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https://www.readbyqxmd.com/read/29136336/effect-of-polymorphisms-on-the-pharmacokinetics-pharmacodynamics-and-safety-of-sertraline-in-healthy-volunteers
#1
Miriam Saiz-Rodríguez, Carmen Belmonte, Manuel Román, Dolores Ochoa, Dora Koller, María Talegón, María C Ovejero-Benito, Rosario López-Rodríguez, Teresa Cabaleiro, Francisco Abad-Santos
Sertraline is a selective serotonin reuptake inhibitor (SSRI) widely metabolized in the liver by cytochrome P450 (CYP) enzymes. Besides, it is a P-glycoprotein substrate. Moreover, serotonin transporters and serotonin receptors are involved in its efficacy and safety. The aim of the present study was to evaluate the role of polymorphisms of metabolizing enzymes, transporters and receptors on the pharmacokinetics, pharmacodynamics and tolerability of sertraline in healthy volunteers. Forty-six healthy volunteers (24 men and 22 women) receiving a 100-mg single oral dose of sertraline were genotyped for 17 genetic variants of CYP enzymes (CYP2B6, CYP2C9, CYP2C19, CYP2D6), ATP binding cassette subfamily B member 1 (ABCB1), Solute carrier family 6 member 4 (SLC6A4), 5-Hydroxytryptamine receptor 2A (HTR2A) and 5-Hydroxytryptamine receptor 2C (HTR2C) genes...
November 14, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29120849/genetic-analysis-of-impulsive-personality-traits-examination-of-a-priori-candidates-and-genome-wide-variation
#2
Joshua C Gray, James MacKillop, Jessica Weafer, Kyle M Hernandez, Jianjun Gao, Abraham A Palmer, Harriet de Wit
Impulsive personality traits are heritable risk factors and putative endophenotypes for addiction and other psychiatric disorders involving disinhibition. This study examined the genetic basis of impulsive personality traits, defined as scores on the Barratt Impulsiveness Scale (BIS-11) and the UPPS-P Impulsive Behavior Scale (UPPS-P). In 983 healthy young adults of European ancestry, the study examined genetic variation in relation to a combined phenotype of seven subscales based on high phenotypic intercorrelations...
November 8, 2017: Psychiatry Research
https://www.readbyqxmd.com/read/29108778/the-timing-and-duration-of-estradiol-treatment-in-a-rat-model-of-the-perimenopause-influences-on-social-behavior-and-the-neuromolecular-phenotype
#3
Alexandra N Garcia, Christina Depena, Kelsey Bezner, Weiling Yin, Andrea C Gore
This study tested the effects of timing and duration of estradiol (E2) treatment, factors that are clinically relevant to hormone replacement in perimenopausal women, on social behavior and expression of genes in brain regions that regulate these behaviors. Female rats were ovariectomized (OVX) at 1year of age, roughly equivalent to middle-age in women, and given E2 or vehicle for different durations (3 or 6months) and timing (immediately or after a 3-month delay) relative to OVX. Social and ultrasonic vocalization (USV) behaviors were assessed at the 3 and 6month timepoints, and the rats' brains were then used for gene expression profiling in hypothalamus (supraoptic nucleus, paraventricular nucleus), bed nucleus of the stria terminalis, medial amygdala, and prefrontal cortex using a 48-gene qPCR platform...
November 8, 2017: Hormones and Behavior
https://www.readbyqxmd.com/read/29068870/multiple-tissue-methylation-analysis-of-htr2a-exon-i-in-suicidal-behavior
#4
Ali Bani-Fatemi, John Strauss, Clement Zai, Albert H C Wong, Vincenzo de Luca
OBJECTIVE: The main aim of the current study was to investigate epigenetic alterations in serotonin 2A receptor (HTR2A) exon I CpG sites as possible risk factors for suicidal behavior. We also aimed to analyze the epigenetic alterations in two different tissues as epigenetic mechanisms are tissue specific. These epigenetic changes may lead to a better prediction of suicidal behavior. METHODS: Direct CpG methylation analysis was carried out on genomic DNA from the saliva of 20 schizophrenia suicide attempters and 27 non-attempters, and from post-mortem brain tissues of nine suicide victims and 11 controls...
