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16 results on '"MESH: Obsessive-Compulsive Disorder"'

1. Trouble obsessionnel compulsif à début tardif : prodrome de la démence à corps de Lewy ?

Author

Frileux, Solène, Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), and Philippe Fossati

Subjects
MESH: Obsessive-Compulsive Disorder, Trouble obsessionnel-compulsif à début tardif, Démence à corps de Lewy, MESH: Late Onset Disorders, MESH: Dementia, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, MESH: Lewy Body Disease
Abstract

Le trouble obsessionnel-compulsif (TOC) débute habituellement dans l’adolescence ou le jeune âge adulte. Les cas de TOC débutant après l’âge de 40 ans sont rares, et le plus souvent associés à une comorbidité inflammatoire, lésionnelle ou neurodégénérative. Par ailleurs, on constate que les maladies neurodégénératives peuvent se manifester plusieurs années avant les premiers troubles cognitifs, parfois par des symptômes psychiatriques atypiques et résistants. Nous présentons ici le cas de deux patients ayant présenté un TOC de novo après l’âge de 50 ans. Durant leur prise en charge, une intolérance aux neuroleptiques a permis le diagnostic d’une Démence à Corps de Lewy (DCL). Nous nous sommes alors posés la question d’un lien entre le TOC et la DCL, avec plusieurs hypothèses : le TOC à début tardif serait un prodrome de la DCL ; les symptômes de nos patients seraient en fait des stéréotypies frontales, ou des signes atypiques de dépression à début tardif ; le TOC et la DCL seraient seulement comorbides ; le TOC à début tardif et la DCL seraient le résultat évolutif d’une même maladie. Afin de discuter ces différentes hypothèses, nous présentons la physiopathologie commune à la DCL et au TOC ainsi que les cas de TOC secondaires à des lésions cérébrales rapportés dans la littérature. Avec les deux cas cliniques présentés ici, l’ensemble de ces constats renforce le rôle du lobe temporal et du putamen dans la physiopathologie du TOC. Nous posons également la question d’une entité distincte dans le TOC : le TOC débutant après l’âge de 50 ans, qui serait sous-tendu par des bases neurales différentes du TOC « classique ». On parlerait dès lors des troubles obsessionnels-compulsifs. Cette hypothèse nécessite désormais d’être étayée par des études cliniques et de neuroimagerie de grande ampleur, avec une approche dimensionnelle, afin d’explorer la réalité d’un TOC à début tardif, débutant après l’âge de 50 ans et non après l’âge de 18 ans, comme il est actuellement désigné dans la littérature.

Published
2019

2. From impulses to maladaptive actions: the insula is a neurobiological gate for the development of compulsive behavior

Author

Morgane Besson, David Belin, D Howett, Jeffrey W. Dalley, Mickaël Puaud, Bianca Jupp, Trevor W. Robbins, Aude Belin-Rauscent, Stephen J. Sawiak, Daniele Caprioli, M-L Daniel, Colin McKenzie, Barry J. Everitt, University of Cambridge [UK] (CAM), CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), National National Institute on Drug Abuse Intramural Research Program, National Institute of Health, Neurobiologie intégrative des Systèmes cholinergiques (NISC), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), It was supported by an INSERM AVENIR grant and a FYSSEN foundation grant to DB. MLD was supported by a PhD fellowship from the Fondation pour la Recherche Médicale (FRM) and ABR was supported by a post-doctoral fellowship from the INSERM. BJE was supported by the United Kingdom Medical Research Council (MRC) Grant 9536855, This research was carried out within the Department of Psychology and the Department of Pharmacology of the University of Cambridge, as well as the INSERM AVENIR team Psychobiology of Compulsive Disorders of the University of Poitiers., Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Belin, D [0000-0002-7383-372X], and Apollo - University of Cambridge Repository

Subjects
Male, 0301 basic medicine, Serial reaction time, Obsessive-Compulsive Disorder, Neural substrate, [SDV]Life Sciences [q-bio], Neuropsychological Tests, Choice Behavior, Developmental psychology, [SCCO]Cognitive science, 0302 clinical medicine, 5 - Choice serial reaction time task, MESH: Animals, Insular cortex, Cerebral Cortex, MESH: Neuropsychological Tests, Compulsivity, 3. Good health, Psychiatry and Mental health, Schizophrenia, Compulsive behavior, animals, behavior, addictive, cerebral cortex, choice behavior, compulsive behavior, impulsive behavior, male, neuropsychological tests, obsessive-compulsive disorder, rats, reaction time, molecular biology, psychiatry and mental health, cellular and molecular neuroscience, Compulsive Behavior, MESH: Compulsive Behavior, MESH: Impulsive Behavior, medicine.symptom, Psychology, Impulsivity, Schedule induced polydipsia, MESH: Rats, MESH: Choice Behavior, 03 medical and health sciences, Cellular and Molecular Neuroscience, MESH: Behavior, Addictive, Reaction Time, medicine, Animals, Molecular Biology, MESH: Obsessive-Compulsive Disorder, behavior, [SCCO.NEUR]Cognitive science/Neuroscience, addictive, medicine.disease, MESH: Cerebral Cortex, MESH: Male, Rats, MESH: Reaction Time, Behavior, Addictive, 030104 developmental biology, Endophenotype, Impulsive Behavior, Neuroscience, Insula, 030217 neurology & neurosurgery
Abstract

International audience; Impulsivity is an endophenotype of vulnerability for compulsive behaviors. However, the neural mechanisms whereby impulsivity facilitates the development of compulsive disorders, such as addiction or obsessive compulsive disorder, remain unknown. We first investigated, in rats, anatomical and functional correlates of impulsivity in the anterior insular (AI) cortex by measuring both the thickness of, and cellular plasticity markers in, the AI with magnetic resonance imaging and in situ hybridization of the immediate early gene zif268, respectively. We then investigated the influence of bilateral AI cortex lesions on the high impulsivity trait, as measured in the five-choice serial reaction time task (5-CSRTT), and the associated propensity to develop compulsivity as measured by high drinking levels in a schedule-induced polydipsia procedure (SIP). We demonstrate that the AI cortex causally contributes to individual vulnerability to impulsive-compulsive behavior in rats. Motor impulsivity, as measured by premature responses in the 5-CSRTT, was shown to correlate with the thinness of the anterior region of the insular cortex, in which highly impulsive (HI) rats expressed lower zif268 mRNA levels. Lesions of AI reduced impulsive behavior in HI rats, which were also highly susceptible to develop compulsive behavior as measured in a SIP procedure. AI lesions also attenuated both the development and the expression of SIP. This study thus identifies the AI as a novel neural substrate of maladaptive impulse control mechanisms that may facilitate the development of compulsive disorders.

