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 1281 brains available for distribution, with the following diagnoses (numbers of subjects listed in parentheses): attention deficit disorder (23); anxiety disorders (27); autism spectrum disorders (5); Bipolar disorder (156), Non-psychiatric controls (328), severe psychotic disorders (including schizophrenia and schizoaffective disorder: 189), substance use disorders (123), Major depressive disorder (276), post-traumatic stress disorder (13), obsessive compulsive disorder (13), Other psychiatric diagnoses (55), Undetermined (28). In 16 cases, the diagnosis is still pending. From Oct 1, 2021, until July 18, 2022 we collected 29 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 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 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 2021, we have responded to 39 requests, including 22 from the Intramural Research Program (tissue, data or services), 4 letters of support for grant applications, and 10 external requests for tissue or data. We have distributed 1409 tissue samples this 9 month period, including 402 to NIH and 1007 to other institutions. We now test all donors for COVID-19 with a cadaveric naso-pharingeal swab of the cadaver and serology testing. We have identified six cases positive for active SARS-CoV2 infection and 20 cases with evidence of prior exposure to SARS-CoV2, and 12 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. Develop a Novel Pipeline for High-throughput and High-depth Single Cell RNAseq of Human Dorsal Root Ganglia (DRG) and Trigeminal Ganglia (TG) Neurons 2. The association between microRNA, connectivity and myelin integrity in Schizophrenia 3. Severe COVID-19 is associated with molecular signatures of aging in the human brain 4. Discovery of Metabolome-Based Biomarkers in Psychotic Disorders 5. Uncovering the genetic mechanisms of the Chromosome 17q21.31 Tau haplotype on neurodegeneration risk in FTD and PSP 6. Characterization of spatial and single cell transcriptome of bipolar disorder versus control samples in the anterior insula and subgenual cingulate, a pilot study. 7. Deciphering the role of neuronal and peripheral DNA methylation in suicide and bipolar disorder 8. A new transmembrane protein Drinker controls GABA A receptor for alcohol sedation and addiction 9. A role for the medial pulvinar in schizophrenia 10. Single-nucleus multiome profiling of mediodorsal thalamus in psychiatric cases and controls 11. Characterization of gene expression and chromatin accessibility in the Entorhinal Cortex during clinicopathologically-defined normal neurological aging at the single cell level 12. Transfer of cases with Substance Abuse Disorders to Sepulveda 13. Investigation of cerebrovascular micro-damage in major depressive disorder 14. Omic Analysis of Dorsal Root Ganglia from Diabetic Patients with Chronic Pain 15. AVPR1A Circuits Regulating Social Isolation-Induced Anxiety 16. Understanding Gaucher Disease and the Role of Glucocerebrosidase in Synucleinopathies 17. Unraveling the role of GBA1-mutations in parkinsonism 18. Transcriptomic profiling of Attention Deficit Hyperactivity Disorder through single-cell genomics: a focus on glutamatergic neurons. 19. A 3D multimodal micron-scale human brain atlas bridging single cell data, neuropathology and neuroradiology 20. Transcriptional profiling of the suprachiasmatic nucleus in humans 21. Autopsy Studies in the NINDS Translational Neuroradiology Section 22. Cell-type Specific Distribution of Glycine Receptor Subunits in the Central Nervous System 23. Synaptojanin 2 binding protein (SYNJ2BP) analysis from Parkinsons disease patients and controls 24. Investigating Complex Neurodegenerative Disorders Related to Amyotrophic Lateral Sclerosis and Frontotemporal Dementia 25. Radiological-Histopathological Correlation in PML Brains 26. Neuropathology of COVID 27. Intersection of Lifetime Axis I and Axis III Comorbidities and Suicides in Gene Expression Studies 28. Whole genome sequencing with genotype verification