DOCSLIB.ORG

The Serotonergic System in Obsessive Compulsive Disorder

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
The Serotonergic System in Obsessive Compulsive Disorder UvA-DARE (Digital Academic Repository) Understanding deep brain stimulation in obsessive compulsive disorder: A preclinical study into the mechanism of action and behaviour van Dijk, A. Publication date 2013 Link to publication Citation for published version (APA): van Dijk, A. (2013). Understanding deep brain stimulation in obsessive compulsive disorder: A preclinical study into the mechanism of action and behaviour. General rights It is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulations If you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: https://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. UvA-DARE is a service provided by the library of the University of Amsterdam (https://dare.uva.nl) Download date:02 Oct 2021 Chapter The serotonergic2 system in obsessive compulsive disorder Addy van Dijk, Andre Klompmakers, Damiaan Denys Handbook of the behavioral neurobiology of serotonin (2010) Amsterdam: Academic Press Chapter 2 Abstract Obsessive compulsive disorder (OCD) is a psychiatric disorder consisting of obsessions and compulsions. Over the past two decades, it has been suggested that OCD might be related to the functioning of brain serotonin systems, mainly because of the anti-obsessional efficacy of selective serotonin reuptake inhibitors (SSRIs). Though the efficacy of SSRIs suggests a role of the serotonergic system in OCD, the exact function of serotonin is still unclear. Is the serotonergic system implicated in the pathophysiology of OCD, or is it implicated in the treatment effect in OCD? Do SSRIs compensate for a fundamental abnormality of the serotonergic system, or do SSRIs modulate an intact serotonergic system to compensate for another neurotransmitter mechanism? This chapter reviews five lines of evidence that have been cited in support of the serotonin hypothesis: (1) pharmacotherapy, (2) pharmacologic challenge studies, (3) receptor binding studies, (4) genetic association studies, and (5) animal models. 20 The serotonergic system in obsessive compulsive disorder 2.1 Introduction Obsessive compulsive disorder (OCD) is a psychiatric disorder which consists of obsessions and compulsions. Obsessions are unwanted ideas or impulses that repeatedly well up in the mind, such as persistent fears to harm a loved one, an unreasonable concern with becoming contaminated or an excessive need to do things correctly or perfectly. Compulsions are repetitive behaviours or rituals such as washing and checking, counting, mentally repeating phrases, list making, or endlessly rearranging objects. Over the past two decades, it has been suggested that OCD might be related to the functioning of brain serotonin systems, mainly because of the anti-obsessional efficacy of SSRIs. The serotonin hypothesis originated from the observed efficacy of SSRIs in OCD, compared to inefficacy of selective noradrenergic and dopaminergic reuptake inhibitors, suggesting a specific abnormality of the serotonergic system in OCD (Baumgarten and Grozdanovic1998). However, the exact function of serotonin in OCD is still unclear. This chapter provides an overview of the evidence supporting a role for the serotonergic system in OCD. It reviews five lines of evidence that have been cited in support of the serotonin hypothesis: (1) pharmacotherapeutic studies, (2) pharmacotherapy, (3) receptor binding studies, (4) genetic association studies, and (5) animal models. 2.2 Pharmacotherapy A common method to unravel the pathophysiology of a disorder in psychiatry is to study the mechanism of action of effective drug therapy. The cornerstone of pharmacotherapy for OCD is serotonin reuptake inhibition, either with clomipramine or with selective serotonin reuptake inhibitors. Over the past 25 years, a number of double blind, randomized, placebo controlled studies in OCD have confirmed the efficacy of clomipramine and the selective serotonin reuptake inhibitors: fluvoxamine, paroxetine, sertraline, fluoxetine and citalopram. Efficacy of drug trials in OCD is commonly expressed in absolute changes of Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores. The Y-BOCS is a clinician rated 10-item scale with a total range of 0 to 40 that measures severity of obsessions and compulsions (Goodman et al.1989a; Goodman et al.1989b). In many cases, patients are classified as responders when their scores on the Y-BOCS decrease by 25 to 35%. The efficacy of clomipramine was established in more than 10 placebo-controlled trials. In a recent meta-analysis, clomipramine shows a net improvement (difference) compared with placebo of 8.20 points on the Y-BOCS (Ackerman and Greenland2002). Responder rates to clomipramine vary between 40-50% of