Published
2016
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3. Cognitive distortions and eating pathology: Specificity of thought–shape fusion

Author

Audrey Pitet, Céline Baeyens, Martine Bouvard, Jennifer S. Coelho, Christine Purdon, Laboratoire Inter-universitaire de Psychologie : Personnalité, Cognition, Changement Social (LIP-PC2S), Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry]), Department of Psychology, University of Waterloo [Waterloo], Laboratoire de Psychologie et NeuroCognition (LPNC), and Centre National de la Recherche Scientifique (CNRS)-Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])

Subjects
MESH: Psychiatric Status Rating Scales, Obsessive-Compulsive Disorder, 050103 clinical psychology, MESH: Self Report, Thinking, 0302 clinical medicine, Behavior Therapy, Surveys and Questionnaires, MESH: Thinking, MESH: Middle Aged, 05 social sciences, Eating pathology, MESH: Behavior Therapy, Cognition, Middle Aged, MESH: Case-Control Studies, Psychiatry and Mental health, Clinical Psychology, Distress, Eating disorders, MESH: Young Adult, Trait, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Female, MESH: Eating Disorders, Psychology, Adult, medicine.medical_specialty, Adolescent, Experimental and Cognitive Psychology, Feeding and Eating Disorders, Young Adult, 03 medical and health sciences, Cognitive distortion, MESH: Analysis of Variance, Body Image, medicine, Humans, 0501 psychology and cognitive sciences, Psychiatry, MESH: Body Image, Thought shape fusion, MESH: Adolescent, MESH: Obsessive-Compulsive Disorder, Psychiatric Status Rating Scales, Analysis of Variance, MESH: Humans, MESH: Questionnaires, MESH: Adult, medicine.disease, 030227 psychiatry, MESH: Cognition Disorders, Case-Control Studies, Self Report, Cognition Disorders, MESH: Female
Abstract

International audience; Thought-shape fusion (TSF) is a cognitive distortion that has been linked with eating pathology; however, the specificity of this distortion to eating disorders has not yet been examined. The current study set out to investigate the effects of a TSF induction on susceptibility to TSF in three groups of women: individuals with an eating disorder (n = 33), individuals with obsessive-compulsive disorder (OCD; n = 24), and control women with no history of either an eating disorder or obsessive-compulsive disorder (n = 26). Participants were assigned to receive either a TSF induction or a neutral induction, and their cognitive, emotional, and behavioral responses were assessed. As expected, the results demonstrated that individuals with eating disorders were more susceptible to TSF than were women with OCD and control participants, reporting higher state TSF, more negative affect, and more neutralization behavior. The results also supported the specificity of this distortion by demonstrating that individuals with OCD were not particularly susceptible to TSF. In fact, control participants demonstrated an increased susceptibility to TSF relative to women with OCD, as evidenced by their higher levels of trait TSF, and increased self-reported distress/difficulty in imagining a food-related situation.

Published
2012
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4. Application des psychothérapies mindfulness au traitement du trouble obsessionnel-compulsif : revue des connaissances et mise en place d'un protocole expérimental

Author

Gasnier, Matthieu, Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), and Antoine Pelissolo

Subjects
Psychothérapie, MESH: Obsessive-Compulsive Disorder, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, MESH: Psychiatry, Neurosciences, MESH: Mindfulness, Trouble obsessionnel-compulsif, Innovation thérapeutique, MESH: Neurosciences, Mindfulness, MESH: Psychotherapy, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Psychiatrie
Abstract

Obsessive-compulsive disorder (OCD) is a frequent and severe disease, leading to impairment for the patient and his family. Recent research in psychiatry and neuroscience led to better comprehension of disease’s mechanisms and helped to improve the treatment. However, a large quantity of patients show a resistance to the existent therapeutics, leading the practitioners to try find new treatments. The mindfulness psychotherapy is a new type of therapy developed successfully in some psychiatric diseases, such generalized anxiety disorder (GAD) and depression. Its action relies on the specific correction of cognitive caracteristics shared by OCD, GAD and depression. This thesis proposes a review of the existing literature about OCD and mindfulness psychotherapy, hypothesis on the mechanism of action of this therapy in OCD, and finally presents the results of a clinical studies aiming to prove the interest of the use of mindfulness in OCD.; Le Trouble obsessionnel-compulsif (TOC) est une pathologie fréquente, potentiellement sévère, entraînant un handicap important pour le patient et son entourage. Les avancées récentes de la psychiatrie et des neurosciences ont permis une meilleure compréhension de la maladie et la mise au point de traitements plus efficaces. Pour autant, une part importante de patients présente des résistances, motivant la recherche de thérapeutiques nouvelles. Les psychothérapies mindfulness sont un type de thérapie récemment développé avec succès dans certaines pathologies psychiatriques, comme le trouble anxieux généralisé (TAG) et la dépression. Leur action est sous tendue par la correction de certaines caractéristiques neuropsychologiques pouvant se retrouver aussi bien dans le TOC que dans le TAG et la dépression. Nous proposons ici une revue des connaissances sur le TOC et les thérapies mindfulness, des hypothèses sur leur mécanisme d’action dans cette pathologie, et les résultats d’un protocole expérimental que nous avons mis en place au cours de notre troisième cycle.

Published
2015

5. Therapeutic electrical stimulation of the central nervous system

Author

Paul Krack, Alim-Louis Benabid, Brigitte Piallat, Bradley Wallace, Valérie Fraix, John Mitrofanis, Celine Xia, Alina Batir, Pierre Pollak, François Berger, Neurosciences précliniques, Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Issartel, Jean-Paul

Subjects
Central Nervous System, Nervous system, Obsessive-Compulsive Disorder, Anorexia Nervosa, Parkinson's disease, medicine.medical_treatment, Stimulation, 0302 clinical medicine, Central Nervous System Diseases, Basal ganglia, MESH: Obesity, MESH: Animals, 0303 health sciences, Electric Stimulation Therapy/*methods, Brain, MESH: Electric Stimulation, Parkinson Disease, General Medicine, 3. Good health, Subthalamic nucleus, medicine.anatomical_structure, Brain/physiology/*physiopathology, General Agricultural and Biological Sciences, MESH: Anorexia Nervosa, Central Nervous System/*physiology/physiopathology, Obesity/therapy, Deep brain stimulation, Parkinson Disease/therapy, Central nervous system, MESH: Electric Stimulation Therapy, Electric Stimulation Therapy, Anorexia Nervosa/therapy, General Biochemistry, Genetics and Molecular Biology, MESH: Brain, 03 medical and health sciences, medicine, Animals, Humans, MESH: Central Nervous System, Obesity, 030304 developmental biology, MESH: Obsessive-Compulsive Disorder, MESH: Humans, General Immunology and Microbiology, Thalamotomy, business.industry, medicine.disease, Central Nervous System Diseases/physiopathology/*therapy, Electric Stimulation, MESH: Central Nervous System Diseases, Obsessive-Compulsive Disorder/therapy, business, Neuroscience, MESH: Parkinson Disease, 030217 neurology & neurosurgery
Abstract

International audience; The electrical effects on the nervous system have been known for long. The excitatory effect has been used for diagnostic purposes or even for therapeutic applications, like in pain using low-frequency stimulation of the spinal cord or of the thalamus. The discovery that High-Frequency Stimulation (HFS) mimics the effect of lesioning has opened a new field of therapeutic application of electrical stimulation in all places where lesion of neuronal structures, such as nuclei of the basal ganglia, had proven some therapeutic efficiency. This was first applied to the thalamus to mimic thalamotomy for the treatment of tremor, then to the subthalamic nucleus and the pallidum to treat some advanced forms of Parkinson's disease and control not only the tremor but also akinesia, rigidity and dyskinesias. The field of application is increasingly growing, currently encompassing dystonias, epilepsy, obsessive compulsive disease, cluster headaches, and experimental approaches are being made in the field of obesity and food intake control. Although the effects of stimulation are clear-cut and the therapeutic benefit is clearly recognized, the mechanism of action of HFS is not yet understood. The similarity between HFS and the effect of lesions in several places of the brain suggests that this might induce an inhibition-like process, which is difficult to explain with the classical concept of physiology where electrical stimulation means excitation of neural elements. The current data coming from either clinical or experimental observations are providing elements to shape a beginning of an understanding. Intra-cerebral recordings in human patients with artefact suppression tend to show the arrest of electrical firing in the recorded places. Animal experiments, either in vitro or in vivo, show complex patterns mixing inhibitory effects and frequency stimulation induced bursting activity, which would suggest that the mechanism is based upon the jamming of the neuronal message, which is by this way functionally suppressed. More recent data from in vitro biological studies show that HFS profoundly affects the cellular functioning and particularly the protein synthesis, suggesting that it could alter the synaptic transmission by reducing the production of neurotransmitters. It is now clear that this method has a larger field of application than currently known and that its therapeutical applications will benefit to several diseases of the nervous system. The understanding of the mechanism has opened a new field of research, which will call for reappraisal of the basic effects of electricity on the living tissues.

