A Serotonin Receptor with a Possible Role in Joint Diseases
Total Page:16
File Type:pdf, Size:1020Kb
Load more
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. -
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. -
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: -
Activation of 5-HT2C (But Not 5-HT1A) Receptors in the Amygdala Enhances Fear-Induced Antinociception: Blockade with Local 5-HT2C Antagonist Or Systemic fluoxetine
Neuropharmacology 135 (2018) 376e385 Contents lists available at ScienceDirect Neuropharmacology journal homepage: www.elsevier.com/locate/neuropharm Activation of 5-HT2C (but not 5-HT1A) receptors in the amygdala enhances fear-induced antinociception: Blockade with local 5-HT2C antagonist or systemic fluoxetine Lígia Renata Rodrigues Tavares a, b, Daniela Baptista-de-Souza a, c, * Azair Canto-de-Souza a, b, c, d, a Psychobiology Group, Department of Psychology/CECH- Federal University of Sao~ Carlos-UFSCar, Sao~ Carlos, Sao~ Paulo, 13565-905, Brazil b Joint Graduate Program in Physiological Sciences UFSCar/UNESP, Sao~ Carlos, Sao~ Paulo, 13565-905, Brazil c Neuroscience and Behavioral Institute-IneC, Ribeirao~ Preto, Sao~ Paulo, 14040-901, Brazil d Program in Psychology UFSCar, Sao~ Carlos, Sao~ Paulo, 13565-905, Brazil article info abstract Article history: It is well-known that the exposure of rodents to threatening environments [e.g., the open arm of the Received 17 August 2017 elevated-plus maze (EPM)] elicits pain inhibition. Systemic and/or intracerebral [e.g., periaqueductal gray Received in revised form matter, amygdala) injections of antiaversive drugs [e.g., serotonin (5-HT) ligands, selective serotonin 5 March 2018 reuptake inhibitors (SSRIs)] have been used to change EPM-open arm confinement induced anti- Accepted 6 March 2018 nociception (OAA). Here, we investigated (i) the role of the 5-HT and 5-HT receptors located in the Available online 13 March 2018 1A 2C amygdaloid complex on OAA as well as (ii) the effects of systemic pretreatment with fluoxetine (an SSRI) on the effects of intra-amygdala injections of 8-OH-DPAT (a 5-HT1A agonist) or MK-212 (a 5-HT2C agonist) Keywords: fi Amygdala on nociception in mice con ned to the open arm or enclosed arm of the EPM. -
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. -
Paradoxical Actions of the Serotonin Precursor 5-Hydroxytryptophan on the Activity of Identified Serotonergic Neurons in a Simple Motor Circuit
The Journal of Neuroscience, February 15, 2000, 20(4):1622–1634 Paradoxical Actions of the Serotonin Precursor 5-hydroxytryptophan on the Activity of Identified Serotonergic Neurons in a Simple Motor Circuit David J. Fickbohm and Paul S. Katz Department of Biology, Georgia State University, Atlanta, Georgia 30302 Neurotransmitter synthesis is regulated by a variety of factors, cated an increase in a putative 5-HT electrochemical signal yet the effect of altering transmitter content on the operation of during swim CPG activation. Paradoxically, the spiking activity neuronal circuits has been relatively unexplored. We used elec- of the serotonergic neurons decreased to a single burst at the trophysiological, electrochemical, and immunohistochemical onset of the rhythmic motor program, whereas the overall techniques to investigate the effects of augmenting the seroto- duration of the episode remained about the same. 5-HTP treat- nin (5-HT) content of identified serotonergic neurons embed- ment gradually reduced the rhythmicity of the CPG output. ded in a simple motor circuit. The dorsal swim interneurons Thus, more serotonin did not result in a more robust swim (DSIs) are serotonergic neurons intrinsic to the central pattern motor program, suggesting that serotonin synthesis must be generator (CPG) for swimming in the mollusc Tritonia diom- kept within certain limits for the circuit to function correctly and edea. As expected, treatment with the serotonin precursor indicating that altering neurotransmitter synthesis can have 5-hydroxytryptophan (5-HTP) increased the intensity of seroto- serious consequences for the output of neural networks. nin immunolabeling and enhanced the potency of synaptic and Key words: intrinsic neuromodulation; central pattern gener- modulatory actions elicited by the DSIs. -
(DMT), Harmine, Harmaline and Tetrahydroharmine: Clinical and Forensic Impact
