Currently, the HBCC resources include brains from individuals with the following diagnoses (numbers of subjects listed in parentheses): Bipolar disorder (153), Non-psychiatric controls (307), Schizophrenia and schizoaffective disorder (202), Substance Abuse (59), Major depressive disorder (237), Other psychiatric/neurological diagnoses 136, Not diagnosed (79). A total number of subjects in the database is 1580. From Oct 1, 2017, until July 31, 2018 we collected 78 brains through the DC and Northern and Central VA Medical Examiners Offices. Number of cases Diagnosis 1 Anxiety Disorder 2 Bipolar Disorder 4 Control 2 Undetermined depressive disorder 5 Major depressive disorder 1 Neurological 1 Obsessive Compulsive Disorder 2 Other 48 pending 1 Post-traumatic stress disorder 10 Substance use disorder 1 Undetermined 1 was excluded due to sepsis 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 mental disorders and controls -microarray expression and genotyping data (publicly available at dbGAP accession ID: phs000979.v1.p1) 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 data for 400 subjects, to become publicly available soon -RNA sequencing data from 200 individuals from the subgenual ACC will become available probably in the next year. We share information with Neurobiobank (NBB) and HBCC resources. We obtain detailed quantitative electronic toxicological data from NMS on hundreds of our specimens and share them with NBB. We implemented a transition to DSM5/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 (work in progress as we have over 53,700 barcoded biospecimens available). 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 125 approved projects since the inception of the HBCC, most in the last 2 years. The projects/collaborations that are still in progress or have been initiated in the last year are: 1. Qualitative and quantitative analysis of immature neurons in adult human brain 2. Fluorescent in situ hybridization for marker genes in human thalamus 3. Na+ and K+ ATPases and endogenous cardiac steroids in bipolar disorder 4. Insulin production in the human brain. 5. Single nucleus RNA sequencing in the subgenual anterior cingulate and dorsolateral prefrontal cortex 6. Methylation of the dopamine transporter gene as a biomarker for dopamine transporter binding in normal volunteers and patients with ADHD (blood, pulverized tissue of caudate, DNA and RNA from substantia nigra) 7. Oxytocin receptor expression in the dorsolateral prefrontal cortex and hippocampus 8. Somatic mosaicism in microglia in neurodegenerative disorders and schizophrenia 9. Transposable elements in psychiatric disorders 10. Characterization of human anterior insula postmortem genome expression in affective disorders using RNA-Sequencing 11. Accelerated epigenetic aging and mitochondrial DNA copy number in bipolar disorder 12. RNA-seq in ADHD in caudate and medial prefrontal cortex 13. Radioligand development for oxytocin receptors. 14. Whole genome genotyping of individuals with serious mental illness. 15. Development of a psychiatrically relevant genotyping panel of Short Tandem Repeats (STRs) that regulate gene expression in brain. 16. The role of iron dysregulation in the orbito-frontal cortex of individuals with schizophrenia. 17. Pharmacochaperone activity of antipsychotics at D2-Dopamine receptors. 18. Transcriptome and epigenome mapping in dopamine neurons from individuals with schizophrenia and bipolar disorder. 19. The kynurenine pathway in the human subventricular zone. 20. Stratifying people with schizophrenia based on neuroinflammation. 21. Proteomics of postsynaptic density and synaptosomal preparations. 22. Expression of Ghrelin receptors in hippocampus of individuals with serious mental illness. 23. Physiology of mir137 host gene and schizophrenia. 24. GABA related transcripts: aging and genetics. 25. qPCR validation of RNAseq findings from sgACC. 26. Human brain transcriptome changes during aging in the dorsolateral prefrontal and posterior cingulate cortices. 27. RNA-seq of the superior temporal gyrus and dorsal anterior cingulate cortex in serious mental illness 28. Molecular profiling (single cell + ATAC-seq) of schizophrenia. Manuscripts published in the last year using HBCC resources: Erben L, He MX, Laeremans A, Park E, Buonanno A (2017). A Novel Ultrasensitive In Situ Hybridization Approach to Detect Short Sequences and Splice Variants with Cellular Resolution. Mol Neurobiol. 55(7):6169-6181 Hoffman GE, Hartley BJ, Flaherty E, Ladran I, Gochman P, Ruderfer DM, et al (2017). Transcriptional signatures of schizophrenia in hiPSC-derived NPCs and neurons are concordant with post-mortem adult brains. Nat Commun 8(1): 2225. LaPaglia DM, Sapio MR, Burbelo PD, Thierry-Mieg J, Thierry-Mieg D, Raithel SJ, et al (2017). RNA-Seq investigations of human post-mortem trigeminal ganglia. Cephalalgia: 333102417720216.
Showing the most recent 10 out of 50 publications
