PMID- 25364290
OWN - NLM
STAT- MEDLINE
DCOM- 20150624
LR  - 20211203
IS  - 1958-5969 (Electronic)
IS  - 1294-8322 (Print)
IS  - 1294-8322 (Linking)
VI  - 16
IP  - 3
DP  - 2014 Sep
TI  - DNA methylation and demethylation as targets for antipsychotic therapy.
PG  - 419-29
AB  - Schizophrenia (SZ) and bipolar disorder (BPD) patients show a downregulation of 
      GAD67, reelin (RELN), brain-derived neurotrophic factor (BDNF), and other genes 
      expressed in telencephalic GABAergic and glutamatergic neurons. This 
      downregulation is associated with the enrichment of 5-methylcytosine and 
      5-hydroxymethylcytosine proximally at gene regulatory domains at the respective 
      genes. A pharmacological strategy to reduce promoter hypermethylation and to 
      induce a more permissive chromatin conformation is to administer drugs, such as 
      the histone deacetylase (HDAC) inhibitor valproate (VPA), that facilitate 
      chromatin remodeling. Studies in mouse models of SZ indicate that clozapine 
      induces DNA demethylation at relevant promoters, and that this action is 
      potentiated by VPA. By activating DNA demethylation, clozapine or its derivatives 
      with VPA or other more potent and selective HDAC inhibitors may be a promising 
      treatment strategy to correct the gene expression deficits detected in postmortem 
      brain of SZ and BPD patients.
FAU - Guidotti, Alessandro
AU  - Guidotti A
AD  - Psychiatric Institute, Department of Psychiatry, College of Medicine, University 
      of Illinois at Chicago, Illinois, USA.
FAU - Grayson, Dennis R
AU  - Grayson DR
AD  - Psychiatric Institute, Department of Psychiatry, College of Medicine, University 
      of Illinois at Chicago, Illinois, USA.
LA  - eng
GR  - IROIMH093348/PHS HHS/United States
GR  - IROIMH101043/PHS HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Review
PL  - England
TA  - Dialogues Clin Neurosci
JT  - Dialogues in clinical neuroscience
JID - 101238198
RN  - 0 (Antipsychotic Agents)
RN  - 0 (Reelin Protein)
RN  - EC 3.4.21.- (RELN protein, human)
RN  - EC 3.4.21.- (Reln protein, mouse)
SB  - IM
MH  - Animals
MH  - Antipsychotic Agents/*pharmacology/*therapeutic use
MH  - Chromatin Assembly and Disassembly/drug effects
MH  - DNA Methylation/*drug effects
MH  - Down-Regulation/drug effects
MH  - Humans
MH  - Mental Disorders/*drug therapy/enzymology/genetics
MH  - Reelin Protein
PMC - PMC4214182
OTO - NOTNLM
OT  - bipolar
OT  - chromatin remodeling
OT  - clozapine epigenetics
OT  - histone deacetylase inhibitor
OT  - neuroleptic
OT  - psychosis
OT  - schizophrenia
EDAT- 2014/11/05 06:00
MHDA- 2015/06/25 06:00
PMCR- 2014/09/01
CRDT- 2014/11/04 06:00
PHST- 2014/11/04 06:00 [entrez]
PHST- 2014/11/05 06:00 [pubmed]
PHST- 2015/06/25 06:00 [medline]
PHST- 2014/09/01 00:00 [pmc-release]
AID - 10.31887/DCNS.2014.16.3/aguidotti [doi]
PST - ppublish
SO  - Dialogues Clin Neurosci. 2014 Sep;16(3):419-29. doi: 
      10.31887/DCNS.2014.16.3/aguidotti.