Published
2005
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6. ALZHEIMER'S DISEASE AND VASCULAR FACTORS: FACTS AND THEORIES

Author

Pansari, K., Gupta, Anupam, Thomas, P., Indian Institute of Technology Bombay (IIT Bombay), Water Engineering and Management, Centre de Recherches sur les Très Basses Températures (CRTBT), Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique de Grenoble (INPG)-Université Joseph Fourier - Grenoble 1 (UJF), Laboratoire de Neurosciences Fonctionnelles et Pathologies (LNFP), and Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, MESH: Globus Pallidus, MESH: Psychiatry, MESH: Antigens, CD3, MESH: Comorbidity, MESH: Magnetic Resonance Imaging, MESH: Putamen, MESH: Basal Ganglia, MESH: Tourette Syndrome, MESH: Paraproteinemias, MESH: Neural Conduction, Risk Factors, MESH: Risk Factors, MESH: Child, MESH: Microcirculation, MESH: Caudate Nucleus, MESH: Aged, MESH: Polyneuropathies, MESH: Middle Aged, MESH: Vasculitis, General Medicine, MESH: Electrophysiologic Techniques, Cardiac, MESH: Immunoglobulin M, MESH: Review Literature as Topic, MESH: Conflict of Interest, Cardiovascular Diseases, MESH: Paraproteins, MESH: Great Britain, Female, MESH: Cerebrovascular Disorders, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], MESH: Attention Deficit Disorder with Hyperactivity, MESH: Microscopy, Electron, MESH: Endothelium, MESH: Brain, MESH: Mononeuropathies, Alzheimer Disease, Humans, Aged, MESH: Lymphoma, B-Cell, MESH: Adolescent, MESH: Age Factors, MESH: Obsessive-Compulsive Disorder, MESH: Fascia, MESH: Humans, MESH: Cardiovascular Diseases, MESH: Adult, MESH: Male, Cerebrovascular Disorders, MESH: Drug Industry, MESH: Female, MESH: Alzheimer Disease
Abstract

International audience; Although Alzheimer s disease is classified as a neurodegenerative dementia, in Alzheimer s dementia there is increasing evidence of an association with vascular risk factors and vascular pathology. These observations are supported by epidemiological and pathological studies. Vascular factors may play a significant role in the pathogenesis of Alzheimer s dementia. Further research is needed to explore this relationship. Modification of vascular risk factors could make a significant impact towards prevention and treatment of Alzheimer s disease, which is a distressing and prevalent condition in the community. This article considers the relationship of these vascular risk factors and potential mechanisms associated with the aetiopathogenesis of Alzheimer s dementia.

Published
2002
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7. Is deep brain stimulation able to make antidepressants effective in resistant obsessive-compulsive disorder?

Author

Aouizerate, Bruno, Cuny, Emmanuel, Rotgé, Jean-Yves, Martin-Guehl, Corinne, Doumy, Olivier, Benazzouz, Abdelhamid, Allard, Michele, Rougier, Alain, Bioulac, Bernard, Tignol, Jean, Guehl, Dominique, Burbaud, Pierre, Hôpital Charles Perrens, Unité de recherche clinique intersectorielle du Centre Hospitalier Henri Laborit, Centre Hospitalier Henri Laborit (CHL), Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Institut de Neurosciences cognitives et intégratives d'Aquitaine (INCIA), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie de la Matière Condensée de Bordeaux (ICMCB), and Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut Polytechnique de Bordeaux-Université de Bordeaux (UB)

Subjects
MESH: Basal Ganglia, MESH: Obsessive-Compulsive Disorder, MESH: Combined Modality Therapy, MESH: Humans, MESH: Middle Aged, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, MESH: Antidepressive Agents, MESH: Deep Brain Stimulation, ComputingMilieux_MISCELLANEOUS, MESH: Male
Abstract

International audience

Published
2012

8. Is deep brain stimulation able to make antidepressants effective in resistant obsessive-compulsive disorder?

Author

Aouizerate, Bruno, Cuny, Emmanuel, Rotgé, Jean-Yves, Martin-Guehl, Corinne, Doumy, Olivier, Benazzouz, Abdelhamid, Allard, Michele, Rougier, Alain, Bioulac, Bernard, Tignol, Jean, Guehl, Dominique, Burbaud, Pierre, Hôpital Charles Perrens, Unité de recherche clinique intersectorielle du Centre Hospitalier Henri Laborit, Centre Hospitalier Henri Laborit (CHL), Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Institut de Neurosciences cognitives et intégratives d'Aquitaine (INCIA), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie de la Matière Condensée de Bordeaux (ICMCB), and Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut Polytechnique de Bordeaux-Université de Bordeaux (UB)

Subjects
MESH: Basal Ganglia, MESH: Obsessive-Compulsive Disorder, MESH: Combined Modality Therapy, MESH: Humans, MESH: Middle Aged, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, MESH: Antidepressive Agents, MESH: Deep Brain Stimulation, ComputingMilieux_MISCELLANEOUS, MESH: Male
Abstract

International audience

Published
2012

9. The associative and limbic thalamus in the pathophysiology of obsessive-compulsive disorder: an experimental study in the monkey

Author

Virginie Lambrecq, Nicolas Langbour, Dominique Guehl, Pierre Burbaud, Bernard Bioulac, Bruno Aouizerate, T H Nguyen, S Dovero, V Amestoy, L Cardoit, Jean-Yves Rotge, Jean Tignol, Unité de recherche clinique intersectorielle du Centre Hospitalier Henri Laborit, Centre Hospitalier Henri Laborit (CHL), Centre hospitalier Charles Perrens [Bordeaux], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Institut de Neurosciences cognitives et intégratives d'Aquitaine (INCIA), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS), Hôpital Charles Perrens, Service de neurologie 1 [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
Obsessive-Compulsive Disorder, Deep Brain Stimulation, medicine.medical_treatment, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, pharmacological manipulations, 0302 clinical medicine, MESH: Behavior, Animal, MESH: Animals, MESH: GABA-A Receptor Antagonists, Behavior, Animal, Muscimol, Psychiatry and Mental health, Schizophrenia, Anxiety, Original Article, monkey, medicine.symptom, Psychology, medicine.drug, Deep brain stimulation, Mediodorsal Thalamic Nucleus, Thalamus, MESH: Mediodorsal Thalamic Nucleus, Context (language use), Bicuculline, MESH: Macaca mulatta, 03 medical and health sciences, Cellular and Molecular Neuroscience, MESH: Bicuculline, thalamus, medicine, Animals, GABA-A Receptor Antagonists, Biological Psychiatry, MESH: Obsessive-Compulsive Disorder, medicine.disease, Macaca mulatta, 030227 psychiatry, Functional imaging, Disease Models, Animal, MESH: Anterior Thalamic Nuclei, Anterior Thalamic Nuclei, nervous system, MESH: Deep Brain Stimulation, MESH: Disease Models, Animal, Hypoactivity, Neuroscience, 030217 neurology & neurosurgery, MESH: Muscimol
Abstract

