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Schizophrenia pharmacogenetics

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https://www.readbyqxmd.com/read/27606316/inflammatory-cytokines-and-antipsychotic-induced-weight-gain-review-and-clinical-implications
#1
REVIEW
Trehani M Fonseka, Daniel J Müller, Sidney H Kennedy
Antipsychotic medications (APs), particularly second-generation APs, are associated with significant weight gain in schizophrenia patients. Recent evidence suggests that the immune system may contribute to antipsychotic-induced weight gain (AIWG) via AP-mediated alterations of cytokine levels. Antipsychotics with a high propensity for weight gain, such as clozapine and olanzapine, influence the expression of immune genes, and induce changes in serum cytokine levels to ultimately down-regulate neuroinflammation...
May 2016: Molecular Neuropsychiatry
https://www.readbyqxmd.com/read/27546373/pharmacogenetic-study-of-the-effects-of-raloxifene-on-negative-symptoms-of-postmenopausal-women-with-schizophrenia-a-double-blind-randomized-placebo-controlled-trial
#2
Javier Labad, Lourdes Martorell, Elena Huerta-Ramos, Jesús Cobo, Elisabet Vilella, Elena Rubio-Abadal, Gemma Garcia-Pares, Marta Creus, Cristian Núñez, Laura Ortega, Eva Miquel, Judith Usall
Several double-blind clinical trials have reported improvement in positive, negative and cognitive symptoms of schizophrenia with raloxifene, a selective receptor estrogen modulator. However, there are some inconsistencies in replicating findings between studies of different countries. The failure to replicate these findings may result from genetic factors that could explain some of the variability in the treatment response. However, pharmacogenetic studies exploring this topic in women with schizophrenia are lacking...
October 2016: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27469238/pharmacogenetics-of-tardive-dyskinesia-an-updated-review-of-the-literature
#3
Rachel K Lanning, Clement C Zai, Daniel J Müller
Tardive dyskinesia (TD) is a serious and potentially irreversible side effect of long-term exposure to antipsychotic medication characterized by involuntary trunk, limb and orofacial muscle movements. Various mechanisms have been proposed for the etiopathophysiology of antipsychotic-induced TD in schizophrenia patients with genetic factors playing a prominent role. Earlier association studies have focused on polymorphisms in CYP2D6, dopamine-, serotonin-, GABA- and glutamate genes. This review highlights recent advances in the genetic investigation of TD...
August 2016: Pharmacogenomics
https://www.readbyqxmd.com/read/27414739/-759c-t-polymorphism-of-the-htr2c-gene-is-associated-with-second-generation-antipsychotic-induced-weight-gain-in-female-patients-with-schizophrenia
#4
F M Daray, D Rodante, L G Carosella, M E Silva, M Martínez, M V Fernández Busch, D F Faccone, R P Rothlin, P C Maffía
Introduction: The HTR2C gene is an important candidate in pharmacogenetic studies of antipsychotic-induced weight gain (AIWG). However, inconsistent results have been obtained. The present study investigated the association between -759C>T, functional polymorphism of the HTR2C receptor, and AIWG. Methods: A prospective cohort of 48 female inpatients with schizophrenia and related illness treated according to normal clinical practice with second generation antipsychotics (SGAs) risperidone, clozapine, quetiapine, and olanzapine were evaluated...
July 14, 2016: Pharmacopsychiatry
https://www.readbyqxmd.com/read/27396334/somatostatin-interneurons-control-a-key-component-of-mismatch-negativity-in-mouse-visual-cortex
#5
Jordan P Hamm, Rafael Yuste
Patients with schizophrenia have deficient sensory processing, undermining how they perceive and relate to a changing environment. This impairment can be captured by the reduced mismatch negativity (MMN) index, an electroencephalographic biomarker of psychosis. The biological factors contributing to MMN are unclear, though mouse research, in which genetic and optical methods could be applied, has given some insight. Using fast two-photon calcium imaging and multielectrode recordings in awake mice, we find that visual cortical circuits display adapted (decreased) responses to repeated stimuli and amplified responses to a deviant stimulus, the key component of human MMN...
