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: 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
• Journal: Human molecular genetics (Hum Mol Genet) Vol. 23 Issue 22 Pg. 5859-65 (Nov 15 2014) ISSN: 1460-2083 [Electronic] England
• PMID: 24934694 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected].

Chemical References

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

Topics

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