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https://www.readbyqxmd.com/read/28431800/genetic-predictors-of-antipsychotic-response-to-lurasidone-identified-in-a-genome-wide-association-study-and-by-schizophrenia-risk-genes
#1
Jiang Li, Akane Yoshikawa, Mark D Brennan, Timothy L Ramsey, Herbert Y Meltzer
Biomarkers which predict response to atypical antipsychotic drugs (AAPDs) increases their benefit/risk ratio. We sought to identify common variants in genes which predict response to lurasidone, an AAPD, by associating genome-wide association study (GWAS) data and changes (Δ) in Positive And Negative Syndrome Scale (PANSS) scores from two 6-week randomized, placebo-controlled trials of lurasidone in schizophrenia (SCZ) patients. We also included SCZ risk SNPs identified by the Psychiatric Genomics Consortium using a polygenic risk analysis...
April 18, 2017: Schizophrenia Research
https://www.readbyqxmd.com/read/28429622/pharmacoepigenomic-responses-of-antipsychotic-drugs-on-pharmacogenes-are-likely-to-be-modulated-by-mirnas
#2
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/28429077/-implementation-of-the-german-s3-guidelines-on-dementia-in-clinical-practice-wish-or-reality
#3
H Lohmann, F Kulessa, H Holling, A Johnen, S Reul, G Lueg, T Duning
BACKGROUND: Published in 2009, the German S3 guidelines on dementia define a milestone in quality improvement of the diagnostics and treatment of dementia. In clinical practice patients suffering from dementia are primarily treated by physicians in private practice; therefore, this study examined how the guidelines are implemented in outpatient clinical settings. Furthermore, it aimed at the identification of behavioral determinants that govern the actual diagnostic and therapeutic approach in clinical practice...
April 20, 2017: Der Nervenarzt
https://www.readbyqxmd.com/read/28422528/effect-of-psychopharmacotherapy-on-body-mass-index-among-children-and-adolescents-with-bipolar-disorders
#4
Ayush Patel, Wenyaw Chan, Rajender R Aparasu, Melissa Ochoa-Perez, Jeff T Sherer, Rohan Medhekar, Hua Chen
OBJECTIVE: To assess the long-term effect of all treatment options for pediatric bipolar disorders on body mass index (BMI) and to explore individual characteristics associated with less BMI increase during psychotropic medication exposures. METHODS: A retrospective cohort study was conducted by using the 1995 to 2010 General Electric Electronic Medical Record database. Individuals aged 18 years or younger who had a new bipolar disorder episode were identified. Treatment exposure was defined based on the medication regimens patients received, which include atypical antipsychotic (AT) monotherapy, mood stabilizer (MS) monotherapy, antidepressant (AD) monotherapy, AT+MS polytherapy, AT+AD polytherapy, MS+AD polytherapy, and no treatment...
April 19, 2017: Journal of Child and Adolescent Psychopharmacology
https://www.readbyqxmd.com/read/28421257/histone-deacetylase-inhibitors-reverse-age-related-increases-in-side-effects-of-haloperidol-in-mice
#5
Janitza L Montalvo-Ortiz, Daniel W Fisher, Guadalupe Rodríguez, Deyu Fang, John G Csernansky, Hongxin Dong
BACKGROUND: Older patients can be especially susceptible to antipsychotic-induced side effects, and the pharmacodynamic mechanism underlying this phenomenon remains unclear. We hypothesized that age-related epigenetic alterations lead to decreased expression and functionality of the dopamine D2 receptor (D2R), contributing to this susceptibility. METHODS: In this study, we treated young (2-3 months old) and aged (22-24 months old) C57BL/6 mice with the D2R antagonist haloperidol (HAL) once a day for 14 days to evaluate HAL-induced motor side effects...
