Rightmed Comprehensive Test Report

Total Page:16

File Type:pdf, Size:1020Kb

Rightmed Comprehensive Test Report Making prescriptions personal RightMed® comprehensive test report The RightMed comprehensive test is a pharmacogenomic test that identi]es how a patient’s DNA affects their response to hundreds of medications. This report can be used to help determine safer, more effective medications and doses tailored to a patient’s unique genomic pro]le. Additional reports, including RightMed Advisor custom reports and specialty reports, are available through the provider portal at portal.oneome.com. Patient and report summary Patient name: Jane Doe Ordering provider: Sample Doctor Patient date of birth: 1972-07-08 Ordering facility: Healthcare Institution OneOme report date: 2018-05-17 Product type: Comprehensive Report type: Original Report legend Based on the genes in our panel, medications are reported according to genotype-predicted interactions described below. Major gene-drug Major genotype-drug interaction identi]ed that affects the metabolism of the medication and/or interaction indicates an elevated risk of adverse reaction or loss of e_cacy. Moderate gene-drug Moderate genotype-drug interaction identi]ed that affects the metabolism of the medication and/or interaction indicates an elevated risk of adverse reaction or loss of e_cacy. Minimal gene-drug Minimal genotype-drug interaction identi]ed that does not signi]cantly impact medication interaction metabolism or predict an elevated risk of adverse reaction or loss of e_cacy. Icon legend Some medications are reported with icons to indicate that additional information is available. Consult the RightMed Advisor for more information on speci]c clinical annotations and/or dosing guidelines provided by the Clinical Pharmacogenetics Implementation Consortium (CPIC), the Dutch Pharmacogenomics Working Group (DPWG), the Food and Drug Administration (FDA), and/or other professional guidelines. Increased exposure Total exposure to active compound(s) may be increased. Monitor for adverse effects. Decreased exposure Total exposure to active compound(s) may be decreased. Monitor for lack of therapeutic response. Di_cult to predict Total exposure to active compound(s) is di_cult to predict. Monitor patient response. Response to medication may be lowered due to genetic changes impacting mechanisms other than Reduced response exposure (e.g. receptor function). Additional testing According to FDA labeling, additional laboratory testing may be indicated. Medication has professional guidelines associated with this patient's genetic test results. Avoidance, Professional guideline dose adjustment, or heightened monitoring may be indicated. OneOme order ID: 459CE | Patient name: Jane Doe | Patient date of birth: 1972-07-08 | Report version: 4.0.0 Page 1 / 14 Lab director: Bronwyn R. Hartung, PhD | CLIA: 24D2109855 | NPI: 1669836227 | CAP: 9432670 Making prescriptions personal Personalized medication report summary This list was generated from the medications entered during the order process. Providers can ]nd more information about each medication in the Personalized medication report or in the RightMed Advisor. Note: The associated genes listed for each medication do not imply that a speci]c gene-drug interaction exists, as some genes may only be informative in nature. Medication PGx result Overview Associated gene(s) Predicted carbamazepine metabolism is normal. Genotype suggests a normal exposure to carbamazepine. Carbamazepine Negative for the presence of the HLA-B*15:02 allele. CYP3A5 (Carbatrol, Increased risk of hypersensitivity reactions related to HLA-A Major gene-drug Tegretol) HLA-A*31:01 genotype. HLA-B interaction Professional guidelines exist for the use of carbamazepine in patients with this genotype and/or phenotype. Predicted citalopram metabolism is increased. Genotype suggests a possible decrease