Procurement and Characterization of Postmortem Brain Tissue

National Institute Of Mental Health

Investigators

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Abstract

Currently, the Human Brain Collection Core (HBCC) has 1238 brains available for distribution, with the following diagnoses (numbers of subjects listed in parentheses): attention deficit disorder (21); anxiety disorders (25); autism spectrum disorders (3); Bipolar disorder (156), Non-psychiatric controls (325), severe psychotic disorders (including schizophrenia and schizoaffective disorder: 188), substance use disorders (109), Major depressive disorder (270), post-traumatic stress disorder (13), obsessive compulsive disorder (12), Other psychiatric diagnoses (49), Undetermined (21). In 42 cases, the diagnosis is still pending. Three cases with neurological disorders will be transferred to other banks. From Oct 1, 2020, until August 5, 2021 we collected 40 brains through Northern and Central Virginias Medical Examiners Offices. 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 on hundreds of our specimens and share them with NBB. We use international classification of diseases (ICD10) codes for diagnostic definitions. In the last year, we have responded to 47 requests for tissue or data, including 18 from NIH, 8 letters of support for grant applications, and 21 requests from other institutions. We have distributed 2533 tissue samples this year, including 829 to NIH and 1704 to other institutions. We now characterize COVID-19 status in all cases received by a naso-pharingeal swab of the cadaver and serological testing. We have identified three cases positive for Sars-CoV2 with recent infection and four more with evidence of past infection. All were asymptomatic or pauci-symptomatic at the time of their death. Some of the tissue distribution requests that are still in progress or have been initiated in the last year are: 1. Single-nucleus differential gene expression in schizophrenia 2. Whole genome sequencing with Illumina technology of 809 HBCC cases 3. snRNA-seq and bulk RNA-seq profiling for carriers of high-risk structural and copy-number variants 4. Optimization of dissection of the mediodorsal thalamus, for genomics and histological characterization 5. Sex related differences in cell composition of the human cortex 6. Investigation of cerebrovascular micro-damage in major depressive disorder 7. Dynorphin/kappa-opioid receptor regulation of prefrontal cortical circuitry 8. RNA-seq and methylomics in Attention Deficit Disorder 9. Mapping gene expression in PD-relevant human brain regions 10. Mapping gene expression and cell populations during healthy aging 11. Neuropathology of COVID 12. Genetic characterization of neurodegenerative dementias 13. Long-read DNA sequencing of human brain tissue 14. Gene expression and protein analysis from spinal bulbar and muscular atrophy patients and controls 15. Post-Mortem Brain Anatomy of Chronic Pain and Fatiguing Disorders 16. Astrovirus encephalitis in immunocompromised humans 17. 3D genomic characterization of autism and schizophrenia 18. Integrated, cell type specific functional genomics analyses of regulatory sequence elements in neuropsychiatric brain tissues 19. Fine-Mapping Genome-Wide Associated Loci using Multi-omics Data to Identify Mechanisms Affecting Serious Mental Illness 20. RNA sequencing of single nuclei from postnatal and adult human neural progenitors 21. Molecular and cellular profiling of spoken-language brain circuits in humans 22. Maturation of psychiatric circuits 23. Identifying the differences in single-cell transcriptomes between schizophrenia and bipolar disorder in the anterior cingulate cortex 24. Mapping the role of long noncoding RNAs in gene regulatory networks in schizophrenia 25. Creating a resource of genetic variables for postmortem brains in the Human Brain Collection Core (HBCC) 26. Human Brain Plasticity Across the Life Span 27. Utilizing Single-Nucleus Sequencing to Understand APOE Biology in the Brain 28. Profiling cell-type transcriptional changes induced by chronic cannabis exposure 29. Characterization of postmortem brain and blood inflammatory transcriptomic overlaps in mood disorder 30. Unraveling the molecular mechanisms of myelination deficits in Schizophrenia 31. Diagnostic Use of Exosomal mRNA 32. Investigating Schizophrenia Brain Subtypes using PET Sphingosine-1-Phosphate Receptor-1 (S1PR1) Imaging 33. Association of SARS-CoV-2 infection and Alzheimer's-like neuropathology