April 18, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28419874/oral-administration-of-a-specific-kynurenic-acid-synthesis-kat-ii-inhibitor-attenuates-evoked-glutamate-release-in-rat-prefrontal-cortex
#6
D M Bortz, H-Q Wu, R Schwarcz, J P Bruno
Cognitive deficits represent core symptoms in schizophrenia (SZ) and predict patient outcome; however, they remain poorly treated by current antipsychotic drugs. Elevated levels of the endogenous alpha7 nicotinic receptor negative allosteric modulator and NMDA receptor antagonist, kynurenic acid (KYNA), are commonly seen in post-mortem tissue and cerebrospinal fluid of patients with SZ. When acutely or chronically elevated in rodents, KYNA produces cognitive deficits similar to those seen in the disease, making down-regulation of KYNA, via inhibition of kynurenine aminotransferase II (KAT II), a potential treatment strategy...
April 15, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28419824/effect-of-risperidone-on-serum-homocysteine-levels-in-first-episode-drug-na%C3%A3-ve-patients-with-schizophrenia
#7
Ning Fan, Yunlong Tan, Fude Yang, Li Tian, Song Chen, Jia Li, Zhiren Wang, Xiangyang Zhang
Some studies have shown that homocysteine (Hcy) levels are increased in patients with schizophrenia, and may be involved in its pathophysiology. The purpose of this study was to investigate the effect of the atypical antipsychotic drug risperidone on serum Hcy levels and to explore the relationship between the changes in Hcy levels and the therapeutic outcome, which, to our best knowledge have not been investigated. Fifty-six first-episode and drug-naïve inpatients with schizophrenia were assigned to a 12-week treatment regime with risperidone...
April 15, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28418011/more-than-25-years-of-genetic-studies-of-clozapine-induced-agranulocytosis
#8
REVIEW
S A J de With, S L Pulit, W G Staal, R S Kahn, R A Ophoff
Clozapine is one of the most effective atypical antipsychotic drugs prescribed to patients with treatment-resistant schizophrenia. Approximately 1% of patients experience potential life-threatening adverse effects in the form of agranulocytosis, greatly hindering its applicability in clinical practice. The etiology of clozapine-induced agranulocytosis (CIA) remains unclear, but is thought to be a heritable trait. We reviewed the genetic studies of CIA published thus far. One recurrent finding from early candidate gene study to more recent genome-wide analysis is that of the involvement of human leukocyte antigen locus...
April 18, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28417028/general-anaesthesia-protocols-for-patients-undergoing-electroconvulsive-therapy-retrospective-analysis-of-504-sessions-over-a-five-year-period-at-a-tertiary-care-hospital-in-oman
#9
Aravind Narayanan, Chandar Lal, Hamed Al-Sinawi
OBJECTIVES: This study aimed to review general anaesthesia protocols for patients undergoing electroconvulsive therapy (ECT) at a tertiary care hospital in Oman, particularly with regards to clinical profile, potential drug interactions and patient outcomes. METHODS: This retrospective study took place at the Sultan Qaboos University Hospital (SQUH), Muscat, Oman. The electronic medical records of patients undergoing ECT at SQUH between January 2010 and December 2014 were reviewed for demographic characteristics and therapy details...
February 2017: Sultan Qaboos University Medical Journal
https://www.readbyqxmd.com/read/28415586/promoting-oligodendroglial-oriented-differentiation-of-glioma-stem-cell-a-repurposing-of-quetiapine-for-the-treatment-of-malignant-glioma
#10
Yun Wang, Nanxin Huang, Hongli Li, Shubao Liu, Xianjun Chen, Shichang Yu, Nan Wu, Xiu-Wu Bian, Hai-Ying Shen, Chengren Li, Lan Xiao
As a major contributor of chemotherapy resistance and malignant recurrence, glioma stem cells (GSCs) have been proposed as a target for the treatment of gliomas. To evaluate the therapeutic potential of quetiapine (QUE), an atypical antipsychotic, for the treatment of malignant glioma, we established mouse models with GSCs-initiated orthotopic xenograft gliomas and subcutaneous xenograft tumors, using GSCs purified from glioblastoma cell line GL261. We investigated antitumor effects of QUE on xenograft gliomas and its underlying mechanisms on GSCs...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415443/3-month-parenteral-plga-microsphere-formulations-of-risperidone-fabrication-characterization-and-neuropharmacological-assessments
#11
Sundeep Chaurasia, Kuchukuntla Mounika, Vasudha Bakshi, Vure Prasad
The study aims at formulation and characterization of three months parenteral risperidone loaded polymeric microspheres (p-RLPMs) as a sustained delivery system and established their in vitro and in vivo assessments. The p-RLPMs formulations were prepared by solvent extraction and diffusion method. The optimized p-RLPMs (batch RPLGA-1) formulation demonstrated favorable different physicochemical properties such as mean particle size (104±5.34μm), percent porosity (44.56±3.11%) and percent drug loading (38...
