经退行性变发展中的作用 17.对三名在尸检中偶然发现艾滋病毒感染的患者的脑、硬脑膜、脑垂体部的艾滋病毒感染进行评估。 18.强啡肽/kappa阿片受体对前额叶皮质回路的调节 19.确定精神分裂症和双相情感障碍在前扣带回皮质的单细胞转录差异 20.跨主要精神障碍的亚膝状体前扣带回的RNA编辑的比较分析(数据要求) 21.孤独症和精神分裂症的单细胞空间转录和3D基因组特征 700个HBCC样品的WGS分析 22.厚壁组织清除和标记程序的发展 23.终生轴心I和轴心III在基因表达研究中的合并症和自杀(数据要求)。 24.利用单核细胞测序了解脑内载脂蛋白E生物学 25.胞外体mRNA在诊断中的应用 26.根据死亡时间和月份更新CMC队列的临床数据(数据请求)。 27.注意缺陷多动障碍的神经基因表达和甲基组分析 28.调节大脑基因表达的短串联重复序列(STR)基因分型小组的建立

Currently, the Human Brain Collection Core (HBCC) distributes tissues from brains of 1209 individuals with the following diagnoses (numbers of subjects listed in parentheses): Attention Deficit Disorder (20); Anxiety disorders (23); Bipolar disorder (155), Non-psychiatric controls (323), Schizophrenia and schizoaffective disorder (193), Substance Abuse (105), Major depressive disorder (265), Other psychiatric diagnoses (71), Undetermined (19); Diagnosis pending (35). 19 cases with neurological degenerative disorders have been transferred to NINDS. From Oct 1, 2019, until August 11th, 2020 we collected 31 brains through the DC and Northern and Central VA Medical Examiners Offices. The diagnoses for these are still 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 the NIMH data archive (NDA: https://nda.nih.gov/edit_collection.html?id=3151) 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 NDA: https://nda.nih.gov/edit_collection.html?id=3151), 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 are also available on NDA (https://nda.nih.gov/edit_collection.html?id=3151). 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 200 approved projects since the inception of the HBCC, most in the last 3 years. In the last year, we have responded to 32 requests for tissue or data. Of these, 5 were denied or cancelled. HBCC provided 5 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. Functional genomic resource and integrative model of dopaminergic circuitry associated with psychiatric disease 2. Deciphering the role of neuronal and peripheral DNA methylation in suicide and bipolar disorder 3. WGS supplement on CMC cases 4. Transcriptome-wide Effects of Psychiatrically-Relevant Structural Variants within Individual Neurons Derived from Human Brain Tissue. 5. RNAscope of alcohol metabolism in brain 6. Analysis of brain tissues and GNAS gene in the brain of a patient with McCune-Albright syndrome and Lewy body dementia. 7. Transfer of substance use disorders banked cases from HBCC to NIH Brain and Tissue Repository-California, the NIH Neurobiobank. 8. RNA sequencing of single nuclei from postnatal and adult human neural progenitors 9. Transcriptome of astrovirus encephalitis in humans 10. Analysis of cell type specific eQTLs (data request) 11. Pilot study for optimization of dissection of mediodorsal thalamus for single-nucleus RNA-seq 12. Brain transfer to University of Miami Biobank 13. Profiling cell-type transcriptional changes induced by chronic cannabis exposure 14. UCLA rare epilepsy and Brain Disease Tissue Bank 15. Spatially targeted single cell transcriptomic characterization of sex-differences in human cortical anatomy 16. The role of traumatic brain injury and repetitive head impacts in the development of CTE and multiple neurodegenerations 17. Evaluation of HIV infection in brain, dura, pituitary from three patients with incidentally discovered HIV infection at autopsy. 18. Dynorphin/kappa-opioid receptor regulation of prefrontal cortical circuitry 19. Identifying the differences in single-cell transcriptomes between schizophrenia and bipolar disorder in the anterior cingulate cortex 20. Comparative analysis of RNA editing in the subgenual anterior cingulate cortex across major psychiatric disorders (data request) 21. Single-cell spatial transcriptomic and 3D genomic characterization of autism and schizophrenia WGS on 700 HBCC samples 22. Development of thick tissue clearing and labeling procedures 23. Intersection of Lifetime Axis I and Axis III Comorbidities and Suicides in Gene Expression Studies (data request). 24. Utilizing Single-Nucleus Sequencing to Understand APOE Biology in the Brain 25. Diagnostic Use of Exosomal mRNA 26. Updating clinical data on the CMC cohort with time and month of death (data request). 27. Profiling neural gene expression and the methylome in attention deficit hyperactivity disorder 28. Development of a psychiatrically relevant genotyping panel of Short Tandem Repeats (STRs) that regulate gene expression in brain