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Epigenetics antipsychotic response

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https://www.readbyqxmd.com/read/29589131/recent-progress-in-pharmacogenomics-of-antipsychotic-drug-response
#1
REVIEW
Jian-Ping Zhang, Anil K Malhotra
PURPOSE OF REVIEW: Pharmacogenomics (PGx) of antipsychotic drug response is an active area of research in the past few years. We reviewed recent PGx studies with an emphasis of development of new methodologies and new research directions. RECENT FINDINGS: Traditional candidate gene approach continues to generate evidence to support the associations of antipsychotic response with genes coding for drug targets such as DRD2. Genome-wide association studies have found a few novel genes that may be associated with drug efficacy and adverse events...
March 27, 2018: Current Psychiatry Reports
https://www.readbyqxmd.com/read/29499474/dna-methylation-of-ankk1-and-response-to-aripiprazole-in-patients-with-acute-schizophrenia-a-preliminary-study
#2
Itaru Miura, Yasuto Kunii, Mizuki Hino, Hiroshi Hoshino, Junya Matsumoto, Keiko Kanno-Nozaki, Sho Horikoshi, Haruka Kaneko, Miki Bundo, Kazuya Iwamoto, Hirooki Yabe
Epigenetic modification including DNA methylation may affect pathophysiology and the response to antipsychotic drugs in patients with schizophrenia. The objective of the present study was to investigate the effect of the DNA methylation of ANKK1 (ankyrin repeat and kinase domain containing 1) on the response to aripiprazole and plasma levels of monoamine metabolites in antipsychotic-free acute schizophrenia patients. The subjects were 34 Japanese patients with schizophrenia who had been treated with aripiprazole for 6 weeks...
February 23, 2018: Journal of Psychiatric Research
https://www.readbyqxmd.com/read/29448178/modification-of-the-association-between-antipsychotic-treatment-response-and-childhood-adversity-by-mmp9-gene-variants-in-a-first-episode-schizophrenia-cohort
#3
Nathaniel McGregor, Nicole Thompson, Kevin Sean O'Connell, Robin Emsley, Lize van der Merwe, Louise Warnich
Antipsychotics remain the most effective, and wide used option for ameliorating the symptoms of schizophrenia. However, inter-individual differences in treatment outcome are vast and suggest a role for genetic and environmental factors in affording favourable outcomes. A notable epigenetic relationship which has gained considerable traction in recent literature is the way in which the severity of childhood trauma can modify associations seen between genetic variation and antipsychotic treatment response. A potential mechanism of action which may facilitate this relationship is synaptic plasticity...
February 7, 2018: Psychiatry Research
https://www.readbyqxmd.com/read/29343074/understanding-the-influence-of-antipsychotic-drugs-on-global-methylation-events-and-its-relevance-in-treatment-response
#4
Babu Swathy, Koramannil R Saradalekshmi, Indu V Nair, Chandrasekharan Nair, Moinak Banerjee
AIM: The present study intends to evaluate whether antipsychotic drugs can modulate the host epigenome and if so whether drug-induced epigenetic modulation can explain the heterogeneity in drug response. METHODS: Present study was conducted in in vitro cells and significance of these in vitro observations was further evaluated in a clinical setting, between drug responsive and nonresponsive schizophrenia patients. A number of DNA modifications were assessed at global level using 5-methylcytosine, 5-hydroxymethylcytosine and 5-formylcytosine followed by evaluating the expression of epigenetic modifier genes and their crosstalk with miRNAs...
January 18, 2018: Epigenomics
https://www.readbyqxmd.com/read/29017764/dna-methylation-and-antipsychotic-treatment-mechanisms-in-schizophrenia-progress-and-future-directions
#5
REVIEW
Ellen S Ovenden, Nathaniel W McGregor, Robin A Emsley, Louise Warnich
Antipsychotic response in schizophrenia is a complex, multifactorial trait influenced by pharmacogenetic factors. With genetic studies thus far providing little biological insight or clinical utility, the field of pharmacoepigenomics has emerged to tackle the so-called "missing heritability" of drug response in disease. Research on psychiatric disorders has only recently started to assess the link between epigenetic alterations and treatment outcomes. DNA methylation, the best characterised epigenetic mechanism to date, is discussed here in the context of schizophrenia and antipsychotic treatment outcomes...