June 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28414930/antipsychotics-promote-gabaergic-interneuron-genesis-in-the-adult-rat-brain-role-of-heat-shock-protein-production
#12
Hiroo Kaneta, Wataru Ukai, Hanako Tsujino, Kengo Furuse, Yoshiyasu Kigawa, Masaya Tayama, Takao Ishii, Eri Hashimoto, Chiaki Kawanishi
Current antipsychotics reduce positive symptoms and reverse negative symptoms in conjunction with cognitive behavioral issues with the goal of restoring impaired occupational and social functioning. However, limited information is available on their influence on gliogenesis or their neurogenic properties in adult schizophrenia brains, particularly on GABAergic interneuron production. In the present study, we used young adult subventricular zone (SVZ)-derived progenitor cells expressing proteoglycan NG2 cultures to examine the oligodendrocyte and GABAergic interneuron genesis effects of several kinds of antipsychotics on changes in differentiation function induced by exposure to the NMDA receptor antagonist MK-801...
March 10, 2017: Journal of Psychiatric Research
https://www.readbyqxmd.com/read/28414178/short-and-long-term-effects-of-risperidone-on-catalepsy-sensitisation-and-acquisition-of-conditioned-avoidance-response-adolescent-vs-adult-rats
#13
Aung Aung Kywe Moe, Gregory A Medely, Timothy Reeks, Thomas H J Burne, Darryl W Eyles
The effects of antipsychotic drugs (APDs) on the adolescent brain are poorly understood despite a dramatic increase in prescription of these drugs in adolescents over the past twenty years. Neuronal systems continue to be remodeled during adolescence. Therefore, when given in adolescence, antipsychotic drugs (APDs) have the potential to affect this remodeling. In this study we investigated the effects of chronic 22-day risperidone treatment (1.3mg/kg/day) in both adolescent and adult rats. We examined short- and long-term changes in behaviour (catalepsy, locomotion and conditioned avoidance response (CAR)), and dopaminergic and serotonergic neurochemistry in the striatum and the nucleus accumbens...
April 13, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28413414/comedication-and-treatment-length-in-users-of-acetylcholinesterase-inhibitors
#14
Anne Sverdrup Efjestad, Hege Ihle-Hansen, Vidar Hjellvik, Hege Salvesen Blix
BACKGROUND/AIMS: Reduced clinical effect on cognitive decline in dementia by acetylcholinesterase inhibitors (AChEIs) may be due to concurrent use of drugs with anticholinergic properties. The aim was to analyze the incidence of AChEI use and comedication with drugs with anticholinergic properties and other potential unfavorable effects. METHODS: A prospective study applying drug use data from the Norwegian Prescription Database. Anticholinergic Drug Scale (ADS) scores were used as a measure of overall anticholinergic burden...
January 2017: Dementia and Geriatric Cognitive Disorders Extra
https://www.readbyqxmd.com/read/28412910/aripiprazole-a-drug-that-displays-partial-agonism-and-functional-selectivity
#15
Erin W Tuplin, Matthew R Holahan
The treatment of schizophrenia is challenging due to the wide range of symptoms (positive, negative, cognitive) associated with the disease. Typical antipsychotics that antagonize D2 receptors are effective in treating positive symptoms, but extrapyramidal side-effects (EPS) are a common occurrence. Atypical antipsychotics targeting 5-TH2A and D2 receptors are more effective at treating cognitive and negative symptoms compared to typical antipsychotics, but these drugs also result in side-effects such as metabolic syndromes...
