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Clozapine epigenetics

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https://www.readbyqxmd.com/read/25138234/antipsychotic-induced-weight-gain-genetics-epigenetics-and-biomarkers-reviewed
#1
REVIEW
Tahireh A Shams, Daniel J Müller
Antipsychotic-induced weight gain (AIWG) is a prevalent side effect of antipsychotic treatment, particularly with second generation antipsychotics, such as clozapine and olanzapine. At this point, there is virtually nothing that can be done to predict who will be affected by AIWG. However, hope for the future of prediction lies with genetic risk factors. Many genes have been studied for their association with AIWG with a variety of promising findings. This review will focus on genetic findings in the last year and will discuss the first epigenetic and biomarker findings as well...
October 2014: Current Psychiatry Reports
https://www.readbyqxmd.com/read/24345457/clozapine-ameliorates-epigenetic-and-behavioral-abnormalities-induced-by-phencyclidine-through-activation-of-dopamine-d1-receptor
#2
Yuki Aoyama, Akihiro Mouri, Kazuya Toriumi, Takenao Koseki, Shiho Narusawa, Natsumi Ikawa, Takayoshi Mamiya, Taku Nagai, Kiyofumi Yamada, Toshitaka Nabeshima
Accumulating evidence suggests that dysregulation of histone modification is involved in the pathogenesis and/or pathophysiology of psychiatric disorders. However, the abnormalities in histone modification in the animal model of schizophrenia and the efficacy of antipsychotics for such abnormalities remain unclear. Here, we investigated the involvement of histone modification in phencyclidine-induced behavioral abnormalities and the effects of antipsychotics on these abnormalities. After repeated phencyclidine (10 mg/kg) treatment for 14 consecutive days, mice were treated with antipsychotics (clozapine or haloperidol) or the histone deacetylase inhibitor sodium butyrate for 7 d...
May 2014: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/24308257/pharmacotherapy-of-suicidal-behaviour-in-major-depression-schizophrenia-and-bipolar-disorder
#3
REVIEW
Pavo Filaković, Anamarija Petek Erić
The psychopathological dynamics in suicidality overcomes actual diagnostic distribution therefore pharmacotherapy has restricted role in overall prevention of suicidal behaviour among mentally ill and is demanding for clinician. This role is achieved through reduction and alleviation of suicidal risk with rational and individual pharmacotherapeutic approach emphasising effective, safe and tolerable treatment. The genetic and epigenetic factors, dysfunction of neurotransmitter, neuroendocrine system and stress response system has been determining for neurobiology of suicidality...
September 2013: Collegium Antropologicum
https://www.readbyqxmd.com/read/23864674/conserved-chromosome-2q31-conformations-are-associated-with-transcriptional-regulation-of-gad1-gaba-synthesis-enzyme-and-altered-in-prefrontal-cortex-of-subjects-with-schizophrenia
#4
Rahul Bharadwaj, Yan Jiang, Wenjie Mao, Mira Jakovcevski, Aslihan Dincer, Winfried Krueger, Krassimira Garbett, Catheryne Whittle, Jogender Singh Tushir, Jia Liu, Adolfo Sequeira, Marquis P Vawter, Paul D Gardner, Patrizia Casaccia, Theodore Rasmussen, William E Bunney, Karoly Mirnics, Kensuke Futai, Schahram Akbarian
Little is known about chromosomal loopings involving proximal promoter and distal enhancer elements regulating GABAergic gene expression, including changes in schizophrenia and other psychiatric conditions linked to altered inhibition. Here, we map in human chromosome 2q31 the 3D configuration of 200 kb of linear sequence encompassing the GAD1 GABA synthesis enzyme gene locus, and we describe a loop formation involving the GAD1 transcription start site and intergenic noncoding DNA elements facilitating reporter gene expression...
July 17, 2013: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/23777937/antidepressants-and-mood-stabilizers-effects-on-histone-deacetylase-expression-in-c57bl-6-mice-brain-region-specific-changes
#5
Masanori Ookubo, Hirohiko Kanai, Harusuke Aoki, Naoto Yamada
To determine whether treatment with various antidepressants or mood stabilizers leads to region-specific changes, we investigated the effects of their subchronic (14 days of intraperitoneal injection) administration on the tissue concentration of monoamines, dopamine, serotonin, and norepinephrine, and the protein expression of acetylated histone H3 (AcH3) and histone deacetylases (HDACs) in the mouse striatum (ST), nucleus accumbens (Acb), hippocampus (Hip), cingulate cortex (Cg), and amygdala (Amy). Subchronic administration with the antidepressants (S)-citalopram oxalate (ECM), duloxetine hydrochloride (DLX), and mirtazapine (MIR) commonly induced significant increases in dopamine and serotonin levels in the ST and Cg...