October 7, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28696411/combined-study-of-genetic-and-epigenetic-biomarker-risperidone-treatment-efficacy-in-chinese-han-schizophrenia-patients
#6
Y Shi, M Li, C Song, Q Xu, R Huo, L Shen, Q Xing, D Cui, W Li, J Zhao, L He, S Qin
Nowadays, risperidone is an atypical antipsychotic drug that has been increasingly used for treatment and maintenance therapy in schizophrenia. However, partially affected by genetic or environmental factors, there is significant difference in treatment outcomes among patients. In this study, we aimed to interpret the difference between good and poor responders treated with risperidone in both genetic and epigenetic levels in 288 mainland Chinese patients. We recruited a Henan cohort including 98 patients as initial discovery group and then confirmed our results in Shanghai cohort...
July 11, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28470099/understanding-epigenetics-of-schizophrenia-in-the-backdrop-of-its-antipsychotic-drug-therapy
#7
REVIEW
Babu Swathy, Moinak Banerjee
The diatheses of gene and environment interaction in schizophrenia (SCZ) are becoming increasingly evident. Genetic and epigenetic backgrounds are being considered in stratifying and addressing phenotypic variation and drug response in SCZ. But how much of these epigenetic alterations are the primary contributing factor, toward disease pathogenesis and drug response, needs further clarity. Evidence indicates that antipsychotic drugs can also alter the epigenetic homeostasis thereby inducing pharmacoepigenomic effects...
May 2017: Epigenomics
https://www.readbyqxmd.com/read/28429622/pharmacoepigenomic-responses-of-antipsychotic-drugs-on-pharmacogenes-are-likely-to-be-modulated-by-mirnas
#8
Babu Swathy, Koramannil R Saradalekshmi, Indu V Nair, Chandrasekharan Nair, Moinak Banerjee
AIM: It is imperative to differentiate the role of host epigenetics from pharmacoepigenetics in resolving therapeutic response. Therefore, the objective was to identify how antipsychotic drugs influence epigenetic response on pharmacogenes. MATERIALS & METHODS: The study design was based on in vitro evaluation of pharmacoepigenetic response of haloperidol, clozapine and olanzapine. Post antipsychotic treatment, the alterations in expression of ABCB1, CYP1A2 and CYP3A4 were monitored, and followed up by promoter methylation and their target miRNA expression studies...
April 21, 2017: Epigenomics
https://www.readbyqxmd.com/read/27913254/quetiapine-treatment-reverses-depressive-like-behavior-and-reduces-dna-methyltransferase-activity-induced-by-maternal-deprivation
#9
Zuleide M Ignácio, Gislaine Z Réus, Helena M Abelaira, Amanda L Maciel, Airam B de Moura, Danyela Matos, Júlia P Demo, Júlia B I da Silva, Fernanda F Gava, Samira S Valvassori, André F Carvalho, João Quevedo
Stress in early life has been appointed as an important phenomenon in the onset of depression and poor response to treatment with classical antidepressants. Furthermore, childhood trauma triggers epigenetic changes, which are associated with the pathophysiology of major depressive disorder (MDD). Treatment with atypical antipsychotics such as quetiapine, exerts therapeutic effect for MDD patients and induces epigenetic changes. This study aimed to analyze the effect of chronic treatment with quetiapine (20mg/kg) on depressive-like behavior of rats submitted to maternal deprivation (MD), as well as the activity of histone acetylation by the enzymes histone acetyl transferases (HAT) and deacetylases (HDAC) and DNA methylation, through DNA methyltransferase enzyme (DNMT) in the prefrontal cortex (PFC), nucleus accumbens (NAc) and hippocampus...
March 1, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/26491327/etiology-of-cardiovascular-disease-in-patients-with-schizophrenia-current-perspectives
#10
REVIEW
Murat Emul, Tevfik Kalelioglu
Cardiovascular morbidity and mortality are important problems among patients with schizophrenia. A wide spectrum of reasons, ranging from genes to the environment, are held responsible for causing the cardiovascular risk factors that may lead to shortening the life expectancy of patients with schizophrenia. Here, we have summarized the etiologic issues related with the cardiovascular risk factors in schizophrenia. First, we focused on heritable factors associated with cardiovascular disease and schizophrenia by mentioning studies about genetics-epigenetics, in the first-episode or drug-naïve patients...