International audience; Obsessive-compulsive disorder (OCD) is a frequent psychiatric disorder characterized by repetitive intrusive thoughts and severe anxiety, leading to compulsive behaviors. Although medical treatment is effective in most cases, resistance is observed in about 30% of patients. In this context, deep brain stimulation (DBS) of the caudate or subthalamic nuclei has been recently proposed with encouraging results. However, some patients were unimproved or exhibited awkward side effects. Therefore, exploration of new targets for DBS remains critical in OCD. In the latter, functional imaging studies revealed overactivity in the limbic and associative cortico-subcortical loops encompassing the thalamus. However, the role of the thalamus in the genesis of repetitive behaviors and related anxiety is unknown. Here, we tested the hypothesis that pharmacological-induced overactivity of the medial thalamus could give rise to abnormal behaviors close to that observed in OCD. We modulated the ventral anterior (VA) and medial dorsal (MD) nuclei activity by in situ bicuculline (GABA(A) antagonist) microinjections in subhuman primates and assessed their pharmacological-induced behavior. Bicuculline injections within the VA caused significant repetitive and time-consuming motor acts whereas those performed within the MD induced symptoms of dysautonomic dysregulation along with abnormal vocalizations and marked motor hypoactivity. These findings suggest that overactivation of the VA and MD nuclei of the thalamus provokes compulsive-like behaviors and neurovegetative manifestations usually associated with the feeling of anxiety in OCD patients. In further research, this translational approach should allow us to test the effectiveness and side effects of these thalamic nuclei DBS in monkey and perhaps, in a second step, to propose a transfer of this technique to severely disabled OCD patients.

Published
2011

10. Subthalamic neuronal firing in obsessive-compulsive disorder and Parkinson disease

Author

Napoleon Torres, Paul Krack, Thierry Bougerol, Olivier David, Pierre Pollak, Laurent Goetz, Stephan Chabardes, Mircea Polosan, Valérie Fraix, Albert J. Fenoy, Brigitte Piallat, Alim L. Benabid, Jean-Louis Quesada, Eric Seigneuret, INSERM U836, équipe 11, Fonctions cérébrales et neuromodulation, Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Service de Psychiatrie, CHU Grenoble-CHU Grenoble, INSERM U836, équipe 10, Dynamique des réseaux neuronaux du mouvement, Département de neurologie, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de neuroradiologie, Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Commissariat à l'énergie atomique et aux énergies alternatives - Laboratoire d'Electronique et de Technologie de l'Information (CEA-LETI), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), CIC - Grenoble, INSERM U836, équipe 7, Nanomédecine et cerveau, Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de neurochirurgie, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-CHU Grenoble, Service de Psychiatrie, CHU Grenoble, and David, Olivier

Subjects
Male, Action Potentials/physiology, Obsessive-Compulsive Disorder, medicine.medical_treatment, MESH: Neurons, Action Potentials, Functional Laterality, Functional Laterality/physiology, Magnetic Resonance Imaging/methods, MESH: Magnetic Resonance Imaging, 0302 clinical medicine, Degenerative disease, Basal ganglia, Premovement neuronal activity, MESH: Action Potentials, Neurons, MESH: Aged, 0303 health sciences, MESH: Middle Aged, Parkinson Disease, Middle Aged, Magnetic Resonance Imaging, Subthalamic nucleus, medicine.anatomical_structure, Imaging, Three-Dimensional/methods, Neurology, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Psychology, Anxiety disorder, Adult, Deep brain stimulation, Parkinson Disease/pathology, MESH: Imaging, Three-Dimensional, Central nervous system disease, 03 medical and health sciences, Imaging, Three-Dimensional, Subthalamic Nucleus, medicine, Humans, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], MESH: Functional Laterality, Obsessive-Compulsive Disorder/pathology, 030304 developmental biology, Aged, MESH: Subthalamic Nucleus, MESH: Obsessive-Compulsive Disorder, MESH: Humans, MESH: Adult, Subthalamic Nucleus/pathology, medicine.disease, MESH: Male, ddc:616.8, Neurology (clinical), Neuron, Neurons/physiology, Neuroscience, MESH: Female, 030217 neurology & neurosurgery, MESH: Parkinson Disease
Abstract

International audience; OBJECTIVE: Although electrophysiologic dysfunction of the subthalamic nucleus is putative, deep brain stimulation of this structure has recently been reported to improve obsessions and compulsions. In Parkinson disease, sensorimotor subthalamic neurons display high-frequency burst firing, which is considered as an electrophysiologic signature of motor loop dysfunction. We addressed whether such neuronal dysfunction of the subthalamic nucleus also exists in the nonmotor loops involved in patients with obsessive-compulsive disorder. METHODS: We compared the neuronal activity of the subthalamic nucleus recorded in 9 patients with obsessive-compulsive disorder with that of 11 patients with Parkinson disease measured during intraoperative exploration for deep brain stimulation. RESULTS: The mean subthalamic neuron discharge rate was statistically lower in patients with obsessive-compulsive disorder than in patients with Parkinson disease (20.5 ± 11.0 Hz, n = 100 and 30.8 ± 15.6 Hz, n = 93, respectively, p < 0.001). The relative proportion of burst neurons did not differ significantly between the 2 diseases (75% vs 73%). Interestingly, burst neurons were predominantly left-sided in obsessive-compulsive disorder. INTERPRETATION: The recording of burst neurons within the nonmotor subthalamic nucleus in patients with obsessive-compulsive disorder is a novel finding that suggests the existence of deregulation of the nonmotor basal ganglia loop, possibly left-sided. Potentially, burst activity might interfere with normal processes occurring within nonmotor loops.

Published
2011
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11. Decrease of prefrontal metabolism after subthalamic stimulation in obsessive-compulsive disorder: a positron emission tomography study