patients. Though in some cases low doses of clomipramine over a short period of time may result in significant improvement of symptoms, 21 Chapter 2 clomipramine treatment should last at least 10 to 12 weeks in a dose of 250-300 mg/day to demonstrate a full effect. Clomipramine has never been tested in a controlled fixed-dose study to assess optimal doses. Fluvoxamine is superior to placebo in 4 placebo-controlled trials and equipotent to clomipramine in 5 comparison trials (Dell’osso et al.2005). The pooled difference of fluvoxamine compared with placebo in these trials was 4.8 points on the Y-BOCS. Fluvoxamine has never been examined in a fixed dose trial, but appears to be efficacious from 150-300 mg/day. Fluoxetine is effective in 3 placebo-controlled trials and equipotent to clomipramine in 2 comparison trials. The pooled difference on the Y-BOCS of fluoxetine compared with placebo was 1.6 points (Ackerman and Greenland2002). Responder rates to fluoxetine vary between 25-30% of patients. Sertraline was effective in 4 placebo- controlled trials and equipotent to clomipramine in 1 comparison trial. The pooled difference of sertraline compared with placebo in these trials was 2.5 points on the Y-BOCS (Ackerman and Greenland2002). Although no correlation was found of sertraline plasma levels with treatment outcome, in a large multicenter trial, sertraline 50 mg/day and 200 mg/day were superior to placebo whereas 100 mg/day was not. For a long time, paroxetine was shown to be effective in just one published placebo-controlled trial and equipotent to clomipramine in the same trial (Ackerman and Greenland2002; Zohar and Judge1996; Ninan2003). The difference of paroxetine compared with placebo was 3.1 points on the Y-BOCS. Forty and 60 mg/day doses were significantly better than placebo whereas 20 mg was not. The efficacy of citalopram in OCD recently was established in a placebo-controlled study including 401 patients who were randomized to receive citalopram 20, 40 or 60 mg/day or placebo for 12 weeks (Montgomery et al.2001). The difference of citalopram compared with placebo was 3.6 points on the Y-BOCS. The highest responder rate (65%), defined as 25% improvement in Y-BOCS entry score, was observed in the 60 mg group compared with 52% and 57.4% in the 40 mg and 20 mg groups, respectively. Surprisingly, the responder rate on placebo was 36.6% with a mean decrease on the Y-BOCS of 5.6 points. This high improvement rate on placebo, uncommon in OCD, has been explained as a result of inclusion of milder, atypical cases, in which spontaneous remission is more frequent. Patients with longer duration of OCD, more severe OCD symptoms or previous SSRI use were less likely to be responders to citalopram, whereas patients who received adequate medication doses for sufficient periods of time were more likely to be responders (Stein et al.2001). In a small study, clinical response does not appear to be related to citalopram plasma concentrations (Bareggi et al.2004). The efficacy of clomipramine and five SSRIs has been established with placebo-controlled trials, but are clomipramine, fluvoxamine, paroxetine, sertraline, citalopram and fluoxetine equally effective (Soomro et al.2008)? Meta-analyses using statistical methods to pool 22 The serotonergic system in obsessive compulsive disorder samples from different studies may answer this question offering a precise estimate of the treatment effect from separate drug trials. Consistent with previous meta-analyses, Ackerman et al recently confirmed that clomipramine is more effective than SSRIs in placebo-controlled trials (Ackerman and Greenland2002). For 7 clomipramine trials, the net Y-BOCS decrease compared with placebo was 8.19, whereas for 4 fluvoxamine trials the net Y-BOCS decrease was 4.84, for 3 fluoxetine trials 1.61, and for 4 sertraline trials 2.47. It is worth noting, however, that the largest effect sizes for clomipramine were found in early studies and have not been as clearly replicated in more recent studies comparing it with SSRIs. Moreover, on the long term, drop-out rates in clomipramine-treated patients are higher than SSRI-treated patients. In another meta-analysis which included 32 studies covering a total number of 3588 OCD patients, again, clomipramine had the largest effect size (1.55) versus 0.81 for fluoxetine to 1.36 for sertraline (Eddy et al.2004). This meta-analysis also demonstrated that two-thirds of the patients who completed a medication trial improved. Across all active treatments, the mean Y-BOCS decrease was 7.1 resulting in a mean post-treatment Y-BOCS score of 17.9 whereas for placebo conditions the Y-BOCS decrease was 1.8. Clearly, in effectiveness, clomipramine is superior to all the SSRIs. In practice, however, the choice of a drug also depends on side effect profile and potential for drug interactions.