2015: Neuropsychiatric Disease and Treatment
https://www.readbyqxmd.com/read/26137221/insights-into-the-origin-of-dna-methylation-differences-between-monozygotic-twins-discordant-for-schizophrenia
#11
Melkaye G Melka, Christina A Castellani, Richard O'Reilly, Shiva M Singh
BACKGROUND: DNA methylation differences between monozygotic twins discordant for schizophrenia have been previously reported. However, the origin of methylation differences between monozygotic twins discordant for schizophrenia is not clear. The findings here argue that all DNA methylation differences may not necessarily represent the cause of the disease; rather some may result from the effect of antipsychotics. METHODS: Methylation differences in rat brain regions and also in two pairs of unrelated monozygotic twins discordant for schizophrenia have been studied using genome-wide DNA methylation arrays at Arraystar Inc...
2015: Journal of Molecular Psychiatry
https://www.readbyqxmd.com/read/26120009/epigenetic-signaling-in-schizophrenia
#12
REVIEW
Daisuke Ibi, Javier González-Maeso
Histone modifications and DNA methylation represent central dynamic and reversible processes that regulate gene expression and contribute to cellular phenotypes. These epigenetic marks have been shown to play fundamental roles in a diverse set of signaling and behavioral outcomes. Psychiatric disorders such as schizophrenia and depression are complex and heterogeneous diseases with multiple and independent factors that may contribute to their pathophysiology, making challenging to find a link between specific elements and the underlying mechanisms responsible for the disorder and its treatment...
October 2015: Cellular Signalling
https://www.readbyqxmd.com/read/25415458/olanzapine-induced-dna-methylation-in-the-hippocampus-and-cerebellum-in-genes-mapped-to-human-22q11-and-implicated-in-schizophrenia
#13
Melkaye G Melka, Nagalingam Rajakumar, Richard O'Reilly, Shiva M Singh
BACKGROUND: Although there is indirect evidence that the effects of antipsychotic drugs may involve modulation of dopamine transmission, their mechanism of action is poorly understood. We hypothesized that antipsychotic drugs mediate their effects by epigenetic modulation. Here, we tested the effect of an antipsychotic, olanzapine, on the DNA methylation status of genes following chronic treatment using rat-specific methylation arrays. METHODS: Forty-eight hours after the last dose of olanzapine/vehicle, rats were habituated to an open-field activity-monitoring chamber for 30 min to verify whether stress-induced locomotor activity was reduced in olanzapine-treated rats...
April 2015: Psychiatric Genetics
https://www.readbyqxmd.com/read/25408910/olanzapine-induced-dna-methylation-changes-support-the-dopamine-hypothesis-of-psychosis
#14
Melkaye G Melka, Christina A Castellani, Benjamin I Laufer, Raj N Rajakumar, Richard O'Reilly, Shiva M Singh
BACKGROUND: The dopamine (DA) hypothesis of schizophrenia proposes the mental illness is caused by excessive transmission of dopamine in selected brain regions. Multiple lines of evidence, including blockage of dopamine receptors by antipsychotic drugs that are used to treat schizophrenia, support the hypothesis. However, the dopamine D2 receptor (DRD2) blockade cannot explain some important aspects of the therapeutic effect of antipsychotic drugs. In this study, we hypothesized that antipsychotic drugs could affect the transcription of genes in the DA pathway by altering their epigenetic profile...
2013: Journal of Molecular Psychiatry
https://www.readbyqxmd.com/read/25340734/polymorphisms-of-serotonin-neurotransmission-and-their-effects-on-antipsychotic-drug-action
#15
REVIEW
Hao Tang, Olga O McGowan, Gavin P Reynolds
The receptor pharmacology of many antipsychotic drugs includes actions at various serotonin (5-hydroxytryptamine [5-HT]) receptors. The 5-HT neurotransmitter system is thought to be involved in many of the consequences of treatment with antipsychotic drugs, including both symptom response, primarily of negative and depressive symptoms, and adverse effects, notably extrapyramidal side effects and weight gain. There is substantial interindividual variability in these drug effects, to which genetic variability contributes...
