Procurement and Characterization of Postmortem Brain Tissue

National Institute Of Mental Health

Investigators

Linked publications & trials

Abstract

Currently, the Human Brain Collection Core (HBCC) has 1422 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 (165), non-psychiatric controls (351), severe psychotic disorders (including schizophrenia and schizoaffective disorder: 200), substance use disorders (141), major depressive disorder (292), unspecified depressive disorders (38), post-traumatic stress disorder (23), obsessive compulsive disorder (15), other psychiatric diagnoses (27), undetermined (72), Sars-cov2 infections at time of death (16), progressive multifocal leukoencephalopathy (4), various neurological disorders (30). In 26 cases, the diagnosis is still pending. From Oct 1, 2023, until July 18, 2024 we collected 48 brains through Northern and Central Virginia OCMEs. Additional resources include: -cDNA libraries constructed from hippocampus, anterior cingulate cortex (ACC) and subgenual anterior cingulate cortex (sgACC), and dura from hundreds of subjects with psychiatric disorders and controls -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. -The following datasets are available through our NDA collection (https://nda.nih.gov/edit_collection.html?id=3151) : -microarray expression and genotyping data from DLPFC, hippocampus and dura -qPCR data obtained from the DLPFC of 810 cases for several genes: HDAC1, HDAC2, OXT, OXTR, C1QL3, ADGRB3, MIR137HG_203, MIR137HG_202, C1QL2 -Whole genome sequencing (WGS), RNA sequencing, and Chip-sequencing (acetylation and methylation marks) data for DLPFC of 400 subjects, part of the CommonMind Consortium portal and PsychEncode resources http://resource.psychencode.org/) -Additional WGS datasets for more than 800 cases. -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. -DNA methylation data from cases with schizophrenia (dorso-lateral prefrontal cortex N=216), bipolar disorder (hippocampus, N=64), ADHD (caudate and dACC, N=30) and neurotypical controls. -single nucleus RNA-sequencing data of two brain regions (subgenual anterior cingulate and dorso-lateral prefrontal cortex) for eight neurotypical cases -RNA-seq from homogenate tissue from the dorsal Anterior cingulate cortex and the caudate for 30 cases with ADHD and 30 matched controls. - RNA-seq from homogenate tissue from the insula in 30 cases with MDD, 37 with bipolar disorder and 33 controls. -snRNA-seq from 6 younger and 6 older cases in four brain regions: entorhinal cortex, middle temporal gyrus, putamen and subventricular zone. We share our inventory of cases with the NIH Neurobiobank (NBB), making it accessible through their website (https://neurobiobank.nih.gov/). We use international classification of diseases (ICD10) codes for diagnostic classification. Since Oct 1 2023, we have responded to 55 requests, including 5 HBCC generated scientific projects, 25 from the Intramural Research Program (tissue, data or services), three letters of support for grant applications, and 22 external requests for tissue or data. We have distributed 1656 tissue samples this nine month period, including 821 to NIH and 835 to other institutions. We have also shared large genomic datasets (2270 cases) with intra- and extra-mural investigators. We test all donors for COVID-19 with a nasopharingeal swab of the cadaver and serology testing. We have identified 16 cases positive for active SARS-CoV2 infection, 133 cases with evidence of prior exposure to SARS-CoV2, and 32 cases with evidence of immunization but no prior exposure to the virus. Of the cases with recent infection, only one died of COVID19, the others were not symptomatic at the time of death. A list of tissue distributions in the last fiscal year follows: 1) Exploring host pathogen interactions in sites of active JCV infection. 2) Transcriptome of Chronic Pain and Disease 3) Alternative splicing and proteomics study of human post-mortem brains 4) Creating Cell Lines from Meninges 5) Brain network and cell-type elucidation of molecular dysregulations in bipolar disorder suicide 6) Validating striatal regional vulnerabilities in human disease 7) Insights into the pathophysiology of obsessive-compulsive disorder from single-cell analysis of the human brain 8) Distribution of HIV-infected cells in anatomic compartments 9) Anatomical and immunological characterization of the superior sagittal sinus 10) Investigating the Brain Lipidomic Signature through MALDI-TOF 11) Elucidating hormonally driven transcriptional responses in brain 12) Investigation of GABAA receptor proteomes in major depression human brain samples 13) Mapping sex- and cell type-specific molecular interactions in the anterior hippocampus in pubertal major depressive disorder via spatial transcriptomics 14) Single molecule genome-scale chromatin fiber profiling in frontal pole of schizophrenia, bipolar disorder and controls 15) Molecular and cellular characterization of the human brain across menopausal transition 16) Aging and Transcriptional Regulation in Bipolar-Disorder and Schizophrenia 17) Identification of the neural circuit in Major Depressive Disorder 18) Genetic, Epigenetic, and Transcriptomic Profiling with Long-Reads in Brains of Patients with Bipolar Disorder and Schizophrenia 19) Exploring cell-specific transcriptomic changes in the nucleus accumbens across adolescence using pseudo-longitudinal profiling. 20) Evaluating the role of glymphatic dysfunction in bipolar disorder 21) Molecular Mechanisms of APOE4 vulnerability to Alzheimer's disease and identification of novel therapeutic targets 22) Spatial transcriptomics of the amygdala 23) Pathological investigation of early Multiple sclerosis lesion underlying EBV infection 24) Cryo-ET based intracellular and cell-cell ultrastructural analysis of aS aggregation 25) Comparative RNAseq analysis of iPSC-derived cortical organoids to human cortical tissue 26) Molecular basis of choroid plexus-brain barrier in depressive and alcohol use disorders 27) Diffusion and sodium MRI used to probe ex vivo human brain macro-, meso-, and microstructure 28) Development of a PET radioligand for FLAP, a potential biomarker of inflammation 29) Isoform and Multi-Omic analysis of ADHD cases and controls 30) Characterizing the impacts of menopause stage, sex hormones, and sex chromosomes on brain aging and disease 31) High-Resolution MRI of the Brain Borders Publications generated from HBCC distributions in FY 2025: Vicario, R., et al. (2025). "A microglia clonal inflammatory disorder in Alzheimer's disease." Elife 13. Vicario, R., ….. F. Geissmann (2025). "Role of clonal inflammatory microglia in histiocytosis-associated neurodegeneration." Neuron 113(7): 1065–1081 e1013. Sapio, M. R., et al. (2025). "Efficient removal of naturally-occurring lipofuscin autofluorescence in human nervous tissue using high-intensity white light." The Journal of Pain 30: 105359. Fries, G. R., ….. et al. (2025). "Preliminary investigation of the association between epigenetic aging acceleration and amyloid biomarkers in bipolar disorder." The American Journal of Geriatric Psychiatry. Di Re, J., et al. (2025). "betaIV spectrin abundancy, cellular distribution and sensitivity to AKT/GSK3 regulation in schizophrenia." Mol Psychiatry 30(7): 3090–3102. Zhou, B., et al. (2024). "Detection and analysis of complex structural variation in human genomes across populations and in brains of donors with psychiatric disorders." Cell 187(23): 6687–6706 e6625. Wang, G. et al. (2024). "The TMEM132B-GABA(A) receptor complex controls alcohol actions in the brain." Cell 187(23): 6649–6668 e6635.