July 19, 2016: Cell Reports
https://www.readbyqxmd.com/read/27333159/variants-in-the-drd2-locus-and-antipsychotic-related-prolactin-levels-a-meta-analysis
#6
Itaru Miura, Jian-Ping Zhang, Katsuhiko Hagi, Todd Lencz, John M Kane, Hirooki Yabe, Anil K Malhotra, Christoph U Correll
BACKGROUND: Although dopamine D2 receptor antagonists lead to dose-dependent prolactin (PRL) elevations proportionate to their D2 affinity, considerable inter-individual differences exist. We conducted a meta-analytic review of associations between genetic variations in the dopamine D2 receptor gene (DRD2) and PRL levels in antipsychotic-treated subjects. METHODS: Systematic literature search (5/8/2015) was performed to find published studies of pharmacogenetic associations between two DRD2 variants, Taq1A (rs1800497) and -141C Ins/Del (rs1799732), and PRL levels during antipsychotic treatment (excluding aripiprazole)...
October 2016: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/27269905/african-specific-variability-in-the-acetylcholine-muscarinic-receptor-m4-association-with-cocaine-and-heroin-addiction
#7
Orna Levran, Matthew Randesi, Einat Peles, Joel Correa da Rosa, Jurg Ott, John Rotrosen, Miriam Adelson, Mary Jeanne Kreek
AIM: This study was designed to determine whether polymorphisms in acetylcholine receptors contribute to opioid dependence and/or cocaine dependence. PATIENTS & METHODS: The sample (n = 1860) was divided by drug and ancestry, and 55 polymorphisms (nine genes) were analyzed. RESULTS: Of the 20 SNPs that showed nominally significant associations, the association of the African-specific CHRM4 SNP rs2229163 (Asn417=) with cocaine dependence survived correction for multiple testing (Pcorrected = 0...
June 2016: Pharmacogenomics
https://www.readbyqxmd.com/read/27217270/pharmacogenetic-associations-of-antipsychotic-drug-related-weight-gain-a-systematic-review-and-meta-analysis
#8
Jian-Ping Zhang, Todd Lencz, Ryan X Zhang, Masahiro Nitta, Lawrence Maayan, Majnu John, Delbert G Robinson, W Wolfgang Fleischhacker, Rene S Kahn, Roel A Ophoff, John M Kane, Anil K Malhotra, Christoph U Correll
Although weight gain is a serious but variable adverse effect of antipsychotics that has genetic underpinnings, a comprehensive meta-analysis of pharmacogenetics of antipsychotic-related weight gain is missing. In this review, random effects meta-analyses were conducted for dominant and recessive models on associations of specific single nucleotide polymorphisms (SNP) with prospectively assessed antipsychotic-related weight or body mass index (BMI) changes (primary outcome), or categorical increases in weight or BMI (≥7%; secondary outcome)...
November 2016: Schizophrenia Bulletin
https://www.readbyqxmd.com/read/27092952/pde7b-nmbr-and-epm2a-variants-and-schizophrenia-a-case-control-and-pharmacogenetics-study
#9
Stefano Porcelli, Beatrice Balzarro, Soo-Jung Lee, Changsu Han, Ashwin A Patkar, Chi-Un Pae, Alessandro Serretti
BACKGROUND: We investigated phosphodiesterase 7B (PDE7B), neuromedin B receptor (NMBR) and epilepsy progressive myoclonus type 2A (EPM2A) genes in schizophrenia (SCZ). To the best of our knowledge, these genes have been poorly investigated in studies of SCZ. METHODS: Five hundred and seventy-three SCZ inpatients of Korean ethnicity and 560 healthy controls were genotyped for 2 PDE7B, 3 NMBR and 3 EPM2A polymorphisms. Differences in the allelic and genetic frequencies among healthy subjects and patients were calculated using the x03C7;2 statistics...
2016: Neuropsychobiology
https://www.readbyqxmd.com/read/27069875/kynurenine-pathway-and-cognitive-impairments-in-schizophrenia-pharmacogenetics-of-galantamine-and-memantine
#10
Maju Mathew Koola
The Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) project designed to facilitate the development of new drugs for the treatment of cognitive impairments in people with schizophrenia, identified three drug mechanisms of particular interest: dopaminergic, cholinergic, and glutamatergic. Galantamine is an acetylcholinesterase inhibitor and a positive allosteric modulator of the α7 nicotinic receptors. Memantine is an N-methyl-D-aspartate (NMDA) receptor antagonist. There is evidence to suggest that the combination of galantamine and memantine may be effective in the treatment of cognitive impairments in schizophrenia...