Load more

Recommended publications
  • Obsessive-Compulsive Disorder. [Revised.) INSTITUTION National Inst
    DOCUMENT RESUME ED 408 729 EC 305 600 AUTHOR Strock, Margaret TITLE Obsessive-Compulsive Disorder. [Revised.) INSTITUTION National Inst. of Mental Health (DHHS), Rockville, Md. REPORT NO NIH-pub-96-3755 PUB DATE Sep96 NOTE 24p. AVAILABLE FROM National Institute of Mental Health, Information Resources and Inquiries Branch, 5600 Fishers Lane, Room 7C-02, Rockville, MD 20857. PUB TYPE Guides Non-Classroom (055) EDRS PRICE MF01/PC01 Plus Postage. DESCRIPTORS *Behavior Disorders; *Behavior Modification; *Disability Identification; *Drug Therapy; Incidence; Intervention; Mental Disorders; *Neurological Impairments; Outcomes of Treatment; *Symptoms (Individual Disorders) IDENTIFIERS *Obsessive Compulsive Behavior ABSTRACT This booklet provides an overview of the causes, symptoms, and incidence of obsessive-compulsive disorder (OCD) and addresses the key features of OCD, including obsessions, compulsions, realizations of senselessness, resistance, and shame and secrecy. Research findings into the causes of OCD are reviewed which indicate that the brains of individuals with OCD have different patterns of brain activity than those of people without mental illness or with some other mental illness. Other types of illness that may be linked to OCD are noted, such as Tourette syndrome, trichotillomania, body dysmorphic disorder and hypochondriasis. The use of pharmacotherapy and behavior therapy to treat individuals with OCD is evaluated and a screening test for OCD is presented, along with information on how to get help for OCD. Lists of organizations that can be contacted and related books on the subject are also provided. Case histories of people with OCD are included in the margins of the booklet. (Contains 11 references.) (CR) ******************************************************************************** Reproductions supplied by EDRS are the best that can be made from the original document.
    [Show full text]
  • Effects of Stress-Induced Depression on Parkinson's Disease
    Effects of stress-induced depression on Parkinson’s disease symptomatology A dissertation submitted to the Division of Research and Advanced Studies of the University of Cincinnati in partial fulfillment of the requirements for the degree of Doctor of Philosophy (Ph.D.) in the Graduate Program in Neuroscience of the College of Medicine 2011 By Ann Marie Hemmerle B.S., University of Dayton Advisor: Kim B. Seroogy, Ph.D. Committee Chair: Neil Richtand, M.D., Ph.D. James P. Herman, Ph.D. Kathy Steece-Collier, Ph.D. Aaron Johnson, Ph.D. Abstract Parkinson’s disease (PD) is a chronic neurodegenerative disorder that primarily affects dopaminergic neurons of the nigrostriatal pathway resulting in debilitating motor symptoms. Parkinson’s patients also have a high risk of comorbid depression, though this aspect of the disorder is less well studied. Understanding the underlying pathology of the comorbidity is important in improving clinical treatments and the quality of life for PD patients. To address this issue, we have developed a new model combining the unilateral striatal 6-hydroxydopamine lesion model of PD with the chronic variable stress model (CVS) of depression. Dysfunction of the hypothalamic-pituitary-adrenal axis and its relationship to depression symptomatology is well established. Stress dysfunction may also have a role in the etiology of preclinical PD non- motor symptoms, and later in the course of the disease, may worsen motor symptoms. The combined model allows us to test the hypothesis that experimental depression exacerbates PD symptoms and to ascertain the mechanisms behind the increased neuronal loss. In the first study, we examined several temporal paradigms of the combined model.
