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Antipsychotic response methylation

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https://www.readbyqxmd.com/read/29017764/dna-methylation-and-antipsychotic-treatment-mechanisms-in-schizophrenia-progress-and-future-directions
#1
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/28704275/agonist-e-6837-and-antagonist-sb-271046-of-5-ht6-receptors-both-reverse-the-depressive-like-effect-induced-in-mice-by-subchronic-ketamine-administration
#2
José E Suárez-Santiago, Alfredo Briones-Aranda, Judith Espinosa-Raya, Ofir Picazo
Major depression is one of the most common affective disorders caused by schizophrenia. The administration of N-methyl-D-aspartate receptor antagonists, such as ketamine, can reproduce the negative and affective symptoms of this disorder in animals. Preclinical studies have shown that 5-HT6 receptor (5-HT6R) agonists and antagonists have a considerable antipsychotic response. The aim of the present study was to evaluate the effect of an acute treatment with an agonist, E-6837, and an antagonist, SB-271046, of 5-HT6R on the immobility induced in mice by a subchronic ketamine regimen (5 days; 10 mg/kg/day, intraperitoneal)...
July 12, 2017: Behavioural Pharmacology
https://www.readbyqxmd.com/read/28701225/association-of-schizophrenia-onset-age-and-white-matter-integrity-with-treatment-effect-of-d-cycloserine-a-randomized-placebo-controlled-double-blind-crossover-study
#3
Kazuo Takiguchi, Akihito Uezato, Michio Itasaka, Hidenori Atsuta, Kenji Narushima, Naoki Yamamoto, Akeo Kurumaji, Makoto Tomita, Kazunari Oshima, Kosaku Shoda, Mai Tamaru, Masahito Nakataki, Mitsutoshi Okazaki, Sayuri Ishiwata, Yasuyoshi Ishiwata, Masato Yasuhara, Kunimasa Arima, Tetsuro Ohmori, Toru Nishikawa
BACKGROUND: It has been reported that drugs which promote the N-Methyl-D-aspartate-type glutamate receptor function by stimulating the glycine modulatory site in the receptor improve negative symptoms and cognitive dysfunction in schizophrenia patients being treated with antipsychotic drugs. METHODS: We performed a placebo-controlled double-blind crossover study involving 41 schizophrenia patients in which D-cycloserine 50 mg/day was added-on, and the influence of the onset age and association with white matter integrity on MR diffusion tensor imaging were investigated for the first time...
July 12, 2017: BMC Psychiatry
https://www.readbyqxmd.com/read/28696411/combined-study-of-genetic-and-epigenetic-biomarker-risperidone-treatment-efficacy-in-chinese-han-schizophrenia-patients
#4
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/28602646/the-effects-of-glycine-on-auditory-mismatch-negativity-in-schizophrenia
#5
Lisa-Marie Greenwood, Sumie Leung, Patricia T Michie, Amity Green, Pradeep J Nathan, Paul Fitzgerald, Patrick Johnston, Nadia Solowij, Jayashri Kulkarni, Rodney J Croft
Glycine increases N-methyl-d-aspartate receptor (NMDAR) mediated glutamatergic function. Mismatch negativity (MMN) is a proposed biomarker of glutamate-induced improvements in clinical symptoms, however, the effect of glycine-mediated NMDAR activation on MMN in schizophrenia is not well understood. This study aimed to determine the effects of acute and 6-week chronic glycine administration on MMN in schizophrenia patients. MMN amplitude was compared at baseline between 22 patients (schizophrenia or schizoaffective disorder; receiving stable antipsychotic medication; multi-centre recruitment) and 21 age- and gender-matched controls...