December 2017: Psychiatric Genetics
https://www.readbyqxmd.com/read/29057124/systems-biology-genetic-approach-identifies-serotonin-pathway-as-a-possible-target-for-obstructive-sleep-apnea-results-from-a-literature-search-review
#5
Ram Jagannathan, Azizi Seixas, David St-Jules, Lakshmanan Jagannathan, April Rogers, Lu Hu, Girardin Jean-Louis, Mary Ann Sevick
RATIONALE: Overall validity of existing genetic biomarkers in the diagnosis of obstructive sleep apnea (OSA) remains unclear. The objective of this systematic genetic study is to identify "novel" biomarkers for OSA using systems biology approach. METHODS: Candidate genes for OSA were extracted from PubMed, MEDLINE, and Embase search engines and DisGeNET database. The gene ontology (GO) analyses and candidate genes prioritization were performed using Enrichr tool...
2017: Sleep Disorders
https://www.readbyqxmd.com/read/29042551/integrating-evolutionary-and-regulatory-information-with-a-multispecies-approach-implicates-genes-and-pathways-in-obsessive-compulsive-disorder
#6
Hyun Ji Noh, Ruqi Tang, Jason Flannick, Colm O'Dushlaine, Ross Swofford, Daniel Howrigan, Diane P Genereux, Jeremy Johnson, Gerard van Grootheest, Edna Grünblatt, Erik Andersson, Diana R Djurfeldt, Paresh D Patel, Michele Koltookian, Christina M Hultman, Michele T Pato, Carlos N Pato, Steven A Rasmussen, Michael A Jenike, Gregory L Hanna, S Evelyn Stewart, James A Knowles, Stephan Ruhrmann, Hans-Jörgen Grabe, Michael Wagner, Christian Rück, Carol A Mathews, Susanne Walitza, Daniëlle C Cath, Guoping Feng, Elinor K Karlsson, Kerstin Lindblad-Toh
Obsessive-compulsive disorder is a severe psychiatric disorder linked to abnormalities in glutamate signaling and the cortico-striatal circuit. We sequenced coding and regulatory elements for 608 genes potentially involved in obsessive-compulsive disorder in human, dog, and mouse. Using a new method that prioritizes likely functional variants, we compared 592 cases to 560 controls and found four strongly associated genes, validated in a larger cohort. NRXN1 and HTR2A are enriched for coding variants altering postsynaptic protein-binding domains...
October 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/29032150/functional-analysis-of-schizophrenia-genes-using-geneanalytics-program-and-integrated-databases
#7
Tharani Sundararajan, Ann M Manzardo, Merlin G Butler
Schizophrenia (SCZ) is a chronic debilitating neuropsychiatric disorder with multiple risk factors involving numerous complex genetic influences. We examined and updated a master list of clinically relevant and susceptibility genes associated with SCZ reported in the literature and genomic databases dedicated to gene discovery for characterization of SCZ genes. We used the commercially available GeneAnalytics computer-based gene analysis program and integrated genomic databases to create a molecular profile of the updated list of 608 SCZ genes to model their impact in select categories (tissues and cells, diseases, pathways, biological processes, molecular functions, phenotypes and compounds) using specialized GeneAnalytics algorithms...
October 12, 2017: Gene
https://www.readbyqxmd.com/read/29021832/pharmacogenomics-in-the-treatment-of-mood-disorders-strategies-and-opportunities-for-personalized-psychiatry
#8
REVIEW
Azmeraw T Amare, Klaus Oliver Schubert, Bernhard T Baune
Personalized medicine (personalized psychiatry in a specific setting) is a new model towards individualized care, in which knowledge from genomics and other omic pillars (microbiome, epigenomes, proteome, and metabolome) will be combined with clinical data to guide efforts to new drug development and targeted prescription of the existing treatment options. In this review, we summarize pharmacogenomic studies in mood disorders that may lay the foundation towards personalized psychiatry. In addition, we have discussed the possible strategies to integrate data from omic pillars as a future path to personalized psychiatry...