pharmaceuticals Review Toxicokinetics and Toxicodynamics of Ayahuasca Alkaloids N,N-Dimethyltryptamine (DMT), Harmine, Harmaline and Tetrahydroharmine: Clinical and Forensic Impact Andreia Machado Brito-da-Costa 1 , Diana Dias-da-Silva 1,2,* , Nelson G. M. Gomes 1,3 , Ricardo Jorge Dinis-Oliveira 1,2,4,* and Áurea Madureira-Carvalho 1,3 1 Department of Sciences, IINFACTS-Institute of Research and Advanced Training in Health Sciences and Technologies, University Institute of Health Sciences (IUCS), CESPU, CRL, 4585-116 Gandra, Portugal; [email protected] (A.M.B.-d.-C.); ngomes@ff.up.pt (N.G.M.G.); [email protected] (Á.M.-C.) 2 UCIBIO-REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal 3 LAQV-REQUIMTE, Laboratory of Pharmacognosy, Department of Chemistry, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal 4 Department of Public Health and Forensic Sciences, and Medical Education, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal * Correspondence: [email protected] (D.D.-d.-S.); [email protected] (R.J.D.-O.); Tel.: +351-224-157-216 (R.J.D.-O.) Received: 21 September 2020; Accepted: 20 October 2020; Published: 23 October 2020 Abstract: Ayahuasca is a hallucinogenic botanical beverage originally used by indigenous Amazonian tribes in religious ceremonies and therapeutic practices. While ethnobotanical surveys still indicate its spiritual and medicinal uses, consumption of ayahuasca has been progressively related with a recreational purpose, particularly in Western societies. The ayahuasca aqueous concoction is typically prepared from the leaves of the N,N-dimethyltryptamine (DMT)-containing Psychotria viridis, and the stem and bark of Banisteriopsis caapi, the plant source of harmala alkaloids. -
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. -
Molecular Genetics of Human Personality Traits for Psychiatric, Behav- Ioral, and Substance-Related Disorders Eugene Lin*,1 and Po See Chen*,2,3
The Open Translational Medicine Journal, 2009, 1, 1-8 1 Open Access Molecular Genetics of Human Personality Traits for Psychiatric, Behav- ioral, and Substance-Related Disorders Eugene Lin*,1 and Po See Chen*,2,3 1Vita Genomics, Inc., 7 Fl., No. 6, Sec. 1, Jung-Shing Road, Wugu Shiang, Taipei, Taiwan 2Department of Psychiatry, National Cheng Kung University, Tainan, Taiwan 3National Cheng Kung University Hospital and Dou-Liou Branch, Taiwan Abstract: The investigation of personality genetics had received much attention since the three seminal reports showing an association between genes and personality traits in the general population. Accumulating evidences suggested that per- sonality traits have significant genetic components. Although currently available data are not enough for proof, more and more genetic variants associated with personality traits are being discovered. In this paper, we review related studies of gene polymorphisms and human personality traits for psychiatric, behavioral, and substance-related disorders. First, we briefly describe the commonly-used self-reported temperament measures that define personality dimensions. Then, we summarize the characteristics of the candidate genes for personality traits, and investigate gene variants which have been suggested to be linked with personality traits for individuals with psychiatric, behavioral, and substance-related disorders. Keywords: Molecular genetics, personality, psychiatric disorders, temperament measures. 1. INTRODUCTION and 5-HTTLPR but not other anxiety-related personality traits [14,15]. The investigation of personality genetics had received much attention since the three seminal reports [1-3] in 1996 We reviewed related studies of gene polymorphisms and showing an association between genes and personality traits human personality traits for psychiatric, behavioral, and sub- in the general population. -
Serotonin Autoreceptors on Dorsal Raphe Neurons: Structure-Activity Relationships of Tryptamine Analogs’
0270.6474/81/0110-1148$o2.oo/0 The Journal of Neuroscience Copyright 0 Society for Neuroscience Vol. 1, No. 10, pp. 1148-1154 Printed in U.S.A. October 1981 SEROTONIN AUTORECEPTORS ON DORSAL RAPHE NEURONS: STRUCTURE-ACTIVITY RELATIONSHIPS OF TRYPTAMINE ANALOGS’ MICHAEL A. ROGAWSKI’ AND GEORGE K. AGHAJANIAN Departments of Pharmacology and Psychiatry, Yale University School of Medicine and the Connecticut Mental Health Center, New Haven, Connecticut 06510 Abstract A series of indole-ethylamines were tested for their ability to suppress the spontaneous firing of single dorsal raphe serotonergic neurons in the rat. The compounds were all derivatives of either tryptamine or N,N-dimethyltryptamine possessing hydroxy or methoxy substituents on the benzene ring portion of the indole nucleus. Their activity was assessed using quantitative microiontophoresis or following systemic (intravenous) administration. The serotonin autoreceptor or so-called “S2 receptor” mediating the inhibition of raphe serotonergic neurons was