in exposure to citalopram. CYP2C19 Citalopram GRIK4 Typical to increased expression of the SLC6A4 (Celexa) HTR2A Major gene-drug transporter. interaction SLC6A4 Professional guidelines exist for the use of citalopram in patients with this genotype and/or phenotype. Predicted phenytoin metabolism is reduced. Genotype suggests a possible increase in exposure to phenytoin. CYP2C9 Phenytoin Negative for the presence of the HLA-B*15:02 allele. HLA-A (Dilantin) Major gene-drug Increased risk of hypersensitivity reactions related to HLA-B interaction HLA-A*31:01 genotype. Professional guidelines exist for the use of phenytoin in patients with this genotype and/or phenotype. Predicted bupropion metabolism is normal. Genotype suggests a normal exposure to bupropion. Bupropion Allele(s) have demonstrated substrate-speci]c function CYP2B6 (Wellbutrin) Minimal gene-drug with bupropion, therefore cytochrome P450 phenotype interaction may differ from bupropion-speci]c phenotype. Genotype suggests a normal exposure to ^uoxetine. CYP2C9 Fluoxetine Typical to increased expression of the SLC6A4 CYP2D6 (Prozac, Sarafem) Minimal gene-drug transporter. SLC6A4 interaction OneOme order ID: 459CE | Patient name: Jane Doe | Patient date of birth: 1972-07-08 | Report version: 4.0.0 Page 2 / 14 Lab director: Bronwyn R. Hartung, PhD | CLIA: 24D2109855 | NPI: 1669836227 | CAP: 9432670 Making prescriptions personal Genotype-derived recommendations for medications Major gene-drug interaction Analgesic/Anesthesiology Immunosuppression Clobazam 1 Psychiatry Morphine 12, 17, 23, 24, 96, 102, Azathioprine 1, 2, 106, 161, 162 Fosphenytoin 1, 2, 6, 18, 26, Amitriptyline 1, 2, 56, 215 164, 180, 181, 194 114, 135 Citalopram 1, 2, 8, 15, 41, 55, Infectious disease Phenytoin 1, 2, 6, 18, 26, 114, 58, 59, 60, 64, 84, 85, 97, 100, 103, 116, 120, Cardiovascular 135 124, 132, 142, 148, 151, 219 Atovaquone/Proguanil 1 Clomipramine 1, 2, 56 Labetalol 21 Voriconazole 1, 2 Oncology Diazepam 1, 66 Doxepin 1, 2, 56 Gastroenterology Mercaptopurine 1, 2, 161, 162 Neurology Escitalopram 1, 2, 8, 15, 41, Thioguanine 1, 2, 161, 162 Esomeprazole 1, 2 55, 59, 60, 64, 97, 103, 116, 124, 132, 151, 219 Brivaracetam 1 Lansoprazole 1, 2, 130 Imipramine 1, 2, 56, 212 Carbamazepine 1, 5, 6, 27, 28, 1, 2, 63, 221 Omeprazole 1, 2 61, 101, 114, 121, 122, 134, 145, 149, 153, 175, Risperidone Pantoprazole 1 228 Trimipramine 1, 2, 56, 91 Moderate gene-drug interaction Analgesic/Anesthesiology Guanabenz 30 Infectious disease Psychiatry Carisoprodol 1, 50 Irbesartan 1 Nel]navir 1 Asenapine 1 Fentanyl 1, 45, 53, 67, 89, 98, 195, Losartan 1 Peginterferon alfa-2a- Duloxetine 1 220, 226, 232, 233, 234 containing regimens 1, Nicotine 31, 36, 75, 126 Ketamine 1, 104, 105, 158, 222 125 Dietary Olanzapine 1, 2, 99, 111 Peginterferon alfa-2b- Selegiline 57, 78, 170 Caffeine 1 containing regimens 1, Anti-in^ammatory Sertraline 1, 2, 40, 42, 55, 107, 125 128, 131, 136, 160, 166, 203, 211 Celecoxib 1 Endocrinology Diclofenac 1 Neurology 1, 179 Flurbiprofen 1, 191 Chlorpropamide Rheumatology Glimepiride 1 Eslicarbazepine 1, 6, 79, 149 Meloxicam 1 Lesinurad 1 1, 88, 92, 198 Frovatriptan 1 Piroxicam 1 Glipizide Glyburide 1 Lamotrigine 1, 6, 114, 149 Sleep medicine Anticoagulant/Antiplatelet Nateglinide 1 Oxcarbazepine 1, 6, 149 Tolbutamide 2 Rasagiline 1 Ramelteon 1 Clopidogrel 1, 172, 173 Selegiline 57, 78, 170 Warfarin 1, 20, 73, 74 Gastroenterology Oncology Cardiovascular Dexlansoprazole 1 Dronabinol 1 Bortezomib 1 Azilsartan 1 Rabeprazole 1 Fluvastatin 1 Minimal gene-drug interaction Allergy Analgesic/Anesthesiology Hydrocodone 1, 32, 33 Midazolam 1, 201 Loratadine 227 Alfentanil 1, 47, 138, 235 Methadone 1 Oxycodone 1, 32, 33 Buprenorphine 1 Tramadol 1, 2, 32, 33, 110, 187, 190, Codeine 1, 2, 9, 17, 32, 33, 182, 196 202 Cyclobenzaprine 1, 214 OneOme order ID: 459CE | Patient name: Jane Doe | Patient date of birth: 1972-07-08 | Report