Read by QxMD icon Read

Epigenetics antipsychotic response

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...
November 29, 2016: Behavioural Brain Research
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
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
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
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
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
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
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
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
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
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
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
Hao Tang, Caroline F Dalton, Umarat Srisawat, Zhi Jun Zhang, Gavin P Reynolds
Individual variability and inadequate response of negative symptoms are major limitations of antipsychotic treatment in schizophrenia. A functional polymorphism, rs6295, in the 5-HT1A-receptor gene (HTR1A) contributes to this variability in negative symptom response. The DNA sequence containing rs6295 is rich in cytosine methylation (CpG) sites; CpG methylation is an epigenetic factor that, like rs6295, can modify transcriptional control. To investigate whether DNA methylation influences response to antipsychotic treatment, we determined methylation at CpG sites close to rs6295 in DNA from 82 Chinese subjects with a first psychotic episode...
April 2014: International Journal of Neuropsychopharmacology
Qingqing Xu, Xi Wu, Yuyu Xiong, Qinghe Xing, Lin He, Shengying Qin
Schizophrenia is a widespread mental disease with a prevalence of about 1% in the world population, and heritability of up to 80%. Drug therapy is an important approach to treating the disease. However, the curative effect of antipsychotic is far from satisfactory in terms of tolerability and side effects. Many studies have indicated that about 30% of the patients exhibit little or no improvements associated with antipsychotics. The response of individual patients who are given the same dose of the same drug varies considerably...
June 2013: Frontiers of Medicine
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
Se Hyun Kim, Hee Young Lee, Heesun Yi, Yong Min Ahn, Yong Sik Kim
AIMS: The effects of antipsychotics on various gene expressions through change in DNA methylation have been reported. Dual-specificity phosphatase 6 (DUSP6) is an extracellular signal regulated kinase 1/2 (ERK1/2)-selective phosphatase, and its expression can be suppressed by intronic methylation. Antipsychotic agent haloperidol affects ERK1/2 activity and could induce changes in DNA methylation as well as histone acetylation. In this study, we examined the effects of haloperidol on DUSP6 expression related to DNA methylation changes...
December 17, 2012: Life Sciences
Kunio Yui
It is important to note that risperidone solution, intranasal administration of oxytocin, and dietary supplementation with large doses of arachidonic acid added to docosahexaenoic acid (DHA) have been reported to improve impaired social interaction. In addition, atypical antipsychotics aripiprazole and SSRI fluvoxamine were useful in treating some aspects of social relatedness or the core deficits of communication and socialization. The evaluation of treatments for ASD should be directed at neurobiological targets known to be important in the brain's response to abnormal developmental trajectories or toward enhancing plasticity during the highly sensitive period in gene-environment interaction (epigenetic mechanism)...
2012: Seishin Shinkeigaku Zasshi, Psychiatria et Neurologia Japonica
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
George Anderson, Michael Maes
In 1995, the macrophage-T lymphocyte theory of schizophrenia (Smith and Maes, 1995) considered that activated immuno-inflammatory pathways may account for the higher neurodevelopmental pathology linked with gestational infections through the detrimental effects of activated microglia, oxidative and nitrosative stress (O&NS), cytokine-induced activation of the tryptophan catabolite (TRYCAT) pathway and consequent modulation of the N-methyl d-aspartate receptor (NMDAr) and glutamate production. The aim of the present paper is to review the current state-of-the art regarding the role of the above pathways in schizophrenia...
April 5, 2013: Progress in Neuro-psychopharmacology & Biological Psychiatry
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
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"