September 2017: EPMA Journal
https://www.readbyqxmd.com/read/28951738/serotonin-related-gene-variants-in-patients-with-irritable-bowel-syndrome-and-depressive-or-anxiety-disorders
#9
Magdalena Grzesiak, Jan Aleksander Beszłej, Ewa Waszczuk, Marcin Szechiński, Monika Szewczuk-Bogusławska, Dorota Frydecka, Tadeusz Dobosz, Anna Jonkisz, Arleta Lebioda, Małgorzata Małodobra, Agata Mulak
AIM: To assess the association of six polymorphisms in serotonin-related genes with depressive or anxiety disorders in patients with irritable bowel syndrome (IBS). METHODS: The lifetime prevalence of depressive and anxiety disorders was assessed in 95 IBS patients (85% women) using the Munich version of the Composite International Diagnostic Interview (CIDI). IBS was diagnosed according to the Rome III criteria. SCL6A4 HTTLPR polymorphism (rs4795541) was determined using PCR-based method...
2017: Gastroenterology Research and Practice
https://www.readbyqxmd.com/read/28947721/behavioural-genetic-differences-between-chinese-and-european-pigs
#10
Qingpo Chu, Tingting Liang, Lingling Fu, Huizhi Li, Bo Zhou
Aggression is a heritable trait and genetically related to neurotransmitter-related genes. Behavioural characteristics of some pig breeds are different. To compare the genetic differences between breeds, backtest and aggressive behaviour assessments, and genotyped using Sequenom iPLEX platform were performed in 50 Chinese indigenous Mi pigs and 100 landrace-large white (LLW) cross pigs with 32 SNPs localized in 11 neurotransmitter-related genes. The genetic polymorphisms of 26 SNPs had notable differences (P < 0...
September 2017: Journal of Genetics
https://www.readbyqxmd.com/read/28939587/expression-and-genetic-variation-in-neuroendocrine-signaling-pathways-in-lethal-and-nonlethal-prostate-cancer-among-men-diagnosed-with-localized-disease
#11
Donghao Lu, Jessica Carlsson, Kathryn L Penney, Sabina Davidsson, Swen-Olof Andersson, Lorelei A Mucci, Unnur Valdimarsdóttir, Ove Andrén, Fang Fang, Katja Fall
BACKGROUND: Recent data suggest that neuroendocrine signaling pathways may play a role in the progression of prostate cancer, particularly for early-stage disease. We aimed to explore whether expression of selected genes in the adrenergic, serotoninergic, glucocorticoid, and dopaminergic pathways differs in prostate tumor tissue from men with lethal disease compared to men with nonlethal disease. METHODS: Based on the Swedish Watchful Waiting Cohort, we included 511 men diagnosed with incidental prostate cancer through TURP during 1977-1998 with follow-up up to 30 years...
September 22, 2017: Cancer Epidemiology, Biomarkers & Prevention
https://www.readbyqxmd.com/read/28902619/a-case-control-association-study-of-12-candidate-genes-and-attempted-suicide-in-french-adolescents
#12
Bojan Mirkovic, David Cohen, Claudine Laurent, Malaika Lasfar, Christophe Marguet, Prsicille Gerardin
Background Suicide is the second leading cause of death for 10-19-year-olds. Evidence has shown that attempted suicide is a complex interplay of genes and environmental factors. In the adult population, possible associations between genetic polymorphisms and suicidal behaviors have been investigated for several genes, most often with inconsistent findings and poor replicability of significant associations. This study aimed to identify gene variants conferring risk for adolescent suicide attempt. Methods We selected the genes and variants after an analysis of the literature and a selection of the most significant associations identified...