version: 4.0.0 Page 3 / 14 Lab director: Bronwyn R. Hartung, PhD | CLIA: 24D2109855 | NPI: 1669836227 | CAP: 9432670 Making prescriptions personal Minimal gene-drug interaction (cont.) Anticoagulant/Antiplatelet Immunosuppression Docetaxel 1 Lurasidone 1 Apixaban 1 Cyclosporine 1 Enzalutamide 1 Mirtazapine 1, 2, 90, 108, 189, 197 Cilostazol 1, 201 Everolimus 1, 201 Erlotinib 1, 71 Nefazodone 1, 165, 209 Ticagrelor 1 Sirolimus 1 Etoposide 1, 237 Nortriptyline 1, 2, 56, 140, 207 Tacrolimus 1, 14, 201 Everolimus 1, 201 Paroxetine 1, 2, 55, 68, 83, 127, 152, 167, Cardiovascular Exemestane 1 186, 199, 224 Infectious disease Fluorouracil 1, 2, 19 Perphenazine 1, 139 Aliskiren 1 Ge]tinib 1 Pimozide 1, 205 Amiodarone 1 Abacavir 1, 2, 43, 112, 113, 117, 118, 168, 192 Ifosfamide 1, 25 Protriptyline 1 Amlodipine 1 Atazanavir 46, 72 Imatinib 1 Quetiapine 1, 201 Atorvastatin 1 Clarithromycin 1, 201 Irinotecan 1, 48, 93 Thioridazine 1 Carvedilol 1 Darunavir 1 Ixabepilone 1 Trazodone 1 Clonidine 1 Delavirdine 1 Lapatinib 1, 171 Venlafaxine 1, 2, 210 Diltiazem 1, 201 Efavirenz 1 Methotrexate 1, 154, 157, 200, 231 Vilazodone 1 Disopyramide 1 Erythromycin 201 Nilotinib 1, 4 Vortioxetine 1 Dofetilide 1 Fosamprenavir 1 Paclitaxel 1 Dronedarone 1, 201 Indinavir 1, 201 Pazopanib 1 Pulmonary Eplerenone 1 Isavuconazole 1 Ponatinib 1 Felodipine 1 Itraconazole 1 Dextromethorphan 1 Regorafenib 1 Flecainide 1, 2 Ivermectin 1, 230 Indacaterol 1, 76 Ruxolitinib 1 Lidocaine 37, 141 Ketoconazole 1 Salmeterol 1 Sorafenib 1 Lomitapide 1 Maraviroc 1 Sildena]l 1 Sunitinib 1 Lovastatin 1 Me^oquine 1 Tadala]l 1 Tamoxifen 1, 2, 49 Metoprolol 1, 2 Nevirapine 1 Temsirolimus 1 Nifedipine 1, 201 Quinidine 1 Rheumatology Teniposide 95, 163 Nisoldipine 1, 201 Quinine 1, 201 Trabectedin 1 Allopurinol 38, 54, 62, 87, 169 Pravastatin 1, 133 Ritonavir 1 Vemurafenib 1 Cevimeline 1
Recommended publications
  • Serotonin Receptor 2A (HTR2A) Gene Polymorphism Predicts Treatment Response to Venlafaxine XR in Generalized Anxiety Disorder
    The Pharmacogenomics Journal (2013) 13, 21–26 & 2013 Macmillan Publishers Limited. All rights reserved 1470-269X/13 www.nature.com/tpj ORIGINAL ARTICLE Serotonin receptor 2A (HTR2A) gene polymorphism predicts treatment response to venlafaxine XR in generalized anxiety disorder FW Lohoff1,2, TD Aquino1, Generalized anxiety disorder (GAD) is a chronic psychiatric disorder with 2 2 significant morbidity and mortality. Antidepressant drugs are the preferred S Narasimhan , PK Multani , choice for treatment; however, treatment response is often variable. Several 1 1 B Etemad and K Rickels studies in major depression have implicated a role of the serotonin receptor gene (HTR2A) in treatment response to antidepressants. We tested the 1Mood & Anxiety Disorders Section, Department of Psychiatry, University of Pennsylvania School of hypothesis that the genetic polymorphism rs7997012 in the HTR2A gene Medicine, Philadelphia, PA, USA and predicts treatment outcome in GAD patients treated with venlafaxine XR. 2Department of Psychiatry, Psychiatric Treatment response was assessed in 156 patients that participated in a Pharmacogenetics Laboratory, Center for 6-month open-label clinical trial of venlafaxine XR for GAD. Primary analysis Neurobiology and Behavior, University of Pennsylvania School of Medicine, Philadelphia, included Hamilton Anxiety Scale (HAM-A) reduction at 6 months. Secondary PA, USA outcome measure was the Clinical Global Impression of Improvement (CGI-I) score at 6 months. Genotype and allele frequencies were compared between Correspondence: groups using w2 contingency analysis. The frequency of the G-allele differed Dr FW Lohoff, Department of Psychiatry, significantly between responders (70%) and nonresponders (56%) at Translational Research Laboratory, Center for Neurobiology and Behavior, University of 6 months (P ¼ 0.05) using the HAM-A scale as outcome measure.