June 8, 2017: Schizophrenia Research
https://www.readbyqxmd.com/read/28587776/pharmacological-characterization-of-a-novel-potent-selective-and-orally-active-phosphodiesterase-2a-inhibitor-pdm-631
#6
Shunsuke Maehara, Keita Arakawa, Kotaro Hoshida, Hiroshi Nagasue, Noboru Chida, Kazunari Nakao, Shoji Furusako
Recently, we identified a novel phosphodiesterase 2A (PDE2A) inhibitor, PDM-631 ((S)-3-cyclopropyl-6-methyl-1-(1-(4-(trifluoromethoxy)phenyl)propan-2-yl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one). PDM-631 showed potent inhibitory activities for human and rat PDE2A with IC50 values of 1.5 and 4.2nM, respectively and more than 2000-fold selectivity against other phosphodiesterases. In rat studies, PDM-631 showed oral bioavailability and good brain penetration, and increased the cGMP levels in the cortex...
September 15, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28429622/pharmacoepigenomic-responses-of-antipsychotic-drugs-on-pharmacogenes-are-likely-to-be-modulated-by-mirnas
#7
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/28096877/efficacy-and-safety-of-bitopertin-in-patients-with-schizophrenia-and-predominant-negative-symptoms-subgroup-analysis-of-japanese-patients-from-the-global-randomized-phase-2-trial
#8
Yoshio Hirayasu, Shin-Ichi Sato, Norifumi Shuto, Miwa Nakano, Teruhiko Higuchi
OBJECTIVE: The aim of the present study was to perform a subgroup analysis of data from a phase II global, multi-center, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of bitopertin, a glycine reuptake inhibitor that activates N-methyl-D-aspartate receptors by increasing the concentration of glycine in the synaptic cleft, in Japanese and non-Japanese patients with schizophrenia and predominant negative symptoms. METHODS: Patients with schizophrenia and predominant negative symptoms on one or two antipsychotic drugs, including atypical antipsychotic drugs (olanzapine, risperidone, quetiapine, aripiprazole, and paliperidone) as the primary treatment, received bitopertin (10, 30, or 60 mg/day) or placebo once daily for 8 weeks as an add-on treatment...
January 2017: Psychiatry Investigation
https://www.readbyqxmd.com/read/28094812/putative-presynaptic-dopamine-dysregulation-in-schizophrenia-is-supported-by-molecular-evidence-from-post-mortem-human-midbrain
#9
T D Purves-Tyson, S J Owens, D A Rothmond, G M Halliday, K L Double, J Stevens, T McCrossin, C Shannon Weickert
The dopamine hypothesis of schizophrenia posits that increased subcortical dopamine underpins psychosis. In vivo imaging studies indicate an increased presynaptic dopamine synthesis capacity in striatal terminals and cell bodies in the midbrain in schizophrenia; however, measures of the dopamine-synthesising enzyme, tyrosine hydroxylase (TH), have not identified consistent changes. We hypothesise that dopamine dysregulation in schizophrenia could result from changes in expression of dopamine synthesis enzymes, receptors, transporters or catabolic enzymes...
January 17, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/27913254/quetiapine-treatment-reverses-depressive-like-behavior-and-reduces-dna-methyltransferase-activity-induced-by-maternal-deprivation
#10
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
https://www.readbyqxmd.com/read/27793672/critical-involvement-of-the-orbitofrontal-cortex-in-hyperlocomotion-induced-by-nmda-receptor-blockade-in-mice
#11
Kaoru Seiriki, Atsushi Kasai, Takahiro Kuwaki, Takanobu Nakazawa, Shun Yamaguchi, Hitoshi Hashimoto
Glutamatergic N-methyl-d-aspartate (NMDA) receptors play critical roles in several neurological and psychiatric diseases. Blockade by noncompetitive NMDA receptor antagonist leads to psychotomimetic effects; however, the brain regions responsible for the effects are not well understood. Here, we determined the specific brain regions responsive to MK-801, a noncompetitive NMDA receptor antagonist, by mapping Arc expression as an indicator of neuronal activity using Arc::dVenus reporter mice. MK-801 increased dVenus expression predominantly in the orbitofrontal cortex (OFC) and, as expected, induced a marked hyperlocomotion...