    [Show full text]
  • Debbie Sookman Is an Outstanding Contribution to the Science and Clinical Practice Related to the Full Range of Obsessive Com- Pulsive Disorder
    Downloaded by [New York University] at 04:59 12 August 2016 “I strongly recommend this expert clinical guide to the psychological treat- ment of obsessive compulsive disorders. The depth of Dr. Sookman’s clinical experience and her command of the literature are evident in the thorough coverage of assessment procedures, how to optimize the effects of therapy and deal with problems. The numerous case illustrations are well-chosen and clearly described.” —S. Rachman, Emeritus Professor, Institute of Psychiatry, London University, and University of British Columbia. “Specialized Cognitive Behavior Therapy for Obsessive Compulsive Disorder: An Expert Clinician Guidebook by Dr. Debbie Sookman is an outstanding contribution to the science and clinical practice related to the full range of Obsessive Com- pulsive Disorder. This is an excellent book in every way imaginable. Clearly written and organized, Sookman provides a critical and scholarly review of the state of the art on OCD. Every researcher and clinician can benefit from this superb book. The reader benefits from the considerable clinical expe- rience and scholarship that Dr Sookman possesses, while learning specific and powerful tools in helping those who suffer from OCD. Case examples illustrate the importance of conceptualization and the value of empirically supported treatments. I am particularly impressed that Sookman was able to balance such sophistication in her critical and scientific understanding of OCD, while still writing a clear and concise book on the topic. This is a book I will recommend to both beginning clinicians in training and to seasoned researchers and practitioners.” —Robert L. Leahy, Ph.D., Director, American Institute for Cognitive Therapy “Dr.
    [Show full text]
  • 200750261.Pdf
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Apollo Compulsivity in obsessive-compulsive disorder and addictions Martijn Figeea, Tommy Pattijb, Ingo Willuhna,c, Judy Luigjesa, Wim van den Brinka,d, Anneke Goudriaana,d, Marc N. Potenzae, Trevor W. Robbinsf, Damiaan Denysa,c a Academic Medical Center, Department of Psychiatry, Amsterdam, the Netherlands b Neuroscience Campus Amsterdam, Department of Anatomy and Neurosciences, VU University Medical Center, Amsterdam, The Netherlands. c The Institute for Neuroscience, an institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands d Amsterdam Institute for Addiction Research, Amsterdam, the Netherlands e Department of Psychiatry, Yale University School of Medicine, New Haven, CT, United States; Department of Neurobiology, Yale University School of Medicine, New Haven, CT, United States; Child Study Center, Yale University School of Medicine, New Haven, CT, United States. f Department of Psychology and Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, United Kingdom Please address all correspondence to: Damiaan Denys, M.D., Academic Medical Center, University of Amsterdam, Department of Psychiatry, Postbox 75867, 1070 AW Amsterdam, The Netherlands. E-mail: [email protected] ABSTRACT Compulsive behaviors are driven by repetitive urges and typically involve the experience of limited voluntary control over these urges, a diminished ability to delay or inhibit these behaviors, and a tendency to perform repetitive acts in a habitual or stereotyped manner. Compulsivity is not only a central characteristic of obsessive-compulsive disorder (OCD) but is also crucial to addiction. Based on this analogy, OCD has been proposed to be part of the concept of behavioral addiction along with other non-drug-related disorders that share compulsivity, such as pathological gambling, skin-picking, trichotillomania and compulsive eating.