    [Show full text]
  • Pharmacogenomic Characterization in Bipolar Spectrum Disorders
    pharmaceutics Review Pharmacogenomic Characterization in Bipolar Spectrum Disorders Stefano Fortinguerra 1,2 , Vincenzo Sorrenti 1,2,3 , Pietro Giusti 2, Morena Zusso 2 and Alessandro Buriani 1,2,* 1 Maria Paola Belloni Center for Personalized Medicine, Data Medica Group (Synlab Limited), 35131 Padova, Italy; [email protected] (S.F.); [email protected] (V.S.) 2 Department of Pharmaceutical & Pharmacological Sciences, University of Padova, 35131 Padova, Italy; [email protected] (P.G.); [email protected] (M.Z.) 3 Bendessere™ Study Center, Solgar Italia Multinutrient S.p.A., 35131 Padova, Italy * Correspondence: [email protected] Received: 25 November 2019; Accepted: 19 December 2019; Published: 21 December 2019 Abstract: The holistic approach of personalized medicine, merging clinical and molecular characteristics to tailor the diagnostic and therapeutic path to each individual, is steadily spreading in clinical practice. Psychiatric disorders represent one of the most difficult diagnostic challenges, given their frequent mixed nature and intrinsic variability, as in bipolar disorders and depression. Patients misdiagnosed as depressed are often initially prescribed serotonergic antidepressants, a treatment that can exacerbate a previously unrecognized bipolar condition. Thanks to the use of the patient’s genomic profile, it is possible to recognize such risk and at the same time characterize specific genetic assets specifically associated with bipolar spectrum disorder, as well as with the individual response to the various therapeutic options. This provides the basis for molecular diagnosis and the definition of pharmacogenomic profiles, thus guiding therapeutic choices and allowing a safer and more effective use of psychotropic drugs. Here, we report the pharmacogenomics state of the art in bipolar disorders and suggest an algorithm for therapeutic regimen choice.
    [Show full text]
  • Gene Polymorphisms of Serotonin Receptors and Drug-Induced Hyperprolactinemia in Patients with Schizophrenia
    Poster number: P.3.b.037 Gene polymorphisms of serotonin receptors and drug-induced hyperprolactinemia in patients with schizophrenia Diana Z. Оsmanova1, Anastasia S. Boiko1, Olga Yu. Fedorenko1, Ivan V. Pozhidaev1, M.B. Freidin1 Elena G. Kornetova1, Svetlana A. Ivanova1 , Bob Wilffert2, Anton J.M. Loonen2 1. Mental Health Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, Russia 2. Department of Pharmacy, University of Groningen, Groningen, The Netherlands BACKGROUND RESULTS Antipsychotic drug-induced hyperprolactinemia is an All patients with schizophrenia were divided into two increasingly prevalent problem in current psychiatric practice and groups: those with and without hyperprolactinemia. Patients responsible for troublesome side effects like loss of libido and from both groups were genotyped for HTR1A variants: rs6295, impotence. The chance to develop hyperprolactinemia depends rs1364043, rs10042486, rs1800042, rs749099; for HTR1B: upon the pharmacological properties of antipsychotic medication rs6298, rs6296, rs130058; for HTR2A: rs6311, rs6313, rs6314, used, of its dosage and treatment duration, as well as from the rs7997012, rs1928040, rs9316233, rs2224721, rs6312; for genetic make-up and other characteristics which determine the HTR2C: rs6318, rs5946189, rs569959, rs17326429, rs4911871, individual sensitivity of the individual patient. rs3813929, rs1801412, rs12858300; for HTR3A: rs1062613, Second generation antipsychotics are (often) more potent rs33940208, rs1176713; for HTR3B:
    [Show full text]
  • Exploration of 19 Serotoninergic Candidate Genes in Adults and Children with Attention-Deficit/Hyperactivity Disorder Identifies