November 25, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27577742/the-influence-of-the-cb1-receptor-ligands-on-the-schizophrenia-like-effects-in-mice-induced-by-mk-801
#12
Marta Kruk-Slomka, Barbara Budzynska, Tomasz Slomka, Izabela Banaszkiewicz, Grazyna Biala
A growing body of psychiatric research has emerged, focusing on the role of endocannabinoid system in psychiatric disorders. For example, the endocannabinoid system, via cannabinoid CB (CB1 and CB2) receptors, is able to control the function of many receptors, such as N-methyl-D-aspartate (NMDA) receptors connected strictly with psychosis or other schizophrenia-associated symptoms. The aim of the present research was to investigate the impact of the CB1 receptor ligands on the symptoms typical for schizophrenia...
November 2016: Neurotoxicity Research
https://www.readbyqxmd.com/read/27536115/cycloid-psychoses-in-the-psychosis-spectrum-evidence-for-biochemical-differences-with-schizophrenia
#13
Nora Wa van de Kerkhof, Durk Fekkes, Frank Mma van der Heijden, Witte Jg Hoogendijk, Gerald Stöber, Jos Im Egger, Willem Ma Verhoeven
Cycloid psychoses (CP) differ from schizophrenia regarding symptom profile, course, and prognosis and over many decades they were thought to be a separate entity within the psychosis spectrum. As to schizophrenia, research into the pathophysiology has focused on dopamine, brain-derived neurotrophic factor, and glutamate signaling in which, concerning the latter, the N-methyl-d-aspartate receptor plays a crucial role. The present study aims to determine whether CP can biochemically be delineated from schizophrenia...
2016: Neuropsychiatric Disease and Treatment
https://www.readbyqxmd.com/read/27526039/progressive-supranuclear-palsy-and-corticobasal-degeneration-pathophysiology-and-treatment-options
#14
REVIEW
Ruth Lamb, Jonathan D Rohrer, Andrew J Lees, Huw R Morris
There are currently no disease-modifying treatments for progressive supranuclear palsy (PSP) or corticobasal degeneration (CBD), and no approved pharmacological or therapeutic treatments that are effective in controlling their symptoms. The use of most pharmacological treatment options are based on experience in other disorders or from non-randomized historical controls, case series, or expert opinion. Levodopa may provide some improvement in symptoms of Parkinsonism (specifically bradykinesia and rigidity) in PSP and CBD; however, evidence is conflicting and where present, benefits are often negligible and short lived...
September 2016: Current Treatment Options in Neurology
https://www.readbyqxmd.com/read/27471446/taurine-and-epidermal-growth-factor-belong-to-the-signature-of-first-episode-psychosis
#15
Kati Koido, Jürgen Innos, Liina Haring, Mihkel Zilmer, Aigar Ottas, Eero Vasar
This study evaluated the levels of two amino acid derivatives taurine and spermine in first-episode psychosis (FEP) patients and their response to antipsychotic treatment. The levels of taurine and spermine were significantly up-regulated in antipsychotic-naïve FEP patients compared to control subjects (CS). Treatment of FEP patients with antipsychotic drugs significantly reduced the positive symptoms of schizophrenia. This positive effect was accompanied by a significant reduction of taurine and spermine to the levels measured in CS...
2016: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/27391101/persistent-gating-deficit-and-increased-sensitivity-to-nmda-receptor-antagonism-after-puberty-in-a-new-mouse-model-of-the-human-22q11-2-microdeletion-syndrome-a-study-in-male-mice
#16
Michael Didriksen, Kim Fejgin, Simon R O Nilsson, Michelle R Birknow, Hannah M Grayton, Peter H Larsen, Jes B Lauridsen, Vibeke Nielsen, Pau Celada, Noemi Santana, Pekka Kallunki, Kenneth V Christensen, Thomas M Werge, Tine B Stensbøl, Jan Egebjerg, Francois Gastambide, Francesc Artigas, Jesper F Bastlund, Jacob Nielsen
BACKGROUND: The hemizygous 22q11.2 microdeletion is a common copy number variant in humans. The deletion confers high risk for neurodevelopmental disorders, including autism and schizophrenia. Up to 41% of deletion carriers experience psychotic symptoms. METHODS: We present a new mouse model (Df(h22q11)/+) of the deletion syndrome (22q11.2DS) and report on, to our knowledge, the most comprehensive study undertaken to date in 22q11.2DS models. The study was conducted in male mice...
