Procurement and Characterization of Postmortem Brain Tissue

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Currently, the Human Brain Collection Core (HBCC) resources include brains from individuals with the following diagnoses (numbers of subjects listed in parentheses): Bipolar disorder (152), Non-psychiatric controls (311), Schizophrenia and schizoaffective disorder (186), Substance Abuse (81), Major depressive disorder (256), Other psychiatric diagnoses (123), Neurological disorders (52), Not diagnosed (63). The total number of subjects in the database is 1598. From Oct 1, 2018, until July 31, 2019 we collected 61 brains through the DC and Northern and Central VA Medical Examiners Offices. Number of cases per diagnosis: 2 ADHD 1 Autism 1 Bipolar Disorder 1 Control 4 Major depressive disorder 2 Neurological 5 Substance use disorder 1 Undetermined 44 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 dbGAP accession ID: phs000979.v2.p2) 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 dbGAP accession ID: phs000979.v2.p2, 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 will become available soon. 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 180 approved projects since the inception of the HBCC, most in the last 2 years. In the last year, we have responded to 25 requests for tissue and 6 requests for 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. Mapping gene expression in Parkinsons Disease (PD)-relevant human brain regions by snRNA-seq 2. Single-Nuclei Transcriptomic Profiling to Determine the Impact of Inflammation on the Cerebellar Vermis During Early Childhood 3. Chromatin conformation analysis of Children with 7q11.23 CNVs (Williams Syndrome and Dup7) 4. Transcriptome-wide Effects of Psychiatrically-Relevant Structural Variants within Individual Neurons Derived from Human Brain Tissue. 5. Aberrant protein S-nitrosylation in autism spectrum disorders 6. Identifying and characterizing immune cell infiltration in high inflammation versus low inflammation cases of schizophrenia 7. Molecular and cellular profiling of spoken-language brain circuits in humans 8. The effects of perinatal selective serotonin reuptake inhibitor (SSRI) exposure on neurodevelopment and emotional behavior. 9. Dopamine D2 and D1 expression in opiate users 10. Routine Processing of Blood and DNA extraction from blood clinical samples 11. Elisa Development for Inflammatory Markers 12. Developing PET Radioligands for Translocator Protein 13. Exploring the non-protein coding transcripts in serious mental illness 14. Investigation of cerebrovascular micro-damage in major depressive disorder 15. Control brains for cerebral malaria cases 16. RNA seq of single nuclei from postnatal and adult human neural progenitor cells 17. Large-scale gene expression analysis of disease and brain region signatures in schizophrenia and bipolar disorder 18. A Comprehensive Study of Brain Methylation in Alcohol Dependent Patients 19. FKBP5 expression in serotonin neurons in suicide. 20. Age-associated molecular differences between midbrain dopamine neuron groups 21. Deciphering the role of non-coding gene regulatory elements in human brain 22. Synaptic damage in multiple sclerosis 23. Single cell characterization of nigra, ceruleus and dorsal raphe 24. Qualitative and quantitative analysis on immature neurons in the adult human brain 25. Developing a PET radioligand for the orexin receptors.