2014: Pharmacogenomics
https://www.readbyqxmd.com/read/25266742/olanzapine-induced-methylation-alters-cadherin-gene-families-and-associated-pathways-implicated-in-psychosis
#16
Melkaye G Melka, Christina A Castellani, Nagalingam Rajakumar, Richard O'Reilly, Shiva M Singh
BACKGROUND: The complex aetiology of most mental disorders involves gene-environment interactions that may operate using epigenetic mechanisms particularly DNA methylation. It may explain many of the features seen in mental disorders including transmission, expression and antipsychotic treatment responses. This report deals with the assessment of DNA methylation in response to an antipsychotic drug (olanzapine) on brain (cerebellum and hippocampus), and liver as a non-neural reference in a rat model...
September 29, 2014: BMC Neuroscience
https://www.readbyqxmd.com/read/25207264/exploring-the-complexity-of-intellectual-disability-in-fetal-alcohol-spectrum-disorders
#17
REVIEW
Aniruddho Chokroborty-Hoque, Bonnie Alberry, Shiva M Singh
Brain development in mammals is long lasting. It begins early during embryonic growth and is finalized in early adulthood. This progression represents a delicate choreography of molecular, cellular, and physiological processes initiated and directed by the fetal genotype in close interaction with environment. Not surprisingly, most aberrations in brain functioning including intellectual disability (ID) are attributed to either gene(s), or environment or the interaction of the two. The ensuing complexity has made the assessment of this choreography, ever challenging...
2014: Frontiers in Pediatrics
https://www.readbyqxmd.com/read/24491429/comprehensive-dna-methylation-analysis-of-human-neuroblastoma-cells-treated-with-blonanserin
#18
Yui Murata, Masaki Nishioka, Miki Bundo, Fumiko Sunaga, Kiyoto Kasai, Kazuya Iwamoto
Blonanserin is a second-generation antipsychotic drug for schizophrenia. The pharmacological actions of blonanserin are shown to be the antagonism of dopamine receptor 2 and serotonin receptors. However, its molecular mechanisms in brain cells have not been fully characterized. Accumulating evidence suggests that antipsychotic drugs and mood stabilizers show epigenetic effects on a wide range of genes in animal and cellular models. We performed genome-wide DNA methylation analysis targeting 479,814 CpG sites of cultured human neuroblastoma cells administered with blonanserin...
March 20, 2014: Neuroscience Letters
https://www.readbyqxmd.com/read/24366052/hdac-inhibitors-restore-the-capacity-of-aged-mice-to-respond-to-haloperidol-through-modulation-of-histone-acetylation
#19
Janitza L Montalvo-Ortiz, Jack Keegan, Christopher Gallardo, Nicolas Gerst, Kazuhiro Tetsuka, Chris Tucker, Mitsuyuki Matsumoto, Deyu Fang, John G Csernansky, Hongxin Dong
Antipsychotic drugs are widely prescribed to elderly patients for the treatment of a variety of psychopathological conditions, including psychosis and the behavioral disturbances associated with dementia. However, clinical experience suggests that these drugs may be less efficacious in the elderly individuals than in the young. Recent studies suggest that aging may be associated with epigenetic changes and that valproic acid (VPA), a histone deacetylase inhibitor, may reverse such changes. However, it is not yet known whether HDAC inhibitors can modulate age-related epigenetic changes that may impact antipsychotic drug action...
May 2014: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/24354796/pharmacogenomics-in-psychiatry-the-relevance-of-receptor-and-transporter-polymorphisms
#20
REVIEW
Gavin P Reynolds, Olga O McGowan, Caroline F Dalton
The treatment of severe mental illness, and of psychiatric disorders in general, is limited in its efficacy and tolerability. There appear to be substantial interindividual differences in response to psychiatric drug treatments that are generally far greater than the differences between individual drugs; likewise, the occurrence of adverse effects also varies profoundly between individuals. These differences are thought to reflect, at least in part, genetic variability. The action of psychiatric drugs primarily involves effects on synaptic neurotransmission; the genes for neurotransmitter receptors and transporters have provided strong candidates in pharmacogenetic research in psychiatry...
April 2014: British Journal of Clinical Pharmacology
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