September 13, 2017: International Journal of Adolescent Medicine and Health
https://www.readbyqxmd.com/read/28900078/-polymorphic-variants-of-glutamate-receptor-grik5-grin2b-and-serotonin-receptor-htr2a-genes-are-associated-with-chronic-obstructive-pulmonary-disease
#13
G F Korytina, L Z Akhmadishina, O V Kochetova, Y G Aznabaeva, Sh Z Zagidullin, T V Victorova
Chronic obstructive pulmonary disease (COPD) is a complex chronic inflammatory disease of the respiratory system that affects primarily distal respiratory pathways and lung parenchyma. Smoking tobacco is a major risk factor for COPD. The relationship of HTR4 (rs3995090), HTR2A (rs6313), GRIK5 (rs8099939), GRIN2B (rs2268132), and CHRNB4 (rs1948) gene polymorphisms and COPD, as well as the contribution of these polymorphisms to the variations in quantitative characteristics that describe respiratory function, smoking behavior, and nicotine dependence was assessed in an ethnically homogeneous Tatar population...
July 2017: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/28837927/parental-transfer-of-microcystin-lr-induced-transgenerational-effects-of-developmental-neurotoxicity-in-zebrafish-offspring
#14
Qin Wu, Wei Yan, Houcheng Cheng, Chunsheng Liu, Tien-Chieh Hung, Xiaochun Guo, Guangyu Li
Microcystin-LR (MCLR) has been reported to cause developmental neurotoxicity in zebrafish, but there are few studies on the mechanisms of MCLR-induced transgenerational effects of developmental neurotoxicity. In this study, zebrafish were exposed to 0, 1, 5, and 25 μg/L MCLR for 60 days. The F1 zebrafish embryos from the above-mentioned parents were collected and incubated in clean water for 120 h for hatching. After examining the parental zebrafish and F1 embryos, MCLR was detected in the gonad of adults and F1 embryos, indicating MCLR could potentially be transferred from parents to offspring...
December 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28825719/central-amygdala-circuits-modulate-food-consumption-through-a-positive-valence-mechanism
#15
Amelia M Douglass, Hakan Kucukdereli, Marion Ponserre, Milica Markovic, Jan Gründemann, Cornelia Strobel, Pilar L Alcala Morales, Karl-Klaus Conzelmann, Andreas Lüthi, Rüdiger Klein
The complex behaviors underlying reward seeking and consumption are integral to organism survival. The hypothalamus and mesolimbic dopamine system are key mediators of these behaviors, yet regulation of appetitive and consummatory behaviors outside of these regions is poorly understood. The central nucleus of the amygdala (CeA) has been implicated in feeding and reward, but the neurons and circuit mechanisms that positively regulate these behaviors remain unclear. Here, we defined the neuronal mechanisms by which CeA neurons promote food consumption...
October 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28809398/precision-medicine-for-suicidality-from-universality-to-subtypes-and-personalization
#16
A B Niculescu, H Le-Niculescu, D F Levey, P L Phalen, H L Dainton, K Roseberry, E M Niculescu, J O Niezer, A Williams, D L Graham, T J Jones, V Venugopal, A Ballew, M Yard, T Gelbart, S M Kurian, A Shekhar, N J Schork, G E Sandusky, D R Salomon
Suicide remains a clear, present and increasing public health problem, despite being a potentially preventable tragedy. Its incidence is particularly high in people with overt or un(der)diagnosed psychiatric disorders. Objective and precise identification of individuals at risk, ways of monitoring response to treatments and novel preventive therapeutics need to be discovered, employed and widely deployed. We sought to investigate whether blood gene expression biomarkers for suicide (that is, a 'liquid biopsy' approach) can be identified that are more universal in nature, working across psychiatric diagnoses and genders, using larger cohorts than in previous studies...
