Neuropeptide precursor VGF is genetically associated with social anhedonia and underrepresented in the brain of major mental illness: its downregulation by DISC1

Adriana Ramos; Carmen Rodríguez-Seoane; Isaac Rosa; Svenja V Trossbach; Alfredo Ortega-Alonso; Liisa Tomppo; Jesper Ekelund; Juha Veijola; Marjo-Riitta Järvelin; Jana Alonso; Sonia Veiga; Akira Sawa; William Hennah; Angel García; Carsten Korth; Jesús R Requena

doi:10.1093/hmg/ddu303

Neuropeptide precursor VGF is genetically associated with social anhedonia and underrepresented in the brain of major mental illness: its downregulation by DISC1

Hum Mol Genet. 2014 Nov 15;23(22):5859-65. doi: 10.1093/hmg/ddu303. Epub 2014 Jun 16.

Authors

Adriana Ramos¹, Carmen Rodríguez-Seoane², Isaac Rosa³, Svenja V Trossbach⁴, Alfredo Ortega-Alonso⁵, Liisa Tomppo⁵, Jesper Ekelund⁶, Juha Veijola⁷, Marjo-Riitta Järvelin⁸, Jana Alonso⁹, Sonia Veiga², Akira Sawa¹⁰, William Hennah⁵, Angel García³, Carsten Korth⁴, Jesús R Requena¹¹

Affiliations

¹ CIMUS Biomedical Research Institute, University of Santiago de Compostela-IDIS, 15782 Santiago de Compostela, Spain, adriana.ramos@jhmi.edu jesus.requena@usc.es.
² CIMUS Biomedical Research Institute, University of Santiago de Compostela-IDIS, 15782 Santiago de Compostela, Spain.
³ 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.
⁴ Department of Neuropathology, Medical School Düsseldorf, 40225 Düsseldorf, Germany.
⁵ Institute for Molecular Medicine Finland (FIMM), University of Helsinki, 00290 Helsinki, Finland, National Institute for Health and Welfare, 00280 Helsinki, Finland.
⁶ National Institute for Health and Welfare, 00280 Helsinki, Finland, Department of Psychiatry, University of Helsinki, 00100 Helsinki, Finland, Vaasa Hospital District, 65130 Vaasa, Finland.
⁷ Department of Psychiatry, University of Oulu Central Hospital, 90014 Oulu, Finland.
⁸ 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.
⁹ Proteomics Unit, IDIS, Hospital Clínico Universitario, 15706 Santiago de Compostela, Spain.
¹⁰ Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA and.
¹¹ 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.

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Anhedonia
Brain / metabolism*
Cohort Studies
Down-Regulation*
Humans
Mental Disorders / genetics*
Mental Disorders / metabolism
Mental Disorders / psychology
Nerve Growth Factors / genetics*
Nerve Growth Factors / metabolism
Nerve Tissue Proteins / genetics
Nerve Tissue Proteins / metabolism*
Neurons / metabolism
Pedigree
Polymorphism, Single Nucleotide

Substances

DISC1 protein, human
Nerve Growth Factors
Nerve Tissue Proteins
VGF protein, human

Abstract

Publication types

MeSH terms

Substances

Grants and funding