Author

Julie Anne Peron, Mircea Polosan, Florence Le Jeune, Denys Fontaine, Sophie Tezenas du Montcel, Marie-Odile Krebs, Antoine Pelissolo, Aurélie Bourguignon, Dominique Drapier, Nicolas Baup, Bertrand Devaux, Paul Sauleau, Bruno Millet, Sylvie Raoul, Nematollah Jaafari, Isabelle Chereau, Etienne Garin, Marc Vérin, Emmanuelle Leray, Luc Mallet, K. N’Diaye, Jérôme Yelnik, Département de médecine nucléaire [Rennes], CRLCC Eugène Marquis (CRLCC), Comportement et noyaux gris centraux = Behavior and Basal Ganglia [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes (INCR), Service de Neurologie [Rennes] = Neurology [Rennes], CHU Pontchaillou [Rennes], Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de psychiatrie, CHU Pontchaillou [Rennes]-Hôpital Guillaume Régnier, Service de santé publique et d'épidémiologie, Hôpital Pontchaillou-CHU Pontchaillou [Rennes], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Hôpital Sainte-Anne, CIC AP-HP (pitie-Salpetriere)/inserm, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), ANTE-INSERM U836, équipe 11, Fonctions cérébrales et neuromodulation, CHU Grenoble-CHU Grenoble, Service de Neurochirurgie, Centre Hospitalier Universitaire de Nice (CHU Nice), CHU Clermont-Ferrand, Service de physiologie, Service de neurochirurgie, CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), This study was supported by a grant from Medtronic to Dr. Millet., French Stimulation dans le trouble obsessionnel compulsif (STOC) study group, Pollak, Pierre, David, Olivier, Université de Rennes (UR)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes (INCR), Laboratoire de psychologie cognitive et sociale (LPCS), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), The French Stimulation dans le trouble obsessionnel compulsif (STOC) study group, CHU Pontchaillou [Rennes]-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université européenne de Bretagne - European University of Brittany (UEB)-Institut des Neurosciences Cliniques de Rennes (INCR), Recherche en Pharmaco-épidémiologie et Recours aux Soins (REPERES), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP), EA Management des Organisations de Santé (EA MOS), École des Hautes Études en Santé Publique [EHESP] (EHESP)-PRES Sorbonne Paris Cité, École des Hautes Études en Santé Publique [EHESP] (EHESP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de psychiatrie adulte [CHU Pitié-Salpêtière], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Psychiatrie, CHU Grenoble, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5), Service de neurochirurgie [Rennes] = Neurosurgery [Rennes], Microenvironnement et remodelage, Service de médecine nucléaire [Rennes], CRLCC Eugène Marquis (CRLCC)-CRLCC Eugène Marquis (CRLCC)-Foie, métabolismes et cancer, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Guillaume Régnier (CHGR), CH Régnier, Université de Rennes (UR)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes = Institute of Clinical Neurosciences of Rennes (INCR), CRLCC Eugène Marquis ( CRLCC ), Comportement et noyaux gris centraux [Rennes], Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Université européenne de Bretagne ( UEB ) -CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes (INCR), Service de Neurologie [Rennes], Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière ( CRICM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Service d'informatique médicale, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -Hôpital Sainte-Anne, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), CHU Nice, Université de Poitiers-Centre hospitalier universitaire de Poitiers ( CHU Poitiers ) -Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut des Neurosciences Cliniques de Rennes (INCR)-CHU Pontchaillou [Rennes]-Université européenne de Bretagne - European University of Brittany (UEB)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-Hôpital Sainte-Anne, Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [APHP], Service de neurochirurgie [Rennes], Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )

Subjects
Male, Obsessive-Compulsive Disorder, Deep Brain Stimulation, medicine.medical_treatment, MESH : Prefrontal Cortex, Severity of Illness Index, 0302 clinical medicine, obsessive compulsive disorder, MESH : Obsessive-Compulsive Disorder, MESH : Gyrus Cinguli, MESH: Treatment Outcome, subthalamic nucleus, MESH: Middle Aged, MESH: Image Processing, Computer-Assisted, 3. Good health, MESH: Adult Brain Mapping Cross-Over Studies Deep Brain Stimulation Double-Blind Method Female Gyrus Cinguli/radionuclide imaging Humans Image Processing, Computer-Assisted Male Middle Aged Obsessive-Compulsive Disorder/radionuclide imaging* Obsessive-Compulsive Disorder/therapy* Positron-Emission Tomography Prefrontal Cortex/radionuclide imaging* Severity of Illness Index Statistics, Nonparametric Subthalamic Nucleus/surgery* Treatment Outcome, MESH : Image Processing, Computer-Assisted, medicine.medical_specialty, Deep brain stimulation, behavioral disciplines and activities, Statistics, Nonparametric, 03 medical and health sciences, MESH: Severity of Illness Index, MESH: Gyrus Cinguli, MESH : Double-Blind Method, Humans, MESH : Middle Aged, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Biological Psychiatry, MESH: Subthalamic Nucleus, MESH: Obsessive-Compulsive Disorder, MESH: Humans, MESH : Deep Brain Stimulation, MESH : Humans, MESH : Positron-Emission Tomography, MESH: Adult, nervous system diseases, 030227 psychiatry, Subthalamic Nucleus/surgery, nervous system, Positron-Emission Tomography, MESH: Deep Brain Stimulation, orbitofrontal cortex, Gyrus Cinguli/radionuclide imaging, Neuroscience, MESH: Female, 030217 neurology & neurosurgery, Cingulate cortex, 18FDG-PET, MESH : Brain Mapping, Gyrus, Image Processing, Computer-Assisted, MESH : Female, MESH: Double-Blind Method, Prefrontal cortex, MESH: Brain Mapping, Brain Mapping, MESH: Statistics, Nonparametric, Cross-Over Studies, Putamen, MESH : Adult, Middle Aged, MESH: Positron-Emission Tomography, deep brain stimulation, Subthalamic nucleus, surgical procedures, operative, Treatment Outcome, medicine.anatomical_structure, Cingulate gyrus, Cardiology, MESH : Severity of Illness Index, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Internal capsule, Psychology, therapeutics, Adult, MESH : Male, MESH : Subthalamic Nucleus, Prefrontal Cortex, MESH : Treatment Outcome, Gyrus Cinguli, MESH: Cross-Over Studies, Double-Blind Method, Internal medicine, medicine, MESH : Statistics, Nonparametric, Prefrontal Cortex/radionuclide imaging, Postcentral gyrus, [SCCO.NEUR]Cognitive science/Neuroscience, MESH : Cross-Over Studies, MESH: Male, ddc:616.8, [ SDV.NEU ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Orbitofrontal cortex, MESH: Prefrontal Cortex, Obsessive-Compulsive Disorder/radionuclide imaging/therapy
Abstract

International audience; Background:High-frequency bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) is a promising treatment in refractory obsessive-compulsive disorder (OCD). Method Using the crossover, randomized, and double-blind procedure adopted by the STOC study, 10 patients treated with high-frequency bilateral STN DBS underwent am 18-fluorodeoxyglucose positron emission tomography (PET) investigation to highlight the neural substratum of this therapeutic approach. Results The median YaleBrown Obsessive Compulsive Scale (Y-BOCS) scores for all 10 patients were 31 (minimum = 18, maximum = 36) with "Off-Stimulation" status and 19 (minimum = 0, maximum = 30) with "On-Stimulation" status (p = .05). The OCD patients in Off-Stimulation status showed a hypermetabolism in the right frontal middle and superior gyri, right parietal lobe, postcentral gyrus, and bilateral putamen compared with healthy control subjects. A significant decrease in cerebral metabolism was observed in the left cingulate gyrus and the left frontal medial gyrus in On-Stimulation conditions compared with Off-Stimulation conditions. In addition, the improvement assessed by Y-BOCS scores during the On-Stimulation conditions was positively correlated with PET signal changes at the boundary of the orbitofrontal cortex and the medial prefrontal cortex, between PET signal changes and the Y-BOCS scores modifications in On-Stimulation status. Conclusion This study suggests that the therapeutic effect of STN DBS is related to a decrease in prefrontal cortex metabolism. © 2010 Society of Biological Psychiatry.

Published
2010
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12. Deep brain stimulation: from neurology to psychiatry?