September 2013: Journal of Psychiatric Research
https://www.readbyqxmd.com/read/23157625/effects-of-antipsychotics-on-the-bdnf-in-schizophrenia
#6
REVIEW
T L Huang
Brain-derived neurotropic factor (BDNF) is involved in the development of the brain, and likely influences the neuroplasticity in schizophrenia. BDNF is also believed to interact with other neurotransmitter systems implicated in schizophrenia, such as dopamine, glutamate, serotonin and GABA. Therefore, BDNF is a candidate gene for schizophrenia. In past decades, the blood (serum or plasma) BDNF protein levels and BDNF gene alleles and genotypes to the clinical features of schizophrenia, such as age of onset, clinical subtypes, symptom severity, and drug response, have been evaluated among different populations...
2013: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/22864611/hdac2-regulates-atypical-antipsychotic-responses-through-the-modulation-of-mglu2-promoter-activity
#7
Mitsumasa Kurita, Terrell Holloway, Aintzane García-Bea, Alexey Kozlenkov, Allyson K Friedman, José L Moreno, Mitra Heshmati, Sam A Golden, Pamela J Kennedy, Nagahide Takahashi, David M Dietz, Giuseppe Mocci, Ane M Gabilondo, James Hanks, Adrienne Umali, Luis F Callado, Amelia L Gallitano, Rachael L Neve, Li Shen, Joseph D Buxbaum, Ming-Hu Han, Eric J Nestler, J Javier Meana, Scott J Russo, Javier González-Maeso
Histone deacetylases (HDACs) compact chromatin structure and repress gene transcription. In schizophrenia, clinical studies demonstrate that HDAC inhibitors are efficacious when given in combination with atypical antipsychotics. However, the molecular mechanism that integrates a better response to antipsychotics with changes in chromatin structure remains unknown. Here we found that chronic atypical antipsychotics downregulated the transcription of metabotropic glutamate 2 receptor (mGlu2, also known as Grm2), an effect that was associated with decreased histone acetylation at its promoter in mouse and human frontal cortex...
September 2012: Nature Neuroscience
https://www.readbyqxmd.com/read/22564440/epigenetic-modifications-of-gabaergic-interneurons-are-associated-with-the-schizophrenia-like-phenotype-induced-by-prenatal-stress-in-mice
#8
Francesco Matrisciano, Patricia Tueting, Ishani Dalal, Bashkim Kadriu, Dennis R Grayson, John M Davis, Ferdinando Nicoletti, Alessandro Guidotti
Human studies suggest that a variety of prenatal stressors are related to high risk for cognitive and behavioral abnormalities associated with psychiatric illness (Markham and Koenig, 2011). Recently, a downregulation in the expression of GABAergic genes (i.e., glutamic acid decarboxylase 67 and reelin) associated with DNA methyltransferase (DNMT) overexpression in GABAergic neurons has been regarded as a characteristic phenotypic component of the neuropathology of psychotic disorders (Guidotti et al., 2011)...
May 2013: Neuropharmacology
https://www.readbyqxmd.com/read/22253875/influence-of-antipsychotic-drugs-on-human-endogenous-retrovirus-herv-transcription-in-brain-cells
#9
Olivia Diem, Marisa Schäffner, Wolfgang Seifarth, Christine Leib-Mösch
Human endogenous retroviruses (HERVs) have been associated with various neurological and neuropsychiatric disorders. Transcripts and proteins of at least three HERV groups, HERV-W, ERV9 and HERV-K(HML-2) have been detected repeatedly in brain samples or cerebrospinal fluid of patients with schizophrenia suggesting that alterations in HERV activity may play a role in etiopathogenesis. Current therapies otherwise include neuroleptics and/or antidepressants that may induce epigenetic alterations and thus influence HERV expression...
2012: PloS One
https://www.readbyqxmd.com/read/21505039/activation-of-group-ii-metabotropic-glutamate-receptors-promotes-dna-demethylation-in-the-mouse-brain
#10
Francesco Matrisciano, Erbo Dong, David Peter Gavin, Ferdinando Nicoletti, Alessandro Guidotti
Activation of group II metabotropic glutamate receptors (mGlu2 and -3 receptors) has shown a potential antipsychotic activity, yet the underlying mechanism is only partially known. Altered epigenetic mechanisms contribute to the pathogenesis of schizophrenia and currently used medications exert chromatin remodeling effects. Here, we show that systemic injection of the brain-permeant mGlu2/3 receptor agonist (-)-2-oxa-4-aminobicyclo[3.1.0]hexane-4,6-dicarboxylic acid (LY379268; 0.3-1 mg/kg i.p.) increased the mRNA and protein levels of growth arrest and DNA damage 45-β (Gadd45-β), a molecular player of DNA demethylation, in the mouse frontal cortex and hippocampus...
July 2011: Molecular Pharmacology
https://www.readbyqxmd.com/read/21312415/epigenetics-of-schizophrenia
#11
Schahram Akbarian
Epigenetic regulators of gene expression including DNA cytosine methylation and posttranslational histone modifications could play a role for some of the molecular alterations associated with schizophrenia. For example, in prefrontal cortex of subjects with schizophrenia, abnormal DNA or histone methylation at sites of specific genes and promoters is associated with changes in RNA expression. These findings are of interest from a neurodevelopmental perspective because there is increasing evidence that epigenetic markings for a substantial portion of genes and loci are highly regulated during the first years of life...
