title: Brain-derived neurotrophic factor (BDNF)-epigenetic regulation in unipolar and bipolar affective disorder.
abstract: BACKGROUND
  Alterations of brain-derived neurotrophic factor (BDNF) DNA methylation at specific BDNF promoters and corresponding gene expressions are associated with pathology and the response to antidepressant (AD) therapy in affective disorders such as major depressive disorder (MDD) and bipolar disorder (BD).
  
  
  METHODS
  Genomic DNA was derived from peripheral blood mononuclear cells (PBMCs) and was bisulfite converted. Percentage of methylated reference (PMR) was calculated based on results from quantitative real-time PCR following the MethyLight protocol. For statistical analysis parametric procedures were performed as appropriate.
  
  
  RESULTS
  In this study 544 subjects were included, 207 MDD subjects, 59 BD subjects and 278 control subjects. The BDNF exon I promoter methylation resulted to be significantly increased in MDD subjects compared to BD subjects (p=0.0089) and control subjects (p<0.001). Furthermore, the increase of methylation in MDD subjects was significantly associated with AD therapy (p=0.0019) but not to the clinical features of depression such as the severity of symptoms (p=n.s.). None of the 12 investigated single nucleotide polymorphisms (SNP) showed significant genotype-methylation interactions.
  
  
  CONCLUSIONS
  Although based on previous findings, the DNA methylation was evaluated within only one CpG island of the different alternative BDNF gene transcripts.
  
  
  CONCLUSIONS
  The results suggest that the methylation status might not only be affected by the disease phenotype but might also be further influenced by pharmacological treatment, therefore harbouring the possibility of identifying new insights for treatment options.
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
authors.forename: Laura
authors.initials: L
authors.lastname: Carlberg
authors.affiliation: Clinical Institute of Pathology, Medical University of Vienna, Austria.
authors.forename: Janine
authors.initials: J
authors.lastname: Scheibelreiter
authors.affiliation: Clinical Institute of Pathology, Medical University of Vienna, Austria.
authors.forename: Melanie R
authors.initials: MR
authors.lastname: Hassler
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
authors.forename: Monika
authors.initials: M
authors.lastname: Schloegelhofer
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
authors.forename: Michaela
authors.initials: M
authors.lastname: Schmoeger
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
authors.forename: Birgit
authors.initials: B
authors.lastname: Ludwig
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
authors.forename: Siegfried
authors.initials: S
authors.lastname: Kasper
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
authors.forename: Harald
authors.initials: H
authors.lastname: Aschauer
authors.affiliation: Clinical Institute of Pathology, Medical University of Vienna, Austria.
authors.forename: Gerda
authors.initials: G
authors.lastname: Egger
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria; Zentrum für Seelische Gesundheit LEOpoldau, Vienna, Austria. Electronic address: alexandra.schosser@meduniwien.ac.at.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Schosser
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000235:genetics*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D018899:CpG Islands; D019175:DNA Methylation; D003865:Major Depressive Disorder / Q000235:genetics*; D044127:Epigenesis, Genetic; D005091:Exons; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic
chemical_list: D019208:Brain-Derived Neurotrophic Factor
keywords: Affective disorders; Antidepressant therapy; BDNF methylation; Depression; Epigenetics; Genetic association study