    [Show full text]
  • Brain Imaging
    Publications · Brochures Brain Imaging A Technologist’s Guide Produced with the kind Support of Editors Fragoso Costa, Pedro (Oldenburg) Santos, Andrea (Lisbon) Vidovič, Borut (Munich) Contributors Arbizu Lostao, Javier Pagani, Marco Barthel, Henryk Payoux, Pierre Boehm, Torsten Pepe, Giovanna Calapaquí-Terán, Adriana Peștean, Claudiu Delgado-Bolton, Roberto Sabri, Osama Garibotto, Valentina Sočan, Aljaž Grmek, Marko Sousa, Eva Hackett, Elizabeth Testanera, Giorgio Hoffmann, Karl Titus Tiepolt, Solveig Law, Ian van de Giessen, Elsmarieke Lucena, Filipa Vaz, Tânia Morbelli, Silvia Werner, Peter Contents Foreword 4 Introduction 5 Andrea Santos, Pedro Fragoso Costa Chapter 1 Anatomy, Physiology and Pathology 6 Elsmarieke van de Giessen, Silvia Morbelli and Pierre Payoux Chapter 2 Tracers for Brain Imaging 12 Aljaz Socan Chapter 3 SPECT and SPECT/CT in Oncological Brain Imaging (*) 26 Elizabeth C. Hackett Chapter 4 Imaging in Oncological Brain Diseases: PET/CT 33 EANM Giorgio Testanera and Giovanna Pepe Chapter 5 Imaging in Neurological and Vascular Brain Diseases (SPECT and SPECT/CT) 54 Filipa Lucena, Eva Sousa and Tânia F. Vaz Chapter 6 Imaging in Neurological and Vascular Brain Diseases (PET/CT) 72 Ian Law, Valentina Garibotto and Marco Pagani Chapter 7 PET/CT in Radiotherapy Planning of Brain Tumours 92 Roberto Delgado-Bolton, Adriana K. Calapaquí-Terán and Javier Arbizu Chapter 8 PET/MRI for Brain Imaging 100 Peter Werner, Torsten Boehm, Solveig Tiepolt, Henryk Barthel, Karl T. Hoffmann and Osama Sabri Chapter 9 Brain Death 110 Marko Grmek Chapter 10 Health Care in Patients with Neurological Disorders 116 Claudiu Peștean Imprint 126 n accordance with the Austrian Eco-Label for printed matters.
    [Show full text]
  • Personalized Treatment of Alcohol Dependence
    Curr Psychiatry Rep DOI 10.1007/s11920-012-0296-5 SUBSTANCE USE AND RELATED DISORDERS (JR MCKAY, SECTION EDITOR) Personalized Treatment of Alcohol Dependence Henry R. Kranzler & James R. McKay # Springer Science+Business Media, LLC 2012 Abstract Pharmacogenetic and adaptive treatment approaches Ondansetron . Sertraline . Adaptive trial designs . can be used to personalize care for alcohol-dependent patients. Adaptive protocol . Stepped care . Treatment algorithm Preliminary evidence shows that variation in the gene encoding the μ-opioid receptor moderates the response to naltrexone when used to treat alcohol dependence. Studies have also shown moderating effects of variation in the gene encoding Introduction the serotonin transporter on response to serotonergic treatment of alcohol dependence. Adaptive algorithms that modify alco- Traditionally, diagnostic tests and medical treatments have hol treatment based on patients’ progress have also shown been developed and evaluated using group data, a “one-size promise. Initial response to outpatient treatment appears to be fits all” approach that leaves little room for individual variation a particularly important in the selection of optimal continuing [1]. Personalized medicine, which uses individual features to care interventions. In addition, stepped-care algorithms can diagnose and treat disease, is of growing interest, having reduce the cost and burden of treatment while maintaining good produced notable successes in oncology and cardiology [2•, outcomes. Finally, matching treatment to specific problems 3]. To date, there have been fewer advances in the personalized present at intake or that emerge during treatment can also diagnosis and treatment of addictive disorders. However, on- improve outcomes. Although all of these effects require repli- going developments in genetics and pharmacogenetics and in cation and further refinement, the future of personalized care for the use of adaptive trial designs offer great potential to extend alcohol dependence appears bright.