2010: Current Topics in Behavioral Neurosciences
https://www.readbyqxmd.com/read/21074545/epigenetic-gabaergic-targets-in-schizophrenia-and-bipolar-disorder
#12
REVIEW
A Guidotti, J Auta, Y Chen, J M Davis, E Dong, D P Gavin, D R Grayson, F Matrisciano, G Pinna, R Satta, R P Sharma, L Tremolizzo, P Tueting
It is becoming increasingly clear that a dysfunction of the GABAergic/glutamatergic network in telencephalic brain structures may be the pathogenetic mechanism underlying psychotic symptoms in schizophrenia (SZ) and bipolar (BP) disorder patients. Data obtained in Costa's laboratory (1996-2009) suggest that this dysfunction may be mediated primarily by a downregulation in the expression of GABAergic genes (e.g., glutamic acid decarboxylase₆₇[GAD₆₇] and reelin) associated with DNA methyltransferase (DNMT)-dependent hypermethylation of their promoters...
June 2011: Neuropharmacology
https://www.readbyqxmd.com/read/19961320/structure-function-regulation-and-polymorphism-and-the-clinical-significance-of-human-cytochrome-p450-1a2
#13
REVIEW
Shu-Feng Zhou, Bo Wang, Li-Ping Yang, Jun-Ping Liu
Human CYP1A2 is one of the major CYPs in human liver and metabolizes a number of clinical drugs (e.g., clozapine, tacrine, tizanidine, and theophylline; n > 110), a number of procarcinogens (e.g., benzo[a]pyrene and aromatic amines), and several important endogenous compounds (e.g., steroids). CYP1A2 is subject to reversible and/or irreversible inhibition by a number of drugs, natural substances, and other compounds. The CYP1A gene cluster has been mapped on to chromosome 15q24.1, with close link between CYP1A1 and 1A2 sharing a common 5'-flanking region...
May 2010: Drug Metabolism Reviews
https://www.readbyqxmd.com/read/19590965/insights-into-the-substrate-specificity-inhibitors-regulation-and-polymorphisms-and-the-clinical-impact-of-human-cytochrome-p450-1a2
#14
REVIEW
Shu-Feng Zhou, Li-Ping Yang, Zhi-Wei Zhou, Ya-He Liu, Eli Chan
Human CYP1A2 is one of the major CYPs in human liver and metabolizes a variety of clinically important drugs (e.g., clozapine, tacrine, tizanidine, and theophylline), a number of procarcinogens (e.g. benzo[a]pyrene and aflatoxin B(1)), and several important endogenous compounds (e.g. steroids and arachidonic acids). Like many of other CYPs, CYP1A2 is subject to induction and inhibition by a number of compounds, which may provide an explanation for some drug interactions observed in clinical practice. A large interindividual variability in the expression and activity of CYP1A2 and elimination of drugs that are mainly metabolized by CYP1A2 has been observed, which is largely caused by genetic (e...
September 2009: AAPS Journal
https://www.readbyqxmd.com/read/19102671/gabaergic-promoter-hypermethylation-as-a-model-to-study-the-neurochemistry-of-schizophrenia-vulnerability
#15
REVIEW
Erminio Costa, Ying Chen, Erbo Dong, Dennis R Grayson, Marija Kundakovic, Ekrem Maloku, William Ruzicka, Rosalba Satta, Marin Veldic, Adrian Zhubi, Alessandro Guidotti
The neuronal GABAergic mechanisms that mediate the symptomatic beneficial effects elicited by a combination of antipsychotics with valproate (a histone deacetylase inhibitor) in the treatment of psychosis (expressed by schizophrenia or bipolar disorder patients) are unknown. This prompted us to investigate whether the beneficial action of this combination results from a modification of histone tail covalent esterification or is secondary to specific chromatin remodeling. The results suggest that clozapine, or sulpiride associated with valproate, by increasing DNA demethylation with an unknown mechanism, causes a chromatin remodeling that brings about a beneficial change in the epigenetic GABAergic dysfunction typical of schizophrenia and bipolar disorder patients...
January 2009: Expert Review of Neurotherapeutics
https://www.readbyqxmd.com/read/14699448/the-serotonin-2a-receptor-gene-locus-does-not-contain-common-polymorphism-affecting-mrna-levels-in-adult-brain
#16
N J Bray, P R Buckland, H Hall, M J Owen, M C O'Donovan
The serotonin-2A (HTR2A) receptor is a molecule of particular interest in biological psychiatry, as it is an important target for psychotropic drugs, and altered HTR2A expression has been found in several neuropsychiatric conditions, including depression and schizophrenia. Genetic association has been reported between a synonymous 102T/C polymorphism in the gene encoding HTR2A and a number of clinical phenotypes, including schizophrenia, clozapine response, psychotic symptoms in Alzheimer's disease and certain features of depression...
January 2004: Molecular Psychiatry
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