Author

Jorge Guridi, Jose A. Obeso, Paul Krack, Christelle Baunez, Marwan Hariz, INSERM U836, équipe 10, Dynamique des réseaux neuronaux du mouvement, Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Unité de Désordres du Mouvement, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-CHU Grenoble, Sobell Department of Motor Neuroscience and Movement Disorders, The National Hospital for Neurology and Neurosurgery-UCL Institute of Neurology, Department of Clinical Neuroscience, Umeå University, Laboratoire de Neurosciences Cognitives [Marseille] (LNC), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Department of Neurology and Neurosurgery, Universidad de Navarra [Pamplona] (UNAV)-Medical School-Clinica Universitaria and Neuroscience Centre, Centro de Investigacion Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III [Madrid] (ISC), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), and Savasta, Marc

Subjects
Obsessive-Compulsive Disorder, Neurology, MESH: Psychiatry, Deep Brain Stimulation, medicine.medical_treatment, MESH: Depressive Disorder, Tourette syndrome, Basal Ganglia, MESH: Basal Ganglia, MESH: Tourette Syndrome, Tourette Syndrome/therapy, 0302 clinical medicine, Thalamus, Psychosurgery/methods, Basal ganglia, Limbic System, MESH: Psychosurgery, Brain/*physiopathology, Cerebral Cortex, Psychiatry, MESH: Thalamus, 0303 health sciences, Basal Ganglia/physiopathology, Mental Disorders, General Neuroscience, Brain, Parkinson Disease, Neuromodulation (medicine), 3. Good health, MESH: Limbic System, Mental Disorders/*therapy, MESH: Neurology, MESH: Substance-Related Disorders, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Thalamus/physiopathology, Deep Brain Stimulation/utilization, Psychology, Psychosurgery, Nerve Net/*physiopathology, medicine.medical_specialty, Deep brain stimulation, Substance-Related Disorders, Cerebral Cortex/physiopathology, Parkinson Disease/*therapy, 03 medical and health sciences, MESH: Brain, Substance-Related Disorders/therapy, medicine, Humans, MESH: Mental Disorders, Depressive Disorder/therapy, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], 030304 developmental biology, MESH: Obsessive-Compulsive Disorder, Depressive Disorder, MESH: Humans, Limbic System/physiopathology, medicine.disease, Lobotomy, MESH: Cerebral Cortex, nervous system, MESH: Nerve Net, Obsessive-Compulsive Disorder/therapy, Nerve Net, MESH: Deep Brain Stimulation, Neuroscience, Treatment-resistant depression, 030217 neurology & neurosurgery, MESH: Parkinson Disease, Tourette Syndrome
Abstract

International audience; Functional stereotaxy was introduced in the late 1940s to reduce the morbidity of lobotomy in psychiatric disease by using more focal lesions. The advent of neuroleptics led to a drastic decline in psychosurgery for several decades. Functional stereotactic neurosurgery has recently been revitalized, starting with treatment of Parkinson's disease, in which deep brain stimulation (DBS) facilitates reversible focal neuromodulation of altered basal ganglia circuits. DBS is now being extended to treatment of neuropsychiatric conditions such as Gilles de la Tourette syndrome, obsessive-compulsive disorder, depression and addiction. In this review, we discuss the concept that dysfunction of motor, limbic and associative cortico-basal ganglia-thalamocortical loops underlies these various disorders, which might now be amenable to DBS treatment.

Published
2010
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13. Mutation screening of NOS1AP gene in a large sample of psychiatric patients and controls

Author

Isabelle Scheid, Stéphane Jamain, Catalina Betancur, Marion Leboyer, Evelyn Herbrecht, Henrik Anckarsäter, Anne Dumaine, Richard Delorme, Christopher Gillberg, Maria Råstam, Pauline Chaste, Gudrun Nygren, Franck Schuroff, Thomas Bourgeron, Marie Christine Mouren, Service de psychopathologie de l'enfant et de l'adolescent, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Génétique Humaine et Fonctions Cognitives, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie des Maladies du Système Nerveux Central, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Child and Adolescent Psychiatry, University of Gothenburg (GU), Service de psychiatrie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Saint George's Hospital Medical School, Université Paris Diderot - Paris 7 (UPD7), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, and Guellaen, Georges

Subjects
Male, Obsessive-Compulsive Disorder, MESH: Amino Acid Sequence, MESH: Protein Isoforms, Bioinformatics, medicine.disease_cause, MESH: Child Development Disorders, Pervasive, MESH: Genotype, 0302 clinical medicine, Gene Frequency, NOS1AP, MESH: Child, Genotype, Protein Isoforms, Genetics(clinical), Child, Genetics (clinical), Genetics, MESH: Aged, 0303 health sciences, Mutation, MESH: Middle Aged, Middle Aged, MESH: Amino Acid Substitution, 3. Good health, Pedigree, Schizophrenia, Female, Research Article, Adult, medicine.medical_specialty, lcsh:Internal medicine, MESH: Mutation, lcsh:QH426-470, MESH: Pedigree, Molecular Sequence Data, Biology, behavioral disciplines and activities, 03 medical and health sciences, mental disorders, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, medicine, MESH: Gene Frequency, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Amino Acid Sequence, Allele, Psychiatry, lcsh:RC31-1245, Allele frequency, Alleles, 030304 developmental biology, Adaptor Proteins, Signal Transducing, Aged, MESH: Adaptor Proteins, Signal Transducing, MESH: Obsessive-Compulsive Disorder, MESH: Humans, MESH: Molecular Sequence Data, MESH: Alleles, MESH: Adult, medicine.disease, Human genetics, MESH: Male, MESH: Schizophrenia, lcsh:Genetics, Amino Acid Substitution, Child Development Disorders, Pervasive, Autism, MESH: Female, 030217 neurology & neurosurgery
Abstract

Background The gene encoding carboxyl-terminal PDZ ligand of neuronal nitric oxide synthase (NOS1AP) is located on chromosome 1q23.3, a candidate region for schizophrenia, autism spectrum disorders (ASD) and obsessive-compulsive disorder (OCD). Previous genetic and functional studies explored the role of NOS1AP in these psychiatric conditions, but only a limited number explored the sequence variability of NOS1AP. Methods We analyzed the coding sequence of NOS1AP in a large population (n = 280), including patients with schizophrenia (n = 72), ASD (n = 81) or OCD (n = 34), and in healthy volunteers controlled for the absence of personal or familial history of psychiatric disorders (n = 93). Results Two non-synonymous variations, V37I and D423N were identified in two families, one with two siblings with OCD and the other with two brothers with ASD. These rare variations apparently segregate with the presence of psychiatric conditions. Conclusions Coding variations of NOS1AP are relatively rare in patients and controls. Nevertheless, we report the first non-synonymous variations within the human NOS1AP gene that warrant further genetic and functional investigations to ascertain their roles in the susceptibility to psychiatric disorders.