    Molecular Psychiatry (2009) 14,71–85 & 2009 Nature Publishing Group All rights reserved 1359-4184/09 $32.00 www.nature.com/mp ORIGINAL ARTICLE Exploration of 19 serotoninergic candidate genes in adults and children with attention-deficit/hyperactivity disorder identifies association for 5HT2A, DDC and MAOB M Ribase´s1,11, JA Ramos-Quiroga1,2,11, A Herva´s3, R Bosch1, A Bielsa1, X Gastaminza1, J Artigas4, S Rodriguez-Ben3, X Estivill5,6,7, M Casas1,2, B Cormand8,9,10 and M Baye´s5,6,7 1Department of Psychiatry, Hospital Universitari Vall d’Hebron, Barcelona, Catalonia, Spain; 2Department of Psychiatry and Legal Medicine, Universitat Auto´noma de Barcelona, Barcelona, Catalonia, Spain; 3Child and Adolescent Mental Health Unit, Department of Psychiatry, Hospital Mu´tua de Terrassa, Barcelona, Catalonia, Spain; 4Unitat de Neuropediatria, Hospital de Sabadell, Corporacio´ Sanita`ria Parc Taulı´, Barcelona, Catalonia, Spain; 5Genes and Disease Program, Center for Genomic Regulation (CRG), UPF, Barcelona, Catalonia, Spain; 6Centro Nacional de Genotipado (CeGen), Barcelona, Catalonia, Spain; 7CIBER Epidemiologı´a y Salud Pu´blica, Instituto de Salud Carlos III (CRG), Barcelona, Catalonia, Spain; 8Departament de Gene`tica, Facultat de Biologia, Universitat de Barcelona, Barcelona, Catalonia, Spain; 9CIBER Enfermedades Raras, Instituto de Salud Carlos III, Barcelona, Catalonia, Spain and 10Institut de Biomedicina de la Universitat de Barcelona (IBUB), Barcelona, Catalonia, Spain Attention-deficit/hyperactivity disorder (ADHD) is a common psychiatric disorder in which different genetic and environmental susceptibility factors are involved. Several lines of evidence support the view that at least 30% of ADHD patients diagnosed in childhood continue to suffer the disorder during adulthood and that genetic risk factors may play an essential role in the persistence of the disorder throughout lifespan.
    [Show full text]
  • Pharmacogenetics of Antidepressants, a Review Of
    al Depres ic sio lin n C Reyes-Barron et al., Clin Depress 2016, 2:2 Clinical Depression Research Article Article OpenOpen Access Access Pharmacogenetics of Antidepressants, A Review of Significant Genetic Variants in Different Populations Cynthia Reyes-Barron1, Silvina Tonarelli1, Andrew Delozier1, David F. Briones1, Brenda B. Su2, Lewis P. Rubin1 and Chun Xu1* 1Texas Tech University Health Sciences Centre, Paul L. Foster School of Medicine 2College of Medicine and Health Sciences, UAE University, Department of Internal Medicine Abstract Major depressive disorder is a highly prevalent disease that is challenging to treat, often requiring medication and dose adjustments. Genetic factors play an important role in psychotropic medication responses. However, the translation of pharmacogenetics findings to clinical recommendations with regards to antidepressant responses is still in its early stages. We reviewed recent primary research articles, meta-analyses, and reviews on the pharmacogenetics of antidepressant treatment for major depressive disorder in different populations. We identified eight genes with likely associations with treatment responses and summarized genetic variants most likely to influence treatment responses. We determined the frequency of these variants in Caucasian, Asian, Hispanic, and African American populations. The genes are related to functions in drug metabolism, transport, signalling, stress response, and neuroplasticity. Clinical recommendations already exist for CYP2D6 and CYP2C19 cytochrome P450 drug metabolism genes. The other genes are: ABCB1 with single nucleotide polymorphisms (SNPs) rs2032583 and rs2235015; FKBP5 with SNPs rs1360780, rs3800373, and rs4713916; GNB3 with SNP rs5443; BDNF with SNP rs6265; HTR2A with SNPs rs7997012 and rs6313; and SLC6A4 with polymorphisms 5-HTTLPR and STin2. There is significant variability of the frequencies of these polymorphisms in the different populations we reviewed.