    [Show full text]
  • A Nonlinear Relationship Between Cerebral Serotonin Transporter And
    The Journal of Neuroscience, March 3, 2010 • 30(9):3391–3397 • 3391 Cellular/Molecular A Nonlinear Relationship between Cerebral Serotonin Transporter and 5-HT2A Receptor Binding: An In Vivo Molecular Imaging Study in Humans David Erritzoe,1,3 Klaus Holst,3,4 Vibe G. Frokjaer,1,3 Cecilie L. Licht,1,3 Jan Kalbitzer,1,3 Finn Å. Nielsen,3,5 Claus Svarer,1,3 Jacob Madsen,2 and Gitte M. Knudsen1,3 1Neurobiology Research Unit and 2PET and Cyclotron Unit, University Hospital Rigshospitalet, DK-2100 Copenhagen, Denmark, 3Center for Integrated Molecular Brain Imaging, DK-2100 Copenhagen, Denmark, 4Department of Biostatistics, University of Copenhagen, DK-2200 Copenhagen, Denmark, and 5DTU Informatics, Technical University of Denmark, DK-2800 Lyngby, Denmark Serotonergic neurotransmission is involved in the regulation of physiological functions such as mood, sleep, memory, and appetite. Withintheserotonintransmittersystem,boththepostsynapticallylocatedserotonin2A(5-HT2A )receptorandthepresynapticserotonin transporter (SERT) are sensitive to chronic changes in cerebral 5-HT levels. Additionally, experimental studies suggest that alterations in either the 5-HT2A receptor or SERT level can affect the protein level of the counterpart. The aim of this study was to explore the covariation betweencerebral5-HT2A receptorandSERT invivointhesamehealthyhumansubjects.Fifty-sixhealthyhumansubjectswithameanage of 36 Ϯ 19 years were investigated. The SERT binding was imaged with [ 11C]3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)- 18 benzonitrile (DASB) and 5-HT2A receptor binding with [ F]altanserin using positron emission tomography. Within each individual, a regionalintercorrelationforthevariousbrainregionswasseenwithbothmarkers,mostnotablyfor5-HT2A receptorbinding.Aninverted U-shaped relationship between the 5-HT2A receptor and the SERT binding was identified. The observed regional intercorrelation for both the 5-HT2A receptor and the SERT cerebral binding suggests that, within the single individual, each marker has a set point adjusted through a common regulator.
    [Show full text]
  • Symptom Dimensions in OCD: Item-Level Factor Analysis and Heritability Estimates
    Symptom Dimensions in OCD: Item-Level Factor Analysis and Heritability Estimates The MIT Faculty has made this article openly available. Please share how this access benefits you. Your story matters. Citation Katerberg, Hilga et al. “Symptom Dimensions in OCD: Item-Level Factor Analysis and Heritability Estimates.” Behavior Genetics 40 (2010): 505-517. As Published http://dx.doi.org/10.1007/s10519-010-9339-z Publisher Springer Science + Business Media B.V. Version Final published version Citable link http://hdl.handle.net/1721.1/65885 Terms of Use Creative Commons Attribution Noncommercial License Detailed Terms http://creativecommons.org/licenses/by-nc/2.5 Behav Genet (2010) 40:505–517 DOI 10.1007/s10519-010-9339-z ORIGINAL RESEARCH Symptom Dimensions in OCD: Item-Level Factor Analysis and Heritability Estimates Hilga Katerberg • Kevin L. Delucchi • S. Evelyn Stewart • Christine Lochner • Damiaan A. J. P. Denys • Denise E. Stack • J. Michael Andresen • J. E. Grant • Suck W. Kim • Kyle A. Williams • Johan A. den Boer • Anton J. L. M. van Balkom • Johannes H. Smit • Patricia van Oppen • Annemiek Polman • Michael A. Jenike • Dan J. Stein • Carol A. Mathews • Danielle C. Cath Received: 28 May 2009 / Accepted: 19 January 2010 / Published online: 2 April 2010 Ó The Author(s) 2010. This article is published with open access at Springerlink.com Abstract To reduce the phenotypic heterogeneity of and translational studies, numerous factor analyses of obsessive-compulsive disorder (OCD) for genetic, clinical the Yale-Brown Obsessive Compulsive Scale checklist (YBOCS-CL) have been conducted. Results of these analyses have been inconsistent, likely as a consequence of Edited by Michael Lyons.