June 2016: Schizophrenia Research. Cognition
https://www.readbyqxmd.com/read/26953068/association-between-cyp1a2-gene-single-nucleotide-polymorphisms-and-clinical-responses-to-clozapine-in-patients-with-treatment-resistant-schizophrenia
#11
Anto P Rajkumar, B Poonkuzhali, Anju Kuruvilla, Alok Srivastava, Molly Jacob, K S Jacob
OBJECTIVES: Despite clozapine's superior clinical efficacy in treatment-resistant schizophrenia (TRS), its adverse effects, need for periodic leukocyte monitoring, cost and variable clinical outcomes mandate a clinical need to predict its treatment response. Although cytochrome P450 1A2 (CYP1A2) is the principal determinant of metabolism of clozapine, the role of CYP1A2 gene in the clinical response to clozapine is uncertain. Hence, we investigated its association with treatment responses and adverse events of clozapine in TRS...
February 2013: Acta Neuropsychiatrica
https://www.readbyqxmd.com/read/26861400/serotonin-2a-receptor-snp-rs7330461-association-with-treatment-response-to-pomaglumetad-methionil-in-patients-with-schizophrenia
#12
Laura K Nisenbaum, AnnCatherine M Downing, Fangyi Zhao, Brian A Millen, Leanne Munsie, Bruce J Kinon, David H Adams, Juan Carlos Gomez, Michelle Ann Penny
This study aims to confirm the initial pharmacogenetic finding observed within the clinical proof-of-concept trial of an enhanced response to treatment with pomaglumetad methionil (LY2140023 monohydrate) in Caucasian schizophrenia patients homozygous for T/T at single nucleotide polymorphism rs7330461 in the serotonin (5-hydroxytryptamine) 2A receptor gene compared to A/A homozygous patients. The effect of the rs7330461 genotype on the response to pomaglumetad methionil treatment was assessed in three additional clinical trials and in an integrated analysis...
February 5, 2016: Journal of Personalized Medicine
https://www.readbyqxmd.com/read/26856328/snare-complex-in-developmental-psychiatry-neurotransmitter-exocytosis-and-beyond
#13
REVIEW
Renata Basso Cupertino, Djenifer B Kappel, Cibele Edom Bandeira, Jaqueline Bohrer Schuch, Bruna Santos da Silva, Diana Müller, Claiton Henrique Dotto Bau, Nina Roth Mota
Multiple biological processes throughout development require intracellular vesicular trafficking, where the SNARE (soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein (SNAP) receptors) complex plays a major role. The core proteins forming the SNARE complex are SNAP-25 (synaptosomal-associated protein 25), VAMP (vesicle-associated membrane protein) and Syntaxins, besides its regulatory proteins, such as Synaptotagmin. Genes encoding these proteins (SNAP25, VAMP1, VAMP2, STX1A, SYT1 and SYT2) have been studied in relation to psychiatric disorders susceptibility...
August 2016: Journal of Neural Transmission
https://www.readbyqxmd.com/read/26856250/the-grm7-gene-early-response-to-risperidone-and-schizophrenia-a-genome-wide-association-study-and-a-confirmatory-pharmacogenetic-analysis
#14
E Sacchetti, C Magri, A Minelli, P Valsecchi, M Traversa, S Calza, A Vita, M Gennarelli
The search for biomarkers of response to antipsychotic medications is hindered by difficulties inherent in the topic or related to persistent methodological difficulties, such as high rates of anticipated discontinuation and consequent distortions in the imputation of missing data. Because early response to antipsychotics represents a sufficiently reliable index of the subsequent treatment response in patients with schizophrenia, we undertook a real-world, genome-wide association study (GWAS) with the aim of identifying genetic predictors of response to risperidone after 2 weeks in 86 patients with schizophrenia...