Published
2010
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14. Search for copy number variants in chromosomes 15q11-q13 and 22q11.2 in obsessive compulsive disorder

Author

Wolfgang Maier, Michael Wagner, Daniel Moreno-De-Luca, Richard Delorme, Catalina Betancur, Aurélie Gennetier, Peter Falkai, Rainald Mössner, Stephan Ruhrmann, Hans J. Grabe, Marion Leboyer, Marie-Christine Mouren, Pauline Chaste, Service de psychopathologie de l'enfant et de l'adolescent, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Physiopathologie des Maladies du Système Nerveux Central, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Psychiatry and Psychotherapy, Rheinische Friedrich-Wilhelms-Universität Bonn, Universität Greifswald - University of Greifswald, University of Cologne, Georg-August-University = Georg-August-Universität Göttingen, Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7), This research was supported by INSERM, Fondation de France, FondaMental Foundation, and the German Research Foundation (DFG)., Betancur, Catalina, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, and Georg-August-University [Göttingen]

Subjects
Male, Obsessive-Compulsive Disorder, Chromosomes, Human, Pair 22, Gene Dosage, [SDV.GEN] Life Sciences [q-bio]/Genetics, MESH: Gene Dosage, 0302 clinical medicine, Segmental Duplications, Genomic, DiGeorge syndrome, MESH: Child, Genetics(clinical), MESH: Syndrome, Copy-number variation, MESH: Chromosomes, Human, Pair 22, Child, Genetics (clinical), Sequence Deletion, Genetics, 0303 health sciences, MESH: Middle Aged, MESH: Genetic Predisposition to Disease, Syndrome, Middle Aged, MESH: Sequence Deletion, 3. Good health, MESH: Young Adult, Female, MESH: DNA Copy Number Variations, Chromosome Deletion, Prader-Willi Syndrome, Research Article, Adult, medicine.medical_specialty, lcsh:Internal medicine, lcsh:QH426-470, Adolescent, DNA Copy Number Variations, MESH: Chromosome Deletion, Biology, Gene dosage, behavioral disciplines and activities, 03 medical and health sciences, Young Adult, MESH: Segmental Duplications, Genomic, mental disorders, medicine, DiGeorge Syndrome, Humans, Genetic Predisposition to Disease, Multiplex ligation-dependent probe amplification, lcsh:RC31-1245, Gene, 030304 developmental biology, MESH: Adolescent, MESH: Obsessive-Compulsive Disorder, Chromosomes, Human, Pair 15, [SDV.GEN]Life Sciences [q-bio]/Genetics, MESH: Humans, MESH: DiGeorge Syndrome, Cytogenetics, Chromosome, MESH: Adult, medicine.disease, Human genetics, MESH: Male, lcsh:Genetics, MESH: Prader-Willi Syndrome, MESH: Female, 030217 neurology & neurosurgery, MESH: Chromosomes, Human, Pair 15
Abstract

Background Obsessive-compulsive disorder (OCD) is a clinically and etiologically heterogeneous syndrome. The high frequency of obsessive-compulsive symptoms reported in subjects with the 22q11.2 deletion syndrome (DiGeorge/velocardiofacial syndrome) or Prader-Willi syndrome (15q11-13 deletion of the paternally derived chromosome), suggests that gene dosage effects in these chromosomal regions could increase risk for OCD. Therefore, the aim of this study was to search for microrearrangements in these two regions in OCD patients. Methods We screened the 15q11-13 and 22q11.2 chromosomal regions for genomic imbalances in 236 patients with OCD using multiplex ligation-dependent probe amplification (MLPA). Results No deletions or duplications involving 15q11-13 or 22q11.2 were identified in our patients. Conclusions Our results suggest that deletions/duplications of chromosomes 15q11-13 and 22q11.2 are rare in OCD. Despite the negative findings in these two regions, the search for copy number variants in OCD using genome-wide array-based methods is a highly promising approach to identify genes of etiologic importance in the development of OCD.

Published
2010
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15. Exploratory analysis of obsessive compulsive symptom dimensions in children and adolescents: a Prospective follow-up study

Author

Catalina Betancur, Richard Delorme, Arnaud Bille, Flavie Mathieu, Marion Leboyer, Nadia Chabane, Marie Christine Mouren-Simeoni, Neurobiologie et Psychiatrie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de psychopathologie de l'enfant et de l'adolescent, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Département de Psychiatrie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Albert Chenevier, RD is supported by a fellowship from the Fondation pour la Recherche Médicale and NC was the recipient of a fellowship from the INSERM. The authors thank the patients and their families who made this research possible, and the Centre d'Investigation Clinique, Hôpital Robert Debré, for technical assistance., and Betancur, Catalina

Subjects
Male, Obsessive-Compulsive Disorder, MESH: Psychiatric Status Rating Scales, Psychometrics, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, 0302 clinical medicine, Surveys and Questionnaires, MESH: Child, lcsh:Psychiatry, Prospective Studies, Prospective cohort study, Child, Follow up studies, Age Factors, MESH: Genetic Heterogeneity, MESH: Comparative Study, MESH: Follow-Up Studies, Exploratory factor analysis, Psychiatry and Mental health, Phenotype, Female, Psychology, Research Article, medicine.medical_specialty, Adolescent, lcsh:RC435-571, MESH: Factor Analysis, Statistical, MESH: Phenotype, MESH: Psych, 03 medical and health sciences, Genetic Heterogeneity, Obsessive compulsive, medicine, Humans, Family, Psychiatry, MESH: Family, Psychiatric Status Rating Scales, MESH: Adolescent, MESH: Age Factors, MESH: Obsessive-Compulsive Disorder, MESH: Humans, Adult patients, Genetic heterogeneity, Reproducibility of Results, Exploratory analysis, MESH: Male, MESH: Prospective Studies, 030227 psychiatry, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Factor Analysis, Statistical, MESH: Female, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract

BackgroundRecent statistical approaches based on factor analysis of obsessive compulsive (OC) symptoms in adult patients have identified dimensions that seem more effective in symptom-based taxonomies and appear to be more stable over time. Although a phenotypic continuum from childhood to adulthood has been hypothesized, no factor analytic studies have been performed in juvenile patients, and the stability of OC dimensions in children and adolescents has not been assessed.MethodsThis study was designed to perform an exploratory factor analysis of OC symptoms in a sample of children and adolescents with OC disorder (OCD) and to investigate the course of factors over time (mean follow-up period: four years).ResultsWe report for the first time that four symptom dimensions, remarkably similar to those previously described in adults, underlined the heterogeneity of OC symptoms in children and adolescents. Moreover, after follow-up, the symptom dimensions identified remained essentially unmodified. The changes observed concerned the intensity of dimensions rather than shifts from one dimension to another.ConclusionThese findings reinforce the hypothesis of a phenotypic continuum of OC symptoms from childhood to adulthood. They also strengthen the interest for investigating the clinical, neurobiological and genetic heterogeneity of OCD using a dimension-based approach.

Published
2006
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16. Support for the association between the rare functional variant I425V of the serotonin transporter gene and susceptibility to obsessive compulsive disorder

Author

P. Pickering, Christopher Gillberg, Marie-Christine Mouren-Simeoni, Claudia Reck, Richard Delorme, Michael Wagner, Isabelle Roy, Philip Gorwood, Nadia Chabane, Catalina Betancur, Marie-Odile Krebs, Gudrun Nygren, Bruno Millet, Thomas Bourgeron, Friederike Buhtz, Phillip L. Pearl, Marion Leboyer, Jonas Melke, Henrik Anckarsäter, Christelle M. Durand, Stephan Ruhrmann, Amélie Kipman, Wolfgang Maier, Maria Råstam, Génétique Humaine et Fonctions Cognitives, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Neurobiologie et Psychiatrie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de psychopathologie de l'enfant et de l'adolescent, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Department of Psychiatry, Rheinische Friedrich-Wilhelms-Universität Bonn, Physiopathologie des Maladies Psychiatriques, Développement et Vulnérabilité, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Analyse Phenotypique, Developpementale et Genetique des Comportements Addictifs, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Children's National Medical Center, The George Washington University (GW), Department of Child and Adolescent Psychiatry, University of Gothenburg (GU), University of Greifwald, Department of Psychiatry and Psychotherapy, University of Cologne, Département de Psychiatrie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Albert Chenevier, Saint George's Hospital Medical School, Université Paris Diderot - Paris 7 (UPD7), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 ( UPD7 ), Bonn Universität [Bonn], Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), George Washington University ( GW ), University of Gothenburg ( GU ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Albert Chenevier, Université Paris Diderot - Paris 7 ( UPD7 ), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Betancur, Catalina