January 2017: Journal of Psychiatry & Neuroscience: JPN
https://www.readbyqxmd.com/read/27373856/neuropharmacological-efficacy-of-the-traditional-japanese-kampo-medicine-yokukansan-and-its-active-ingredients
#17
REVIEW
Yasushi Ikarashi, Kazushige Mizoguchi
Dementia is a progressive neurodegenerative disorder with cognitive dysfunction, and is often complicated by behavioral and psychological symptoms of dementia (BPSD) including excitement, aggression, and hallucinations. Typical and atypical antipsychotics are used for the treatment of BPSD, but induce adverse events. The traditional Japanese Kampo medicine yokukansan (YKS), which had been originated from the traditional Chinese medicine Yi-Gan-San, has been reported to improve BPSD without severe adverse effects...
October 2016: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27296677/n-n-dimethylglycine-differentially-modulates-psychotomimetic-and-antidepressant-like-effects-of-ketamine-in-mice
#18
Jen-Cheng Lin, Ming-Huan Chan, Mei-Yi Lee, Yi-Chyan Chen, Hwei-Hsien Chen
Ketamine, a dissociative anesthetic, produces rapid and sustained antidepressant effects at subanesthtic doses. However, it still inevitably induces psychotomimetic side effects. N,N-dimethylglycine (DMG) is a derivative of the amino acid glycine and is used as a dietary supplement. Recently, DMG has been found acting at glycine binding site of the N-methyl-d-aspartate receptor (NMDAR). As blockade of NMDARs is one of the main mechanisms responsible for the action of ketamine on central nervous system, DMG might modulate the behavioral responses to ketamine...
November 3, 2016: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/26876050/genetic-association-analysis-of-n-methyl-d-aspartate-receptor-subunit-gene-grin2b-and-clinical-response-to-clozapine
#19
Danielle L Taylor, Arun K Tiwari, Jeffrey A Lieberman, Steven G Potkin, Herbert Y Meltzer, Jo Knight, Gary Remington, Daniel J Müller, James L Kennedy
OBJECTIVE: Approximately 30% of patients with schizophrenia fail to respond to antipsychotic therapy and are classified as having treatment-resistant schizophrenia. Clozapine is the most efficacious drug for treatment-resistant schizophrenia and may deliver superior therapeutic effects partly by modulating glutamate neurotransmission. Response to clozapine is highly variable and may depend on genetic factors as indicated by twin studies. We investigated eight polymorphisms in the N-methyl-D-aspartate glutamate receptor subunit gene GRIN2B with response to clozapine...
March 2016: Human Psychopharmacology
https://www.readbyqxmd.com/read/26756904/behavioral-and-molecular-neuroepigenetic-alterations-in-prenatally-stressed-mice-relevance-for-the-study-of-chromatin-remodeling-properties-of-antipsychotic-drugs
#20
E Dong, P Tueting, F Matrisciano, D R Grayson, A Guidotti
We have recently reported that mice born from dams stressed during pregnancy (PRS mice), in adulthood, have behavioral deficits reminiscent of behaviors observed in schizophrenia (SZ) and bipolar (BP) disorder patients. Furthermore, we have shown that the frontal cortex (FC) and hippocampus of adult PRS mice, like that of postmortem chronic SZ patients, are characterized by increases in DNA-methyltransferase 1 (DNMT1), ten-eleven methylcytosine dioxygenase 1 (TET1) and exhibit an enrichment of 5-methylcytosine (5MC) and 5-hydroxymethylcytosine (5HMC) at neocortical GABAergic and glutamatergic gene promoters...
January 12, 2016: Translational Psychiatry
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