title: Neuropeptide precursor VGF is genetically associated with social anhedonia and underrepresented in the brain of major mental illness: its downregulation by DISC1.
abstract: In a large Scottish pedigree, disruption of the gene coding for DISC1 clearly segregates with major depression, schizophrenia and related mental conditions. Thus, study of DISC1 may provide a clue to understand the biology of major mental illness. A neuropeptide precursor VGF has potent antidepressant effects and has been reportedly associated with bipolar disorder. Here we show that DISC1 knockdown leads to a reduction of VGF, in neurons. VGF is also downregulated in the cortices from sporadic cases with major mental disease. A positive correlation of VGF single-nucleotide polymorphisms (SNPs) with social anhedonia was also observed. We now propose that VGF participates in a common pathophysiology of major mental disease.
authors.affiliation: CIMUS Biomedical Research Institute, University of Santiago de Compostela-IDIS, 15782 Santiago de Compostela, Spain, adriana.ramos@jhmi.edu jesus.requena@usc.es.
authors.forename: Adriana
authors.initials: A
authors.lastname: Ramos
authors.affiliation: CIMUS Biomedical Research Institute, University of Santiago de Compostela-IDIS, 15782 Santiago de Compostela, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Rodríguez-Seoane
authors.affiliation: CIMUS Biomedical Research Institute, University of Santiago de Compostela-IDIS, 15782 Santiago de Compostela, Spain, Department of Pharmacology, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain.
authors.forename: Isaac
authors.initials: I
authors.lastname: Rosa
authors.affiliation: Department of Neuropathology, Medical School Düsseldorf, 40225 Düsseldorf, Germany.
authors.forename: Svenja V
authors.initials: SV
authors.lastname: Trossbach
authors.affiliation: Institute for Molecular Medicine Finland (FIMM), University of Helsinki, 00290 Helsinki, Finland, National Institute for Health and Welfare, 00280 Helsinki, Finland.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Ortega-Alonso
authors.affiliation: Institute for Molecular Medicine Finland (FIMM), University of Helsinki, 00290 Helsinki, Finland, National Institute for Health and Welfare, 00280 Helsinki, Finland.
authors.forename: Liisa
authors.initials: L
authors.lastname: Tomppo
authors.affiliation: National Institute for Health and Welfare, 00280 Helsinki, Finland, Department of Psychiatry, University of Helsinki, 00100 Helsinki, Finland, Vaasa Hospital District, 65130 Vaasa, Finland.
authors.forename: Jesper
authors.initials: J
authors.lastname: Ekelund
authors.affiliation: Department of Psychiatry, University of Oulu Central Hospital, 90014 Oulu, Finland.
authors.forename: Juha
authors.initials: J
authors.lastname: Veijola
authors.affiliation: Department of Epidemiology and Biostatistics, MRC Health Protection Agency (HPA) Centre for Environment and Health, School of Public Health, Imperial College London, SW7 2AZ London, UK, Institute of Health Sciences and, Biocenter Oulu, University of Oulu, PO Box 5000, Aapistie 5A, FI-90014 Oulu, Finland, Unit of Primary Care, Oulu University Hospital, Kajaanintie 50, PO Box 20, FI-90220 Oulu 90029 OYS, Finland, Department of Children and Young People and Families, National Institute for Health and Welfare, Aapistie 1, Box 310, FI-90101 Oulu, Finland.
authors.forename: Marjo-Riitta
authors.initials: MR
authors.lastname: Järvelin
authors.affiliation: Proteomics Unit, IDIS, Hospital Clínico Universitario, 15706 Santiago de Compostela, Spain.
authors.forename: Jana
authors.initials: J
authors.lastname: Alonso
authors.affiliation: CIMUS Biomedical Research Institute, University of Santiago de Compostela-IDIS, 15782 Santiago de Compostela, Spain.
authors.forename: Sonia
authors.initials: S
authors.lastname: Veiga
authors.affiliation: Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA and.
authors.forename: Akira
authors.initials: A
authors.lastname: Sawa
authors.affiliation: Institute for Molecular Medicine Finland (FIMM), University of Helsinki, 00290 Helsinki, Finland, National Institute for Health and Welfare, 00280 Helsinki, Finland.
authors.forename: William
authors.initials: W
authors.lastname: Hennah
authors.affiliation: CIMUS Biomedical Research Institute, University of Santiago de Compostela-IDIS, 15782 Santiago de Compostela, Spain, Department of Pharmacology, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain.
authors.forename: Angel
authors.initials: A
authors.lastname: García
authors.affiliation: Department of Neuropathology, Medical School Düsseldorf, 40225 Düsseldorf, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Korth
authors.affiliation: CIMUS Biomedical Research Institute, University of Santiago de Compostela-IDIS, 15782 Santiago de Compostela, Spain, Department of Medicine, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain adriana.ramos@jhmi.edu jesus.requena@usc.es.
authors.forename: Jesús R
authors.initials: JR
authors.lastname: Requena
mesh_terms: D059445:Anhedonia; D001921:Brain / Q000378:metabolism*; D015331:Cohort Studies; D015536:Down-Regulation; D006801:Humans; D001523:Mental Disorders / Q000235:genetics* / Q000378:metabolism / Q000523:psychology; D009414:Nerve Growth Factors / Q000235:genetics* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide
chemical_list: C412476:DISC1 protein, human; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; C510637:VGF protein, human