April 13, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28412306/time-dependent-sensitization-of-antipsychotic-effect-in-adolescent-male-and-female-rats
#16
Xiaojing Ding, Xiaonan Li, Qing Shu, Ruiyong Wu, Gang Hu, Ming Li
Many behavioral and biological effects of a psychoactive drug often undergo time-dependent change following even one single drug exposure. The present study examined whether one or two exposures of haloperidol, olanzapine or clozapine would also induce a time-dependent change in their behavioral effects in adolescent rats and whether such a change vary between sexes. Adolescent Sprague-Dawley rats (<40days old) were first treated with one single injection of haloperidol (0.05 and 0.1mg/kg, sc), clozapine (10...
April 12, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28411574/risperidone-versus-olanzapine-in-the-acute-treatment-of-persistent-delusional-disorder-a-retrospective-analysis
#17
Karishma Kulkarni, Rashmi Arasappa, Krishna Prasad M, Amit Zutshi, Prabhat K Chand, Pratima Murthy, Mariamma Philip, Kesavan Muralidharan
There is a dearth of prospective trials studying treatment response in Persistent Delusional Disorder (PDD) to guide clinical practice. Available retrospective data indicate good response to second-generation antipsychotics (SGAs). We selected the data of patients prescribed either olanzapine or risperidone from a retrospective chart review of PDD (n=455) at our centre. We compared the two groups olanzapine (n =86) versus risperidone (n =280) on dose, drug adherence, response and adverse effects. The two groups were comparable on socio-demographic and clinical characteristics of PDD...
April 9, 2017: Psychiatry Research
https://www.readbyqxmd.com/read/28411046/different-influence-of-antipsychotics-on-the-balance-between-pro-and-anti-inflammatory-cytokines-depends-on-glia-activation-an-in-vitro-study
#18
Ewa Obuchowicz, Anna M Bielecka-Wajdman, Monika Paul-Samojedny, Marta Nowacka
The microglial hypothesis of schizophrenia suggests that its neuropathology is closely associated with neuroinflammation manifested, inter alia, by an increased expression of cytokines. However, clinical investigations imply that schizophrenia is a heterogeneous disease and in some groups of patients the activated inflammatory process does not contribute to the disease-associated impairment of brain function. Clinical studies revealed also an equivocal impact of antipsychotics on peripheral and CSF cytokines, whereas experimental research performed on the stimulated glia cultures showed their inhibitory effect on pro-inflammatory cytokine levels...
April 11, 2017: Cytokine
https://www.readbyqxmd.com/read/28410959/the-involvement-of-bdnf-creb-signaling-pathways-in-the-pharmacological-mechanism-of-combined-ssri-antipsychotic-treatment-in-schizophrenia
#19
Reef Einoch, Orly Weinreb, Nina Mandiuk, Moussa B H Youdim, Warren Bilker, Henry Silver
Previous studies into the mechanism of SSRI-antipsychotic synergism in our laboratory identified unique changes in the brain, particularly in the γ-aminobutyric acid (GABA)-A receptor and its modulators. This study examined the role of brain derived neurotrophic factor (BDNF)-cAMP response element binding (CREB) protein signaling pathways, including protein kinase B (AKT), glycogen synthase kinase (GSK)-3β and related molecules in the molecular response to haloperidol, fluvoxamine, combined haloperidol+fluvoxamine and clozapine treatments in rat frontal cortex, hippocampus and primary cortical neuronal cultures...
April 11, 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28408985/new-drugs-in-psychiatry-focus-on-new-pharmacological-targets
#20
REVIEW
Filippo Caraci, Gian Marco Leggio, Salvatore Salomone, Filippo Drago
The approval of psychotropic drugs with novel mechanisms of action has been rare in recent years. To address this issue, further analysis of the pathophysiology of neuropsychiatric disorders is essential for identifying new pharmacological targets for psychotropic medications. In this report, we detail drug candidates being examined as treatments for psychiatric disorders. Particular emphasis is placed on agents with novel mechanisms of action that are being tested as therapies for depression, schizophrenia, or Alzheimer's disease...
2017: F1000Research
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