February 9, 2016: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/26780210/candidate-gene-analysis-of-pharmacodynamic-targets-for-antipsychotic-dosage
#15
Nuwan C Hettige, Gustavo H F de Moraes, James L Kennedy, Vincenzo De Luca
AIM: In order to administer antipsychotic medication with the most beneficial outcome, the appropriate drug and dose needs to be identified. Though often not considered in pharmacogenetic studies, dosage plays an important role in treatment outcome. This study set out to analyze the association between 109 SNPs and antipsychotic dosage among schizophrenia patients. In a previous study, we tested 134 SNPs in regards to antipsychotic dosage. In the current study, we tested additional markers in the same candidate genes that we investigated in the previous study to confirm our previous findings...
February 2016: Pharmacogenomics
https://www.readbyqxmd.com/read/26710776/-brain-neurotransmitter-systems-gene-polymorphism-the-search-for-pharmacogenetic-markers-of-efficacy-of-haloperidol-in-russians-and-tatars
#16
A E Gareeva, K O Kinyasheva, D Yu Galaktionova, E T Sabirov, R G Valinourov, A V Chudinov, A S Zasedatelev, T V Nasedkina, E K Khusnutdinova
Antipsychotics are the main drugs for the treatment of severe mental illness--schizophrenia affects about 1% of the population. The mechanism of action of neuroleptics is still up to the end. Several studies in the field of pharmacogenetics confirm enourmous influence of several neurotransmitter systems in the brain on the efficiency and the development of side effects. In this paper, we analyzed the association of nine polymorphic variants of five genes of dopaminergic and serotonergic systems DRD4, HTR2A, TPH1, SLC18A1, COMT in Russian and Tatars patients living in the Republic of Bashkortostan (RB) with the efficiency of a typical antipsychotic haloperidol on the scale of positive and negative systems of PANSS...
November 2015: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/26405684/olanzapine-reversed-brain-gene-expression-changes-induced-by-phencyclidine-treatment-in-non-human-primates
#17
Maureen V Martin, Karoly Mirnics, Laura K Nisenbaum, Marquis P Vawter
The NMDA receptor antagonist phencyclidine (PCP) creates schizophrenia-like symptoms in normal controls. The effect of PCP on non-human primate brain gene expression was examined and compared to changes induced by olanzapine treatment. Experimental studies of PCP and antipsychotic drugs have direct relevance to understanding the patho-physiology and treatment of schizophrenia. Genome-wide changes in prefrontal cortex gene expression revealed alterations of 146 transcripts in the PCP treatment group compared to vehicle controls...
July 2015: Molecular Neuropsychiatry
https://www.readbyqxmd.com/read/26400144/personalized-treatment-of-schizophrenia-in-everyday-clinical-practice-reality-or-fiction
#18
Blanka Kores Plesničar
Each day clinical practice tries to follow the idea and principles of personalized medicine. Besides predicting an individual's sensibility or predisposition for developing schizophrenia, pharmacogenetic and pharmacogenomic approaches attempt to define and acknowledge important indicators of clinical response to antipsychotics namely their efficacy and adverse effects. The main focus of our article were not facts regarding the role CYP450 liver enzymes have in this; our purpose is introducing other, new genetic and epigenetic factors which could introduce important biomarkers in diagnostics of the disease itself, the efficacy and tolerance for antipsychotics...
September 2015: Psychiatria Danubina
https://www.readbyqxmd.com/read/26398733/perspective-be-clear-about-the-real-risks
#19
Matthew Hill
No abstract text is available yet for this article.
September 24, 2015: Nature
https://www.readbyqxmd.com/read/26364648/pharmacogenetics-of-clozapine-treatment-response-and-side-effects-in-schizophrenia-an-update
#20
REVIEW
Venuja Sriretnakumar, Eric Huang, Daniel J Müller
INTRODUCTION: Clozapine (CLZ) is the most effective treatment for treatment-resistant schizophrenia (SCZ) patients, with potential added benefits of reduction in suicide risk and aggression. However, CLZ is also mainly underused due to its high risk for the potentially lethal side-effect of agranulocytosis as well as weight gain and related metabolic dysregulation. Pharmacogenetics promises to enable the prediction of patient treatment response and risk of adverse effects based on patients' genetics, paving the way toward individualized treatment...
2015: Expert Opinion on Drug Metabolism & Toxicology
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