    [Show full text]
  • A Serotonin Receptor with a Possible Role in Joint Diseases
    Anders Kling 5-HT2 A – a serotonin receptor with a possible role in joint diseases role with a possible receptor – a serotonin 5-HT2A – a serotonin receptor with a possible role in joint diseases Anders Kling Umeå University 2013 Umeå University Department of Pharmacology and Clinical Neuroscience New Serie 1547 Department of Pharmacology and Clinical Neurosciences Umeå University ISSN: 0346-6612 Umeå University, Sweden 2013 SE-901 87 Umeå, Sweden ISBN 978-91-7459-549-9 5-HT2A – a serotonin receptor with a possible role in joint diseases Anders Kling Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi/ Department of Pharmacology and Clinical Neuroscience, Clinical Pharmacology Umeå universitet/ Umeå University Umeå 2013 Responsible publisher under swedish law: the Dean of the Medical Faculty This work is protected by the Swedish Copyright Legislation (Act 1960:729) ISBN: 978-91-7459-549-9 ISSN: 0346-6612 New series No: 1547 Elektronisk version tillgänglig på http://umu.diva-portal.org/ Tryck/Printed by: Print och Media, Umeå universitet Umeå, Sweden 2013 Innehåll/Table of Contents Innehåll/Table of Contents i Abstract iv Abbreviations vi List of studies viii Populärvetenskaplig sammanfattning ix 5-HT2A – en serotoninreceptor med möjlig betydelse för ledsjukdomar ix Introduction 1 The serotonin system 1 Serotonin 1 Serotonin receptors 2 The serotonin system and platelets 2 Serotonin receptor 5-HT2A 3 Localisation/expression of 5-HT2A receptors 3 Functions of the 5-HT2A receptor 4 Regulation of the 5-HT2A receptor
    [Show full text]
  • Variation in the HTR1A and HTR2A Genes and Social Adjustment in Depressed Patients
    Journal of Affective Disorders 150 (2013) 649–652 Contents lists available at ScienceDirect Journal of Affective Disorders journal homepage: www.elsevier.com/locate/jad Brief report Variation in the HTR1A and HTR2A genes and social adjustment in depressed patients Niki Antypa a, Raffaella Calati b, Daniel Souery c, Silvia Pellegrini d, Othman Sentissi e, Daniela Amital f, Ulrike Moser g, Stuart Montgomery h, Siegfried Kasper g, Joseph Zohar i, Diana De Ronchi a, Julien Mendlewicz j, Alessandro Serretti a,* a Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy b IRCCS Centro S. Giovanni di Dio, Fatebenefratelli, Brescia, Italy c Laboratoire de Psychologie Medicale, Université Libre de Bruxelles and Psy Pluriel, Centre Européen de Psychologie Medicale, Brussels, Belgium d Department of Experimental Pathology, Medical Biotechnology, Epidemiology and Infectious diseases, University of Pisa, Pisa, Italy e Département de Psychiatrie Hôpitaux Universitaires de Genève, Faculté de Médecine de Genève, Geneva, Switzerland f Ness-Ziona Mental Health Center, Israel g Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria h Imperial College School of Medicine, London, UK i Chaim Sheba Medical Center, Tel-Hashomer, Israel j Université Libre de Bruxelles, Brussels, Belgium article info abstract Article history: Background: Social adjustment is impaired in depressed patients. The difficulty to adjust to social Received 14 June 2012 circumstances has been hypothesized to be one of the causes of depression, as well as a consequence of Received in revised form the disorder. Genetic variation in the serotonin transporter gene has been previously associated with 15 February 2013 social adjustment levels in patients with mood disorders.
