PMID- 31004918
OWN - NLM
STAT- MEDLINE
DCOM- 20200625
LR  - 20200625
IS  - 1879-1379 (Electronic)
IS  - 0022-3956 (Linking)
VI  - 114
DP  - 2019 Jul
TI  - Exploring the role of BDNF DNA methylation and hydroxymethylation in patients 
      with obsessive compulsive disorder.
PG  - 17-23
LID - S0022-3956(18)31412-2 [pii]
LID - 10.1016/j.jpsychires.2019.04.006 [doi]
AB  - Obsessive-compulsive disorder (OCD) is a clinically heterogeneous 
      neuropsychiatric condition associated with profound disability, whose 
      susceptibility, stemming from genetic and environmental factors that intersect 
      with each other, is still under investigation. In this perspective, we sought to 
      explore the transcriptional regulation of Brain Derived Neurotrophic Factor 
      (BDNF), a promising candidate biomarker in both development and etiology of 
      different neuropsychiatric conditions, in peripheral blood mononuclear cells from 
      OCD patients and healthy controls. In particular, we focused on BDNF gene 
      expression and interrogated in depth DNA methylation and hydroxymethylation at 
      gene promoters (exons I, IV and IX) in a sample of OCD patients attending a 
      tertiary OCD Clinic to receive guidelines-recommended treatment, and matched 
      controls. Our preliminary data showed a significant increase in BDNF gene 
      expression and a significant correlation with changes in the two epigenetic 
      modifications selectively at promoter exon I, with no changes in the other 
      promoters under study. We can conclude that transcriptional regulation of BDNF in 
      OCD engages epigenetic mechanisms, and can suggest that this is likely evoked by 
      the long-term pharmacotherapy. It is important to underline that many different 
      factors need to be taken into account (i.e. age, sex, duration of illness, 
      treatment), and thus further studies are mandatory to investigate their role in 
      the epigenetic regulation of BDNF gene. Of note, we provide unprecedented 
      evidence for the importance of analyzing 5-hydroxymethylcytosine levels to 
      correctly evaluate 5-methylcytosine changes.
CI  - Copyright (c) 2019 Elsevier Ltd. All rights reserved.
FAU - D'Addario, Claudio
AU  - D'Addario C
AD  - University of Teramo, Bioscience, Teramo, Italy; Karolinska Institutet, 
      Department of Clinical Neuroscience, Stockholm, Sweden. Electronic address: 
      cdaddario@unite.it.
FAU - Bellia, Fabio
AU  - Bellia F
AD  - University of Teramo, Bioscience, Teramo, Italy.
FAU - Benatti, Beatrice
AU  - Benatti B
AD  - University of Milan, Department of Biomedical and Clinical Sciences Luigi Sacco, 
      Milano, Italy.
FAU - Grancini, Benedetta
AU  - Grancini B
AD  - University of Milan, Department of Biomedical and Clinical Sciences Luigi Sacco, 
      Milano, Italy.
FAU - Vismara, Matteo
AU  - Vismara M
AD  - University of Milan, Department of Biomedical and Clinical Sciences Luigi Sacco, 
      Milano, Italy.
FAU - Pucci, Mariangela
AU  - Pucci M
AD  - University of Teramo, Bioscience, Teramo, Italy.
FAU - De Carlo, Vera
AU  - De Carlo V
AD  - University of Milan, Department of Biomedical and Clinical Sciences Luigi Sacco, 
      Milano, Italy.
FAU - Vigano, Caterina
AU  - Vigano C
AD  - University of Milan, Department of Biomedical and Clinical Sciences Luigi Sacco, 
      Milano, Italy.
FAU - Galimberti, Daniela
AU  - Galimberti D
AD  - University of Milan, Dino Ferrari Center, Milan, Italy; Fondazione IRCCS Ca' 
      Granda, Ospedale Policlinico, Neurodegenerative Diseases Unit, Milan, Italy.
FAU - Fenoglio, Chiara
AU  - Fenoglio C
AD  - University of Milan, Dino Ferrari Center, Milan, Italy; Fondazione IRCCS Ca' 
      Granda, Ospedale Policlinico, Neurodegenerative Diseases Unit, Milan, Italy.
FAU - Scarpini, Elio
AU  - Scarpini E
AD  - University of Milan, Dino Ferrari Center, Milan, Italy; Fondazione IRCCS Ca' 
      Granda, Ospedale Policlinico, Neurodegenerative Diseases Unit, Milan, Italy.
FAU - Maccarrone, Mauro
AU  - Maccarrone M
AD  - Department of Medicine, Campus Bio-Medico University of Rome, Rome, Italy; 
      Fondazione IRCCS Santa Lucia, Unit of Lipid Neurochemistry, Rome, Italy.
FAU - Dell'Osso, Bernardo
AU  - Dell'Osso B
AD  - University of Milan, Department of Biomedical and Clinical Sciences Luigi Sacco, 
      Milano, Italy; CRC "Aldo Ravelli", University of Milan, Milano, Italy; Department 
      of Psychiatry and Behavioral Sciences, Stanford University, CA, USA. Electronic 
      address: bernardo.dellosso@unimi.it.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190406
PL  - England
TA  - J Psychiatr Res
JT  - Journal of psychiatric research
JID - 0376331
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 7171WSG8A2 (BDNF protein, human)
SB  - IM
MH  - Adult
MH  - Brain-Derived Neurotrophic Factor/*genetics/metabolism
MH  - *DNA Methylation
MH  - Female
MH  - Gene Expression Regulation
MH  - Humans
MH  - Male
MH  - Obsessive-Compulsive Disorder/*genetics/metabolism
MH  - Polymorphism, Single Nucleotide/genetics
MH  - Young Adult
OTO - NOTNLM
OT  - BDNF
OT  - DNA hydroxymethylation
OT  - DNA methylation
OT  - Obsessive compulsive disorder
EDAT- 2019/04/21 06:00
MHDA- 2020/06/26 06:00
CRDT- 2019/04/21 06:00
PHST- 2018/12/03 00:00 [received]
PHST- 2019/03/20 00:00 [revised]
PHST- 2019/04/05 00:00 [accepted]
PHST- 2019/04/21 06:00 [pubmed]
PHST- 2020/06/26 06:00 [medline]
PHST- 2019/04/21 06:00 [entrez]
AID - S0022-3956(18)31412-2 [pii]
AID - 10.1016/j.jpsychires.2019.04.006 [doi]
PST - ppublish
SO  - J Psychiatr Res. 2019 Jul;114:17-23. doi: 10.1016/j.jpsychires.2019.04.006. Epub 
      2019 Apr 6.