title: Explore the Features of Brain-Derived Neurotrophic Factor in Mood Disorders.
abstract: OBJECTIVE
  Brain-derived neurotrophic factor (BDNF) plays important roles in neuronal survival and differentiation; however, the effects of BDNF on mood disorders remain unclear. We investigated BDNF from the perspective of various aspects of systems biology, including its molecular evolution, genomic studies, protein functions, and pathway analysis.
  
  
  METHODS
  We conducted analyses examining sequences, multiple alignments, phylogenetic trees and positive selection across 12 species and several human populations. We summarized the results of previous genomic and functional studies of pro-BDNF and mature-BDNF (m-BDNF) found in a literature review. We identified proteins that interact with BDNF and performed pathway-based analysis using large genome-wide association (GWA) datasets obtained for mood disorders.
  
  
  RESULTS
  BDNF is encoded by a highly conserved gene. The chordate BDNF genes exhibit an average of 75% identity with the human gene, while vertebrate orthologues are 85.9%-100% identical to human BDNF. No signs of recent positive selection were found. Associations between BDNF and mood disorders were not significant in most of the genomic studies (e.g., linkage, association, gene expression, GWA), while relationships between serum/plasma BDNF level and mood disorders were consistently reported. Pro-BDNF is important in the response to stress; the literature review suggests the necessity of studying both pro- and m-BDNF with regard to mood disorders. In addition to conventional pathway analysis, we further considered proteins that interact with BDNF (I-Genes) and identified several biological pathways involved with BDNF or I-Genes to be significantly associated with mood disorders.
  
  
  CONCLUSIONS
  Systematically examining the features and biological pathways of BDNF may provide opportunities to deepen our understanding of the mechanisms underlying mood disorders.
authors.affiliation: Department of Public Health & Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.
authors.forename: Fan-Chi
authors.initials: FC
authors.lastname: Yeh
authors.affiliation: Department of Public Health & Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.
authors.forename: Chung-Feng
authors.initials: CF
authors.lastname: Kao
authors.affiliation: Department of Public Health & Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan; Research Center for Genes, Environment and Human Health, National Taiwan University, Taipei, Taiwan.
authors.forename: Po-Hsiu
authors.initials: PH
authors.lastname: Kuo
mesh_terms: D000595:Amino Acid Sequence; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism*; D019295:Computational Biology; D019143:Evolution, Molecular; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D019964:Mood Disorders / Q000235:genetics* / Q000378:metabolism*; D010802:Phylogeny; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism; D012641:Selection, Genetic; D016415:Sequence Alignment; D015398:Signal Transduction
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D011498:Protein Precursors; C426674:brain-derived neurotrophic factor precursor