    [Show full text]
  • Defining Compulsive Behavior
    Neuropsychology Review (2019) 29:4–13 https://doi.org/10.1007/s11065-019-09404-9 REVIEW Defining Compulsive Behavior Judy Luigjes1,2 & Valentina Lorenzetti3 & Sanneke de Haan4 & George J. Youssef5,6 & Carsten Murawski7 & Zsuzsika Sjoerds8,9 & Wim van den Brink1 & Damiaan Denys1,10 & Leonardo F. Fontenelle11,12,13 & Murat Yücel11 Received: 22 January 2018 /Accepted: 27 March 2019 /Published online: 23 April 2019 # The Author(s) 2019 Abstract Compulsive tendencies are a central feature of problematic human behavior and thereby are of great interest to the scientific and clinical community. However, no consensus exists about the precise meaning of ‘compulsivity,’ creatingconfusioninthefieldandhamperingcomparisonacross psychiatric disorders. A vague conceptualization makes compulsivity a moving target encompassing a fluctuating variety of behaviors, which is unlikely to improve the new dimension-based psychiatric or psychopathology approach. This article aims to help progress the definition of what constitutes compulsive behavior, cross-diagnostically, by analyzing different definitions in the psychiatric literature. We searched PubMed for articles in human psychiatric research with ‘compulsive behavior’ or ‘compul- sivity’ in the title that focused on the broader concept of compulsivity—returning 28 articles with nine original definitions. Within the definitions, we separated three types of descriptive elements: phenomenological, observational and explanatory. The elements most applicable, cross-diagnostically, resulted in this definition: Compulsive behavior consists of repetitive acts that are characterized by the feeling that one ‘has to’ perform them while one is aware that these acts are not in line with one’s overall goal. Having a more unified definition for compulsive behavior will make its meaning precise and explicit, and therefore more transferable and testable across clinical and non-clinical populations.
    [Show full text]
  • [18F] Altanserin Bolus Injection in the Canine Brain Using PET Imaging
    Pauwelyn et al. BMC Veterinary Research (2019) 15:415 https://doi.org/10.1186/s12917-019-2165-5 RESEARCH ARTICLE Open Access Kinetic analysis of [18F] altanserin bolus injection in the canine brain using PET imaging Glenn Pauwelyn1*† , Lise Vlerick2†, Robrecht Dockx2,3, Jeroen Verhoeven1, Andre Dobbeleir2,5, Tim Bosmans2, Kathelijne Peremans2, Christian Vanhove4, Ingeborgh Polis2 and Filip De Vos1 Abstract 18 Background: Currently, [ F] altanserin is the most frequently used PET-radioligand for serotonin2A (5-HT2A) receptor imaging in the human brain but has never been validated in dogs. In vivo imaging of this receptor in the canine brain could improve diagnosis and therapy of several behavioural disorders in dogs. Furthermore, since dogs are considered as a valuable animal model for human psychiatric disorders, the ability to image this receptor in dogs could help to increase our understanding of the pathophysiology of these diseases. Therefore, five healthy laboratory beagles underwent a 90-min dynamic PET scan with arterial blood sampling after [18F] altanserin bolus injection. Compartmental modelling using metabolite corrected arterial input functions was compared with reference tissue modelling with the cerebellum as reference region. 18 Results: The distribution of [ F] altanserin in the canine brain corresponded well to the distribution of 5-HT2A receptors in human and rodent studies. The kinetics could be best described by a 2-Tissue compartment (2-TC) model. All reference tissue models were highly correlated with the 2-TC model, indicating compartmental modelling can be replaced by reference tissue models to avoid arterial blood sampling. Conclusions: This study demonstrates that [18F] altanserin PET is a reliable tool to visualize and quantify the 5- HT2A receptor in the canine brain.
