PMID- 25106037 OWN - NLM STAT- MEDLINE DCOM- 20150528 LR - 20181202 IS - 1573-2517 (Electronic) IS - 0165-0327 (Linking) VI - 168 DP - 2014 Oct TI - Brain-derived neurotrophic factor (BDNF)-epigenetic regulation in unipolar and bipolar affective disorder. PG - 399-406 LID - S0165-0327(14)00453-4 [pii] LID - 10.1016/j.jad.2014.07.022 [doi] AB - 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. LIMITATIONS: 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. CI - Copyright (c) 2014. Published by Elsevier B.V. FAU - Carlberg, Laura AU - Carlberg L AD - Department of Psychiatry and Psychotherapy, Medical University of Vienna, Wahringer Gurtel 18-20, 1090 Vienna, Austria. FAU - Scheibelreiter, Janine AU - Scheibelreiter J AD - Clinical Institute of Pathology, Medical University of Vienna, Austria. FAU - Hassler, Melanie R AU - Hassler MR AD - Clinical Institute of Pathology, Medical University of Vienna, Austria. FAU - Schloegelhofer, Monika AU - Schloegelhofer M AD - Department of Psychiatry and Psychotherapy, Medical University of Vienna, Wahringer Gurtel 18-20, 1090 Vienna, Austria. FAU - Schmoeger, Michaela AU - Schmoeger M AD - Department of Psychiatry and Psychotherapy, Medical University of Vienna, Wahringer Gurtel 18-20, 1090 Vienna, Austria. FAU - Ludwig, Birgit AU - Ludwig B AD - Department of Psychiatry and Psychotherapy, Medical University of Vienna, Wahringer Gurtel 18-20, 1090 Vienna, Austria. FAU - Kasper, Siegfried AU - Kasper S AD - Department of Psychiatry and Psychotherapy, Medical University of Vienna, Wahringer Gurtel 18-20, 1090 Vienna, Austria. FAU - Aschauer, Harald AU - Aschauer H AD - Department of Psychiatry and Psychotherapy, Medical University of Vienna, Wahringer Gurtel 18-20, 1090 Vienna, Austria. FAU - Egger, Gerda AU - Egger G AD - Clinical Institute of Pathology, Medical University of Vienna, Austria. FAU - Schosser, Alexandra AU - Schosser A AD - Department of Psychiatry and Psychotherapy, Medical University of Vienna, Wahringer Gurtel 18-20, 1090 Vienna, Austria; Zentrum fur Seelische Gesundheit LEOpoldau, Vienna, Austria. Electronic address: alexandra.schosser@meduniwien.ac.at. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140719 PL - Netherlands TA - J Affect Disord JT - Journal of affective disorders JID - 7906073 RN - 0 (Brain-Derived Neurotrophic Factor) SB - IM MH - Adult MH - Bipolar Disorder/*genetics MH - Brain-Derived Neurotrophic Factor/*genetics MH - CpG Islands MH - *DNA Methylation MH - Depressive Disorder, Major/*genetics MH - *Epigenesis, Genetic MH - Exons MH - Female MH - Genotype MH - Humans MH - Male MH - Middle Aged MH - Polymorphism, Single Nucleotide MH - Promoter Regions, Genetic OTO - NOTNLM OT - Affective disorders OT - Antidepressant therapy OT - BDNF methylation OT - Depression OT - Epigenetics OT - Genetic association study EDAT- 2014/08/12 06:00 MHDA- 2015/05/29 06:00 CRDT- 2014/08/09 06:00 PHST- 2014/01/29 00:00 [received] PHST- 2014/06/16 00:00 [revised] PHST- 2014/07/12 00:00 [accepted] PHST- 2014/08/09 06:00 [entrez] PHST- 2014/08/12 06:00 [pubmed] PHST- 2015/05/29 06:00 [medline] AID - S0165-0327(14)00453-4 [pii] AID - 10.1016/j.jad.2014.07.022 [doi] PST - ppublish SO - J Affect Disord. 2014 Oct;168:399-406. doi: 10.1016/j.jad.2014.07.022. Epub 2014 Jul 19.