    [Show full text]
  • Association of BDNF, HTR2A, TPH1, SLC6A4, and COMT
    Braz J Psychiatry. 2019 xxx-xxx;00(00):000-000 doi:10.1590/1516-4446-2019-0620 Brazilian Psychiatric Association 00000000-0002-7316-1185 ORIGINAL ARTICLE Association of BDNF, HTR2A, TPH1, SLC6A4, and COMT polymorphisms with tDCS and escitalopram efficacy: ancillary analysis of a double-blind, placebo-controlled trial Andre R. Brunoni0000-0000-0000-0000 ,1,2 Angel Carracedo,3 Olalla M. Amigo,3 Ana L. Pellicer,3 Leda Talib,2 Andre F. Carvalho0000-0000-0000-0000 ,4 Paulo A. Lotufo,1 Isabela M. Bensen˜ or,1 Wagner Gattaz,2 Carolina Cappi5 1Departamento de Medicina Interna, Faculdade de Medicina, Universidade de Sa˜o Paulo (USP), Sa˜o Paulo, SP, Brazil. 2Laborato´rio de Neurocieˆncias (LIM-27) and Instituto Nacional de Biomarcadores em Psiquiatria (INBION), Departamento e Instituto de Psiquiatria, Faculdade de Medicina, USP, Sa˜o Paulo, SP, Brazil. 3Grupo de Medicina Xeno´mica/Pharmacogenetics Research, Laboratorio SSL1, Centro Singular de Investigacio´n en Medicina Molecular y Enfermedades Cro´nicas (CiMUS), Santiago de Compostela, Spain. 4Department of Psychiatry, Faculty of Medicine, University of Toronto & Centre for Addiction & Mental Health (CAMH), Toronto, Canada. 5Programa Transtornos do Espectro Obsessivo-Compulsivo, Departamento e Instituto de Psiquiatria, Faculdade de Medicina, USP, Sa˜o Paulo, SP, Brazil. Objective: We investigated whether single nucleotide polymorphisms (SNPs) associated with neuroplasticity and activity of monoamine neurotransmitters, such as the brain-derived neurotrophic factor (BDNF, rs6265), the serotonin transporter (SLC6A4, rs25531), the tryptophan hydroxylase 1 (TPH1, rs1800532), the 5-hydroxytryptamine receptor 2A (HTR2A, rs6311, rs6313, rs7997012), and the catechol-O-methyltransferase (COMT, rs4680) genes, are associated with efficacy of transcranial direct current stimulation (tDCS) in major depression.
    [Show full text]
  • Variation in the Gene Encoding the Serotonin 2A Receptor Is Associated with Outcome of Antidepressant Treatment Francis J
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Variation in the Gene Encoding the Serotonin 2A Receptor Is Associated with Outcome of Antidepressant Treatment Francis J. McMahon,1,* Silvia Buervenich,1,* Dennis Charney,3 Robert Lipsky,4 A. John Rush,5 Alexander F. Wilson,6 Alexa J. M. Sorant,6 George J. Papanicolaou,6 Gonzalo Laje,1 Maurizio Fava,7 Madhukar H. Trivedi,5 Stephen R. Wisniewski,8 and Husseini Manji2 1Genetic Basis of Mood and Anxiety Disorders and 2Laboratory of Molecular Pathophysiology, Mood and Anxiety Program, National Institute of Mental Health (NIMH), National Institutes of Health (NIH), Department of Health and Human Services (DHHS), Bethesda; 3Departments of Psychiatry, Neuroscience, and Pharmacology & Biological Chemistry, Mount Sinai School of Medicine, New York; 4Section of Molecular Genetics, Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, NIH, DHHS, Rockville, MD; 5Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas; 6Genometrics Section, Inherited Disease Research Branch, National Human Genome Research Institute, NIH, DHHS, Baltimore; 7Massachusetts General Hospital, Boston; and 8Department of Epidemiology, University of Pittsburgh, Pittsburgh Depressive disorders account for a large and increasing global burden of disease. Although the condition of many patients improves with medication, only a minority experience full remission, and patients whose condition responds to one medication may not have a response to others. Individual variation in antidepressant treatment outcome is, at present, unpredictable but may have a partial genetic basis. We searched for genetic predictors of treatment out- come in 1,953 patients with major depressive disorder who were treated with the antidepressant citalopram in the Sequenced Treatment Alternatives for Depression (STAR*D) study and were prospectively assessed.
    [Show full text]
  • Machine Learning Classification of ADHD and HC by Multimodal Serotonergic Data
    Kautzky et al. Translational Psychiatry (2020) 10:104 https://doi.org/10.1038/s41398-020-0781-2 Translational Psychiatry ARTICLE Open Access Machine learning classification of ADHD and HC by multimodal serotonergic data A. Kautzky1,T.Vanicek1,C.Philippe2,G.S.Kranz 1,3,W.Wadsak 2,4,M.Mitterhauser2,5, A. Hartmann6,A.Hahn 1, M. Hacker2,D.Rujescu6,S.Kasper1 and R. Lanzenberger 1 Abstract Serotonin neurotransmission may impact the etiology and pathology of attention-deficit and hyperactivity disorder (ADHD), partly mediated through single nucleotide polymorphisms (SNPs). We propose a multivariate, genetic and positron emission tomography (PET) imaging classification model for ADHD and healthy controls (HC). Sixteen patients with ADHD and 22 HC were scanned by PET to measure serotonin transporter (SERT‘) binding potential with [11C] DASB. All subjects were genotyped for thirty SNPs within the HTR1A, HTR1B, HTR2A and TPH2 genes. Cortical and subcortical regions of interest (ROI) were defined and random forest (RF) machine learning was used for feature selection and classification in a five-fold cross-validation model with ten repeats. Variable selection highlighted the ROI posterior cingulate gyrus, cuneus, precuneus, pre-, para- and postcentral gyri as well as the SNPs HTR2A rs1328684 and rs6311 and HTR1B rs130058 as most discriminative between ADHD and HC status. The mean accuracy for the validation sets across repeats was 0.82 (±0.09) with balanced sensitivity and specificity of 0.75 and 0.86, respectively. With a prediction accuracy above 0.8, the findings underlying the proposed model advocate the relevance of the SERT as well as the HTR1B and HTR2A genes in ADHD and hint towards disease-specific effects.