found to exhibit a high degree of structural specificity among the closely related tryptamine analogs. The following structure- activity rules were demonstrated: (1) for either hydroxy or methoxy derivatives, the relative favorability of the ring positions conforms to the series 5 >> 4 > 6; (2) methoxy derivatives are more sensitive to a shift of the ring substituent from the 5- to the 4- or 6-positions than are hydroxy compounds; and (3) activity is enhanced by N,N-dimethylation. Furthermore, addition of a methyl group at the 7-position of 5-methoxy-N,N-dimethyltryptamine markedly reduces the activity of this potent agonist. Of the radioligands which label brain serotonin receptors, the pharmacological characteristics of D-[“HIlysergic acid diethylamide binding best correspond to those displayed by the SZ receptor as determined in the present physiological analysis, although sufficient data are not yet available to make a complete comparison. -
Psychedelics: a Window to Mental Illness; Psilocybin and Depression
Nova Southeastern University NSUWorks College of Pharmacy Student Articles College of Pharmacy 7-22-2020 Psychedelics: A Window To Mental Illness; Psilocybin And Depression Kiomary Rivera Quintana [email protected] Follow this and additional works at: https://nsuworks.nova.edu/hpd_corx_stuarticles Part of the Pharmacy and Pharmaceutical Sciences Commons Recommended Citation Rivera Quintana, Kiomary, "Psychedelics: A Window To Mental Illness; Psilocybin And Depression" (2020). College of Pharmacy Student Articles. 5. https://nsuworks.nova.edu/hpd_corx_stuarticles/5 This Literature Review is brought to you for free and open access by the College of Pharmacy at NSUWorks. It has been accepted for inclusion in College of Pharmacy Student Articles by an authorized administrator of NSUWorks. For more information, please contact [email protected]. 2020 Psychedelics: A Window to Mental Illness PSILOCYBIN AND DEPRESSION KIOMARY RIVERA QUINTANA STUDENT PHARMACIST CLASS OF 2022 PHRE 5223-DRUGS OF ABUSE NOVA SOUTHEASTERN UNIVERSITY INTRODUCTION Drug abuse is characterized by improper repeated use of drugs to seek outcomes such as pleasure, stress relief and an altered reality.1 It can lead to addiction, a severe form of substance use disorder (SUD) in which a person’s drug habits worsen and they become unable to control the impulse to use drugs despite knowing the negative consequences.1 In addition to drug seeking behavior, brain function also changes affecting the natural inhibition and reward centers. Use of and addiction to alcohol, nicotine, and illicit drugs costs the Nation more than $740 billion a year related to healthcare, crime, and lost productivity.1 Whether a person will abuse drugs or become addicted is influenced by multiple factors; the more risk factors a person has, the greater the chance. -
Case–Control Association Study of 59 Candidate Genes Reveals the DRD2
Journal of Human Genetics (2009) 54, 98–107 & 2009 The Japan Society of Human Genetics All rights reserved 1434-5161/09 $32.00 www.nature.com/jhg ORIGINAL ARTICLE Case–control association study of 59 candidate genes reveals the DRD2 SNP rs6277 (C957T) as the only susceptibility factor for schizophrenia in the Bulgarian population Elitza T Betcheva1, Taisei Mushiroda2, Atsushi Takahashi3, Michiaki Kubo4, Sena K Karachanak5, Irina T Zaharieva5, Radoslava V Vazharova5, Ivanka I Dimova5, Vihra K Milanova6, Todor Tolev7, George Kirov8, Michael J Owen8, Michael C O’Donovan8, Naoyuki Kamatani3, Yusuke Nakamura1,9 and Draga I Toncheva5 The development of molecular psychiatry in the last few decades identified a number of candidate genes that could be associated with schizophrenia. A great number of studies often result with controversial and non-conclusive outputs. However, it was determined that each of the implicated candidates would independently have a minor effect on the susceptibility to that disease. Herein we report results from our replication study for association using 255 Bulgarian patients with schizophrenia and schizoaffective disorder and 556 Bulgarian healthy controls. We have selected from the literatures 202 single nucleotide polymorphisms (SNPs) in 59 candidate genes, which previously were implicated in disease susceptibility, and we have genotyped them. Of the 183 SNPs successfully genotyped, only 1 SNP, rs6277 (C957T) in the DRD2 gene (P¼0.0010, odds ratio¼1.76), was considered to be significantly associated with schizophrenia after the replication study using independent sample sets. Our findings support one of the most widely considered hypotheses for schizophrenia etiology, the dopaminergic hypothesis.