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 1307 brains available for distribution, with the following diagnoses (numbers of subjects listed in parentheses): attention deficit disorder (24); anxiety disorders (27); autism spectrum disorders (5); Bipolar disorder (156), Non-psychiatric controls (339), severe psychotic disorders (including schizophrenia and schizoaffective disorder: 193), substance use disorders (129), Major depressive disorder (281), post-traumatic stress disorder (15), obsessive compulsive disorder (15), Other psychiatric diagnoses (68), Undetermined (32), COVID-19 infections at time of death (6), progressive multifocal leukoencephalopathy (2), various neurological disorders (15). In 19 cases, the diagnosis is still pending. From Oct 1, 2022, until July 18, 2023 we collected 28 brains through Northern and Central Virginia OCMEs. Additional 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 16 patients with schizophrenia and 34 controls remaining), -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: 48 individuals. -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). DNA methylation data from cases with schizophrenia (dorso-lateral prefrontal cortex N=216), bipolar disorder (hippocampus, N=64) and neurotypical controls have been added to the collection in the last year, together with single nucleus RNA-sequencing data of two brain regions (subgenual anterior cingulate and dorso-lateral prefrontal cortex) for eight neurotypical cases . We share information with Neurobiobank (NBB). Our inventory of cases is accessible 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 classification. Since Oct 1 2022, we have responded to 41 requests, including 18 from the Intramural Research Program (tissue, data or services), 6 letters of support for grant applications, and 17 external requests for tissue or data. We have distributed 1170 tissue samples this 9 month period, including 974 to NIH and 196 to other institutions. We have also shared large genomic datasets. We test all donors for COVID-19 with a nasopharingeal swab of the cadaver and serology testing. We have identified six cases positive for active SARS-CoV2 infection and 51 cases with evidence of prior exposure to SARS-CoV2, and 18 cases with evidence of immunization but no prior exposure to the virus. All donors were not known to be symptomatic at the time of death. Our list of active tissue and data requests includes: 1. Characterizing long-read RNA transcriptomes from post-mortem brains of patients with schizophrenia 2. Comprehensive characterization of 1,198 deep whole genomes from the Human Brain Collection Core for genetic and functional studies of suicidal behavior 3. Muscle-brain crosstalk in anxiety disorders: A new avenue for developing effective treatments 4. Postmortem identification of the reproductive/menopausal status in women and other individuals with ovaries 5. Cell type specific single chromatin fiber profiling on a genome-wide scale in frontal cortex of bipolar, schizophrenia and control subjects 6. Multi-Omics of 17q21.31 Haplotypes in brain tissues 7. Characterizing human blood-brain barrier dysfunction during alcohol dependence 8. Investigating the role of hormonal surges during puberty on cell-specific gene transcription and the potential influence on sex-skewed prevalences in major depression 9. Synaptic density in Schizophrenia 10. Fentanyl-induced neurodegeneration in the CA3 region of the hippocampus 11. Single-Cell Transcriptomic Analysis of the PFC and ACC in ADHD patients 12. Effect of diabetes on Biondi body amyloid formation in the choroid plexus 13. Association of SARS-CoV-2 infection and Alzheimers-like neuropathology 14. The regulation of m6A on hypothalamus development and function of energy balance 15. Single-nucleus transcriptomes in the habenula in Major Depressive Disorder 16. Validation of Diffusion Basis Spectrum Imaging of Neuroinflammation in Schizophrenia 17. Spatial transcriptomics (Visium) pilot on the amygdala 18. Multi-omics of the ADHD brain 19. Unraveling the role of GBA1-mutations in parkinsonism 20. Single Nuclei Atlas of the Human Substantia Nigra 21. Single Nuclei Atlas of the Human Prefrontal Cortex 22. Cell-type specific distribution of ALDH2 in human choroid plexus 23. Cell - cell interaction in Multiple sclerosis based on single nucleus RNAseq (snRNAseq) 24. A role for the medial pulvinar in schizophrenia 25. Optimization of spatial transcriptomics profiling of human mediodorsal thalamus 26. Biological sex effects on the human brain transcriptome and metabolome 27. Exploring host pathogen interactions in JC virus infection and PML progression using Visiums FFPE spatial transcriptomics assay. 28. Mapping brain iron variation across cortical surface and subcortical regions with T2-based ultra-high-field 7T magnetic resonance imaging 29. Tubulin polymerization promoting protein (TPPP) aggregation in schizophrenia 30. The relationship between sleep and claustrum. 31. HERV-K Neuropathogenesis in ALS