Subjects
Male, Proband, Obsessive-Compulsive Disorder, Anorexia Nervosa, MESH : Polymorphism, Genetic, Drug Resistance, Alcohol abuse, [SDV.GEN] Life Sciences [q-bio]/Genetics, MESH: Child Development Disorders, Pervasive, 0302 clinical medicine, MESH : Child, Reference Values, MESH: Child, MESH : Obsessive-Compulsive Disorder, MESH : Female, Family history, Child, Serotonin transporter, ComputingMilieux_MISCELLANEOUS, Serotonin Plasma Membrane Transport Proteins, 0303 health sciences, MESH: Middle Aged, biology, MESH: Genetic Predisposition to Disease, Middle Aged, MESH : Adult, Pedigree, 3. Good health, Alcoholism, Psychiatry and Mental health, Anorexia nervosa (differential diagnoses), MESH : Anorexia Nervosa, MESH: Drug Resistance, Female, Psychology, MESH: Anorexia Nervosa, Selective Serotonin Reuptake Inhibitors, Clinical psychology, Adult, medicine.medical_specialty, Adolescent, MESH: Pedigree, MESH : Male, Article, 03 medical and health sciences, Cellular and Molecular Neuroscience, MESH: Alcoholism, MESH : Adolescent, mental disorders, MESH: Polymorphism, Genetic, Pervasive developmental disorder, medicine, Humans, MESH : Child Development Disorders, Pervasive, Family, Genetic Predisposition to Disease, MESH : Middle Aged, Rare functional variant, Psychiatry, Molecular Biology, MESH: Family, 030304 developmental biology, MESH: Adolescent, MESH: Obsessive-Compulsive Disorder, MESH : Drug Resistance, [SDV.GEN]Life Sciences [q-bio]/Genetics, Polymorphism, Genetic, MESH: Humans, MESH : Alcoholism, MESH : Humans, Schedule for Affective Disorders and Schizophrenia, MESH: Adult, medicine.disease, MESH: Male, Child Development Disorders, Pervasive, MESH : Pedigree, biology.protein, MESH : Family, MESH : Genetic Predisposition to Disease, [ SDV.GEN ] Life Sciences [q-bio]/Genetics, MESH: Female, 030217 neurology & neurosurgery
Abstract

SIR—Recently, a rare functional variant, I425V, in the serotonin transporter gene (SLC6A4) has been reported to be associated with a complex neuropsychiatric phenotype that includes obsessive-compulsive disorder (OCD), alcohol abuse/dependence, anorexia nervosa, and pervasive developmental disorder (PDD).1 Our study, performed in a large population of patients with these disorders, confirms the occurrence and the segregation of V425 in OCD. The neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) has been implicated in numerous psychiatric disorders, mostly because of the efficacy of serotonin reuptake inhibitors (SRIs). Among the polymorphisms identified in SLC6A4, three have been shown to be functional. The rare I425V variation, located in exon 9, increases the transport activity of the protein2, whereas the two more frequent polymorphisms, 5-HTTLPR located in the 5′-UTR of the gene, and STin2 located in intron 2, modify the transcriptional activity of the gene3,4. Despite a large number of studies, the functional implications of the two frequent SLC6A4 polymorphisms in psychiatric disorders are still a matter of debate. In the present study, we sought to further explore the influence of the rare but clearly functional I425V variant in a large sample of patients with OCD and other psychiatric conditions previously reported in the two families carrying I425V, i.e., FDD, anorexia nervosa, and alcohol abuse/dependence. To be included in the study, patients had to meet the DSM-IV criteria for OCD, anorexia nervosa, alcohol abuse/dependence, or FDD. The diagnosis of FDD was confirmed using the Autism Diagnostic Interview-Revised.5 For the other disorders, lifetime psychiatric evaluation was carried out using the Diagnostic Interview for Genetic Studies (DIGS)6 for adult patients, or the Kiddie Schedule for Affective Disorders and Schizophrenia for children.7 Healthy controls were included after being interviewed with the DIGS and the Family Interview for Genetic Studies8 to confirm the absence of both personal and family history of major psychiatric disorders. The local Research Ethics Boards reviewed and approved the study. The V425 was found in 3/254 probands with OCD, 1/284 with PDD, 1/124 with anorexia nervosa, in 1/285 healthy controls, but not in alcohol abusers/dependents (0/128) (Table 1). In OCD family 1, V425 was transmitted by the father who also had a lifetime history of OCD and single phobia. The paternal grandfather was alcoholic and tobacco dependant. No genotypic information was available for the paternal grandparents since the grandfather died of throat cancer and the grandmother of breast cancer. In OCD family 2, the mother and two siblings of the proband had committed suicide and the father was also dead, so no genotypic information was available for these individuals. OCD case 1 had only one brother, who committed suicide some years ago, so no genotypic information was available for him. No other clinical data were available concerning the first-degree relatives of OCD case 1. In FDD family 1, V425 was transmitted by the father and was present in the proband and two brothers. The father and one of the brothers carrying the V425 were both alcohol dependent. However, the youngest brother (19 years old), also carrying the V425 variant, did not suffer from alcoholism or any other psychiatric disorder at the time of evaluation. Table 1 SCL6A4 genotypes and clinical features of the subjects included in the study Our results are in accordance with those previously reported by Ozaki et al1 on four points. First, we report a possibly higher occurrence of the V425 variant in OCD compared to controls. Although the variant is rare, the combined results of the two studies indicate a significantly higher frequency of V425 in OCD compared to controls1,9 (5/457 vs. 2/884, Fisher exact test, P= 0.02). Second, despite the limited clinical and genotypic information on the families carrying the V425 variant, our results suggest a possible co-segregation between the V425 and neuropsychiatric phenotypes, specifically in OCD. Third, Ozaki et al. hypothesized that the V425 variant may confer treatment-resistance to SRIs. This was indirectly supported by our findings since all OCD probands carrying the V425 variant in our study were considered resistant to SRIs, i.e., the severity of their obsessive and compulsive symptoms decreased less than 25% with multiple trials of a high dose of SRIs and a good compliance. Specifically, the three probands with OCD carrying the variant showed poor or no response to multiple trials of SRIs at adequate doses over several years. Fourth, the analysis of the two additional polymorphisms of the SCL6A4 gene indicated that the V425 polymorphism might be associated with the L allele of 5-HTTLPR. However, our results do not confirm the hypothesis of a combined gain of function effect of both V425 and L/L genotype as a genetic risk for OCD, since this combined genotype was not present in all affected patients and, by contrast, was present in the control subject carrying the V425 variant. In conclusion, our results are similar to those of the original report by Ozaki et al. and, therefore, lend support for a role of SLC6A4 V425 in the susceptibility to complex neuropsychiatric phenotypes. However, due to its global low frequency and to the fact that it was detected in a few controls, the role of V425 remains uncertain and should be interpreted with caution. We encourage other investigators, especially in the field of OCD, to screen for V425 in their samples. Indeed, the replication of these findings could ultimately implicate SLC6A4 as a true susceptibility gene to complex neuropsychiatric disorders, and consequently shed further light on the results obtained with the more frequent polymorphisms.

Published
2005
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