    [Show full text]
  • Risk Assessment and Management in Obsessive–Compulsive Disorder David Veale, Mark Freeston, Georgina Krebs, Isobel Heyman & Paul Salkovskis
    Advances in psychiatric treatment (2009), vol. 15, 332–343 doi: 10.1192/apt.bp.107.004705 ARTICLE Risk assessment and management in obsessive–compulsive disorder David Veale, Mark Freeston, Georgina Krebs, Isobel Heyman & Paul Salkovskis David Veale is an honorary harm to children may be tempted to play for safety SUMMARY senior lecturer and a consultant when conducting a risk assessment. However, a psychiatrist in cognitive behaviour Some people with obsessive–compulsive disorder person with OCD can be harmed by an incorrect or therapy at the NIHR Biomedical (OCD) experience recurrent intrusive sexual, Research Centre for Mental Health, unduly lengthy risk assessment, responding with aggressive or death-related thoughts and as a The South London and Maudsley increased doubts and fears about the implications result may be subjected to lengthy or inappropriate NHS Foundation Trust, King’s of their intrusive thoughts. At best this will lead College London, and The Priory risk assessments. These apparent ‘primary’ risks Hospital North London. Mark can be dealt with relatively easily through a careful to greater distress, avoidance and compulsive Freeston is Professor of Clinical understanding of the disorder’s phenomenology. behaviours, and mistrust of health professionals; Psychology at Newcastle University, However, there are other, less obvious ‘secondary’ at worst, to complete decompensation of the patient Newcastle upon Tyne. Georgina risks, which require more careful consideration. or break-up of the family. In reality, there is no need Krebs is a clinical psychologist working in the service for young This article discusses the differentiation of intrusive for overcautious reactions. Provided the clinician people with obsessive–compulsive thoughts and urges in people with OCD from has appropriate expertise in OCD, there are very disorder at the Maudsley Hospital, those experienced by sexual or violent offenders; rarely any serious doubts about the diagnosis.
    [Show full text]
  • Disorders, Musical Hallucinations, Musical Obsessions, Neurobiology
    International Journal of Psychology and Behavioral Sciences 2020, 10(3): 51-62 DOI: 10.5923/j.ijpbs.20201003.01 Obsessions and Musical Hallucinations: The Neurobiology Underlying a Differential Diagnosis Mayra E. Dávila-Rivera, Hilda M. Rivera-Marín* Albizu University, San Juan Campus, San Juan, Puerto Rico Abstract This literature review has the purpose of establishing the difference between comorbid disorders with musical obsessions and hallucinations from a neurobiological perspective. Musical obsessions and hallucinations are unusual, with limited research, and their prevalence is underestimated [1,2]. Their pathological etiology can be confusing since it can fall within psychiatry, neurology and biology due to its symptomatic comorbidity; and it may not be recognized as generating suffering for the patient [1]. Neurobiology has made it possible to increase our knowledge of brain structures or circuits responsible for the behavior of subjects who suffer related disorders. Musical obsessions and hallucinations are disabling as they are detrimental to quality of life. Due to new discoveries in the different scientific disciplines, health professionals will establish a differential diagnosis, adequately address primary and underlying pathologies, and also facilitate the implementation of effective evidence-based models. Keywords Disorders, Musical hallucinations, Musical obsessions, Neurobiology 1. Introduction which are unattractive as a clinical research focus [9]. These conditions are chronic and disabling characterized by their Research has identified various disorders sharing similar low prevalence (less than 1,200 individuals), and high characteristics within the neurobiological model of the morbidity. They are scarcely researched, with more than prefrontal cortex. The comorbidity that exists between 80% originating genetically; many of them without a specific psychiatric, neurological and diseases associated with treatment.
    [Show full text]