Procurement and Characterization of Postmortem Brain Tissue

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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