Currently, the HBCC resources include brains from individuals with the following diagnoses (numbers of subjects listed in parentheses): Bipolar disorder (161), Non-psychiatric controls (358), Schizophrenia and schizoaffective disorder (202), Substance Abuse (48), Major depressive disorder (228), Other psychiatric/neurological diagnoses 136, Not diagnosed (60). A total number of subjects 1154. From Oct 1, 2016, until July 31, 2017 we collected 64 brains through the DC and Northern and Central VA Medical Examiners Offices. 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 have undertaken an effort to combine and share as much information as possible between Neurobiobank (NBB) and HBCC resources. For this we obtained detailed quantitative electronic toxicological data from NMS on hundreds of our specimens and shared them with NBB. We are implementing a transition to DSM5/ICD10 codes that will make 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 46,000 biospecimens available). The number of requests for tissue/data in the last year has more than doubled compared to the same period last year. We are still processing and/or evaluating nine projects, while we have distributed tissue/data for 23 collaborative studies. Four requests were not fulfilled after discussions with the investigators. The projects/collaborations that we have accrued in the last year (some include multiple requests for different samples): 1. Examination of inhibitory microcircuits in 3D with CLARITY of postmortem schizophrenia. 2. Transcriptional and epigenetic signatures of human brain development and autism. 3. Molecular bio-signatures of axonal pathology in schizophrenia (measurement of proteins related to the axon initial segment). 4. 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) 5. Risk genetic variants and cis regulation of gene expression in bipolar disorder and schizophrenia (this is further work being done on the DLPFC samples distributed to the Common Mind Consortium). 6. Measurement of antibodies in human Herpes Virus in blood in subjects with and without migraine. 7. New roles for REST during brain maturation (FACS sorted nuclei in controls). 8. The function of miR-3162 in brain development and synaptic physiology (formalin fixed tissue). 9. PTSD and blast exposure (tissue from several brain regions for histological studies). 10. NMDA signaling in amygdala in schizophrenia (pulverized amygdala). 11. Allele-specific expression of vasopressin/orexin and GRIN2A receptors in hippocampus , including bioinformatics for detection of differential allelic expression over the whole genome based on HBCC DLPFC RNAseq data. 12. GABA and AMPA currents in schizophrenia vs controls (DLPFC blocks distributed). 13. Erbb4 isoforms in human brain (tissue blocks of anterior cingulate cortex/corpus callosum: manuscript in preparation (Erben, He et al. in preparation). 14. Sharing of DLPFC RNAseq data with CommonMindConsortium/Psychencode with all consortia users. 15. Rostromedial tegmental nucleus in humans (brainstem sections made available for confirmation of the existence of this nucleus in humans). 16. Transposable elements in psychiatric disorders (whole genome sequencing data made available) 17. Single cell expression analysis of human locus coerulus, dorsal raphe and substantia nigra (fresh dissections for nuclear extraction and single cell sequencing to confirm pattern of expression in animal models). 18. Characterization of human anterior insula postmortem genome expression in affective disorders using RNA-Sequencing (RNA distributed). 19. Single cell sequencing from frozen human tissue (establishing methodology for extraction and sorting of nuclei from frozen tissue for single cell sequencing). 20. Accelerated epigenetic aging and mitochondrial DNA copy number in bipolar disorder (DNA distributed). 21. qPCR validation of RNAseq findings from sgACC (validation of RNAseq results with independent method). 22. RNAseq in ADHD (caudate and medial prefrontal cortex distributed). 23. Molecular profiling of schizophrenia (extension of the Common Mind Consortium project). We continue to actively follow several projects initiated in previous years (for exhaustive list see the 2016 report). These are the ones that generated publication in the last year: 1. RNA sequencing data from DLPFC for 400 subjects were generated, together with whole genome sequencing and Chip-Seq on a subset of these subjects (Fromer, Roussos et al. 2016); posted on BioRxiv (Dobbyn, Huckins et al. 2017). 2. Glutamate receptors in in the DLPFC of individuals with major depression and controls (Funk, Mielnik et al. 2017). 3. Epigenetic study of cell-type specific, high-resolution DNA methylation profiling in the adult cerebral cortex (DLPFC and ACC); Biological Psychiatry (Kundakovic, Jiang et al. 2017); Nature Neuroscience (Girdhar, Hoffman et al. (submitted)). 4.Mapping gene expression by RNA-sequencing in the subgenual anterior cingulate cortex of subjects with depression, bipolar disorder, schizophrenia and controls (200 subjects); abstracts (Akula, Nathan et al. 2016, Akula, Kramer et al. 2017, Akula, Kramer et al. 2017) and a manuscript in preparation. 5. Mapping bioactive lipids and RNA expression by RNA-sequencing in migraine headaches using trigeminal ganglia, blood, blood vessels and dura tissues (100 subjects); (LaPaglia, Sapio et al. 2017). 6. Characterization of binding of a 5HT1a ligand for application in PET; (Shrestha, Liow et al. 2016) 7.Characterization of the role of p53 in astrocytes; (Turnquist, Horikawa et al. 2016).
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