    [Show full text]
  • No Effect of Serotoninergic Gene Variants on Response to Interpersonal Counseling and Antidepressants in Major Depression
    ORIGINAL ARTICLE Print ISSN 1738-3684 / On-line ISSN 1976-3026 http://dx.doi.org/10.4306/pi.2013.10.2.180 OPEN ACCESS No Effect of Serotoninergic Gene Variants on Response to Interpersonal Counseling and Antidepressants in Major Depression Alessandro Serretti1 , Chiara Fabbri1, Silvia Pellegrini2, Stefano Porcelli1, Pierluigi Politi3, Silvio Bellino4, Marco Menchetti1, Veronica Mariotti2, Cristina Demi2, Valentina Martinelli3, Marco Cappucciati3, Paola Bozzatello4, Elena Brignolo4, Paolo Brambilla5, Chi-Un Pae6,7, Matteo Balestrieri5 and Diana De Ronchi1 1Department of Biomedical and NeuroMotor Sciences, University of Bologna, Bologna, Italy 2Department of Experimental Pathology, Medical Biotechnology, Epidemiology and Infectious Diseases, University of Pisa, Pisa, Italy 3Department of Health Sciences, Section of Psychiatry, University of Pavia, Pavia, Italy 4Neuroscience Department, Turin University, Turin, Italy 5Inter-University Centre for Behavioural Neurosciences (ICBN), University of Verona, Verona and DPMSC, Section of Psychiatry, University of Udine, Udine, Italy 6Department of Psychiatry, Bucheon St. Mary’s Hospital, The Catholic University of Korea College of Medicine, Bucheon, Republic of Korea 7Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA ObjectiveaaGene variants within the serotonin pathway have been associated with major depressive disorder (MDD) treatment out- comes, however a possible different modulation on pharmacological or psychological treatments has never been investigated. MethodsaaOne hundred sixty MDD patients were partially randomized to either inter-personal counseling (IPC) or antidepressants. The primary outcome was remission at week 8. Five serotonergic polymorphisms were investigated (COMT rs4680, HTR1A rs6295, HTR2A rs2224721, HTR2A rs7997012 and SLC6A4 rs421417). ResultsaaIPC (n=43) and antidepressant (n=117) treated patients did not show any difference in remission rates at week 8 (corrected for baseline severity, age and center).
    [Show full text]
  • Pharmacogenetics of Antidepressant Response
    Copyright 2007 by Eric James Peters ii ACKNOWLEDGEMENTS Knowledge is priceless. Perhaps this is because the process of acquiring it is painfully slow - entire careers and countless hours of work have been performed in hopes of adding just small pieces to our fragmented understanding of the natural world. Frustrations and setbacks abound, as experiments fail and assays stop working when needed most. But the prospect of improving human health, advancing a field, or simply being the first to know something has a certain appeal. What is clear is that knowledge cannot be pursued as a solo endeavor. I was fortunate to have the support of a tremendous group of colleagues, family and friends. Without them, I would not never made it through the process. First and foremost, I would like to thank Steve Hamilton. His guidance is the reason my graduate school career had the bright spots that it did. He has taught me that science, at its very core, is not about a single experiment or laboratory technique. Instead, it is about the pursuit of knowledge, and to be a successful scientist one cannot succumb to tunnel vision. I’ve spent many engaging hours in his office discussing such varied topics as genetics, psychiatry, and religion, and he has always encouraged any curiosity or interest that I felt a need to discuss, no matter how irrelevant it was to my thesis project. He has also taught me the art of presenting science that is both exciting and accessible to the audience, which is an invaluable tool for any independent investigator.
    [Show full text]