September 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28806488/the-role-of-5-ht2b-receptors-in-mitral-valvulopathy-bone-marrow-mobilization-of-endothelial-progenitors
#17
Estelle Ayme-Dietrich, Roland Lawson, Francine Côté, Claudia de Tapia, Sylvia Da Silva, Claudine Ebel, Béatrice Hechler, Christian Gachet, Jérome Guyonnet, Hélène Rouillard, Jordane Stoltz, Emily Quentin, Sophie Banas, François Daubeuf, Nelly Frossard, Bernard Gasser, Jean-Philippe Mazzucotelli, Olivier Hermine, Luc Maroteaux, Laurent Monassier
BACKGROUND AND PURPOSE: Valvular heart disease (VHD) is highly prevalent in industrialized countries. Chronic use of anorexigens, amphetamine or ergot derivatives targeting the 5-HT system is associated with VHD. Here, we investigated the contribution of 5-HT receptors in a model of valve degeneration induced by nordexfenfluramine, the main metabolite of the anorexigens, dexfenfluramine and benfluorex. EXPERIMENTAL APPROACH: Nordexfenfluramine was infused chronically (28 days) in mice ((WT and transgenic Htr2B   (-/-) , Htr2A   (-/-) , and Htr2B/2A   (-/-) ) to induce mitral valve lesions...
November 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28755876/a-computational-network-analysis-based-on-targets-of-antipsychotic-agents
#18
Lei Gao, Shuo Feng, Zhao-Yuan Liu, Jiu-Qiang Wang, Ke-Ke Qi, Kai Wang
Currently, numerous antipsychotic agents have been developed in the area of pharmacological treatment of schizophrenia. However, the molecular mechanism underlying multi targets of antipsychotics were yet to be explored. In this study we performed a computational network analysis based on targets of antipsychotic agents. We retrieved a total of 96 targets from 56 antipsychotic agents. By expression enrichment analysis, we identified that the expressions of antipsychotic target genes were significantly enriched in liver, brain, blood and corpus striatum...
July 26, 2017: Schizophrenia Research
https://www.readbyqxmd.com/read/28751646/an-integrative-computational-approach-to-evaluate-genetic-markers-for-bipolar-disorder
#19
Yong Xu, Jun Wang, Shuquan Rao, McKenzie Ritter, Lydia C Manor, Robert Backer, Hongbao Cao, Zaohuo Cheng, Sha Liu, Yansong Liu, Lin Tian, Kunlun Dong, Yin Yao Shugart, Guoqiang Wang, Fuquan Zhang
Studies to date have reported hundreds of genes connected to bipolar disorder (BP). However, many studies identifying candidate genes have lacked replication, and their results have, at times, been inconsistent with one another. This paper, therefore, offers a computational workflow that can curate and evaluate BP-related genetic data. Our method integrated large-scale literature data and gene expression data that were acquired from both postmortem human brain regions (BP case/control: 45/50) and peripheral blood mononuclear cells (BP case/control: 193/593)...
July 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28716530/genetic-association-analysis-of-serotonin-and-signal-transduction-pathways-in-suicide-attempters-from-an-italian-sample-of-psychiatric-patients
#20
Maurizio Pompili, Giovanna Gentile, Catia Scassellati, Cristian Bonvicini, Marco Innamorati, Denise Erbuto, Franco Montebovi, Giuseppe Ducci, Alberto Forte, Eleonora De Pisa, Stefano Ferracuti, Gianluca Serafini, Vincenzo De Luca, Mario Amore, Maurizio Simmaco, Paolo Girardi
Genetic factors have been reported to contribute to the liability of suicide. We aimed to investigate functional polymorphisms in eight genes (serotonin transporter, SLC6A4; receptors, 5HTR1A, 1B, 5HTR2A; Tryptophan Hydroxylase, TPH1, TPH2; Monoamine Oxidase, MAOA and G Protein Subunit Beta 3, GNB3) to investigate their predictive value for suicide. The possible confounding effects of gender and phenotypic patients dissection were also valued. A sample of 111 consecutive psychiatric inpatients was recruited and assessed using specific psychometric instruments...
July 14, 2017: Neuroscience Letters
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